100 Questions & Answers about Infertility

DrG on NBC

2012-02-13T18:24:00.000-08:00

This morning one of my favorite patients, Kaet Ruffner, joined me on the Midday Show on NBC channel 4 here in Washington, DC. The topic was the comments that Mr. Gingrich had made concerning oversight of IVF and specifically concern about extra embryos. Of course, there are no extra embryos in Natural Cycle IVF ....one egg, one embryo, one baby. So off we went to NBC to talk about NC-IVF....

View more videos at: http://nbcwashington.com.

Endometriosis and NC IVF

2012-02-06T14:01:00.000-08:00

One thing is true in medicine and that is that you never want to be an interesting patient! Seriously. You should aim to have the condition that your doctor sees all the time and knows exactly what to do. As soon as you start getting a lot of "hmmms" and "wow, that is unusual'" then you may feel free to panic a little bit. Not a lot. Just a little. Because being an interesting patient doesn't preclude a happy outcome! It just means that when you are successful then the medical team feels like they deserve a victory lap. So here is a headline for today's blog about an interesting patient....

NC IVF results in only 2nd pregnancy ever reported in a patient with endometriosis hemorrhagic ascites undergoing IVF!

Ascites is a medical condition in which excess fluid accumulates in the abdomen. Usually we see this in young patients with OHSS. Oncologists see it in patients with cancer. This past year I saw a patient that had recurrent ascites resulting from severe endometriosis. How rare is this condition? Well there have only been 63 reported cases worldwide since 1954 ! That's pretty darn rare.

The patient had first noticed the problem in 2009 and had undergone several procedures to drain the blood fluid that accumulated slowly every day. Lupron dried up the fluid but she came to see me because she wanted to conceive.

We performed a laparoscopy in April 2011 and I was shocked to see how severe the endometriosis was at that time. I thought that it was actually ovarian cancer but the pathology proved it to be endometriosis.

Her options for fertility treatment were limited since we were concerned that the use of fertility drugs could make the whole process a lot worse. Her tubes were very damaged by the endometriosis that was everywhere so she needed IVF…..

Natural Cycle IVF to the rescue! She underwent one cycle of NC IVF. Egg collection was a bit unusual as the ovary was literally floating around in her abdominal fluid but we got a healthy egg, a beautiful embryo and a positive pregnancy test. She is currently almost 12 weeks pregnant and doing great! Another first for NC IVF and Dominion Fertility!

Question 61. I had an allergic reaction to the progesterone in oil shots. Does this mean that I cannot do IVF?

2012-02-03T11:11:00.000-08:00

We often have drug reps in the office at lunchtime. As there are only really 4 companies that make pharmaceuticals that are used in fertility we get to know the reps pretty well. This past week we were speaking with a couple of reps about vaginal progesterone in lieu of PIO. The data is very good regarding success with vaginal progesterone but honestly some patients just prefer the shots because the suppositories are so messy.

Both Endometrin and Crinone may prove less annoying to patients who want a shot-free 2ww but these products are also more expensive. I advise the husbands that they do NOT have a vote in this decision unless they are willing to take IM injections themselves. Just because I am driving a new car with the vanity plates CR1NONE should not be taken as evidence that my support of a product is based on anything except a careful review of the medical literature. But seriously, I really do not believe that most doctors are swayed to prescribe a drug just because they got a free pen or because the drug rep is a former cheerleader (although in fact, most drug companies do advertise in Cheerleader magazine according to this NY Times article).

So as we head into a beautiful weekend here in Washington DC here is the latest excerpt from 100 Questions and Answers about Infertility....

61. I had an allergic reaction to the progesterone in oil shots. Does this mean that I cannot do IVF?

Following follicle aspiration, most clinics place patients on progesterone supplementation. The rationale behind the supplemental progesterone is that following egg collection, ovarian hormone production may be impaired because many of the hormone-producing cells are removed at the time of follicle aspiration. In addition, the use of GnRH agonists such as Lupron may diminish ovarian steroid production following egg collection. Progesterone supplementation has evolved over the years to include patients undergoing both stimulated IUI cycles and IVF.

Although many clinics tend to use progesterone-in-oil injections, equivalent pregnancy rates have been reported in patients using only vaginal progesterone supplementation. Allergic reactions to progesterone are infrequent, but switching patients to vaginal progesterone usually resolves the problem.

Can NC IVF work following a failed stimulated cycle IVF?

2012-01-27T08:01:00.000-08:00

When a stimulated cycle IVF fails it is devastating to say the least....all that money, all those shots, all those morning visits, the bloating, the cramping, the PIO shots....yikes, it's a wonder we can convince anyone to try it again. Thank goodness the husbands don't have to go through all that or our business would fold overnight!

So following a failed stimulated IVF it is typical to ask what other options do I have. In cases of poor responders who may have not even made it to retrieval the answer has been "not much." Some of these patients will still conceive on their own, others will try a new protocol (or add DHEAs or human growth hormone or snake oil or miracle grow..). Donor egg or adoption are great options but not every couple will consider these as viable choices. So can NC IVF work in such a setting? "Certainly not," the critics of NC IVF would opine! After all, this approach to IVF is a terrible choice for any patient and how could this approach work in cases where our best treatment has already failed.

Sound logic. However, it just happens to be disproven on a near weekly basis by our patients who pursue NC IVF. Last year I asked what readers wanted from this blog and the majority stated they wanted patient stories so here are 2 vignettes that illustrate the use of NC IVF in patients over 35 with diminished ovarian reserve and failed stimulated cycle IVF!

Patient #1: Bonus baby with NC IVF after being told FSH levels precluded another IVF attempt!

Just received a wonderful email from a lovely couple who traveled all the way from Georgia to do NC IVF here at Dominion. Having had a previous IVF/ICSI baby in 2006 they had returned to their RE for another attempt at IVF. Previously the response to medications had been poor and this time the response was even worse with no retrieval even attempted. Her FSH was 18.9 and they were told that essentially no good options existed in terms of IVF. Fortunately, they had heard about NC IVF and we had a phone consult in April with an IVF attempt in June. Her AMH was <0.16 consistent with diminished ovarian reserve.

Her NC IVF cycle was picture perfect and they ended up with a beautiful early blast for transfer then headed back home. I received the good news that the blood pregnancy test was positive and rising fast. Then came the first shock...it was a twin pregnancy. Yup identical twins. Then came the second shock...the twins were sharing the same sac (in medical terminology they were mono-amniotic, mono-chorionic twins). Then the final shock...there was possibly a third sac.....Fortunately, this last shock turned was not true...there was just a probable blood clot that ultimately went away.

Pregnancy went amazingly well and the girls were delivered at 32 and a half weeks. They spent 2 days in the Intensive Care Nursery and should be home soon. What a great outcome to such a surprising story...one egg, one embryo, TWO healthy babies!

Patient #2: Ongoing pregnancy with NC IVF at 40 with FSH of 17 and AMH of <0.1

Back in 2009 I met DM who was turning 38 and been referred to me by one of my patients who had succeeded with NC IVF after being told donor egg was her only option. We discussed NC IVF versus stimulated IVF and elected to try stimulated IVF. On a MDL flare protocol we got 3 follicles but only one egg and she failed to conceive with transfer of that embryo. I suggested we consider NC IVF rather than pursue additional medicated cycles.

Her first NC IVF cycle resulted in a pregnancy but unfortunately she had a miscarriage. The second NC IVF cycle resulted in a healthy full term baby. She returned this Fall to try again. On day 3 of that third NC IVF attempt her FSH was 17. But we got a nice egg, a beautiful embryo and she conceived again. That makes her 3 for 3 using NC IVF. Currently she had an ongoing pregnancy and here's hoping for another successful outcome.

Again this demonstrates the limitation of ovarian reserve testing when applied to NC IVF. When one eliminates the use of fertility drugs all bets are off when it comes to ovarian reserve. Makes our job difficult since patients assume that diminished ovarian reserve = poor egg quality and the relationship just isn't that simple!

IUI vs IVF...The FASTT Trial

2012-01-24T06:28:00.000-08:00

Frequently I am asked about IUI compared to IVF and specifically about NC IVF compared with IUI. Although IUI can be successful, there are clear limitations to an IUI. First of all, unless pregnancy occurs an IUI does little to explain why a couple has failed to conceive.

Could the tube have failed to catch an egg(s)?
Could the sperm have failed to find an egg(s)?
Could the sperm have failed to fertilize an egg(s)?
Could the fertilized egg(s) have failed to grow?
Could the embryo(s) have failed to make it to the uterus and failed to implant?

The answer to all of these questions following a failed IUI is "we don't know."

This is the reason that IVF is a powerful diagnostic as well as therapeutic tool. It is so difficult to counsel a patient undergoing a stimulated IUI cycle with multiple dominant follicles. On the one hand you have to say "well, there are 6 good follicles so we could end up with 0-6 babies..." Then when it fails (which is more often than it succeeds) you have to say "well, we really have no idea why it didn't work." Very frustrating indeed.

The FASTT Trial aimed to look at the impact of omitting FSH/IUI for patients with unexplained infertility who were <40 years old. Its results clearly demonstrated the superiority of IVF first compared with FSH/IUI then IVF if FSH/IUI were unsuccessful. I think that NC IVF is also superior to IUI. Perhaps the comparable option would be CC/IUI but I think that NC IVF is likely superior to even FSH/IUI in cases where a couple has no previous pregnancies or there is possible male factor or possible tubal factor or endometriosis. Since many patients do not have a laparoscopy these days, it could be that many of them have an element of tubal disease or endometriosis and clearly IVF would be superior in these patients.
 
So for those wanting to conceive FAST.....think about the results of the FASTT trial and give strong consideration to IVF. It is not the only option but it may be the best option...whether it is NC IVF or stimulated cycle IVF.

Good luck.

DrG

A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2010 Aug;94(3):888-99. Reindollar et al.

Here comes 2012!!

2012-01-21T20:10:00.000-08:00

Happy New Year! (belated)

Good grief, somehow I have failed to post for nearly 6 weeks….How is this possible? Beats me but I am hoping to make up for it in 2012. This past year was full of ups and downs. I am hopeful that 2012 will be a little bit less of a roller coaster ride for the world economy. Last weekend I was camping (yes, in a tent) with the Boy Scouts at the USNA Jambo at Annapolis. It was pretty chilly at night and I may indeed be getting too old to sleep outside in a tent when all standing water freezes solid…Be that as it may, I was so impressed by the young men and women at the Naval Academy. What a great education and what outstanding young people…it gives me hope for the future that I rarely feel when reading about 20 somethings living in their parents' basement playing X Box 15 hours a day and transforming slowly into Jabba the Hut. So last weekend I was too busy to work on the blog.

I did get a week off as well just after Christmas and then there was an avalanche of charts to deal with upon my return. Still not sure where all my time went. I have no recollection of being abducted by space aliens so who knows how i managed to neglect the blog so long but there you have it.

There are still numerous chapters left to cover from our book. There are some very interesting cases from our clinic to share (with no identifying info) and there are some clinical questions that I really want to discuss.

As we start this New Year of 2012 I would also like to address those who wish to post a question or comment.

First of all, when you post a comment it goes to my Inbox before it gets posted to the site. Thus, don't fret if you fail to see your well constructed post appear with a single mouse click. I was getting so many posts about Viagra that I had to change my settings with Google so all posts had to be approved by me before they are posted to the blog.

Secondly, it would be nice for those who post comments to enter some sort of screen name. I get tired of replying to Anonymous #1, #2, #3 etc etc. No salesman will call. No email spam will be sent. I just think that if you are asking for an opinion then you can at least share some sort of name with me…even if it is totally unrelated to your real name.

Finally, if you are dying to read my opinion on a particular issue then please post it as a comment to this post and I will try to cover it this year. Medical issues are preferred but I can certainly weigh in on my favorite DC Pizza restaurant or why my wife hatesd Tom Brady and the New England Patriots and other matters of critical importance….

Happy New Year to all!

Question 60. My reproductive endocrinologist has recommended a protocol that uses birth control pills. Why would birth control pills be used in IVF?

2011-12-09T11:42:00.000-08:00

Last night I was speaking to a group of high school students that are interested in medicine as a career. I have spoken to such groups many times over the past 5 years and sometimes I feel like I am on the TV show "Kids Say the Darndest Things." Sometimes they get hung up on asking about transgendered individuals. Sometimes they ask about multiples like John and Kate plus Eight or the Octomom. Last night we got sidetracked into a discussion of the NuvaRing and oral contraceptives. These are high school kids I remind you....When I was in high school I spent most Saturday nights watching the Love Boat....I certainly was not wondering which girls were on forms of oral contraception. But amazingly enough I was able to eventually date, marry and reproduce...it gives me hope that geeks everywhere will be able to overcome social adversity...just look at Leonard on the Big Bang Theory as another success story!

Ok. So it's Friday afternoon and I am off this weekend so I am a bit punchy....What does all this have to do with IVF? Well some IVF protocols actually use oral contraceptives as part of the medication recipe. Personally, we don't use a lot of OCPs except in high responders. Recently I had a patient that came in for a second opinion prior to stimulated IVF. Her planned protocol was OCPs plus luteal Lupron and then stimulation drugs. She was 38 years old with an AMH of 0.5 and I recommended against that approach because I thought she would be over suppressed. Ultimately she went back to the original clinic, followed that recipe and never came close to egg collection as her stimulation was a total bust. She called me up and we discussed the plan over the phone and she was very upset....why did that clinic use OCPs on everyone? I told her that I couldn't answer that question and she should ask her RE at that clinic. She said that she was calling me since they never return her calls! Oh well. Hopefully next time she will have a better response...

So here is today's Question of the Day from 100 Questions and Answers about Infertility, Second Edition...

60. My reproductive endocrinologist has recommended a protocol that uses birth control pills. Why would birth control pills be used in IVF?

Birth control pills or, more correctly, oral contraceptive pills (OCPs) can be used as a part of the IVF stimulation protocol in several different settings.

First, in patients who are known or suspected to be high responders, OCPs may help mitigate the risk of ovarian hyperstimulation syndrome (OHSS). Second, in patients without predictable regular menstrual cycles, OCPs can be used in combination with Lupron to initiate an IVF cycle. In our practice, we usually start OCPs in such cases after confirming with a blood test that the woman has not recently ovulated. Then, after 1 week on OCPs, we add Lupron. After 1 more week, we stop the OCPs and continue the Lupron and wait for withdrawal bleeding. Once a patient has bled, we begin the gonadotropin stimulation.

Some clinics use OCPs as part of the protocol for microdose Lupron (MDL) flare, traditional flare, or GnRH-antagonist (Antagon, Centrotide) cycles in the hope that pretreatment with OCPs will prevent one follicle from growing faster than the other follicles once the stimulation has begun. We have not routinely used OCPs with our MDL flare patients, as we have rarely had problems with the emergence of a single dominant follicle compared with the more common problem of oversuppression and a cancelled cycle. Given that prolonged OCP use can lead to oversuppression in low responders, we use these medications very carefully.

Question 59. What is natural cycle IVF? And why does my fertility clinic not offer this treatment?

2011-12-03T08:33:00.000-08:00

As readers of this blog are well aware, we have a particular interest in Natural Cycle (unstimulated IVF). All I can say is that the past 4 years have been filled with outcomes that I would never have believed if these were not my own patients. Although it is not surprising that young healthy women with tubal factor infertility can conceive with Natural Cycle IVF, it is the patients that we thought were clearly long-shots that stick in your memory.

Once recent patient was B.W. (not her initials) who was a 41 year old whose husband had a vasectomy reversal 3 years earlier but had failed to conceive. Her evaluation revealed an FSH of 23 and an AMH that was < 0.16 (essentially zero!). We discussed donor egg and donor embryo and adoption. She was really not interested at this time in pursuing those options even though the success rates were clearly markedly superior to those with her own eggs.

So we elected to attempt NC IVF and during the treatment cycle her day 3 FSH came back at 40! I wasn't even sure if she would have normal follicle development but she did and we were able to get a mature egg. It fertilized with ICSI. It grew into a perfect looking blastocyst. She had an easy ET and her first beta was very positive. She currently has a normal ongoing pregnancy. I actually just called her this morning and she had her 20 week anatomy scan and all looks well!

If you made up cases like this, then no one would even believe it because it seems to fly in the face of conventional wisdom. So here is a bit of conventional wisdom from 100 Questions and Answers about Infertility, 2nd Edition...

59. What is natural cycle IVF? And why does my fertility clinic not offer this treatment?

Natural-cycle IVF (NC-IVF) has been proposed as a means of reducing the risk of multiple pregnancies, eliminating the costs and risks associated with fertility drugs, and reducing the stress and time commitment needed for traditional stimulated IVF. This approach has been espoused by a number of leaders in the field of IVF, including Dr. Robert Edwards, whose pioneering work along with Dr. Patrick Steptoe’s led to the birth of the world’s first IVF baby, Louise Brown, using NC IVF in 1978.

NC-IVF avoids the use of expensive ovarian stimulation drugs and their associated cost of about $4000 per treatment cycle. With NC-IVF the risks of ovarian hyperstimulation, multiple pregnancy, and the issues of cryopreserved extra embryos are avoided as only one embryo is produced. Total cost of Natural Cycle IVF is about 20% to 25% of the total cost of a conventional IVF cycle.

However, NC-IVF has its own set of disadvantages. For example, by not using fertility drugs, unexpected premature “LH surging” or ovulation can occur, leading to cancellation of the planned egg retrieval. This occurs in about 10% to 15% of treatment cycles. In such cases, if the fallopian tubes are open, the doctor may recommend converting the treatment to an intrauterine insemination (IUI) and possible a successful pregnacy. Furthermore, because only one egg and one embryo are produced, the chances for pregnancy are less than with conventional IVF when two or more embryos are transferred. Proponents of NC-IVF expect the “cumulative” pregnancy rate for NC-IVF to be similar to a single cycle of conventional IVF within one to three treatment cycles of NC-IVF.

The best candidates for NC-IVF are patients with regular menstrual cycles who are less than 36 years old and have normal ovarian reserve. Patients with tubal-factor infertility or male factor infertility may be good candidates for NC-IVF before resorting to conventional IVF. Older patients, patients with previous stimulated cycle IVF failures, patients with poor ovarian reserve or unexplained infertility all can be considered for NC-IVF but may experience lower pregnancy rates compared with younger patients with well defined fertility issues and no previous fertility treatments.

Many European fertility centers routinely use NC-IVF with good success rates. For a variety of reasons, the availability of NC-IVF in the United States has been limited. We believe that NC-IVF will soon become increasingly available as patients demand less stressful and less costly fertility treatments that utilize little to no fertility drugs with good pregnancy rates. In our clinic we have routinely demonstrated pregnancy rates of 25% per successful egg collection and 30-40% pregnancy rate per embryo transfer with NC-IVF. We have seen success in patients who had previously failed stimulated IVF and were told that donor egg IVF was their only option so NC IVF may represent a viable treatment option for many infertile couples even those with a poor prognosis with stimulated cycle IVF.

Happy Thanksgiving 2011

2011-11-28T05:10:00.000-08:00

Happy Thanksgiving to all!

I usually post this on Turkey Day but honestly I was so busy at work this past week that I never got around to doing it. At my mother-in-law's house in North Carolina we always go around the room before saying Grace and ask everyone to say what they are thankful for this year. It never hurts to count your blessings. In face, several medical studies have indicated that those individuals who have a positive attitude about their life and situation are healthier than those who always see the glass as half-empty. On the other hand my Dad has always been a glass is half-empty guy and he is still hanging in there at 88 years of age.....

I am thankful for my family...they are a source of love, support and joy...even the teenagers.

I am thankful for my health...although I would like my hair loss to slow down.

I am thankful for my career...I remain stimulated and enthusiastic about my profession.

I am thankful for my partners and staff...Couldn't ask for a better partner than DrD (12 years and counting) and Dr Reh and Dr Payson and all the employees at Dominion.

I am thankful for my patients...They have always been my best teachers.

I am thankful for my church....2 years on the Senior Pastor Search Committee failed to dampen my support for the National Presbyterian Church (still there is no politics like church politics!).

I am thankful for God from whom all these blessings flow (just like in the song)!

So that's my list and I am sticking by it!

Hope everyone had a Happy Turkey Day! I will try to get to those recent posts....

DrG

Question 58. Which types of drug protocols are used in IVF, and how is the most appropriate protocol selected?

2011-11-16T12:09:00.000-08:00

So last August I developed a wicked (note Bostonian roots given use of this adjective) toothache while on vacation at the Outer Banks. Naturally, I did what most physicians do...I started myself on antibiotics and ibuprofen and didn't call a dentist. By the next Monday I was not a happy camper and went to my general dentist only to be told I needed a root canal. Ugh. What a way to return from vacation. I took the recommendation of a local specialist and he did a fantastic job. Took 40 minutes and the next day I felt great! Last week it all started again and I went to my general dentist who said that I may need another root canal (different tooth). He proposed doing it himself without a referral to the specialist. I was in the chair already and it was 4:45 PM so I agreed to let him try. In retrospect, this was not a good decision. He found 2 of the 3 roots but ultimately quit the procedure at 6 PM and told me that I needed to see the specialist the next day anyway. I should have gone there first and next time I will. Dr. DiMattina scolded me for not knowing better....

REs are the specialists in this story. Many generalists are truly excellent physicians but infertility work represents only a small percetage of most general Ob/Gyn practices. Your RE only treats infertility and as a result I think that the advice and approach is superior. Of course, I have a jaded view being a specialist but I should have gotten out of that chair and high-tailed it back to the root canal specialist...Think about this carefully before taking 6 months of clomid with your Ob/Gyn!

Not all patients are created equal. Some patients are destined to be high-responders and some are low responders. This past year I had a patient who had PCOS and I was planning on using a lower dose stimulation. She went to another clinic because of insurance and was hit very hard with stimulation meds and ultimately the cycle was a bust. When we tried stimulation again I had her on one of the lowest doses that I had ever used for IVF but it was successful and we were all much relieved that the OHSS did not materialize. More recently we have been using the GnRH-antagonist protocol with Lupron instead of HCG to trigger for retrieval. This approach is very reasonable in the PCOS patient at risk for OHSS but care must be taken to support the endometrium following retrieval as the estrogen levels tend to drop like a rock and that may affect inplantation.....yup, no such thing as a free lunch.

So here is today's Question of the Day...

58. Which types of drug protocols are used in IVF, and how is the most appropriate protocol selected?

Although several drugs and protocols are available to stimulate the ovaries to produce extra eggs for IVF, most clinics utilize only a few of these stimulation protocols.

One of the more common IVF protocols is called luteal suppression (or long luteal or simply just long) and involves suppression of the ovaries using a GnRH-analog (Lupron) during the luteal phase of the menstrual cycle preceding the planned IVF treatment cycle. Once the ovaries are suppressed, ovarian stimulation is accomplished with daily injections of gonadotropins (e.g., Gonal-F, Follistim). Lupron is usually continued until the day of the hCG trigger shot. A common variation of this protocol is to stop Lupron at the time of starting stimulation. Not surprisingly, this protocol is called “stop Lupron.”

Another common protocol is called flare stimulation. In this case, the woman does not take any medications until the second day of her menstrual cycle. At that time, a microdose (most commonly) of Lupron is used to “flare” the pituitary gland and induce it to release its store of FSH and LH. Simultaneously, gonadotropins are started, producing a “one–two punch” in terms of ovarian stimulation. Premature ovulation of the eggs rarely occurs despite the low dose of GnRH agonist utilized in this protocol.

A third, more recent option is GnRH-antagonist stimulation, in which GnRH antagonists are added later in the stimulation to prevent premature ovulation. In this method, the gonadotropins are started on cycle day 2 of a normal menstrual period. Once the follicles have reached a specific size (usually 12 to 14 mm), the woman begins the GnRH-antagonist medication, which almost instantaneously prevents the pituitary gland from generating an LH surge.

Some reproductive endocrinologists prescribe oral contraceptive pills to their female patients prior to beginning the actual ovarian stimulation drugs, but this practice varies between patients and fertility clinics. We have found that the use of birth control pills often results in oversuppression of the ovaries and cycle cancellation except in those patients known to be high responders (women with PCOS, in particular).

The type of protocol selected for any patient (i.e., luteal suppression, flare stimulation or GnRH antagonist) depends on the individual patient and the philosophy of the fertility clinic. Factors that may influence the type of stimulation protocol selected include the patient’s age, her day 3 hormone levels, her follicle antral count as determined by ultrasound, and her previous responses to any other attempts at ovarian stimulation.

Question 57. I was told I need assisted hatching. What is this, and why is it done?

2011-11-10T15:23:00.000-08:00

Families are funny things. Some families are filled with artists and actors. Some are filled with athletes. Some are filled with engineers. Some are beyond simple description.

I grew up in a medical family and I am a 3rd generation physician. My nephew, Andrew, is currently a medical student at Tufts and he represents the first (maybe not the last) of the 4th generation Gordon to be a physician. My older brother Mike (on the far right in the photo) is a general surgeon in Sanford, NC. I don't think that he has gotten a full night's sleep in 25 years as he is regarded as the best surgeon at his hospital and is the most likely to be called when the ER needs a surgeon at 2 am!

My brother Steve was never interested in being a doctor. He is an outstanding hospital sdministrator. We talk several times a week which is incredible to me considering how much we fought as kids (so parents don't give up hope that your kids will someday get along!). But when we fought it was epic. He teased. He tortured. He told me I had been hatched!

But as you will see from today's Question of the Day, we actually all really do hatch! Steve just didn't realize it at the time....In IVF we sometimes recommend Assisted Hatching and let's take a look at what that means and who needs it..

57. I was told I need assisted hatching. What is this, and why is it done?

Dr. Gordon’s older brother Steven used to tease him by claiming that he was hatched and not born, but actually all of us do “hatch” in early embryonic life. The human embryo hatches out of the eggshell (zona pellucida) at the blastocyst stage of development. Assisted hatching involves weakening the zona to facilitate the emergence of the embryo following its transfer into the uterus after IVF. Proponents of assisted hatching suggest that it increases implantation and pregnancy rates.

Assisted hatching can be performed chemically or more recently using a laser. In the chemical technique, a dilute acid solution is used to dissolve the external eggshell. Some clinics still perform mechanical hatching, in which a slit is made in the eggshell. Along with many other clinics, we have moved to laser-assisted hatching, in which a laser is used to thin the zona sparing the embryo from any exposure to the chemicals used in hatching. (See Figure 5).

There is some controversy regarding which patients benefit most from assisted hatching, and the indications for assisted hatching remain somewhat unclear. Most clinics recommend this procedure in cases where the female partner is older than age 37, has diminished ovarian reserve with increased levels of FSH, or is undergoing a frozen embryo transfer (FET) with previously cryopreserved embryos. Patients who have previously failed IVF following replacement of good-quality embryos may also benefit from assisted embryo hatching.

The risks of assisted hatching are believed to be quite low. There have been reports of increased rates of identical twinning following mechanical hatching (but not after chemical or laser assisted hatching). There is no evidence that assisted hatching harms the embryo or causes any increased rate of birth defects in children.

Carol comments:
After my first IVF attempt failed for no obvious reason, the RE suggested that we utilize assisted hatching during our second attempt. We immediately moved into a second fresh cycle and employed assisted hatching. From my perspective, there was no difference. The procedure happened after the egg retrieval, so I was not involved. I did get pregnant during the second cycle, and in theory, the assisted hatching was the primary variable that was different.

Question 56. What is the Sperm Chromatin Structure Assay (SCSA), and should my husband have it done?

2011-10-15T08:01:00.000-07:00

The Holy Grail of Reproductive Endocrinology is the test that definitively tells us whether a patient has a good egg or a good sperm. This is not to be confused with the Holy Grail of Monty Python which is one of the finest films ever made and won the Oscar for "Best Movie Ever" the year after Highlander won that very same award. If you don't get these jokes then don't worry as it probably demonstrates that you are a lot more normal than me and explains why I spent every Saturday night in high school watching the Love Boat....

Back to fertility. So the million dollar question remains is there a good egg and a good sperm that can make a baby? The answer is we don't know until you actually deliver a healthy baby and then the answer is "yes" (obviously).

There have been tests proposed to answer this question. But do not be misguided into thinking that a woman's FSH, estradiol, AMH and antral follicle count answer that question...they do NOT.

Similarly, tests on sperm have been proposed to answer this question for men. I don't think that we have an answer but the SCSA has been proposed as a predictive test. Personally, I have not used this test as my understanding is that there is no level of sperm DNA fragmentation that precludes pregnancy. So let's go to the book and see what Dr D and yours truly had to offer on this subject.

56. What is the Sperm Chromatin Structure Assay (SCSA), and should my husband have it done?

The Sperm Chromatin Structure Assay (SCSA) has been proposed as a means to predict the likelihood of pregnancy in cases of male factor infertility. This test analyzes the degree of DNA fragmentation present in a representative sample of sperm. Increased levels of DNA fragmentation seem to be associated with reduced pregnancy rates, including poorer treatment outcomes with IVF and ICSI. There is no level of fragmentation above which pregnancy is completely ruled out, however, so the SCSA cannot ultimately provide a means to absolutely recommend the use of donor sperm over the sperm from the male partner. If a couple is making a choice between the use of donor sperm compared with partner sperm, then the SCSA may provide a relative indication to use the donor sperm option. At this time, most experts consider this test to be experimental.

Question 55. My husband and I were told by one RE that we needed ICSI, but another RE says that we don’t. What should we do?

2011-09-19T18:54:00.000-07:00

So if you have read the survey results you are aware that most readers like the clinical vignettes that I post to illustrate points of interest. ICSI really is an amazing procedure. It really should not work and yet we have hundreds of thousands of babies born after IVF/ICSI and some clinics do only ICSI and never do just plain IVF....

This year I had a returning patient. She and her husband had been successful with Natural Cycle IVF with ICSI. We did ICSI because they had unexplained infertility and his sperm parameters were slightly abnormal. Since they delivered a healthy baby after the second NC IVF, we thought that this should be a no-brainer.

However, that is not how it worked out. We kept getting tripped up. Almost all possible outcomes were experienced from no fert to embryo arrest. But the couple had absolutely no desire to try regular IVF. They were uncomfortable with many aspects of stimulated IVF and only wanted to try NC IVF.

Finally, on the 6th NC IVF since delivering I suggested that we try no ICSI as sperm quality looked OK. Guess what? Beautiful egg, normal fert, beautiful blast and now an ongoing pregnancy.

So was it doing IVF and not ICSI that made the difference or was it just time for them to have success....who knows.

This case demonstrates the difficulties we face in advising patients. Sometimes the decisions are clear cut but sometimes logic seems to depart. Patients want clear cut decisions and advice but as physicians we should be careful to reconsider all options if success is eluding us...

So as we keep working our way through all 100 Questions here is today's Question of the Day:

55. My husband and I were told by one RE that we needed ICSI, but another RE says that we don’t. What should we do?

ICSI is accepted as a standard treatment option for infertile couples with severe male factor infertility. In most clinics, approximately 50% to 90% of the eggs that are injected with sperm using ICSI will fertilize normally. Some eggs do not survive after injection with the sperm and subsequently degenerate.

The criteria regarding what constitutes severe male factor infertility, however, vary from clinic to clinic. One the one hand, some clinics use ICSI for all (or nearly all) patients based on the theory that assisted fertilization is better than no fertilization at all. Most clinics employ ICSI based upon specific sperm parameters. In general, ICSI is employed in cases where the semen analysis reveals abnormalities related to sperm count (less than 20 million/mL), sperm motility (less than 50% are motile), or sperm morphology (less than 30% have a normal shape). ICSI should also be considered in couples with no previous evidence of fertilization or a history of failed fertilization with a prior IVF attempt. ICSI must be used in cases of sperm obtained from the testicle or epididymis in men with azoospermia. Some clinics use ICSI in all cases of IVF with frozen donor sperm.

Not all cases are clear-cut, for example, in our clinic we often perform an IVF/ICSI split if sperm parameters are normal but the couple have no previous pregnancies. That is, the eggs that are collected during the oocyte retrieval phase are divided between normal fertilization and ICSI. If some component of male factor infertility is present, splitting the eggs between ICSI and IVF may reveal whether the sperm can actually fertilize an egg. If the eggs fail to fertilize with IVF but fertilize normally with ICSI, then the logical conclusion would be that the sperm is incapable of fertilizing the egg with IVF alone. Couples with unexplained fertilization failure with IVF may have a problem with the sperm, the egg, or both. In such cases a repeat cycle of IVF using ICSI will usually yield good fertilization results and, ideally, a pregnancy.

Summer's Over Now Back to Work

2011-09-07T07:54:00.000-07:00

Wow, no blogs in August 2011.....how did I manage to miss an entire month. I suppose I could blame it on the Earthquake that we had here in Northern Virginia....or Hurricane Irene...but the truth is that I was really enjoying summer and was just too tired and busy to post. Mea culpa.

Yesterday in the Wall Street Journal there was an entire article about the Post Labor Day Blues and apparently there is a recognized clinical syndrome called Post Vacation Syndrome. I know it well. Towards the end of my week at the beach on the Outer Banks I started to get a wicked toothache (note my clear Bostonian roots....just like seeing the movie The Town). I started myself on antibiotics and then on the Monday that I returned to work I found myself in the dentist chair in Arlington at 7 am. The news was not good...I needed an urgent root canal. Great. What a way to come back to work! So I got 2 recommendations from my general dentist and off I went at 11 am for my journey into the world of endodontics.

The doctor I saw was outstanding. He was amazingly skilled and I could tell from watching his hands that he was confident and precise in his approach to my procedure. The root canal took about 45 minutes and the next day I was 100% pain free. Amazing.

Out of curiosity I went online to check him out after the fact. Guess what? He had only a 60% positive rating. The reason seemed to be that he didn't spend enough time discussing the various options with some of the patients who posted. Another patient complained that he worked too fast !?! Let me tell you something, I have no knowledge of the ins and outs of endodontics. I have no desire to understand the ins and outs of endodontics. I wanted a skilled professional to do the right thing for me and I am very pleased with the result. That's why I am the patient and he is the dentist...

So as I prepare to get back into the swing of things I would like to share the results of the patient survey that I posted on Survey Monkey. Although nearly 10,000 individuals participated in the survey I have provided 49 of the best responses. Actually, truth be told those were the only responses. None of these are from my Mom.

If you want to see the summary of the survey then click HERE.

This month I have a lot of interesting stories to share and I will try to be a good Doc and post more frequently.

Goodbye Summer 2011.....you will be missed!

Question 54. Who needs ICSI, and how can my reproductive endocrinologist be certain that I need it?

2011-07-21T10:05:00.000-07:00

So as you may recall from Question 53, ICSI is that crazy technique that involves taking a sperm and inserting it into the egg to induce fertilization.....hard to believe that it works but there you have it.

Sometimes it is not that easy to figure out who needs ICSI and who doesn't. I have a nice couple that first came to me a few years ago with mild male factor infertility as the apparent cause. Ultimately they decided to pursue Natural Cycle IVF and were successful on the 2nd attempt of Natural Cycle IVF with ICSI. We used ICSI as they had no previous pregnancies and there was some mild male factor. We have tended to err on the side of ICSI with Natural Cycle IVF as there is only 1 egg and if we don't get fertilization then the cycle is a bust....

In any case, following delivery of a healthy baby from that first NC IVF cycle they returned last year for another round of NC IVF. However, we just couldn't get them pregnant. Several cycles ended in failed fertilization in spite of ICSI. They had no interest in any treatment other than NC IVF as they had moral/philosophical issues with the fertilization of multiple eggs.

So for NC IVF cycle #6, I made the bold recommendation to defer ICSI and go with just IVF. We got a nice egg, it fertilized, it grew, I did the ET of a perfect blastocycst and they are currently pregnant with Baby #2. Was it the IVF without ICSI that did it? Was it just a good egg? Was it the fact that DrG had been off that weekend and was well-rested for a Monday morning ET? Who knows? I am just glad that their persistence paid off.....

Another example of having to treat individuals and not applying cookie-cutter protocols to yoru patients....

So with all that said, here is the latest excerpt from our 100 Questions and Answers about Infertility book. Don't forget to respond to the poll so I can understand who besides my Mother reads this blog....

54. Who needs ICSI, and how can my reproductive endocrinologist be certain that I need it?

Most couples undergoing treatment with IVF do not require ICSI. The most common indication for ICSI is male factor infertility associated with an abnormal semen analysis. Thereore, men with unproven fertility whose sperm count, motility, or morphology is suboptimal are appropriate candidates for IVF with ICSI to ensure fertilization of the ova.

Another common indication for ICSI is unexplained infertility. In these couples, neither the man nor the woman has any apparent fertility-related problems. Their diagnostic evaluation is entirely normal, yet infertility exists. In such couples, traditional IVF may result in fertilization failure in 20-40% of IVF cycles. By using ICSI, the eggs are “forced” to fertilize, and the pregnancy rates are usually high. Fertilization rates with ICSI are usually 60-80% depending upon egg and sperm factors.

To Tweet or not to Tweet..that is the question...

2011-07-13T11:35:00.000-07:00

Although I am not an early adopter of technology, I am not a Luddite either. I have written this blog for a couple of years now and I think that at least 3 other people (besides my Mother) read my posts. I have usually focused on questions from our book on infertility but have commented on a range of other topics ranging from Princeton's epic win over Hahvahd at Yale earlier this year that secured an NCAA invitation for the men's basketball team to the reasons that some clinics fail to offer Natural Cycle IVF and so on.

I am now trying to figure out where Twitter fits into my approach to helping patients. Honestly, I am not really sure what the answer is to that question. I certainly have no plans to end up with a Weinergate type situation and I have had the experience of hitting "reply all" instead of just "reply" on email so I am aware of how embarrassing these miscues can be....

So in order to best serve my loyal base of almost 10 readers, I am asking for you to take about 45 seconds out of your busy days to participate in an anonymous survey about this blog. There is no way for me to identify you, nor do I have any desire to do so. I guess you can always tell me that you were the one who said that you think I should give up medicine and start selling Amway but I leave that to your discretion.

So please help me out here and as they say in Chicago: "Vote early and vote often!"

Click here to go to Survey Monkey and take the Poll. Thanks!

DrG

Question 53: What is ICSI, and how does it differ from IVF?

2011-07-06T13:34:00.000-07:00

In medical school at Duke I took a class in reproductive physiology taught by Dr. Patricia Saling. She was very engaging lecturer and the class was very interesting. During the class we had to memorize the sequence of events that included the fusing of the egg and sperm membranes, the release of the enzymes in the sperm acrosome and a bunch of other steps that I no longer remember. The possibility that you could get a baby from ramming a sperm into the middle of the egg with a micro-injector was just laughable....I would have flunked the class if I suggested it! So when the Belgium group reported on their experience with ICSI at the 1993 ASRM meeting in Boston no one could really believe it....seemed nutty. Yet here we are nearly 20 years later and ICSI seems totally banal! Hard to believe....

More on ICSI in the coming posts but here is today's Question of the Day from 100 Questions and Answers about Infertility, 2nd Edition.

53. What is ICSI, and how does it differ from IVF?

In routine IVF, eggs are placed in a laboratory dish in culture media together with prepared sperm. The eggs and sperm are allowed to spontaneously fertilize overnight. The fertilized eggs then develop and in the incubator until the embryo transfer procedure, which is usually performed 3 to 5 days after the egg retrieval.

Intracytoplasmic sperm injection (ICSI) differs from IVF in that each egg is individually injected with a single sperm using a tiny needle under microscopic guidance (Figure 4). The resulting embryo is then cultured similarly to an embryo produced in a non-ICSI IVF treatment.

ICSI was initially introduced by the IVF team working at the Brussels Free University in Belgium. At that time, assisted fertilization was being attempted through the insertion of the sperm under the eggshell (zona pellucida). The Belgian group took the extra step of injecting the sperm not only under the eggshell but actually into the middle of the egg itself. The first ICSI pregnancies were reported in 1992. Since then, tens of thousands of children have been born as a result of this unique procedure.

Both ICSI and non-ICSI IVF have similar pregnancy rates and outcomes. The embryos produced by either method should not be considered to be superior to those created with the other. ICSI is simply a method to ensure that the egg is fertilized. ICSI is a safe and proven IVF method that does not increase the likelihood that the child conceived in this way will have a birth defect.

Question 52. Are there age or other restrictions on who should do IVF?

2011-06-30T11:25:00.000-07:00

You know, Dear Reader, when I started in practice over 15 years ago I used to get the "you're too young to be my doctor." Now, not so much. Growing older is a fact of life. I personally find it very disturbing that the medical students that I teach at GWU were born in the 80s or even in the 90s (some Doogie Howser types). Unfortunately, the aging process is difficult to fight against. Some patients are now considering freezing eggs for future use, but this process has limitations and usually the patients seeking to freeze eggs probably should have done it 10 years ago but at that time they didn't think that they would need to freeze eggs for future use....

Fertility treatment success rates are age dependent and stimulated cycle IVF pregnancies in patients over 43 years old are very uncommon and usually limited to those patients who are still excellent responders to stimulation in spite of being on the other side of 40... FSH/IUI can be considered in patients with patent fallopian tubes and good sperm but what about the rest of the patients?

More recently we have used Natural Cycle IVF as an option for those patients unwilling to consider adoption or donor egg IVF. Some of these patients have succeeded including a 47 year old who had previously failed 4 stimulated cycle IVF attempts. We believe that patients should be offered the chance to pursue Natural Cycle IVF in such situations, although we are very clear in our expectations. We anticipate that rarely patients will have success. Those who fail to conceive still seem very appreciative that they were given a chance.

Imagine if Oncologists refused to treat cancer patients with a poor prognosis because it would hurt their statistics? I know that infertility and cancer are very different but both carry huge emotional and psychological costs.

So here is today's Question of the Day from 100 Questions and Answers about Infertility. An excellent book, according to my parents (see below), even though it was not written by any alumni of Tufts University or Tufts School of Medicine!

52. Are there age or other restrictions on who should do IVF?

Age restrictions for IVF vary from clinic to clinic. In general, women older than age 40 have a markedly lower chance for a live birth compared with women younger than 40 years old. Age is probably the most important factor influencing the outcome of an IVF cycle. Many clinics will not treat patients older than age 42, and some malpractice carriers dictate that physicians not perform IVF on patients older than 43 years old with their own eggs because of the poor IVF delivery rates related to advancing age.

A woman’s chances for successful stimulated IVF can also be predicted by measurement of her FSH and estradiol levels on cycle day 3. Elevations in either hormone are associated with poor IVF success rates, so many clinics impose additional restrictions once the FSH or estradiol levels are known to be elevated. The clomiphene citrate challenge test (CCCT) is another means by which to assess ovarian reserve and predict IVF success. Older women, those with elevated FSH levels on cycle day 3, and those with elevated estradiol levels may consider IVF with donor eggs or adoption.

Natural Cycle IVF has emerged as another treatment alternative for patients with diminished ovarian reserve. Remember that tests of ovarian reserve predict a patient’s response to fertility medications but no test exists to predict the presence or absence of a healthy egg in a given patient. The only true means to determine the presence of a healthy egg is that of delivering a healthy child – that proves that the patient had at least one good egg! Interestingly, the oldest woman to successfully conceive and deliver a healthy baby with her own egg using IVF was a patient who underwent Natural Cycle IVF and delivered at age 49.

Rebecca comments:
At over 40 years of age, I was fortunate that I had an RE that saw beyond my chronological age and aggressively worked with my husband and me to achieve a pregnancy and live birth using my own eggs. Our third and successful IVF resulted in boy/girl twins from eggs retrieved the day before my 42nd birthday. That said, our family building journey (two IUIs, three IVFs) was not an easy process, nor an inexpensive undertaking. It took an immeasurable amount of commitment on the parts of my husband and me; it was a journey best faced as a strong, unified team. We suffered heartbreaking losses and cycle failures. With each setback we had to regroup, reassess, reevaluate our finances, and discuss our options with our RE. We moved through the medical intervention 'process' gaining an understanding that we took a great deal of emotional and financial risk with every cycle. As we tried to establish realistic expectations from each cycle, we also tried to define the time point or cycle number where we might move on and explore different treatment or family building options. We had a firm belief that it was absurd to bring a child into a family situation that was emotionally and/or financially exhausted. Each patient must face making their own family building decisions, but it is important to consider all the issues (emotional, medical and financial) and enter into discussions with your RE (early and often!), when making decisions to move forward with IVF at advanced maternal age.

Kindle Edition Arrives!

2011-06-21T07:24:00.000-07:00

I really love June. It is my favorite month. The days are getting longer and school is out and the entire summer seems so full of promise. I would prefer to have a year with 3 Junes and no February or March and maybe a shorter November..... My love of the month of June and of early summer is my only excuse, dear readers, for the delay in posting to my blog. I have also been hard at work on a book chapter and some scientific papers but the honest truth is that I have been goofing off in the evenings....catching fireflies, throwing rocks at bats and trying not to be eaten by mosquitoes.

However, there have been some interesting developments with our 2nd Edition of 100 Questions and Answers about Infertility. No, there is no movie version or video game in the works. But there is now a Kindle ebook version available for purchase at Amazon.com! So as your friends and family get ready to head off to the beach tell them to download the Kindle ebook version of your favorite author's guide to infertility!

Next week I am heading up to Boston to check on the parents and participate in an event at Tufts Medical School. I will try to get some additional posts up this week...but if the fireflies are calling I may have to do it while stuck in Logan Airport!

DrG

Question 51. How can you have an ectopic pregnancy after IVF?

2011-05-31T18:20:00.000-07:00

Where does the time go? Here we are the last day of May and there are so many projects that I need to get to before June.....not looking so good here at 9:35 pm. Oh well, tomorrow is another day and I will just have to keep plugging away. Currently, DrD and I are working on several papers simultaneously including a chapter on Natural Cycle IVF for a textbook on infertility. I spent hours this past weekend slogging through paper after paper trying to extract the salient information as we reviewed the experiences with Natural Cycle IVF from clinics around the world (England, Japan, Slovenia, The Netherlands, Norway.....). All those places to visit and here I am unable to get away to New Jersey for the day because I am too busy. Traveling can be tough on anyone. But an embryo that travels out of the uterus following an embryo transfer after IVF can be heart-breaking. Although many patients are emotionally prepared for IVF to fail or for them to possibly suffer a miscarriage, the possibility of ectopic/tubal pregnancy is usually not on the radar screen.

Unfortunately, ectopics can occur following IVF (albeit rarely ~ 1-3%) in spite of all of our best efforts to place the embryo precisely in the uterus under ultrasound. Still it is a real disappointing end to a treatment cycle. Most ectopics can be treated medically with methotrexate but surgery still has a role in the management of ectopics. Years ago, before electricity, when I was a resident in Ob Gyn there was a saying passed down to junior house officers...."Never let the sun set on an ectopic." In other words, get that patient to the operating room now and don't mess around.

Seems a bit dated but not unreasonable advice in some cases....

So as we move to June here is today's Question of the Day...

51. How can you have an ectopic pregnancy after IVF?

The exact mechanism responsible for an ectopic pregnancy following an IVF procedure is unknown. Some believe that embryo migration up into the fallopian tubes occurs because of local cellular activity or fluid mechanics present inside the uterus. Sometimes the opening of the fallopian tube in the uterus is dilated because of disease, making it easier for the embryos to enter the tubes.

As described in Part 3, an ectopic pregnancy can occur within the section of the fallopian tube that passes through the muscle of the uterus or within the short segment of fallopian tube that remains after surgical removal of the tube. The incidence of ectopic pregnancy following IVF ranges from 0.5 % to 3%, but this figure may be decreasing. For the past several years, embryo transfer has been routinely performed using ultrasound to properly guide the embryo catheter to the optimal uterine location, which may help to reduce the risk of an ectopic pregnancy. However, even ultrasound guided embryo transfer cannot eliminate the possibility of an ectopic pregnancy after IVF.

Question 50. How do I decide how many embryos to transfer?

2011-05-10T12:20:00.000-07:00

Well, we are halfway done with the 2nd Edition of 100 Questions and Answers about Infertility. I am still waiting for my invitation to go on Oprah and the book is not on the NY Times bestseller list. I am thinking about having Audible produce an audiobook version but my attorney has warned me that I could be legally responsible for those listeners that nod off while playing the book in the car and then end up off the road in a car wreck. Oh well. Guess I will need to keep coming to work.

Deciding how many embryos to transfer is not an easy decision and raises many questions. Some patients are not comfortable with the concept of embryo freezing and thus elect to transfer all viable embryos. Obviously, the RE needs to be aware of this plan and such patients may need to restrict how many eggs are fertilized in order to avoid becoming the next Jon and Kate plus Eight.... Usually, 50-75% of the eggs will fertilize and half of these will develop into embryos that are good enough to transfer or to freeze BUT this is not always the case....I have seen 6 good embryos from 6 eggs and 2 good embryos from 23 eggs...go figure.

So how can we make educated decisions about the number to transfer? Well that is the Question of the Day!

50. How do I decide how many embryos to transfer?

Determining the number of embryos to transfer in an IVF cycle is a crucial decision that requires careful discussion between the patient/couple and the physician. The goal of every treatment cycle should be the delivery of a full-term, healthy, singleton baby. Although transferring more than one embryo will increase the pregnancy rate, at some point transferring additional embryos merely serves to increase the multiple pregnancy rate without altering the overall pregnancy rate. Several European countries have eliminated all discussion of how many embryos to transfer by mandating that all patients undergo only single-embryo transfers. Whereas elective (or mandatory) single-embryo transfer has been promoted heavily throughout Europe, it has not yet received widespread acceptance in the United States although this attitude may be changing slowly.

One of the major disadvantages of single-embryo transfer is that it leads to a decreased IVF pregnancy rate from the fresh cycle. Proponents of single-embryo transfer claim that the potential reduction in the overall pregnancy rate is well worth the marked reduction in the twin pregnancy rate. Twin pregnancies can be problematic because they are associated with higher rates of preterm labor and preterm delivery. Some couples, however, may desire twins or at least regard them as a neutral outcome. This view is especially prevalent among patients who are paying for the treatment themselves (rather than it being covered by insurance) and regard twins as a “two for the price of one” outcome. As noted in Question 49, the greatest risk to the health of children following IVF is the complications related to prematurity associated with multiple births. Despite the risks associated with multiple pregnancy, couples still tell us every day that they would “love to have twins.”

In the U.S., there is no question that the trend is to transfer of a single embryo in most patients. We fully embrace this concept. In fact, with the recent advances in embryo cryopreservation, such as vitrification our frozen-thawed embryos seem to be as likely to implant and produce a healthy pregnancy as embryos transferred in a fresh cycle. This, in the patients classified as “Most favorable prognosis” we see no need to transfer more than a single embryo and risk a multiple pregnancy when we can safely perform a frozen-thawed embryo using high-quality vitrified embryos. However, convincing patients has proved more difficult. One of the advantages of Natural Cycle IVF is that there is rarely the option to transfer more than a single embryo since nearly all patients produce only a single mature egg in a typical reproductive cycle. Some patients who had planned to undergo single embryo transfer will change their mind at the last minute and elect to transfer 2 embryos greatly increasing the risk of a twin pregnancy. With Natural Cycle IVF the temptation to transfer two embryos has been eliminated entirely.

The ASRM has published guidelines for making the decision of how many embryos to transfer (see Table 1). Patients who fall into the excellent prognosis category should transfer only one or two embryos, whereas those with an exceedingly poor prognosis—because of the woman’s age or multiple failed IVFs, for example—may undergo embryo transfer of five or more embryos.

The most problematic decisions concern those patients who fall between these two extremes. Couples who are paying out of pocket for IVF will often pressure their RE to be more aggressive in terms of the number of embryos transferred. Of course, the expense involved in caring for premature infants is many times greater than the cost of all of the fertility procedures used to initiate those pregnancies. The financial costs are merely one part of the picture, as caring for patients with preterm labor or premature infants is also associated with a variety of emotional, psychological, and physical costs.

If multiple pregnancies occur, a multifetal selective reduction procedure can be considered. This procedure is performed at approximately 10 weeks of pregnancy and involves injecting a salt solution into one or more of the gestational sacs. The overall pregnancy loss rate following this procedure is usually less than 5%. In patients who wish to avoid a triplet gestation (but who will not consider selective reduction), it is best to limit the number of embryos transferred to one or two.

Question 49. Are the children born after IVF normal?

2011-04-13T06:31:00.000-07:00

The goal of all of our patients is to have a normal, healthy child. However, there are risks in life that none of us can eliminate and unfortunately any child can be born with a birth defect. So the real question is whether IVF derived pregnancies result in more complications and birth defects than non-IVF pregnancies. But here's the problem...patients who undergo IVF have a problem....INFERTILITY.

So really what we need to compare are the outcomes of pregnancies in infertile couples that conceived on their own and those that conceived with IVF...otherwise we are truly comparing apples and oranges. One very revealing study looked at pregnancies in gestational carriers (who have proven fertility which is why they were chosen to be gestational carriers in the first place!) and compared these to IVF pregnancies where patients carried themselves. Guess what? All the issues of bleeding, prematurity, low birth weight etc completely went away! So since most infertile patients do not use a gestational carrier, we need to realize that there may not be an easy way to separate out the cause and effect in terms of outcomes as the issue may be related to the patient needing infertility treatment and not necessarily the treatment itself. Twins are the clear exception as twins (at least non-identical twins) can be prevented by sticking with single embryo transfer.

I am proud to report that we have the highest percentage of single embryo transfers in the country. I know that this is true because we perform so much Natural Cycle IVF and 99% of these cycles result in only a single egg and therefore only a single embryo available for transfer.

So after that introduction, let's look at today's Question of the Day. I have included supplemental information that is in the stimulated cycle IVF consent form that we use here at Dominion. This consent form was produced by SART and provided to all US fertility clinics.

Question 49. Are the children born after IVF normal?

The question of the health of children born after advanced fertility treatments is one that has great importance both to patients and fertility physicians alike. In general, the data regarding the outcomes for children born after IVF, either with or without the use of ICSI, have been extremely reassuring.

The problem with these studies is the identification of an appropriate control group with which to compare the rate of problems found in the children conceived with advanced fertility techniques. Overall, most studies suggest a background risk of birth defects in naturally conceived children of approximately 4% to 5%. However, these couples tend to be younger than the couples undergoing IVF and, by definition, do not suffer from infertility. Although the vast majority of studies suggest no increased risk of anomalies in children conceived after IVF, few of these studies have looked at the rate of congenital anomalies in children conceived naturally but born to parents who suffered infertility that spontaneously resolved without treatment. This group of patients clearly represents a more appropriate control group with which to compare with patients who seek out advanced fertility treatments. The few studies that have looked at this question have noted that although patients who suffered from infertility have a higher rate of anomalies and pregnancy related complications, the means by which these couples eventually conceived (spontaneously or with IVF) did not influence the rate of these problems. Therefore it may not be the IVF process per se that is the issue here but rather the underlying infertility that matters.

The following is from the SART stimulated cycle IVF consent form.....

1. Overall risks.

Since the first birth of an IVF baby in 1978, more than 4 million children have been born worldwide following IVF treatments. Numerous studies have been conducted to assess the overall health of IVF children and the majority of studies on the safety of IVF have been reassuring. As more time has passed and the dataset has enlarged, some studies have raised doubts about the equivalence of risks for IVF babies as compared to naturally conceived babies.

A major problem in interpreting the data arises from the fact that comparing a group of infertile couples to a group of normally fertile couples is not the proper comparison to make if one wants to assess the risk that IVF technology engenders. Infertile couples, by definition, do not have normal reproductive function and might be expected to have babies with more abnormalities than a group of normally fertile couples. This said, even if the studies suggesting an increased risk to babies born after IVF prove to be true, the absolute risk of any abnormal outcome appears to be small. Singletons conceived with IVF tend to be born slightly earlier than naturally conceived babies (39.1 weeks as compared to 39.5 weeks). IVF twins are not born earlier or later than naturally conceived twins. The risk of a singleton IVF conceived baby being born with a birth weight under 5 pounds nine ounces (2500 grams) is 12.5% vs. 7% in naturally conceived singletons.

2. Birth Defects.

The risk of birth defects in the normal population is 2-3 %. In IVF babies the birth defect rate may be 2.6-3.9%. The difference is seen predominately in singleton males. Studies to date have not been large enough to prove a link between IVF treatment and specific types of birth defects.

Imprinting Disorders. These are rare disorders having to do with whether a maternal or paternal gene is inappropriately expressed. In two studies approximately 4% of children with the imprinting disorder called Beckwith-Weidemann Syndrome were born after IVF, which is more than expected. A large Danish study however found no increased risk of imprinting disorders in children conceived with the assistance of IVF. Since the incidence of this syndrome in the general population is 1/15,000, even if there is a 2 to 5-fold increase to 2-5/15,000, this absolute risk is very low.

Childhood cancers. Most studies have not reported an increased risk with the exception of retinoblastoma: In one study in the Netherlands, five cases were reported after IVF treatment which is 5 to 7 times more than expected.

Infant Development. In general, studies of long-term developmental outcomes have been reassuring so far; most children are doing well. However, these studies are difficult to do and suffer from limitations. A more recent study with better methodology reports an increased risk of cerebral palsy (3.7 fold) and developmental delay (4 fold), but most of this stemmed from the prematurity and low birth weight that was a consequence of multiple pregnancy.

Potential Risks in Singleton IVF Pregnancies

In this table, the Absolute risk is the percent of IVF Pregnancies in which the risk occurred. The Relative Risk is the risk in IVF versus the risk in non-IVF pregnancies; for example, a relative risk of 2.0 indicates that twice as many IVF pregnancies experience this risk as compared to non-IVF pregnancies. The numbers in parentheses (called the “Confidence Interval”) indicate the range in which the actual Relative Risk lies.

3. Risks of a Multiple Pregnancy

The most important maternal complications associated with multiple gestation are preterm labor and delivery, pre-eclampsia, and gestational diabetes (see prior section on Risks to Woman). Others include gall bladder problems, skin problems, excess weight gain, anemia, excessive nausea and vomiting, and exacerbation of pregnancy-associated gastrointestinal symptoms including reflux and constipation. Chronic back pain, intermittent heartburn, postpartum laxity of the abdominal wall, and umbilical hernias also can occur. Triplets and above increase the risk to the mother of more significant complications including post-partum hemorrhage and transfusion.

Prematurity accounts for most of the excess perinatal morbidity and mortality associated with multiple gestations. Moreover, IVF pregnancies are associated with an increased risk of prematurity, independent of maternal age and fetal numbers. Fetal growth problems and discordant growth among the fetuses also result in perinatal morbidity and mortality. Multifetal pregnancy reduction (where one or more fetuses are selectively terminated) reduces, but does not eliminate, the risk of these complications.

Fetal death rates for singleton, twin, and triplet pregnancies are 4.3 per 1,000, 15.5 per 1,000, and 21 per 1,000, respectively. The death of one or more fetuses in a multiple gestation (vanishing twin) is more common in the first trimester and may be observed in up to 25% of pregnancies after IVF. Loss of a fetus in the first trimester is unlikely to adversely affect the surviving fetus or mother. No excess perinatal or maternal morbidity has been described resulting from a “vanishing” embryo.

Demise of a single fetus in a twin pregnancy after the first trimester is more common when they share a placenta, ranging in incidence from 0.5% to 6.8%, and may cause harm to the remaining fetus. Multiple fetuses (including twins) that share the same placenta have additional risks. Twin-twin transfusion syndrome in which there is an imbalance of circulation between the fetuses may occur in up to 20% of twins sharing a placenta. Excess or insufficient amniotic fluid may result from twin-to-twin transfusion syndrome. Twins sharing the same placenta have a higher frequency of birth defects compared to pregnancies having two placentas. Twins sharing the same placenta appear to occur more frequently after blastocyst transfer.

Placenta previa and vasa previa are more common complications in multiple gestations. Abruptio placenta also is more common and postpartum hemorrhage may complicate 12% of multifetal deliveries. Consequences of multiple gestations include the major sequelae of prematurity (cerebral palsy, retinopathy of prematurity, and chronic lung disease) as well as those of fetal growth restriction (polycythemia, hypoglycemia, necrotizing enterocolitis). It is unclear to what extent multiple gestations themselves affect neuro-behavioral development in the absence of these complications. Rearing of twins and high-order multiples may generate physical, emotional, and financial stresses, and the incidence of maternal depression and anxiety is increased in women raising multiples. At midchildhood, prematurely born offspring from multiple gestations have lower IQ scores, and multiple birth children have an increase in behavioral problems compared with singletons. It is not clear to what extent these risks are affected by IVF per se.

Question 48. How successful is IVF?

2011-04-11T11:15:00.000-07:00

Different physicians have different styles. I have always attempted to involve my patient's in the decision making process so that they look upon the treatment plan as their plan not my plan. Not all patients want this responsibility. Some look to the physician to run the show with little to no input. I always try to make my recommendation clear but I think that there are often alternative pathways.

For the past 4 years we have been promoting Natural Cycle IVF as an alternative pathway to traditional IVF. I believe that many clinics are unable to offer this approach effectively because of cost limitations and volume concerns. However, it certainly represents more of a finesse approach than that of stimulated cycle IVF. On the other hand, no arguing that stimulated cycle IVF has a higher pregnancy rate per initiated cycle and a low cancellation rate. On the other other hand, some patients are willing to trade off the cancellation rate in order to avoid taking fertility drugs....and so on...

So here is today's Question of the Day from the 2nd Edition of 100 Questions and Answers about Infertility. We are almost halfway there!

48. How successful is IVF?

Overall, the success rates for IVF have improved markedly since 1978 (when Louise Brown was conceived), but success rates vary widely depending on the couple’s infertility factors and the clinic performing the IVF procedure. Success rates for U.S. IVF clinics are published on the CDC’s website (www.cdc.gov/ART/index.htm). The standardization of clinic success rates evolved from 1994 passage of the Fertility Clinic Success Rate and Certification Act (the so-called Wyden law), which seeks to protect U.S. consumers from inflated IVF success rates.

Importantly, many subtleties influence clinic-specific IVF pregnancy rates, including patient selection bias (that is, some clinics tend to treat tougher cases, so their success rates might be lower than those of clinics that take only routine cases). The paucity of clinics that offer Natural Cycle IVF is likely related to this reporting requirement. Natural cycle IVF can be an effective fertility treatment but the pregnancy rate will be less than for stimulated cycle IVF and the number of cancelled cycles will also be higher as patients may ovulate before egg collection, or fail to fertilize or fail to have a viable embryo to transfer.

Unfortunately, at the present time all IVF cycles are reported the same way with the CDC failing to segregate results from Natural Cycle IVF from stimulated cycle IVF. Needless to say, this reporting method does not encourage clinics to offer Natural Cycle IVF as the apparent IVF success rate will be reduced by the inclusion of Natural Cycle IVF in the calculations.

Table A: Factors influencing IVF success rates

1. Patient’s age
2. Type of infertility diagnosis
3. Duration of infertility (Best prognosis if <5yrs)
4. Experience/expertise of the clinic
5. Number of embryos transferred
6. Type of IVF performed: Stimulated vs. Natural Cycle IVF

For women younger than 34 years of age, most will achieve pregnancy within one to three treatment cycles; indeed, many succeed in their first attempt. For women older than 35 years, the success rates tend to decrease simply because the aging process affects the quality of these women’s eggs. For a detailed discussion of IVF success rates, couples should visit the website for the clinic where they are considering treatment. They should also discuss their specific likelihood of success with their reproductive endocrinologist. IVF pregnancy rates do vary by clinic, so patients should carefully scrutinize their chances for success at the particular clinic rendering treatment.

Question 47. How do I know if I need IVF?

2011-04-07T08:12:00.000-07:00

Although there are many paths to reproductive success, IVF is usually the fastest road to success. However, not all patients are thrilled about taking that road as the use of stimulation drugs can be intimidating to say the least. Our extensive experience in Natural Cycle IVF has been so encouraging that it makes one reassess how to counsel patients who are considering other options such as clomid/IUI or gonadotropin/IUI treatment cycles. Although our initial inclination was to encourage Natural Cycle IVF mainly in patients < 35 years old with well-defined fertility issues, our results suggest that success can be obtained in older patients and in those with unexplained infertility. Clearly pregnancy rates will be higher in patients < 40 years old but our current record holder was 47 years old with 4 failed stimulated cycle IVF attempts prior to achieving an ongoing pregnancy with Natural Cycle IVF. Go figure.

I spent over an hour on the phone with a reporter from NPR recently. She was very interested in Natural Cycle IVF and was considering running a piece on the topic. However, after speaking with some other local REs who were totally dismissive of Natural Cycle IVF she stopped answering my emails. Sad but true....good news doesn't sell papers or get listeners to stick with one radio station....and we believe that Natural Cycle IVF is very good news indeed!

So although the smug answer to the Question of the Day is that everyone needs IVF...they just don't know it yet.....here is a more balanced view.

47. How do I know if I need IVF?

Not all patients need IVF or are good candidates for IVF. Thus the answer to this question can be determined only after you undergo a comprehensive infertility evaluation by your reproductive endocrinologist. Nevertheless, some situations clearly require the use of IVF. For example, women with absent or severely damaged fallopian tubes should be treated immediately with IVF. Likewise, IVF should be performed first if the male partner has very poor sperm quality. For other patients, the use of IVF may be less clear-cut, especially given that many different treatment options exist. In such cases, the doctor should discuss with the couple the pros and cons of each option, and then all parties should jointly decide on a treatment plan.

Question 46: What is IVF, and how is it performed?

2011-03-28T10:31:00.000-07:00

Sometimes the first step is really the hardest in the entire journey. There is no doubt that IVF can be a roller coaster ride...physically, emotionally and psychologically. As physicians the best we can do is try to educate our patients so they can handle the ups and downs. Personally, I am really wimpy when it comes to riding roller coasters. At Universal Islands of Adventure my knees went weak at the site of the Hulk roller coaster and you can just forget any of the other big kid coasters. The best I can do is the little kid roller coaster as seen in this video. Those little girls thought it was so funny that I looked petrified but it's not my fault....it's my parents' fault for never taking me to Paragon Park in Nantasket Beach back in my formative years....

So as you consider the potential roller coaster ride of infertility treatment here is an overview of the IVF process from 100 Questions and Answers about Infertility, 2nd Edition.

46. What is IVF, and how is it performed?

In vitro fertilization (IVF) was first successfully performed in Oldham, England, in 1978, resulting in the birth of Louise Brown who was conceived using Natural Cycle IVF (NC-IVF). Since then, more than 4 million children have been born using IVF. The introduction of this technique completely changed—and greatly improved—our ability to treat even the most difficult cases of infertility, many of which were previously untreatable. Although it is clearly not a “cure-all” for infertility, IVF has revolutionized our approach to, and understanding of, the disease called infertility.

IVF literally means “the fertilization of eggs with sperm in glass” which translates to fertilization outside of the body in the laboratory. There are two types of IVF: 1) stimulated cycle IVF and 2) Natural Cycle IVF (NC IVF). We will focus on stimulated cycle IVF in this question but for more information on NC IVF please refer to many of the previous blog posts listed). An IVF cycle consists of several discrete phases, as detailed in the sections that follow.

Phase 1: Ovarian Stimulation
A woman’s ovaries contain thousands of fluid-filled sacs called follicles. Inside each follicle is an egg (or ovum). In a normal reproductive cycle, only a single follicle (and egg) reaches maturity. Louise Brown (the world’s first IVF baby) was produced in a natural cycle from a single follicle (NC IVF). Although a few clinics in the US (including our own) remain enthusisastic about NC IVF, most IVF in the USA is performed in a stimulated cycle using injectible fertility medications. The introduction of the medications (called gonadotropins) enabled physicians to increase the efficiency of IVF through the production of multiple mature follicles. Two forms of these medications are used: (1) drugs containing equal parts of the pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [Menopur] or (2) drugs containing only FSH (Bravelle, Gonal-F, Follistim) or LH (Luveris). Both kinds of medications induce the growth of multiple ovarian follicles, so it is important to monitor the woman’s response to them carefully with ultrasound and blood hormone testing.

Estrogen is produced within each of the developing follicles and induces the growth of the lining of the uterus (endometrium). Unfortunately, the rise in estrogen can also induce the pituitary gland to prematurely trigger ovulation, resulting in the cancellation of an IVF cycle. Two other classes of drugs are used to reduce the chance of this problem occurring during an IVF stimulation: (1) GnRH agonists (such as Lupron and Synarel) and (2) GnRH antagonists (such as Centrotide and Antagon) . Lupron (or Synarel) is usually started 1 week prior to the woman’s anticipated next menstrual cycle. Given that a patient may have spontaneously conceived during this cycle, all women beginning Lupron are recommended to use a barrier form of contraception.

Approximately 1 week after starting Lupron, a woman should experience a normal menstrual period. An ultrasound exam is performed at the start of this menstrual cycle to examine the ovaries and measure any existing cysts. In some cases, empty follicles from a previous cycle will persist and may influence the response to FSH. If the baseline ultrasound and blood tests are normal, then the patient receives instructions that afternoon as to when and what dose of medication she should take and when she should report back to the office for repeat ultrasound and blood tests.

Patients remain on Lupron to prevent the premature release of the eggs until the end of the stimulation phase. During a typical treatment cycle, they take daily injections for 9 to 12 days before the follicles reach maturity based on ultrasound results and blood hormone levels. Once the follicles reach a 20- to 24-mm diameter, the woman receives an injection of human chorionic gonadotropin (HCG; Pregnyl, Profasi, Novaryl) at a precise time. This hormone serves as a trigger to incite the final maturation and release of the egg (ovulation). Ovulation typically occurs about 40 hours after this shot, so the egg collection procedure is scheduled for 34–36 hours after the HCG injection. Failure to take the hCG will result in an egg collection with apparently empty follicles as the eggs will not be ready for aspiration or eggs that are retrieved will be immature. Clearly, taking the hCG is absolutely critical which is why we check a blood test for hCG the morning after the shot to ensure that it was given correctly.

Cycles using GnRH antagonists are somewhat different. GnRH antagonists are started several days following the start of ovarian stimulation with gonadotropins. Most clinics add the GnRH antagonist once the largest follicle reaches a diameter of 14 mm. This medication effectively prevents the release of LH from the pituitary within hours of administration. Although many clinics have used GnRH antagonists successfully as part of their IVF stimulation protocols, some studies have demonstrated a trend towards decreased implantation rates in IVF cycles using this class of medications. Some physicians use GnRH agonists (Lupron) instead of hCG to induce follicular maturation. This approach only works in patients who have not already been taking Lupron as part of their stimulation protocol.

Phase 2: Oocyte Retrieval
Many physicians perform IVF as an office-based procedure, whereas others utilize a free-standing surgery center. Some programs are located within a hospital. There are advantages and disadvantages to each of these. We prefer to perform egg collections at our office in a special procedure room, as the location and staff are familiar to the patients undergoing the IVF process. We also find that the location of the IVF lab within the office encourages continuous communication between patient, physician, and embryology staff. However, clearly many successful programs utilize a surgery center or a hospital. The use of a hospital setting may allow patients with significant medical conditions (cardiac disease, severe pulmonary disease) to undergo IVF, whereas such patients would be considered an anesthesia risk in the office setting.

Although many patients are nervous about the oocyte retrieval, in fact the vast majority of women find it to be less uncomfortable than some of the screening tests leading up to IVF. The egg collection is performed under light conscious intravenous sedation using a vaginal ultrasound probe with a special needle guide adapter. The needle passes through the side of the vagina into the ovary, and the follicles are easily aspirated. The fluid containing the eggs is then inspected by the embryologist using a microscope. Both the eggs and the sperm are then placed together in small plastic dishes containing media and incubated for the next 3 to 5 days. If there is a significant male factor, then ICSI is performed several hours after the egg collection.

Phase 3: Embryo Culture
On the day following the egg collection, patients learn how many eggs were fertilized. Remember that although your RE measures all of the follicles during stimulation, mature eggs are usually found only in follicles with a diameter of more than 17 mm. In general, about 70% of the mature eggs will fertilize. Unfortunately, some attrition occurs at each point in an IVF cycle so the total number of healthy embryos is often much less than the original number of follicles or eggs.

Three days after the egg collection procedure, the embryos selected for embryo transfer will be identified. Allowing the embryos to grow for an additional 2-3 days in the laboratory may allow for enhanced embryo selection as some excellent appearing day 3 embryos will fail to continue to grow. Thus, implantation rates are usually higher for day 5-6 transfers because of this improved ability to select the best embryos. Additionally, there is some evidence that suggests waiting until day 5-6 may provide for improved synchronization of embryo and endometrium given that in nature the embryo usually doesn’t arrive in the uterus until day 5-6 after ovulation. On the day of embryo transfer your RE should review the quantity and quality of the embryos with the embryologist and then discuss with you his or her recommendations regarding the number of embryos to transfer.

Embryos that are not selected for transfer may still be of excellent quality, so they may be candidates for cryopreservation (freezing) with liquid nitrogen. These frozen embryos can then be replaced into the uterus during a future cycle, eliminating the need for the woman to undergo the entire IVF process of ovarian stimulation and egg collection. There is little benefit to freezing poor-quality embryos, however, because they are unlikely to result in a pregnancy and may not even survive the thawing process.

Phase 4: Embryo Transfer
Embryo transfer is one of the most critical aspects of an IVF cycle. During this phase, the embryos are transferred into the uterus by a procedure similar to an IUI. At our office, we perform our embryo transfers under abdominal ultrasound guidance to ensure the accurate placement of the embryos into the uterus. On the day of embryo transfer, patients are asked to drink 48 ounces of water and keep a full bladder to enable us to visualize the transfer of the embryos. No anesthesia is usually required for an embryo transfer and this step usually takes only 1-2 minutes to complete.

Phase 5: Post-Transfer and Pregnancy
During the 2 weeks after the embryo transfer, patients take supplemental progesterone (shots and/or suppositories). If a patient’s estrogen level drops significantly during the 2 weeks following embryo transfer, her physician may add supplemental estrogen as well.

Two weeks after the transfer, the woman typically undergoes a blood pregnancy test. Once a pregnancy test is positive, the physician may repeat the test every 2 days until the beta HCG level is high enough to visualize the pregnancy sac on transvaginal ultrasound (the beta HCG level should be more than 2000 IU around 3 to 4 weeks following embryo transfer). A follow-up ultrasound is then performed to confirm fetal cardiac activity. At this point, patients are usually referred back to their obstetrician/gynecologist for prenatal care.

Question 45. How would I know when to pursue more advanced fertility treatments?

2011-03-21T11:16:00.000-07:00

In the Kenny Rogers song the gambler there is a very famous line "you gotta know when to hold them, know when to fold them, know when to walk away, know when to run...." Sometimes I think about that line when counseling patients, but fortunately for them I never break out into song during a consultation. Deciding when to move onto more advanced treatments is a common concern among most fertility patients. Even those that start with IVF have to consider moving to donor egg/embryo if success is eluding us. I wish that I had that crystal ball to provide a glimpse into the future. That way I could advise patients "Don't worry, I know the 3rd IUI will work or the second clomid cycle or the first IVF or the FET or whatever.....But I don't have that ability...and if I did I would have used it to play the Powerball lottery and then it would be "see-ya later."

In general, most successful treatments will occur in the first 3-4 cycles of whatever treatment has been chosen. It can be hard to hold my tongue when a patient describes 18 months of continuous clomiphene or 9 clomid / IUI cycles or 7 FSH /IUI cycles etc etc.

No one wants to be a professional fertility patient....there just isn't any money in it. But seriously, most couples/individuals can only take so much disappointment before they throw in the towel and consider alternative paths to parenting. So if you don't have a Magic Eight Ball handy....how do you know when to "fold 'em" and move on.....well that is the Question of the Day from the 2nd Edition of 100 Questions and Answers about Infertility.

P.S. Princeton lost to Kentucky by 2 points.....oh well.

45. How would I know when to pursue more advanced fertility treatments?

The decision to seek out more advanced fertility treatments is a complex question, and multiple factors must be considered when making it. For most couples undergoing treatment with IUI (either alone or with fertility drugs), the best chances for success usually occur within the first four treatment cycles. After that, the likelihood for pregnancy decreases. In many of our patients, we recommend only one or two IUI treatments. If these efforts are unsuccessful, we suggest that the couple proceed with other more aggressive treatments including both Natural Cycle IVF and traditional IVF using injectible fertility medications.

For some patients, IUI should rarely be utilized. For example, those couples with severe tubal disease, severe endometriosis, pelvic adhesions, or severe male factor infertility may do best by directly proceeding with IVF as their first treatment option. If an age factor is present or if the couple has prolonged infertility (infertility lasting more than 5 years), we often recommend IVF first, as well. Remember that IVF is the only treatment for which even a failed treatment cycle provides some insight into a couple’s fertility potential. IVF does allow us to make some assessment of egg quality, fertilization and embryo development. A failed IUI cycle yields no such information as we only know that the cycle failed but learn nothing about fertilization, embryo growth or embryo quality.

Princeton Beats Hahvahd (WARNING: This Post Has NOTHING to do with Infertility

2011-03-16T14:01:00.000-07:00

I know that world events have been so depressing lately.....from the unrest in the Middle East to the terrible earthquake and tsunami in Japan. It is hard to find something to cheer about and for a moment forget all the troubles and suffering that confront us on a daily basis. And then something completely meaningless (in the cosmic sense) and really quite silly can lift your spirits and make you grin from ear to ear.

Last Saturday afternoon I had just such an experience as I watched the Princeton Men's Basketball team battle Hahvahd in a one-game playoff to determine which team would go to the NCAA Tournament. Princeton battled back from a half-time deficit to finally pull even in the last few minutes. The teams traded baskets and then Princeton had the ball with 2.8 seconds on the clock under the Hahvahd basket but trailing by 1 point.

Here is the YouTube video of what happened next.

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For those few moments I was transfixed watching the joy of the players and fans as they swarmed onto the court.

GO PRINCETON! BEAT KENTUCKY!

DrG
Princeton Class of 1985

Question 44. What complications can occur after IUI?

2011-03-10T08:36:00.000-08:00

Years ago in Long Island I had a patient experience an allergic reactions to an IUI. She got very bad hives and even began to have a bit of laryngospasm (throat tightening). She was taken to the ER and did fine with a dose of epinephrine and some steroids. Such reactions are really really rare but it was so surprising given the number of IUIs that I have done over years without any weird reactions. Clearly the more concerning complications after IUI are those of multiple pregnancy and OHSS. Both have plagued our specialty for years. However, the risk of both can be somewhat mitigated (but not eliminated) through judicious use of fertility medications.

First of all, no one ends up with a litter without seeing it coming. A patient does not have one follicle on Monday and 14 on Tuesday. Secondly, if there are more than 2 follicles > 15-16 mm at trigger then there can be more than 2 babies. It may be too risky to try an IUI when so many follicles can ovulate so often we discuss 3 major options to try to prevent the patient from having to deal with a pregnancy with > 3 babies or having to make a decision about performing a selective reduction. I do not view Jon and Kate plus 8 as a good outcome....

1. Cycle cancellation: stop the medications and let the follicles all regress and avoid intercourse for 2 weeks.

2. Follicle reduction: perform an IVF like egg collection but then just discard the extra eggs and go forward with the IUI leaving behind only 2-3 follicles. This option can be effective and egg collection would be scheduled like we do for IVF using an HCG trigger. I like to have the embryologists at least look at the fluid to tell be how many eggs I retrieved. If the eggs have already ovulated then this option will not be helpful as the "horse is out of the barn."

3. Convert to IVF: simply go for egg collection as if this had been the plan all along. Patients may experience an LH surge before HCG trigger so consideration can be given to using a GnRH antagonist as soon as the decision is made to convert to IVF. Personally, I have not had any patients surge in this setting but the chance of an LH surge is probably 20% so I may just have been lucky so far!

In spite of impeccable logic: "But Dr. Gordon I have a history of recurrent miscarriage and I am 37 years old and I failed IVF....so how is there any chance that I would end up with triplets???" I have ended up with just that in such cases.....Oh well. It's biology and not engineering.....So good luck and as I tell all my patients in these settings: "remember I don't babysit so let's not have any multiples!"

With that introduction, here is today's Question of the Day from 100 Questions and Answers about Infertility.

44. What complications can occur after IUI?

Complications related to the actual IUI procedure are very rare. IUI is a simple, in-office, nonsurgical procedure, usually performed by nurses. Occasionally patients may experience mild to moderate uterine cramps as the catheter is passed through the cervix into their uterus. These cramps usually last 10 to 15 minutes. Infection rarely occurs (its incidence is less than 1%). Many infertility specialists routinely obtain cervical cultures prior to initiating an IUI cycle, and the culture media used to prepare the IUI specimen commonly contains antibiotics. Occasionally, patients may note some light spotting after placement of the IUI catheter, but this is not an indication of a complication or a problem. Multiple pregnancy can occur in any situation when two or more mature follicles are present at the time of HCG. Your physician should discuss with you the risk of multiple pregnancy in cycles using fertility medication to induce the growth of multiple follicles. Similarly, patients with an excessive response to fertility medication can also be at risk for ovarian hyperstimulation synderome (OHSS). However, both multiple gestation and OHSS can result from the stimultion of the ovary with hormones regardless of whether an IUI is performed or not.

Question 43. My doctor wants to use Lupron or Antagon during my IUI cycle. What are these drugs, and why do I need them? I thought they were only for

2011-03-07T11:28:00.000-08:00

The blue screen of death....or in the world of Mac computers...the gray screen of death with the question mark folder. These two phenomenon are terrifying for those of us dependent upon computers on a daily basis. Last week my college-aged son called us with the news that his MacBook Pro was giving him this problem. So naturally we all jumped into the mini-van and raced up Route 95 to his rescue! In our computer based world we are all on that razor's edge between happy computing and disaster!

In Natural Cycle IVF we are always on the razor's edge between wanting the follicle big enough to have a mature egg but not so big that there is an LH surge and the cycle gets canceled. In stimulated cycle IUI, an early LH surge is not such a big deal unless the follicles really were too small and the eggs immature. So what can one do about premature LH surge...well that is the topic of today's Question of the Day from 100 Questions and Answers about Infertility.

43. My doctor wants to use Lupron or Antagon during my IUI cycle. What are these drugs, and why do I need them? I thought they were only for IVF.

Lupron and Antagon are injectible medications that are used to prevent premature release of LH hormone during a stimulation cycle for IUI or IVF. These two medications work through different mechanisms to prevent the LH surge. Lupron usually requires at least 7 days to effectively prevent an LH surge whereas Antagon works within hours. This difference explains why the drug protocols that employ these two medications are so different. Premature ovulation during an IUI cycle can be dealt with by simply adjusting the timing of the IUI, so these medications are primarily used in patients undergoing IVF rather than IUI. For most patients undergoing treatment with IUI unless a patient repeatedly experiences a premature LH surge during the treatment cycle. In such cases, these medications can allow for a more optimal stimulation and larger follicle sizes.

Question 42. Can we have sex during a treatment cycle?

2011-02-28T10:02:00.000-08:00

Sometimes medical advice makes sense and sometimes it doesn't. Historically, fertility patients have been told to contracept during the month that they plan to start luteal lupron in order to avoid conceiving while on lupron. Actually, the registry of patients that have, in fact, conceived on lupron suggest no risk of birth defects in the children born after this little oops. Years ago in Long Island I had a patient that had 8 years of infertility. She and her husband finally got up the nerve to do IVF and boom, she conceived on lupron. Then 2 years later she wanted to have another baby and voila, she conceived on lupron again! Go figure.

So this recommendation against sex during a luteal lupron cycle has morphed into no sex during any treatment cycle which makes little sense except in a few cases as detailed below. Now if a woman is really bloated and unconfortable while on fertility drugs then that is a totally different issue. In that case we send the partner off to take care of business on his own or encourage then to pursue other ways to avoid delaying ejaculation for weeks before an IUI or IVF procedure.

42. Can we have sex during a treatment cycle?

In general, the answer is yes. Many experts, however, recommend no coitus for 2 to 3 days prior to an anticipated IUI to “build up” the male partner’s sperm count and volume. Also, some men may experience difficulty producing a specimen if they have recently had coitus. For men who have a low sperm count or motility, it is recommended that they abstain from sexual relations for 3 to 5 days prior to a planned IUI. In patients who are at risk for hyperstimulation syndrome, it may be wise to refrain from sex until the ovarian response has been assessed. In patients with an excessive response to fertility drugs the cycle may be abandoned and yet ovulation could still occur. Since the sperm can survive up to 5-7 days after intercourse, a pregnancy could occur even in the setting of a cancelled IUI or IVF cycle.

Question 41. I read on the Internet that two inseminations are better than one. Is this true?

2011-02-16T11:29:00.000-08:00

The internet is quite an amazing place. You get anything you need at 2 am and research obscure medical disorders to your heart's content. But that can be a danger as well. I have been a bit under the weather recently and let me tell you that you do not want to type any ailment into that Google search box unless you are prepared to totally freak out. Seriously. Of course, medical professionals make the worst patients because we know too much about too little and often end up feeding into our own worst fears. It's never just a mole...it's melanoma. It's never just a superficial skin infection...it's flesh eating staph. It's never just a headache...it's a brain tumor. How does this relate to today's Question of the Day? I can' t remember because of my headache.

Oh, now I remember. Two IUIs vs. one......Well, here is the answer.

41. I read on the Internet that two inseminations are better than one. Is this true?

In general, one well-timed IUI is as good as two, and no advantage is obtained by performing a second IUI (providing ovulation was well monitored using blood hormone determinations and follicle ultrasound measurements). However, in patients who are undergoing IUI with less intense monitoring of ovulation, such as urine LH testing, or for those women who chose not to monitor their ovulation at all, two inseminations may be a better option.

Using basal body temperatures as the basis for an IUI’s timing is not recommended, because this method cannot prospectively pinpoint the optimal timing of ovulation for an IUI treatment. The rise in basal body temperature occurs after ovulation, so identifying this temperature increase would not help in scheduling an IUI procedure.

Question 40. How many office visits are required during a typical cycle using fertility drugs and IUI?

2011-02-14T12:24:00.001-08:00

TANSTAAFL. This acronym is well known to some. Back in my ill-spent youth I spent a lot of time reading science fiction. One of my favorite authors is Larry Niven (Ringworld, Ringworld Engineers, Children of Ringworld, Fertility Doctors Who Wish They Could Visit Ringworld, etc). He is very fond of acronyms and his protagonists often use these a great deal. TANSTAAFL is an oldie but goodie and means There Ain't No Such Thing As A Free Lunch. In other words, you get what you pay for....In fertility treatment that also can apply. In general, treatments that are more expensive and more invasive cost more than those that are not.

In using fertility drugs and IUI, the number of office visits relates to the goal of therapy and the desire to avoid unwanted complications (Jon and Kate plus 8, OctoMom). So in considering this approach of fertility drugs and IUI we want a couple of follicles but not too many. We also want to catch them before they release the egg so we can time the IUI with an hCG trigger shot. So how many visits does that mean? Or here in DC, how many trips in the HOV lane with an inflatable companion in my passenger seat? Well, that is the Question of the Day from 100 Questions and Answers about Infertility, 2nd Edition....

40. How many office visits are required during a typical cycle using fertility drugs and IUI?

For treatments using Clomid and IUI, only a couple of office visits per month are required. Clomid is usually prescribed at doses of 50-100 mg daily taken on cycle days 5-9. We typically have patients begin monitoring on cycle day 12. At a typical office visit for monitoring, the patient has her blood drawn for hormone analysis, and a pelvic ultrasound is performed to measure the size of the follicles and the thickness of the endometrial lining. The doctor uses this information to determine the optimal timing of the HCG trigger shot and the subsequent IUI. Most patients receive the hCG trigger injection once the follicle size is >20-22 mm mean diameter. This trigger shot will induce ovulation around 36-40 hours later so the IUI is scheduled accordingly or the couple is informed of the best timing for intercourse. Occasionally a patient will demonstrate an LH surge on her own and the timing of the IUI or coitus should take this into account.

For treatment using gonadotropins and IUI, closer monitoring is necessary, perhaps requiring 4 to 6 office visits per treatment cycle. Patients in our practice undergo a baseline sonogram on CD 2-3 to rule out any persistent ovarian cysts from the preceding treatment cycle. If the sonogram is normal, then patients begin the daily injections and usually return to the office after 3-4 days of medication to assess the response to the drugs. Adjustments in the dose of the medications may allow for the optimal treatment response and most patients require 10-12 days of shots before the follicles reach the ideal size. Once again the hCG trigger shot is used to induce ovulation at the appropriate time and the IUI is scheduled accordingly. The actual IUI takes only minutes to perform and is usually painless. We routinely ask our patients to lie on their backs for about 10 to 15 minutes following the IUI procedure. The woman may then return to her normal activities. A pregnancy test is performed usually 14 days following an IUI or 16 days following hCG in couples pursuing timed intercourse.

Let It Snow, Let It Snow, Let It Snow

2011-01-26T10:57:00.000-08:00

Here I sit on a Wednesday afternoon watching DC clear out in anticipation of a "major snow event." In the mid-Atlantic this means that a snowflake may be spotted somewhere on the Beltway. I just returned from Boston where I spent a long weekend visiting my parents. As some of you may recall, Boston was hit with yet another major snowstorm last Friday (8-10 inches). Amazingly enough, we left DC on time Friday PM and I don't think that the kids in Boston even got a snow day! It was pretty impressive to see how clear the streets and sidewalks were within a few hours compared with the days of paralysis that we experience here. Oh well. As the Boy Scout motto says...."Be Prepared!" It helps to have a lot of snow removal equipment.

I am pleased to report that my parents continue to amaze us all with their resilience. Both are 87 years old and honestly I really thought that they were in trouble this past summer. My Mom can no longer climb up to the second floor of her house so she has dropped off of the list of active readers of this blog....that leaves 4....

The highlight of the weekend was a party for my older brother Steven who is off to Vermont to become the CEO of a small hospital in the Green Mountain State. There were 50 guests crammed into his home in Newton and it was fun to see cousins that I hadn't seen in years. Yours truly gave a heartfelt speech lauding my brother's accomplishments. My Dad, in true general surgeon form, first called me his "most verbose" child and then followed it up referring to my brother as "accomplishing more than I ever thought possible given how he was as a teenager..." Oh well. Perhaps verbose is accurate as here we are in the 3rd paragraph and you have learned nothing more about reproductive medicine.

So back to reproductive medicine....One pretty consistent truth about fertility treatment is that the treatments that are cheap and easy and require minimal effort don't work as well as those that are more expensive and more intense. However, some patients are ready for intense therapy and some cannot afford it. Also, some insurance companies mandate IUI before IVF so there are many factors that go into the decision to undergo an IUI treatment cycle. So how are the chances for success? Well, that is an excellent question....so excellent that it is today's Question of the Day from the 2nd Edition of 100 Questions and Answers about Infertility...

39. What are typical pregnancy rates for IUI?

The pregnancy rates for IUI vary widely, depending mostly on the female partner’s age and the presence or absence of any other infertility factors. In patients younger than 35 years old, an estimated one-third to one-half of patients will achieve pregnancy within 1 to 4 treatments. In patients with unexplained infertility, most studies demonstrate a per-cycle pregnancy rate of 6% for the Clomid/IUI combination and 9% to 12% for the gonadotropin/IUI combination, compared with a spontaneous pregnancy rate of less than 5% per month. Many fertility doctors will try 1 to 4 cycles of Clomid/IUI and then 1 to 4 cycles of gonadotropin/IUI. If pregnancy has not occurred after the fourth treatment, most experts would abandon these treatments and proceed with more aggressive therapy such as in vitro fertilization. The optimal number of IUI treatment cycles should be individually determined by the patient and her infertility specialist.

Some patients develop a seeming resistance to fertility medications, demonstrating reduced responses with repeated stimulations. This problem is especially prevalent in women who are more than 37 years old. Thus IVF should be considered as a first-line treatment in these patients as opposed to multiple gonadotropin/IUI cycles.

New Year's Resolution

2011-01-20T11:31:00.000-08:00

So making my New Year's Resolutions on January 20th is probably not a good sign when one of my resolutions is to stop procrastinating....oh well. I hope that all of you are doing well in this new year of 2011. I think that once you get over the hill you start to pick up speed....that is the only way that I can explain how I managed to get to the 3rd week of January with no additional blogs.

My New Year's Resolutions involve the usual assortment of health related issues as well as being a better parent/spouse/friend/doctor/church member etc. In terms of this blog, however, I resolve to get through all 100 questions from the 2nd Edition of 100 Questions and Answers about Infertility before 2012!

So without further ado here is Question 38....and this question about the use of IUI is commonly asked as most patients would prefer less intense therapy compared to more intense therapy if they could be successful. Of course, if I knew who was going to conceive and who wasn't then I would be God and wouldn't have to come to work anymore.....

38. How do I know if IUI is an option for me and should I use fertility drugs in conjunction with an IUI?

IUI is a good option for many infertile couples. It can be performed in conjunction with a woman’s natural cycle or can be combined with the use of fertility drugs. IUI can also be effectively used in couples who have sexual dysfunction or infrequent coitus for either medical or nonmedical reasons. For example, some couples may have busy work schedules such that one or the other partner is frequently out of town around the time of ovulation. If the male partner’s sperm is obtained and cryopreserved (frozen) in advance of ovulation, the physician (or nurse) can perform an IUI and, ideally, facilitate pregnancy without the woman missing a menstrual cycle.

The best candidates for IUI are those couples without tubal disease (female partner) or severe male factor infertility (male partner). Women with severe endometriosis or a history of pelvic adhesions are not good candidates for IUI. Although couples with male factor infertility can attempt IUI, the success rates are fairly low in such cases, and prompt consideration should be given to IVF (and ICSI) if pregnancy fails to occur after three or four attempts.

IUI in combination with fertility medications may provide a reasonable treatment option for some patients. There appears to be a synergistic benefit to the combination of fertility medications (either Clomid or injectable gonadotropins) with IUI compared to either treatment by itself. For this reason, most infertility experts recommend IUI to their patients when treating them with fertility drugs even if the semen analysis is normal.

In women who fail to ovulate regularly, the goal of drug therapy is to induce the growth and release of a single mature egg. This treatment is known as ovulation induction. In contrast, the treatment goal for women with regular menstrual cycles is to induce the growth of multiple follicles with the subsequent release of multiple eggs. Hence the term superovulation (also called controlled ovarian hyperstimulation) is used to describe this treatement. During a cycle of superovulation and IUI, the goal is to develop 3 to 5 mature follicles, whereas the goal in an IVF cycle is to produce more.

Clomid is usually the fertility drug of first choice for both ovulation induction and superovulation with IUI. Women who fail to respond to Clomid or who fail to conceive may be candidates for treatment with injectable fertility medications (gonadotropins) combined with IUI. In some cases, it is best to skip the treatment with Clomid and instead proceed directly with gonadotropin therapy; this decision depends on the severity of the couple’s infertility situation.

In women who have normal menstrual cycles, it would appear on the surface that IUI alone without fertility drugs would be as successful as IUI with fertility drugs. Unfortunately, this simply is not the case. Instead, the combination of IUI and fertility drugs to induce superovulation yields a synergistic benefit over either treatment alone. However, superovulation (either with or without IUI) can lead to multiple pregnancy. Historically, nearly all of the multiple multiples (such as sextuplets and more) have been the result of superovulation. Unfortunately, there is really no way to control the outcome of this game of reproductive Russian Roulette. Patients must understand that if there are more than two follicles present then the possibility of a high order multiple pregnancy is a reality. In such cases a frank discussion needs to be held with the patient to review the risk and alternatives to avoid a poor outcome.

Merry Christmas

2010-12-23T09:40:00.001-08:00

I am wishing you all a very Merry Christmas now as I will be taking some vacation time over these next 10 days. I hope that Santa brings you lots of nice goodies and also hope that you can handle the emotional turmoil that can come with the holiday season. Well-meaning and no so well-meaning friends and relations often feel quite comfortable weighing in on fertility and family matters. All I can say is to hang in there and know that I am hoping and praying for all of you!

And just for grins here is the results of the "Who got photoshopped into the Dominion holiday card" puzzler!

Photoshop and Other Holiday Traditions

2010-12-20T10:11:00.000-08:00

Here at Dominion Fertility we gather each year around the Christmas tree to take a staff photo. Unfortunately, trying to get everyone together is a bit like herding cats so I end up having to photoshop in the missing staff members. Since this photo doctoring represents the only digital work that I do each year, I end up having to relearn Photoshop each December. So here is the result of my hard work. In a future post I plan to identify which staff members were added after the fact. You may ask "what does this have to do with infertility?" The answer is absolutely nothing but there is nothing wrong with a little change of pace....

Happy Holidays!

Happy Thanksgiving!

2010-11-25T08:01:00.000-08:00

Thanksgiving is one of my favorite holidays. It is a time for family togetherness and reflection upon our many blessings. Recently, the Wall Street Journal ran an article about how those individual who express gratitude are healthier, happier and wiser than those who spend a great deal of energy griping.

So as I am about to head home following a busy Thanksgiving morning at Dominion, I would like to take a moment to express my own gratitude before I stuff my face with turkey and all the other yummy food at home!

I am thankful for my wife and my family.
It is always a blessing to share every day with my wife and kids. Some days perhaps a little less so....It has been a stressful year as a member of the sandwich generation but all the Gordons are hanging in there pretty well at present. My Mom is doing just amazingly well and at 87 she is completely in control of her mental faculties. My Dad can now see the dashboard of his car after eye surgery which gives one pause to consider that he was zooming around Boston without reasonable visual acuity.

I am thankful for my career and for my patients.
Our former pastor at National Presbyterian Church, Craig Barnes, often preached on grace and the meaning of life. His message was that we are here to be a blessing to others and to give glory to God. I am blessed to have a job where every day I can go to work hopeful that I can be a blessing to others and make a difference in their lives. Hopefully, that difference will include success with fertility treatment but if not then I hope to be a source of comfort and support to those whose lives may take a different path than the one that they anticipated.

I am thankful for our country.
We live in an amazing nation, blessed with natural resources and with a system of government that allows for open discourse and free elections. Hard to imagine living under a different system or in a country with much more limited resources without acknowledging our gratitude for the United States. Last night at Union Station my 7 year old spontaneously started singing the Star Spangled Banner. Although her older sister was totally horrified and moved away, I could tell that many of the travelers surrounding us were moved by her small voice lifting up those well-known words motivated by nothing more than spontaneity.

Wishing you all the best on Turkey Day 2011!

Natural Cycle IVF. Part 3: It Works

2010-11-16T14:11:00.000-08:00

Although I anticipated posting this final part concerning NC-IVF two weeks ago, it took me longer than I had anticipated to pull all the data together and organize it into a coherent discussion of NC IVF. So after much effort here it is....

In December 2006, my partner here at Dominion, Dr. Michael DiMattina, attended the First World Congress on Natural and Minimal Stimulation IVF in London, England. Now, London is not the greatest place to visit in December but DrD came back completely convinced that Natural Cycle IVF was worth trying. The keynote speech was given by none other than Dr. Robert Edwards (Nobel Prize winner and one of the pioneers of IVF--see my previous Blog post). Only 2 Americans were present among the hundreds of fertility physicians from around the world. In January 2007 we launched our Natural Cycle IVF program and since that time Natural Cycle IVF has become an integral part of our fertility treatment options.

At the ASRM meeting in Denver we were peppered with questions from other physicians and nurses and embryologists about our experience with Natural Cycle IVF. Here are answers to the most commonly asked questions...

Question #1: How many other clinics offer Natural Cycle and how many cycles do they perform?

At the ASRM meeting in Denver last month I presented the national data on utilization of NC-IVF across all IVF clinics reporting their results to SART. As is evident from the table below, about 15% of IVF clinics in the US offer NC-IVF, but the average number of NC-IVF cycles performed at those clinics that offer NC-IVF is less than 10. In looking at NC-IVF in 2006 (the year before we started our program) it is evident that we now perform more NC-IVF than all the other clinics in the US combined. Clearly, we are in a unique situation to comment on the addition of NC-IVF to a busy fertility clinic offering comprehensive fertility care and treatments.
Question #2: How much Natural Cycle IVF do you do?

The quick answer is "quite a bit." In 2007, the year we launched the program, we initiated 66 cycles and this year we are on target to initiate about 500 cycles of Natural Cycle IVF. As a result, every year since 2007, the percentage of Natural Cycle IVF in our clinic has increased....from 20% that first year to almost 70% (predicted) for 2010. Question #3: Has the inclusion Natural Cycle IVF impacted your number of cycle of stimulated IVF?

In fact, we still perform a lot of stimulated cycle IVF. We strongly believe that there is a place for both Natural Cycle and Stimulated Cycle IVF within our practice. Our total number of stimulated IVF cycles has remained fairly stable over the past 4 years, which is very interesting given the economy and the higher costs associated with stimulated IVF.

Question #4: What are the pregnancy rates with Natural Cycle IVF?

There are many ways to answer this question. We can look at pregnancy rate per initiated cycle or per successful retrieval or per embryo transfer. Not every patient will make it to retrieval or transfer in Natural Cycle IVF which is different than stimulated IVF (as nearly all patients go to retrieval and transfer since there is more than just the one egg that is produced in a natural cycle).

Shown below then are the pregnancy rates for 416 completed cycles. In patients under 35 years old the pregnancy rate was 35.4% per embryo transfer and for patients 35-39 years old the chance of pregnancy was 41% per embryo transfer (which is not statistically different than the rate for the younger group).

2007-2009 Success Rates for Natural Cycle IVF

Question #5: How many patients who initiate a cycle make it to retrieval and transfer?

Natural Cycle IVF differs from stimulated IVF in many ways. As the cancellation rate is higher in Natural Cycle IVF we knew that patient expectations and the associated financial implications of canceling a cycle would be important to codify. Thus, we have a sliding scale that takes into account cycle cancellation before retrieval (LH surge or ovulation), after retrieval but before fertilization or after fertilization but before embryo transfer (arrested embryo development).

Here is our data for all patients younger than 40 years old (2007-2009):

Question #6: How does NC-IVF compare with stimulated IVF?

In answering this question I compared NC-IVF to the Society for Assisted Reproductive Technologies (SART) data for all IVF clinics reporting to SART for 2007. The implantation rate (pregnancy per ET) was outstanding for NC-IVF (over 35%). So if a patient made it to transfer the odds of pregnancy were excellent. Does that mean that NC-IVF produced better embryos or a better lining or both? It is hard to say, but the concept that Mother Nature may provide a better outcome is certainly intriguing.

Question #6: What about OHSS and multiples?

Well the incidence of OHSS with NC IVF is 0%. One can't have OHSS without fertility drugs so with Natural Cycle IVF there is essentially no risk of OHSS. Multiples are also very rare. The only twin pregnancy we have had so far was a case of identical twins. Interestingly that patient had a child from stimulated IVF with us but was a very low responder with only 3 eggs. She elected to give NC IVF a try and with her first cycle she had a beautiful blastocyst and ended up with identical twins. Go figure..... 3 eggs for thousands of dollars and one baby vs. one egg for a fraction of the cost and twins. Never a dull moment in reproductive medicine.

The reason for the lack of twins is simply the fact that there is almost always only a single follicle, a single egg retrieved and a single embryo available for transfer. Nationally, we still transfer too many embryos as seen below.

This phenomenon then directly influences the multiple pregnancy rate which is over 30% for patients younger than 30 years old and 24% for those patients between 35 and 39 years old. Elective single embryo transfer is attractive to consider but in reality not that many patients will elect to transfer only one embryo. Natural Cycle IVF solves that dilemma for the patient as there is almost always just a single embryo available.

The risk of twins is mainly that of prematurity. Although patients are often thrilled with twins, we are happier with singletons. The pregnancies are less complicated and the outcomes are better.

Concluding Thoughts:

As far as we are concerned, Natural Cycle IVF is here to stay. Our extensive experience has demonstrated that acceptable pregnancy rates can be achieved, especially if NC IVF is integrated into a fertility practice as a viable treatment option and not relegated to use only in extremely poor prognosis patients. In looking at our data from 2007-2009 we inform our patients that if they are younger than 40 years old then they can anticipate the following odds:I cannot emphasize enough how much patients appreciate having this option as a bridge. Many who have failed clomid/IUI or clomid/FSH/IUI are much happier trying NC IVF than full stimulated cycle IVF. Some patients who have known for years that they need IVF have been ecstatic that they have a new option. Some low responder patients with diminished ovarian reserve have pursued NC IVF as opposed to egg donor IVF or adoption. Although success rates in these patients are certainly lower than with donor egg IVF or adoption (we anticipate that 10-12% of these poor prognosis patients may still achieve a pregnancy with Natural Cycle IVF), many patients are not open to alternative pathways to parenting...at least not until they feel like they have exhausted all options.

Natural Cycle IVF. Part 2: Patient Interest

2010-11-16T05:56:00.000-08:00

So in the last post we discussed the development of stimulated IVF and how it made the entire process more efficient resulting in improvements every year in the IVF success rates. Yet patient interest in Natural Cycle IVF persisted. Why? Well I am not a patient so I offer these opinions based upon 14 years of practice and thousands of patients that I have had the privilege to treat for infertility.

Reason #1: Fear of fertility drugs
The drugs that we use for stimulated IVF have become much more "patient-friendly" over the years. Back in the dark ages, patients had to crack open little glass ampules of saline and then try to avoid slicing open their fingers as they mixed individual doses of fertility drugs. The injections had to be in the gluteus maximus (your backside) and the poor partners ended up having to dart their loved ones for over a week. Yikes. Eventually we moved to subcutaneous (under the skin) medications and now many patients use multi-dose pens. We are not to the level of the hypospray used by Dr. McCoy on Star Trek, but we are moving in the right direction.

However, some patients really have a great fear of injections and how they may feel on the drugs. It doesn't matter to them that the data suggests no increased risk of cancer for infertility patients that use these medications. They have no desire to go down that treatment path. Even if the drugs are free (with a co-pay), they really don't want to use them.

Reason #2: Fear of OHSS
Let's be honest here. OHSS is no fun. The patients feel terrible and as physicians we feel awful that they feel terrible. Although we can tap off the excess fluid and give the patients prompt relief, it is no fun to have OHSS. Of the nearly 200 blog posts that I have written, the one that gets the most hits is the OHSS Woes post that has nearly 80 comments attached to it. Although the risk of OHSS can be reduced by judicious drug dosing, the reality is that we can never eliminate this complication....we can manage it better perhaps but never reduce its incidence to zero...except with Natural Cycle IVF.

For the Hollywood version of OHSS, I refer you to the movie Malice which shows how OHSS can be used in a rather unique fashion....

Reason #3: Fear of multiples
So many patients come into our office asking for twins. I understand the mentality of "buy one baby, get one free" but the risks of twins are significant. Prematurity is a huge issue for babies and there can be life-long issues associated with preterm delivery. Although many patients are recommended to undergo elective single embryo transfer (eSET) in stimulated IVF the reality is that a minority of patients choose this option because the temptation to transfer 2 embryos simply becomes too great after going through the entire IVF cycle. In Natural Cycle IVF there is almost always only a single egg and therefore a single embryo. If you get twins in this situation then they must be identical twins which cannot be prevented!

Clearly, the extreme examples of fertility treatment gone wrong make the headlines much more frequently than do the news about twins. However, the NY Times did run a special series of articles last summer about complications associated with twin pregnancies. It was pretty scary stuff and yet most patients are still willing to roll the dice that their pregnancy will not run into such complications.

Reason #4: Fear of extra embryos
I really don't know when life begins. Clearly many embryos fail to grow, fail to implant and fail to develop into healthy pregnancies. However, the concept of extra embryos cryopreserved for future use is not always a welcome possibility to some couples. The decision to destroy the extra embryos is very difficult for many patients to handle...and yet if they are not interested in having more children and are not willing to donate their embryos to another couple then their options are limited. Some couples elect to undergo stimulated IVF but decline to freeze extra embryos for this reason. Others ask that only as many eggs get fertilized as they are interested in using. Freezing unfertilized eggs is becoming more effective, so that option may become more common in such cases. However, for many patients Natural Cycle IVF seems like a better way to handle their ambivalence.

Our Conclusions
None of these reasons are Natural Cycle IVF works better than stimulated IVF. For those patients who respond well to fertility drugs it is clear that stimulated IVF is more effective on a cycle by cycle analysis. However, I often use the analogy of driving to Leesburg from Arlington. You can take the Dulles Toll Road or you can take Route 7. Both will get you to Leesburg but usually the Toll Road is faster.

Opponents of Natural Cycle IVF seem to forget that patient preference does indeed matter. For some patients, stimulated IVF is just not an attractive option (usually for the reasons listed above). It really doesn't matter to these patients if they get seven cycles for the price of two....or a free toaster....or massage/aromatherapy....they really are not interested in stimulated IVF.

And we think that it is fine for patients to vote with their feet if they are interested in the Natural Cycle approach to IVF.

Natural Cycle IVF. Part 1: History

2010-11-09T10:59:00.000-08:00

Over the next series of blog posts I want to address several specific issues concerning Natural Cycle IVF. First I will cover the early history of IVF. Then I will describe why Natural Cycle IVF remained attractive in spite of lower success rates. Thirdly, I will review some pertinent research on Natural Cycle IVF. Finally, I will discuss our decision to offer Natural Cycle IVF and how our opinions differ from those of other clinics. This will include data about utilization of Natural Cycle IVF in the US and a survey of REs about Natural Cycle IVF. Finally, I will wrap it all up with a point by point discussion of the objections raised by some REs concerning Natural Cycle IVF.

Part 1: History

As I have previously described in an earlier blog post, this year has been a great one for those of us who practice in the field of reproductive medicine as Dr. Robert Edwards was awarded the Nobel Prize for the pioneering work that led to the world’s first IVF baby Louise Brown in 1978.

However, Dr. Edwards did not just wake up one morning and decide to do human IVF on the spur of the moment. His work represented years of careful research into egg/sperm/embryo physiology. In the early 1960s he began research on the development of the human egg and in 1965 worked with Howard and Georgiana Jones at Johns Hopkins in Baltimore. Howard Jones provided Dr. Edwards with slices of human ovary from patients with PCOS who were undergoing ovarian wedge resection as a fertility treatment. The immature eggs were isolated and matured in the laboratory but the process was inefficient and Dr. Edwards was not convinced that fertilization was occurring.

Meanwhile, Dr. Patrick Steptoe, an accomplished gynecologic surgeon, was making startling advances in minimally invasive laparoscopic surgery. Dr. Edwards realized that laparoscopy would enable a less invasive means to retrieve eggs...especially if fertility drugs were used to induce the growth of multiple follicles. You have to remember that this was before high tech ultrasound or rapid hormone assays or GnRH agonists (Lupron) or GnRH antagonists (Centrotide).
By 1971 they had grown fertilized embryos out to the blastocyst stage and decided to begin attempting to transfer the embryos back to the uterus with no success in nearly 100 attempts. Finally, in 1975 they had a positive pregnancy but it was an ectopic. Concerned that the use of fertility medications to induce multiple follicles was the problem, Dr. Edwards dramatically changed course and decided to attempt Natural Cycle IVF with Dr. Steptoe attempting retrieval of the single dominant follicle. Lesley Brown, who had no fallopian tubes as the result of previous surgeries, was the second patient to attempt Natural Cycle IVF. And the rest, as they say, is history....

Louise Brown’s imminent arrival was a worldwide phenomenon in the summer of 1978. I remember reading the Time magazine article about IVF and even remember the striking cover that graced the magazine’s July 30th issue. However, when I realized that the embryo was actually growing in Lesley Brown’s uterus, I was much less impressed. Heck, anyone who reads science fiction knew that IVF was anticipated for years or even decades...but an artificial womb...well that would have been pretty cool to my 13 year old way of thinking.

Natural Cycle IVF was technically more challenging that stimulated IVF and the tide soon turned towards the use of clomiphene or a combination of clomiphene and gonadotropin injections. The next IVF babies were born in Australia and India.

While Steptoe and Edwards were making advances in the mid 1970s, Howard and Georgiana Jones at Johns Hopkins were preparing for retirement. Hopkins had mandatory retirement at age 65 and allowed Howard to stay on for 2 years until his wife reached 65. One of their close friends and proteges was Dr. Mason Andrews, an obstetrician-gynecologist who lived in Norfolk, Virginia. He was able to launch a fledgling medical school (Eastern Virginia Medical School) in Norfolk but was having trouble recruiting faculty. He convinced both of the Jones to join his faculty upon their retirement from Hopkins.

Louise Brown was born the day that the Jones arrived in their new home in Norfolk. Sitting among the packing boxes a reported asked Howard Jones if IVF would be possible in the US. He replied that “all it would take would be money.” His comments were published in the local paper where one of their former patients saw the need and called the next day to pledge support. The Jones Institute was soon launched. Although they initially attempted Natural Cycle IVF they had failure after failure. Finally, they decided to try fertility injections and were successful with Judy Carr who had come to Norfolk from Massachusetts (where IVF was illegal). Dr. Howard Jones is now 100 years old and amazingly bright and energetic. He spoke at this year's ASRM and was amazingly erudite and witty. If only we could all be so lucky. Not bad for someone who "retired" 35 years ago!

So although IVF began with Natural Cycle IVF, the technical challenges of the time made the use of fertility drugs more attractive. Next up..Part 2: Why Natural Cycle IVF Remains Appealing to Patients.

If you are interested in reading more about the early history of IVF, then I recommend the following book by Robin Marantz Henig. Pandora’s baby: How the first test tube babies sparked the reproductive revolution. 2004. Houghton Mifflin Co. Boston, Massachusetts, USA. 256 pp. ISBN: 0-618-22415-7 (hardcover).

Happy Belated Halloween

2010-11-08T12:09:00.000-08:00

I must admit that I still enjoy Halloween. Nothing quite takes you back to your youth like walking around the neighborhood on a crisp fall evening while kids run from house to house extorting treats from the adults who stayed behind to dole out the candy. In particular I enjoy carving pumpkins and each year my kids seem to pick the hardest designs to test my ability. It takes a steady hand and a great deal of patience to carve those overgrown squashes into a jack-o-lantern.

Here are examples of this year's crop of designs with a Disney theme. I thought that Snow White came out pretty well....if I do say so myself.

So what does this discourse have to do with infertility? Honestly, absolutely nothing...but since I spent an entire afternoon scooping out pumpkin guts and carving little wedges out of my pumpkins, I thought somebody should see them besides the neighbors who were fixated on the Sour Patch Kids anyway.

But since we are on the topic of Halloween I wanted to address some fears that patients can have that do not involve Jason or Freddy or Dracula....I think that Dr. Gabe San Ramon covered some of these very nicely at the ASRM meeting.

Fear #1: Patients can be afraid that they need IVF.
Some patients look at IVF as an indication that their case is so hopeless that IVF must be used as a first line treatment. I understand that concern and certainly sympathize with their view. However, IVF is not the only option from which to choose and many patients find Natural Cycle IVF an option that is a bit less intimidating than traditional IVF. Some patients just want to try IUI or IUI and clomid or even just do diagnostic testing only. Walking into the office does not lead to getting hopped up on fertility drugs in a few days!

Fear #2: Patients can fear that they will never have children.
Clearly there are all different paths to parenthood. Some couples are more accepting of alternative pathways (such as adoption, donor egg, donor embryo or gestational carrier IVF) than others, but many will circle back to these options if success eludes them. In addition, unless a couple is truly sterile, spontaneous pregnancies can and do happen...you just can't predict it.

Fear #3: Patients are afraid of twins and triplets.
No argument from me on this front. Although I understand the attraction of twins for some ("buy one baby, get one free"), in truth twins are high-risk and can result in a huge cost to the couple, the babies and to society. If I never end up with another set of twins I would be ecstatic but the reality is that sometimes you just can't predict the outcome. If there are 2 follicles for a clomiphene/IUI then there can be twins....although rarely!

Fear #4: Patients are afraid of fertility drugs.
Although Oprah may believe that fertility drugs cause cancer, medical professionals do not believe that the data supports her view. The reality is that birth control pills, tubal ligations and previous full term pregnancies reduce the incidence of ovarian cancer. Since most fertility patients do not have many of these risk reducing factors, their risk of ovarian cancer is increased compared with the fertile population. However, the real question is whether fertility drugs increase the risk of ovarian cancer over baseline in fertility patients. The answer is no.

Fear #5: Patients are afraid that no one cares about them.
I come to work everyday to a clinic with some outstanding nurses and other clinical staff that care a great deal about each and every patient. I imagine that most other fertility physicians feel the same way about their staff. Patients ultimately vote with their feet. Here in Washington DC there are many options so patients can choose a doctor/clinic/staff that meets their needs. We all work hard to earn the trust of our patients and give the best advice that we can because we know how tough this journey can be on everyone.

Back to familiar topics next post!

ASRM Update #4: Natural Cycle IVF

2010-11-04T05:41:00.000-07:00

I really hate roller coasters. But I hate the spinning tea cup ride even more. All of this dates back to my childhood when I tossed my cookies after playing on the spinning spaceship ride at the playground near my home in Milton, MA. The other children were quite amused by my barfing but what can you expect from 10 year olds.
Here is a classic photo of yours truly at age 10 with my Crazy Car in my driveway in Milton. Note the outstanding fashion sense evident in the checkered polyester pants. This was before I discovered LL Bean. I loved that Crazy Car but did not spin excessively....

Well, on Tuesday morning at the ASRM I awoke at 430 am with the room spinning like crazy. No I was not hung over. And no my friends from VLFC (Very Large Fertility Center) had not slipped me a "micky" the night before at the dinner presentation on IVF. What I had was Benign Positional Vertigo (BPV) which occurs when one of the little grains of sand in your inner ear gets stuck telling your brain that you are orientated in a certain way to vertical while your other ear sends a contradictory signal. The result is a Tea Cup Ride from Hell. I have had this before back when I was living and working on Long Island, so I jumped out of bed and tried to knock the grain of sand loose. The treatment of BPV is completely counter-intuitive....you have to keep tilting your head to elicit the gut-wrenching spinning sensation. With enough repetitions your brain decides to ignore the signal and the spinning stops....usually after you have tossed all your cookies....Well, dear readers, I actually didn't vomit but was able to extinguish the spins in time to get to the Convention Center for our presentations on Natural Cycle IVF.

During the ASRM meeting this year we presented 4 studies on Natural Cycle IVF. The first of these was our 3 year experience with NC-IVF detailing our success rates and number of procedures. The second study was an analysis of the embryology part of NC-IVF including the embryo quality and implantation rate. Finally, yours truly had 2 presentations on the attitudes of physicians about NC-IVF as well as an analysis of the use of NC-IVF nationally based upon the SART reports from 2006 and 2007 (the year we launched our NC-IVF program).

There was a lot of interest in Natural Cycle IVF from fellow physicians, laboratory personnel and from the media. Almost universally the first question asked was "What about your SART statistics?" Readers of this blog may recall my previous posts on this topic (The Politics of Natural Cycle IVF) and although SART Registry Committee is considering our position concerning reporting of NC-IVF separately from stimulated cycle IVF, I am not sure that anything will change in the near future.

We remain committed to Natural Cycle IVF as a viable fertility treatment. Over the next few weeks I will present some rebuttals to the published objections to Natural Cycle IVF. As we remain the largest provider of Natural Cycle IVF in the United States I think that we have a unique perspective on this option and how it fits into other fertility treatment options.

ASRM Update #3: 3rd Party Reproduction

2010-10-25T16:51:00.000-07:00

Greetings from the mile high city where I have yet to sleep past 5 am since I remain on East Coast time. All the zombies have left town and only the attendees of the ASRM remain...some of whom do ressemble zombies although better dressed.

Yesterday I attended a course on the role of mental health professionals in IVF and in particular in 3 rd party reproduction. Well it was certainly an eye-opener. Although I have had some unusual requests over the years (most commonly a woman who wants to use her adult daughter with husband #1 to be an egg donor for her and husband #2) these paled in comparison to some of the absolutely nutty cases that I was hearing about. The one that sticks in my mind was fhe couple in their 70s who wanted to use 2 gestational carriers simultaneously with multiple embryos transferred from egg donors to be able to have 4 children simultaneously! Honestly, you just couldn't make stuff like this up because no one would ever believe you....

This type of reproductive gymnastics can lead to the ultimate question of "just because you can do something doesn't mean that you should do it." We discussed whether gestational carrier on demand was reasonable to offer given that many ob gyns now will offer cesarean section on demand. One case involved a female professional who planned on using her niece as a gestational carrier because "I really like being a size 4." Good grief. Makes me glad that in general practicing in Virginia usually shields me from some of this nuttiness.

Well tomorrow we have 4 presentations on Natural Cycle IVF and then it will be off to the airport so I can wing my way home. I appreciate the understanding of my patients and my family for my absence over these past 5 days. Back to work soon enough!

TTFN

ASRM Update #2: High FSH and Zombies

2010-10-24T15:25:00.000-07:00

Yesterday at the Post Graduate Course that I attended there was a great deal of discussion about ovarian reserve testing (ORT) and what it really means. As I have indicated in several past blogs ORT predicts response to fertility drugs and age predicts egg quality. So ORT does not indicate if a woman has any good eggs left...the only proof of a good egg is of course the delivery of a healthy baby. The overall consensus was that ultrasound and antimullerian hormone (amh) were the best indicators of ovarian reserve and response to fertility drugs. Unfortunately we will probably never have a true test of egg health except repeated treatment failure which is a pretty expensive way to test for healthy eggs!

The following case was presented: 38 year old with no previous pregnancies and an FSH of 18. The question raised was what additional testing should be performed and what treatments offered. First of all the question we asked whether the patient was infertile. Many ObGyns check FSH levels on older patients even before they have tried to conceive. This leaves the patient with a seemingly bad prognosis but she hasn't even tried to conceive yet! So remember that patients with high FSH levels can conceive without assistance but if she tries IVF her response may be suboptimal with a high rate of cancellation.

I presented the following perspective....The data shows that patients with diminished ovarian reserve have a high rate of failing to make it to retrieval in spite of spending thousands of dollars on medications. On the other hand, if these patients do make it to transfer then pregnancy rates are acceptable. In a patient like the one presented it seemed likely that her response to medications will be suboptimal. If she is a one egg a month person, either with or without drugs, then I believe her options are to 1) try on her own if tubes and sperm are ok, 2) try IUI with no drugs or 3) try Natural Cycle IVF. The fact that NC-IVF is even an option has given these patients hope even if many other clinics have refused to attempt stimulated IVF. Last month I had a patient just like the one presented above and we had success on the first cycle.
There is nothing wrong with attempting stimulation in such a patient but the chance of success is clearly much reduced because of the high rate of cycle cancellation. NC IVF could still be looked at if the stimulation was really poor.

OK so what about the zombies.....well as I was leaving the convention center there were thousands of people in the streets around the 16th. St Mall dressed up as zombies. The screaming and moaning was really disturbing. There was a zombie Santa and a zombie Elvis and a zombie spiderman just to name a few. Occcasionally, a human (designated with an x on his/her back) would be chased down and "eaten." Yup, it was quite a sight to say the least.

Apparently the Denver Zombie Crawl broke all previous records and just think I was here to see it,

http://www.examiner.com/zombie-in-denver/2010-denver-zombie-crawl-breaks-world-record

ASRM update #1: Size does matter

2010-10-23T17:48:00.000-07:00

Hello from Denver where the annual meeting of the ASRM is being held. American Society for Reproductive Medicine that it. Well it seems that this is the meeting where I will be unable to keep my big mouth shut. Yesterday at the Practice Retreat for the members of the Society for Reproductive Endocrinologists I spoke my piece about practice size. As a 3rd generation physician I feel strongly that the patient-doctor relationship must be at the center of all care. So that is why we try to do as many sonograms as possible on our own patients and ditto the egg collections and embryo transfers. That doesn't mean that practices where the RE rarely sees the patient don't have good success rates, but in speaking for myself I would not like to practice in such an environment when there is the opportunity to practice as I have at Dominion for the past 11 1/2 years. It seems that many of the practices represented are unable to offer that approach and I thank my lucky stars every day for my good fortune.

Obviously there are economies of scale and one physician from Boston indicated that he believed that 4 physicians is close to ideal. Well, let's see....Dr D, Dr G, Dr Reh and Dr Payson (for some weekend coverage)....I gotta agree.

Tune in for my next post and learn how DrG was surprised to find himself surrounded by thousands of zombies on 16th Street on Saturday PM.

DrG on NBC

2010-10-19T07:03:00.000-07:00

Clearly there was a lot of interest about IVF following the exciting announcement that Dr. Robert Edwards had been awarded the Nobel Prize. I was asked to speak about IVF on the Midday Show on the local NBC station here in Washington. I have been on TV a couple of times and I usually find it very painful to watch but this time I actually was pretty satisfied with how things went. The worst experience I had was on CNN when I was on a panel with Pete Singer and Arthur Caplan. Those two went after each other with a vengeance and I was left just sitting there looking stupid.

So for those who want to hear and see me on local TV check out the video below.... or go to http://gallery.me.com/johndavidgordon/100013.

See you in the movies!

Robert Edwards Wins Nobel Prize for IVF

2010-10-04T10:09:00.000-07:00

Earlier this week the Nobel Prize Committee announced that Robert Edwards had been awarded the Nobel Prize for Medicine in recognition of the groundbreaking work on IVF that led to the birth of Louise Brown in 1978. It is hard to remember a time when IVF was not part of our fertility treatment options and yet just 3 decades ago IVF was more science fiction than science fact.

Drs. Steptoe and Edwards ushered in a new era in reproductive medicine with their success in 1978. But public opinion concerning IVF was hardly united in this seemingly "Brave New World" approach to reproduction.

Time magazine had IVF as its cover story during the summer of 1978. The commentary below is from that article and I know that our current patients would find it hard to imagine the way in which all of us held our collective breaths as the birth of Louise Brown was announced.

"Some commentators heralded the coming birth as a miracle of modern medicine, comparable to the first kidney and heart transplants. Theologians—and more than a few prominent scientists—sounded warnings about its disturbing moral, ethical and social implications. Others, made wary by the recent cloning hoax, remained unconvinced that the child about to be born was indeed the world's first baby conceived in a test tube.....Yet on the eve of what may well be the most awaited birth in perhaps 2,000 years, there are also still many unanswered questions. For the Brown family, it is whether their test-tube child is healthy and can ever hope to have anything resembling a normal life. For the doctors, it is whether they have pushed medicine to a new frontier or set it dramatically back by creating a medical disaster. For the world at large, it is whether doctors should be free to continue such daring exploits or whether new restraints should be posted to keep them from poaching on nature's domain. There is a very large gathering in the waiting room for Baby Brown."

As we know, the story had a happy ending...not only for the Brown family (who had a 2nd daughter by IVF and now have grandchildren from both Louise and her sister [no IVF needed for that generation]) but also for the millions of couples that have used IVF to have their families. Well done, Dr. Edwards and congratulations on a Nobel Prize recognizing the debt that is owed to you and the late Dr. Steptoe for taking those first careful steps into IVF.

Question 36. Do I need endometriosis surgery if I am already planning to pursue IVF?

2010-09-16T13:32:00.000-07:00

I wish sometimes that medicine was more like engineering. In engineering there are lots of straight lines and right angles. You can usually describe any problem with specific equations and most of the time there is clearly one right answer. Unfortunately, medicine is not engineering. There are some questions that cannot so easily be answered with a definitive "yes or no." My wife is an engineering PhD, so I can easily understand why very intelligent people can just want to scream when faced with some of the uncertainty inherent in medicine...especially reproductive medicine. Obviously, the "right" decision is the one that results in a successful pregnancy. But since more than one option may result in pregnancy (including no treatment at all) the situation can often seem "as clear as mud."

The Question of the Day returns to the subject previously raised in Question 34 concerning fertility and surgery for endometriosis. However, today we are specifically dealing with the issue of surgery prior to IVF. In patients that have failed non-IVF treatments and are wondering if they should do a laparoscopy at this junction I offer them the following advice...

If I do a laparoscopy and see terrible endometriosis then I am going to recommend IVF.

If I do a laparoscopy and see some endometriosis then I am going to recommend IVF.

If I do a laparoscopy and see no endometriosis then I am going to recommend IVF.

So why the heck are we off to the operating room? Indeed. That is why surgical volume for fertility patients has fallen off a great deal. However, patients with a known/suspected endometrioma cyst represent a different group and call for a different approach...and that is the topic of today's Question of the Day!

36. Do I need endometriosis surgery if I am already planning to pursue IVF?

The question of endometriosis surgery prior to IVF is a somewhat controversial area of reproductive medicine. Most reproductive endocrinologists do not recommend surgery prior to IVF unless the woman has advanced endometriosis, in particular, an ovarian endometrioma.

IVF is associated with excellent pregnancy rates (even without surgery) in women who have only mild to moderate endometriosis. When advanced endometriosis is present, such as an ovarian endometrioma, its surgical removal prior to IVF may enhance the chances for a successful IVF outcome and may decrease infectious complications related to egg collection. Thus, in such cases, most reproductive endocrinologists often recommend the removal of advanced endometriosis prior to treatment using IVF.

However, severe endometriosis with endometriomas may lead to diminished ovarian responsiveness, and ovarian surgery may further compromise fertility in such cases. So the decision to perform extensive surgery for endometriosis must be weighed against the potential impact of that surgery on the ovary. Also, advanced endometriosis may increase the likelihood for an early pregnancy loss or spontaneous abortion. By first removing the endometriosis, the outcome of pregnancy may be improved. Ultimately, the decision whether or not to remove perform surgery rests between doctor and patient. In general, we believe that the removal of a small 1-2 cm endometrioma is unlikely to impact IVF success but the removal of large endometriomas may be reasonable before attempting IVF. Some doctors advocate a threshold of 4 cm for endometrioma removal but the data supporting this contention warrant further study.

Question 37. What is the difference (if any) between intrauterine insemination and artificial insemination?

2010-09-16T13:29:00.000-07:00

What's in a name? Sometimes not much I guess and certainly we throw around medical jargon quite freely in our practice sometimes forgetting that all this can be quite confusing to patients. I recently had a patient that came in requesting IUI with ICSI. She was very frustrated when I explained that you really cannot do ICSI unless you do IVF. However, she was adamant that she didn't want IVF with ICSI she wanted IUI with ICSI. I just was unable to make her understand the difference between IUI, IVF and ICSI. Oh well, she probably posted on some website that I am an insensitive physician who was unwilling to help her....

Of course, I know that all of you would easily be able to explain the difference between these because you have read this blog (along with my Mother) and have purchased our book.

So for those a bit unclear on some basic terminology here is today's Question of the Day from the soon-to-published 2nd Edition of 100 Questions and Answers about Infertility.

37. What is the difference (if any) between intrauterine insemination and artificial insemination?

Artificial insemination (AI) is a historical term that encompasses any technique involving the introduction of sperm into the female reproductive tract without sexual intercourse. Semen can be placed into the vagina (intravaginal insemination) or into the cervix (intracervical insemination) without any special preparation of the specimen. However, if unprepared semen is placed directly into the uterus [intrauterine insemination (IUI)], then severe spasmodic uterine cramping can occur. Thus, when performing an IUI, the sperm must first be washed and prepared prior to placement inside the uterus. Washing the sperm removes prostaglandins, the hormones that cause the violent uterine contractions. Washing also eliminates substances that might lower the sperm quality and activates the sperm, thereby leading to improved sperm motility. Generally, the IUI specimen is prepared in the doctor’s office just prior to insemination.

The actual IUI is a painless, simple, in-office procedure that is often performed by a nurse. It usually takes just a minute to perform. Physicians typically ask patients to come in with a full bladder so that the angle between the uterus and cervix is altered, which allows for easy passage of the catheter into the uterine cavity.

Today, it is rare for patients to undergo other forms of insemination besides IUI because the pregnancy rates with IUI are better than those obtained by intravaginal insemination or intracervical insemination.

Question 35. Are there medical treatments for endometriosis?

2010-09-09T13:46:00.000-07:00

Occasionally I am asked to see a patient with endometriosis who is not interested in fertility. Although I can certainly manage these patients, I honestly think that they are better served by going to a non-fertility clinic RE. Our practice is pretty much 100% geared to the needs of fertility patients and I wonder if those patients who are not seeking pregnancy ultimately feel like a fish out of water in our waiting room....

Fortunately there are some effective medical treatments for endometriosis. Unfortunately, all of these treatments shut down reproduction so they are not appropriate for the endometriosis patient seeking pregnancy.

Meanwhile I wanted to share the exciting news that the 2nd Edition of 100 Questions and Answers about Infertility is at the printers! Let the presses roll!

35. Are there medical treatments for endometriosis?

Several medications are used to treat endometriosis. All of these medications suppress ovulation and cause a hypoestrogenic state. Understandably, suppressing ovulation also prevents pregnancy from occurring so medical therapy is not appropriate in patients actively seeking fertility. In patients who are not trying to conceive, medical treatment of endometriosis can be very beneficial and relieve symptoms of dysmenorrhea and pelvic pain.

One common medical treatment is to prescribe the combination oral contraceptive pill. Although each of these daily pills contains estrogen, the progestin (progesterone-like component) in the pill overrides the estrogen effect, resulting in suppression of endometriotic lesions. Oral contraceptive pills are effective in 30% to 60% of patients with endometriosis-related pain.

Many physicians prescribe gonadotropin-releasing hormone (GnRH) analogs (such as Lupron), which reduce estrogen levels to postmenopausal levels for their patients with endometriosis. These medications suppress estrogen production, prevent ovulation, and cause atrophy of the endometriosis in 70% to 90% patients. Unfortunately, GnRH analogs are expensive and must be given as injections either once a month or every 3 months. GnRH agonists can cause side effects including headaches, hot flashes, moodiness, insomnia, and vaginal dryness. To counteract these side effects experienced by many patients treated with GnRH agonists, physicians often prescribe oral contraceptive pills or supplemental progestin therapy (such as norethindrone) along with the GnRH analogs. This combined therapy ay allow for improved treatment acceptance through the alleviation of the many side effects associated with the use of the GnRH analogs as single therapy. Patients tolerate this combination very well and achieve maximal benefits in suppressing the disease and its symptoms.

As noted previously, medical therapy is not indicated for patients with endometriosis who are actively trying to conceive, since all of these treatments will suppress ovulation. Instead, for these patients, the goal should be to promptly establish pregnancy before the endometriosis causes any further damage to the reproductive organs. Generally, these women should seek treatment from a fertility expert to maximize their chances for successful pregnancy.

Question 34. Does surgery for endometriosis improve pregnancy rates?

2010-09-03T10:42:00.000-07:00

Where does all the time go? Seems like just yesterday that I was writing the last post before I went on vacation and now I realize that a whole month has passed. You may have wondered "where is Dr. Gordon?" "Why hasn't he posted a new blog that will make our day a little brighter and put a little more zip in our step?" "Why do the 6 of us keep reading this blog if he doesn't care enough about us to spend just a few minutes posting his words of wisdom?" "Why didn't I buy Apple stock at $25?" Wait that last question is the one that I keep asking myself. Not to be a name dropper but my son was in preschool in California with Steve Job's son Reed. Man, if only they had become best buddies.....unfortunately, my son thought that Reed was weird and wouldn't play with him. Apparently, when you are 3 years old it doesn't matter when some kid's father is worth 6 Billion dollars. But I digress....

So in a couple of weeks we are having a CME (doctor's continuing education) course at Fairfax Hospital. One of the questions concerns surgery for endometriosis. Guess what? No one is really sure of what to do in some of these cases. Overall, we seem to be moving away from surgery for the infertile patient, and yet, there are still occasional patients that would benefit from a laparoscopy. The problem is figuring out who would benefit from surgery and who will not. In starting to address that issue I will present today's Question of the Day from the 2nd Edition of 100 Q&A about Infertility (which is currently being printed!):

34. Does surgery for endometriosis improve pregnancy rates?

Well-designed medical studies clearly show that destroying even small implants of endometriosis can improve fertility by as much as 50%. In a large Canadian study, the monthly pregnancy rate following surgical treatment of minimal endometriosis rose from 3% to 4.5%. Although this finding represented a 50% improvement in the patients’ monthly chance of pregnancy, it does not compare very favorably with IVF pregnancy rates, which average above 30% for a single treatment cycle. Nevertheless, because treatment of endometriosis at the time of surgery does improve pregnancy rates, most surgeons will do their best to destroy endometriosis at the time of laparoscopy by using either laser or coagulation techniques. In addition to improving fertility, surgery may often eliminate or improve symptoms of dysmenorrhea and pelvic pain.

Ovarian cysts that contain endometriotic tissue may grow quite large. They are often called “chocolate cysts” because of the dark brown fluid found within them, although endometriosis cysts are more correctly referred to as endometriomas. If left untreated, these growths may destroy part or all of the normal ovarian tissue, including the eggs. Endometriomas must be surgically removed, usually via laparoscopy, as medical therapy is ineffective in the treatment of endometriomas. The ultimate choice of whether to perform a laparoscopy or laparotomy depends on the operative findings and the skill and experience of the surgeon.

Question 33. What is endometriosis and how is it diagnosed?

2010-08-06T11:08:00.001-07:00

You know I should have really been an Orthopedic Surgeon. I have spent so much time in their offices recently that I could have been much more useful to my family if I had specialized in something more practical. Of course, then we probably would have had fertility problems instead.....

On the other hand, endometriosis is a problem that I know something about.....But that being said, our understanding of the link between endometriosis and infertility remains less than clear cut. It was not unusual to diagnose endometriosis in a patient undergoing a laparoscopic tubal ligation in a woman with several children so the impact on fertility may be difficult to predict on a case-by-case basis.

So today's Question of the Day concerns some basics about endometriosis....

33. What is endometriosis and how is it diagnosed?

Endometriosis is a chronic disease characterized by the growth of endometrial-like tissue beyond the normal confines of the uterine cavity, Endometriosis is usually diagnosed at the time of laparoscopic gynecologic surgery although endometriosis cysts (endometriomas) may be presumptively diagnosed on ultrasound. Endometriosis is the presence of endometrial-like tissue located outside of the uterine cavity. Most commonly, it is located on the ovaries, but it can also be found on any of the organs inside the pelvic–abdominal cavities.

Although there are several theories about formation of endometriosis, it seems likely that retrograde menstruation (the passage of menstrual debris out of the ends of the fallopian tubes and into the pelvis) plays a major role. Some women may be unable to effectively remove this tissue allowing lesions to form and grown with continued hormonal stimulation. Since the endometrium sheds through menstrual bleeding every month during menstruation, the endometrial tissue that comprises the endometriosis implants will also respond in kind. This phenomenon leads to inflammation of the pelvic reproductive organs, causing pelvic pain, painful periods (dysmenorrhea), and infertility. Pelvic adhesions or scar tissue may also develop. However, since endometriosis has been described in areas outside of the pelvis (eye, lung, brain, etc.), the retrograde menstruation theory cannot account for all cases of endometriosis.

Endometriosis may be suspected when patients complain of increasingly severe dysmenorrhea, pelvic pain, or infertility, but remember that it can be definitively diagnosed only via surgery. Most often, a diagnostic laparoscopy—a simple outpatient surgical procedure—is used to diagnose endometriosis. Other nonsurgical techniques such as ultrasonography, CT scan, or MRI can occasionally be helpful in their abilities to detect endometriosis.

Question 32. Should I consider using a sperm donor to conceive?

2010-07-28T06:14:00.001-07:00

So first we had Snowmaggedon and the Gordon family was without power for six days and now we have experienced Summerggedon! Sunday afternoon an intense thunderstorm ripped through the Washington DC area and did widespread damage. Over 300,000 taxpayers were without power and that included yours truly. Fortunately the power was restored last night after more than 48 hours of pioneer living. Needless to say we were very happy to rejoin the 21st century. On the other hand, the simplicity of going to sleep soon after sundown and waking up early in the morning fully refreshed should not be underrated. Simple can = good.

This concept can also apply to cases of severe male factor infertility. Not all couples are prepared to go the distance in terms of IVF/ICSI with testicular sperm in cases of azoospermia. A few years ago I had a couple that came to me following a talk that I gave regarding donor egg. She was relatively young and he had extremely low sperm counts. They had already spent almost $100,000 on fertility treatments and were now considering donor egg IVF using his sperm. Apparently no one had discussed the use of donor sperm with them. They quickly decided that this approach made more sense and 3 weeks later she had an IUI with donor sperm in a natural cycle (not even clomid). She delivered a full-term healthy baby 9 months later. Total cost....about $2200. Not a bad deal!

So should you consider using donor sperm or as Lois (our former beloved front-desk manager) used to call it - "man in a can"? Well that is the topic of today's Question of the Day from 100 Questions and Answers about Infertility.

32. Should I consider using a sperm donor to conceive?

Couples who desire a child but in whom the male partner has a very low sperm count (oligospermia) or no sperm at all (azoospermia) often consider using third-party sperm donation and artificial insemination. Donor sperm can also be used by single women or lesbian couples. Many high-quality, reputable commercial sperm banks exist. They recruit and thoroughly test the donors and provide a listing of their available donors and their characteristics from which the couple can then choose. The donated sperm is obtained from the donor, tested, and quarantined for at least 6 months at the sperm bank. The donors are then retested to ensure that they are still free from any sexually transmitted diseases.

The specimen is released for use only after the tests results confirm the donor is free from any infection. The frozen sperm is then shipped to the physician’s office, and artificial insemination is performed around the time of the woman’s ovulation. Placement of the sperm inside the uterus (IUI) results in better pregnancy rates than placement of the sperm in the vagina or cervix. Frozen donor sperm can also be used for more advanced fertility procedures such as gonadotropin/IUI or IVF with or without ICSI. If a woman wishes to use sperm from a known donor with whom she does not have a physical relationship, then the sperm may need to be quarantined for at least 6 months and the donor retested for infectious diseases before the specimen can be used for fertility treatments.

Setting the Record Straight About NC-IVF

2010-07-21T13:51:00.000-07:00

I am posting this recent blog by Dr. DiMattina which addresses some recent inaccurate information about Natural Cycle IVF that is circulating out in cyberspace.

DrG

Hello Everyone!

Recently, there have been many mistruths appearing on-line about our NC-IVF program. So, I am writing to set the record straight and provide you with honest information about our experience with NCIVF. As you well know, the internet provides a platform which all too often provides only one side of a "story" and unfortunately, far from reality too.

By way of background, because of our high success we experienced with our stimulated IVF program, in January, 2007, we decided to add a NCIVF program for our patients as most of our patients achieving pregnancy in our stimulated IVF program had only one or two embryos transferred. Thus, we believed that many of our patients did not require ovarian stimulation drugs and the high costs associated with stimulated IVF.

Six weeks ago, we submitted 4 papers describing our experience with NCIVF to the American Society of Reproductive Medicine(ASRM) annual meeting in October, 2010. All 4 abstracts were accepted by ASRM. First, let me say that after 3 and a half years of performing NCIVF, we remain most enthusiastic about the success of our program and especially so for 2010.

So, here are some of the facts about our NCIVF program from 2007 to 2009 as presented to the ASRM: First, on-line there are individuals claiming that most of our patients never made it to an egg collection and instead they underwent an IUI rather than the intended egg collection. The FACT is: 86% of our patients who started our NCIVF program went to egg collection and an egg was retrieved in 88% of these patients. So, the vast majority of our patients not only made it to an egg collection but also had a successful egg retrieval. IUI occurred in less than 15% of our patients! And successful embryo transfer occurred in 56% of the patients who had an egg obtained. Overall, 35.3% achieved a clinical pregnancy per embryo transfer. In my opinion, not bad for only one egg and one embryo! Cumulatively, of course, with more embryo transfers, the total pregnancy rate is even higher. In fact, our very first patient to deliver from our NCIVF program, delivered again last year from a repeat NCIVF treatment.

Second, misstatements were made concerning our costs and profit motives. We currently charge $4,400 for a completed NCIVF treatment and it is prorated. If a patient does not make it to an egg retrieval, then the cost is prorated to $1,400 and the rest either refunded to the patient or credited towards another treatment. In our NCIVF program, we routinely perform ICSI without an added charge since there is only one egg. Compare these costs to a stimulated IVF cycle where the drugs alone cost about $5,000, the treatment cycle itself about $9,500 and another $1,500 to $2,000 for ICSI. Thus, the total costs for a stimulated IVF cycle can be $15,000 or more. In my opinion, DF is not only cost conscious for our patients, but the most cost conscious fertility center in town since we were the first and perhaps still the only IVF center in the Washington DC area to offer and produce babies using NCIVF. Interesting to me that NCIVF is routinely performed in over 50 countries around the world but not so in the US.

Critics of NCIVF say that it may take many treatments before one achieves pregnancy. The FACT is: 64% of the pregnancies that occurred in our NCIVF program were achieved in the FIRST treatment cycle and 21% in the second. So, we usually only recommend one to three treatments of NCIVF to our patients.

So, here is the truth about our experience with our NCIVF program and we are most proud of our accomplishments and success. NCIVF is not a "cure-all" for infertile couples, rather another option for many. I wish all of you the very best in obtaining your fertility goals.

-Dr. Michael DiMattina

Question 31. What can cause my husband to have no sperm at all and can we still have children together?

2010-07-19T07:23:00.000-07:00

Summer is in full swing here in Washington DC and we are really getting cooked these past few weeks. I have been trying to be a real handyman this past week and have been granted a special dispensation by my wife in regards to the use of power tools. My project has been to strip off the paint and rust of an old patio set by using my power drill and a steel brush. Actually it has been very gratifying to see years of rust submit to my efforts. Does this have anything to do with infertility and IVF? Probably not, except that being a man is more than doing projects around the house and it is more than being able to father children. Being a father or a mother has everything to do with what happens after delivery or adoption.

We understand the desire to be genetic parents and will make every effort to accomplish that goal. However, every couple must decide what being a parent means for them. For some, the use of donor sperm or donor egg or both or adoption are all acceptable choices. For others, these are not options....or at least not options until the others have been fully explored.

Today the Question of the Day concerns men with no sperm at all on semen analysis. It is a true miracle of medicine that some of these men can become genetic parents through IVF and ICSI. So keep the AC cranked and read on. Plus, if anyone can explain why my hands get blue paint on them when I touch my repainted patio set even after it has dried I would really appreciate it....I must not be a real man after all...

31. What can cause my husband to have no sperm at all and can we still have children together?

Assuming that there was not a problem in collecting the specimen, the absence of sperm on a semen analysis—a condition known as azoospermia—requires thorough evaluation. Azoospermia can be divided into two major categories: obstructive and nonobstructive.

Obstructive azoospermia occurs when the duct carrying the sperm from the testicle to the urethra becomes blocked. This blockage may be the result of previous surgery on the scrotum or testicle, or even follow repair of an inguinal hernia. During hernia surgery, the vas deferens may be inadvertently damaged or even cut. Scar tissue that blocks the vas deferens can form either postoperatively or as the result of an infection (most commonly gonorrhea, though other infectious diseases may also cause blockage of the sperm duct).

Congenital bilateral absence of the vas deferens (CBAVD) leads to some men being born without a vas deferens on either side and is associated with the gene for cystic fibrosis. CBAVD is a rather unusual presentation of cystic fibrosis as it occurs in the absence of any chronic lung disease. For this reason, any man with azoospermia associated with congenital absence of the vas deferens should undergo genetic testing to determine whether he carries the gene that causes cystic fibrosis.

Nonobstructive azoospermia results from dysfunctional sperm production as opposed to an anatomic issue and can represent a more problematic situation. The failure of sperm production in an otherwise normal testis may be the result of either a testicular issue or a pituitary or hypothalamus issue. If a hormonal evaluation reveals normal levels of prolactin and thyroid hormone, then testicular sperm production may have failed. If this finding is associated with an elevated FSH level, then the chance of finding any sperm production in the testis is quite unlikely. A testicular biopsy is often performed to assess whether any sperm are present within the testis. Even very low levels of sperm production may allow for attempts at IVF using ICSI. Genetic testing to rule out a chromosomal problem is often suggested in cases of very low or absent sperm production. We suggest that men undergoing a testicular biopsy arrange for cryopreservation (freezing) of viable sperm in order to avoid having to undergo a second biopsy procedure.

The use of IVF with ICSI can allow couples to successfully achieve pregnancy even in cases of obstructive or nonobstructive azoospermia. Sperm that is removed from the epididymis or the testicle may look excellent but is incapable of fertilizing an egg since it has not undergone the final changes that result in fully capacitated sperm. The introduction of ICSI in 1993 revolutionized the treatment of male factor infertility. To obtain sperm for use in IVF/ICSI, a needle aspiration of the testis or epididymis can be performed under local anesthesia in cases of obstructive azoospermia. If the male partner has nonobstructive azoospermia, a urologist usually performs a testicular biopsy in the hospital while the patient is under general anesthesia as sperm production may be severely impaired necessitating the removal of more testicular tissue in order to have an adequate sample. In either case, the testicular tissue or the sperm aspirate can be frozen in liquid nitrogen and maintained relatively indefinitely. If a testicular biopsy reveals no mature sperm, then the only option is to use donor sperm or to pursue adoption.

Occasionally, the sperm retrieved through a testicular biopsy or needle aspiration is of exceedingly poor quality. In such cases, a repeat testicular biopsy on the day of egg collection for IVF or even use of a cryopreserved specimen from an anonymous sperm donor may be considered as a backup plan.

Rarely, men with diabetes or those taking certain antihypertensive medications may suffer from retrograde ejaculation. In this condition, there is no emission of fluid with male orgasm because all of the fluids travel backward into the bladder instead of out through the urethra. Retrograde ejaculation can easily be diagnosed by checking the post-ejaculation voided urine for sperm. Sperm present in the man’s urine can be washed and used for either insemination or IVF. Pretreatment with bicarbonate the night before sperm collection may improve sperm quality by increasing the pH of the urine.

One final (and interesting) cause of azoospermia is anabolic steroid abuse. Some men with azoospermia may have used testosterone or other steroids as part of their strength and conditioning training. High doses of these steroids can suppress sperm production. Sperm production can be reinitiated in such patients by stopping the steroids and starting gonadotropin therapy (analogous to ovulation induction therapy in women). Although clomiphene citrate has been used to improve sperm quality in men, most studies reveal it to have little to no benefit.

Question 30. Is there anything my husband can do to improve his sperm count, such as wearing boxers not briefs, taking vitamins or undergoing surgery?

2010-07-12T13:00:00.001-07:00

As we approach the all-star break in the MLB season (Go Red Sox!) I would like to present a theory I have about guys and their resistance to having a semen analysis. If I had a dollar for every husband or male partner that said "I don't need any tests. I am fine. I have gotten several women pregnant." then I would have a lot of dollars. Now, getting beyond the fact that most women would not choose such an insensitive dolt as the parent of their yet to be conceived child...I always tell the guys that the proof is in the pudding and we need to do the test.

So why the resistance? It could be embarrassment about producing a sample. But I think it is deeper than that....it is all about the numbers. For decades these men have been memorizing batting averages, on-base percentages, ERAs and the like. Suddenly they are going to be reduced down to a number....a sperm number and it is anxiety provoking.

When I tell women their FSH level or their AMH level or their antral follicle count, they almost never yell out or high five their husbands....not so when the guys get their numbers. So what can a guy do if his numbers are more suited to AAA ball than MLB...well, not a lot as we can see in today's Question of the Day from 100 Questions and Answers about Infertility.

30. Is there anything my husband can do to improve his sperm count, such as wearing boxers and not briefs, taking vitamins or undergoing surgery?

Semen analysis results demonstrate considerable variation from sample to sample, which complicates research efforts to identify specific dietary or lifestyle change that might potentially improve sperm quality. Although the presence of a varicocele has been suggested to play a role in male infertility, the benefit of varicocelectomy remains controversial.

Some studies have suggested that wearing boxers instead of briefs can improve a man’s sperm count. The avoidance of extremely high temperature may also improve sperm counts, so care should be taken to avoid prolonged exposure to extremely high temperatures, such as within a sauna or a hot tub. Years ago on Long Island, Dr. Gordon had a patient whose husband owned a pizzeria. Once he stopped working 18 hours a day in front of the pizza ovens and moved to the cash register and away from the heat, his sperm count normalized and they conceived spontaneously.

The effects of a variety of nutritional supplements on semen have been studied with some researchers suggesting that antioxidants may improve sperm quality, thereby leading to improved pregnancy rates (the desired outcome). Although the data on nutritional supplements with antioxidant properties are somewhat limited, a commercially available product based on this research is available (Proxeed, Sigma-Tau Pharmaceuticals). This nutritional supplement is available for purchase only over the Internet. Although it has been frequently prescribed by some urologists, additional studies are required to confirm its benefits.

Surgical treatments for male factor infertility are very limited. Historically, varicocelectomy has been the surgical procedure most commonly used to improve sperm quality. In this procedure, dilated veins in the scrotum (varicocele) are cut or occluded. One theory is that these dilated veins may increase the scrotal-testicular temperature, thereby diminishing the sperm quality. By cutting the veins, the scrotal temperature is restored to normal and fecundity may be improved.

Unfortunately, well-designed controlled studies have not shown any statistical increase in pregnancy rates following varicocelectomy. Furthermore, many fertile men have varicoceles. Today, this procedure is rarely, if ever, indicated. In most cases of male factor infertility, the best treatment involves intrauterine insemination (IUI) or, more often, proceeding directly with in vitro fertilization (IVF) and possibly intracytoplasmic sperm injection (ICSI).

Question 29. If I had a previous ectopic pregnancy, what should I do to avoid another one?

2010-06-23T12:29:00.000-07:00

Sorry for the delay in between blog posts. Unfortunately, my number one fan (my Mom) has been in and out of the hospital in Boston and I just have been too busy to sit down and do some blogging. At 87 years of age there is not a lot that can be done as she has a lot of health problems and a recent round of chemo almost did her in...But she is hanging in there and I try to talk to her every day. It has been said that gynecologists are either perverts or Mothers' boys...I will let you guess which category this Eagle Scout falls into.

Ok so back to the 2nd Edition of the 100 Q&A book (which I am currently doing final editing of for a Fall pub date)....Today we are discussing ectopics. Why? Because it is Question 29.... Let's be honest here....ectopics really stink. Patients that have had an ectopic will do anything possible to avoid another ectopic. Fortunately, with early identification most ectopics can be treated medically with methotrexate avoiding the need for a surgical procedure. However, methotrexate may not always be successful and patients can end up with an emergency surgery in spite of our best efforts.

29. If I had a previous ectopic pregnancy, what should I do to avoid another one?

The reported incidence of tubal or ectopic pregnancy in the general population is 1%. Women who have experienced an ectopic pregnancy generally have a 10% to 15% risk for another ectopic pregnancy. The good news is that most women who have had an ectopic pregnancy will not have another one. The bad news is there are no options available to eliminate this risk entirely except adoption. All women who are attempting to conceive inherently are at risk for an ectopic pregnancy. Even women with absent or obstructed fallopian tubes can experience an ectopic pregnancy if the embryo becomes implanted in the section of the fallopian tube found within the muscle of the uterus (called an interstitial or cornual pregnancy). The rate of ectopic pregnancy following IVF is usually 1% to 2%, far lower than the 15% recurrence risk with a spontaneous pregnancy.

Fortunately, most ectopic pregnancies are readily diagnosed very early in pregnancy using blood hormone assays for beta human chorionic gonadotropin (HCG) combined with transvaginal ultrasonography. It is now uncommon for such pregnancies to go undiagnosed or to lead to tubal rupture, hemorrhage, or death. Most ectopic pregnancies can be treated medically using low doses of methotrexate (a type of chemotherapy that selectively destroys the pregnancy tissue), thereby avoiding surgery. This medical therapy is 80% to 95% effective.

Kristin comments:

I had an ectopic pregnancy after a Clomid cycle that was monitored by my OB. I was 8 to 9 weeks pregnant and thought I was having a miscarriage when the ectopic pregnancy was confirmed at my first RE appointment. Unfortunately, the methotrexate therapy did not work, and I had to have surgery to remove my right fallopian tube. After determining that my remaining tube was not blocked through an HSG, and with the counsel of our new RE, we opted to move on to IVF. This option would offer the greatest chance for us to become pregnant and avoid another ectopic pregnancy.

When I did become pregnant through IVF, my RE agreed to a very early ultrasound to make sure that the pregnancy was in my uterus. I appreciated that my RE understood my concerns of having another ectopic pregnancy. He treated me as an individual instead of requiring me to wait until the typical 7-week mark to perform an ultrasound.

Question 28. If I had my tubes tied, can I have them untied?

2010-06-16T12:59:00.000-07:00

This has been a busy couple of days here at Dominion as DrD is off for a well-deserved bit of R&R. Trying to do the work of 2 doctors is kind of like clapping with one hand...but so it goes. Today I was asked again about what to do in cases of previous tubal ligation. This clinical scenario comes up fairly frequently and so it is certainly a valid question to discuss. I have not done a tubal reversal surgery in many years and usually refer all interested parties to Dr. Gary Berger in Chapel Hill, NC. In spite of Dr. Berger's office being on the Carolina blue side of the Duke blue/Carolina blue divide, he is a skilled and caring MD with an office based surgery center. His price for a tubal reversal is very reasonable and for those patients sure about going down this path I think that he is an excellent choice and well worth the trip to NC.

However, not all patients are good candidates for tubal reversal and many end up considering Natural Cycle IVF or Stimulated Cycle IVF as better choices. Plus after having an IVF baby there are no concerns about birth control as your tubes are still tied!

So here is today's Question of the Day....

28. If I had my tubes tied, can I have them untied?

Fertile women who have had their “tubes tied” (tubal ligation) may do very well and achieve pregnancy with tubal reanastomosis surgery. Pregnancy rates of 70% to 80% are noted in women who undergo a tubal reversal procedure, depending on their age, the type of tubal ligation procedure performed, and the presence (or absence) of other infertility factors.

Most often, this repair (tubal reanastamosis) requires a laparotomy, which involves a bikini-line incision of the lower abdomen. This major surgery requires 2 to 4 weeks for recovery, and most insurers do not cover it. Some physicians have reported good success with laparoscopic tubal reanastamosis, but this approach can be more technically challenging. As a consequence, most women choose to undergo a nonsurgical IVF procedure instead. Studies have shown that IVF is usually more cost-effective than surgical reanastomosis of the fallopian tubes. Specifically, if the surgery fails to establish a pregnancy, then IVF may be necessary anyway. Patients with a previous tubal ligation are usually excellent candidates for IVF, including Natural Cycle or unstimulated IVF, given their previous fertility.

However, patients who are shown to have diminished ovarian reserve with a history of a previous tubal ligation should be carefully advised of the potential for a poor response to fertility medications. In such cases, tubal reanastamosis or Natural Cycle IVF may represent more appropriate options.

Question 27. Can fallopian tubes be repaired and why would a blocked tube be an issue if I am doing IVF anyway?

2010-06-02T13:13:00.000-07:00

Not sure that anyone really missed me over these past 2 weeks but I was out of town for several days and am trying to catch up. This past weekend was my 25th Reunion for Princeton (see DrG in the photo with 2 of his college roomies). Note the traditional Reunion Blazer that is provided to all members of the class to wear at all Princeton events. As always, Princeton Reunions is an event that has to be seen to be believed. Needless to say, orange and black are not the most flattering colors (except at Halloween). So after overdosing on Princeton I am back and ready to catch up with my blog.

Several patients have posted regarding repairing fallopian tubes. In general, most of us have moved away from surgery and towards IVF. However, it is important to know where the blockage is in such cases. Tubes that simply fail to fill on an HSG can be further assessed by fluoroscopic tubal canalization...essentially a Roto-Rooter job performed by an interventional radiologist that is often 80-90% successful at getting a blocked tube open. Repairing the delicate end of the tube (the fimbria) is more problematic and there is a significant risk of ectopic pregnancy in such cases.

So here is today's Question of the Day from the upcoming 2nd Edition of 100 Questions and Answers about Infertility:

27. Can fallopian tubes be repaired and why would a blocked tube be an issue if I am doing IVF anyway?

Prior to the advent of IVF, surgical repair of damaged fallopian tubes was considered standard medical care. Unfortunately, most patients did not become pregnant following this procedure, and 10% to 20% experienced tubal (ectopic) pregnancies. Today, IVF has replaced reparative tubal surgery for most patients with damaged fallopian tubes for two reasons: (1) IVF is a nonsurgical treatment and (2) it results in excellent pregnancy rates, especially for patients with tubal disease.

Some patients ask, “Why is it so difficult to repair damaged tubes?” Unfortunately, the problems that cause tubal disease, such as pelvic infections, usually damage the tubal fimbria—that is, the delicate finger-like projections at the end of the tube that are responsible for capturing the egg when it is released from the ovary. Pelvic infections may also damage the entire thickness of the tube from the tubal muscle to the inner mucosal layer, leaving behind a scarred, nonfunctional organ that is not amenable to surgical repair.

In general, most patients with tubal disease are best treated using IVF. Tubal reparative surgery is usually not effective and, in fact, it may increase the woman’s risk for having an ectopic or tubal pregnancy. If a couple is not interested in IVF or if they are not deemed to be good candidates for IVF, then tubal surgery may be the only option available to them in terms of fertility treatment.

Damage to the fimbria of the fallopian tubes may result in a tube that is blocked at the very distal end—the part farthest away from the uterus. A tube that becomes filled with fluid is called a hydrosalpinx (“hydro” refers to water; “salpinx” refers to the fallopian tube itself). A hydrosalpinx is usually discovered during a hysterosalpingogram (HSG) performed as part of the infertility diagnostic evaluation. This simple x-ray study should be performed in all infertile women unless a diagnostic laparoscopy has already been performed as some assessment of the status of the fallopian tubes is a key part of the fertility evaluation. We advise all patients undergoing a laparoscopy that we recommend removal or ligation of her tube(s) if a hydrosalpinx is discovered.

Over the past decde many studies have demonstrated reduced IVF pregnancy rates in patients who have a hydrosalpinx. It has been theorized that the fluid in the tube may flow backward into the uterine cavity. This fluid may contain toxic substances that may adversely affect the receptivity of the endometrium preventing implantation. Alternatively, the fluid may actually flush the embryo out of the cavity or even prove toxic to the embryo itself. Some studies suggest that the presence of an untreated hydrosalpinx will reduce IVF pregnancy rates by 50%.

In addition, an untreated hydrosalpinx may increase the chance that a woman will experience a spontaneous abortion or miscarriage. For all these reasons, treating a hydrosalpinx should both increase the IVF pregnancy rate and decrease the chances for an early pregnancy loss. A patient with a single normal fallopian tube and a hydrosalpinx will also have a higher chance of achieving a spontaneous pregnancy after removal or ligation of the damaged tube.

Question 26. If I don’t have either PCOS or POF, then what is my problem and why am I not ovulating?

2010-05-20T09:49:00.000-07:00

Some patients really do stick in your mind long after they have left the practice. A couple of years ago we had a patient who had absent periods and had failed to respond to clomid or gonadotropin injections. She had been told by another RE that she needed donor egg and there was no reason to think that she would ever respond to fertility drugs. Now it is pretty uncommon to find yourself in the position of talking a patient out of donor egg IVF...but that is exactly what Dr D had to do. The patient consented to a final go at fertility drugs. But as she had FHA (see below) the stimulation was long with slow increases in drug dose. Ultimately she did respond and ended up with a great pregnancy with her own eggs. The key was to realize that the patient had FHA and not PCOS and use the correct recipe. It is all about cooking those follicles/eggs correctly....bad recipe = bad eggs.

So here is today's Question of the Day from the new and improved 2nd Edition of 100 Questions and Answers about Infertility.

26. If I don’t have either PCOS or POF, then what is my problem and why am I not ovulating?

Hormone abnormalities other than PCOS can also lead to irregular menstrual cycles. Such abnormalities include problems with the thyroid gland (which produces a hormone that controls metabolism), abnormal levels of prolactin (a hormone that induces breast milk production), and a lack of hypothalamic/pituitary stimulation to the ovary known as functional hypothalamic amenorrhea (FHA). The pituitary gland has been called the master gland of the body; it secretes hormones that control a wide range of functions, including reproduction, metabolism, response to stress, water balance, and growth.

Women with irregular cycles should have both their thyroid hormone and prolactin levels measured, as problems with the thyroid gland can indirectly lead to elevations in prolactin. Low levels of thyroid hormone (hypothyroidism) and elevations in prolactin (hyperprolactinemia) can be readily treated with medication. In fact, treatment of hypothyroidism with oral thyroid hormone (levothyroxine) can promptly restore normal menstruation. Similarly, hyperprolactinemia usually responds quickly to bromocriptine therapy, often promptly restoring normal cycles.

An elevation of prolactin in the absence of any thyroid disease requires magnetic resonance imaging (MRI) of the brain to evaluate its cause. In such cases, hyperprolactinemia usually results from an increased growth of the prolactin-secreting cells in the pituitary gland forming a small tumor. If the prolactin-secreting tumor is less than 1 cm in diameter, then it is called a microadenoma, whereas a macroadenoma is greater than 1 cm in diameter.

Women without thyroid or prolactin issues who fail to have menstrual periods following treatment with progesterone are usually referred to as having functional hypothalamic amenorrhea (FHA). These women fail to produce normal levels of estrogen despite an appropriate complement of ovarian follicles. Women who are below ideal body weight and who exercise frequently and vigorously are particularly prone to developing this problem. Women with FHA are at risk for osteoporosis and should discuss with their physician the benefits of hormone therapy (such as oral contraceptives) when not attempting pregnancy. They should also undergo an MRI of the brain to rule out any structural etiology for their condition. Women who are below ideal body weight may resume normal menstrual cycles when they gain weight or decrease their exercise frequency and duration.

Infertility in women with FHA can be readily treated with injectible gonadotropins. In such women, the choice of medication is important as the drug should contain both FSH and L (Menopur) and not just FSH alone (Gonal-F, Follistim). Clomid rarely works in women with FHA, but nearly all women with FHA can undergo successful ovulation induction. As was discussed in the preceding question, an excessive response may lead to high order multiple pregnancy so care should be taken to cancel such a cycle or convert it to IVF or consider a follicle reduction procedure.

Question 25. I have PCOS and am still not having normal cycles with metformin. What comes next

2010-05-18T11:11:00.000-07:00

PCOS is not at all an uncommon problem in our fertility practice. Although many OB GYN physicians advertise that they treat infertility, some really do not approach this common problem in a logical way. Instead, they give the patient a prescription for metformin or clomid and push the patient out the door. However, I still believe that having a logical plan is very important. My wife finds this hard to believe because according to her I am constantly flying by the seat of my pants. But that is my little secret and gets me off the hook for being responsible for many household chores....

So as we await the arrival of the heat and humidity here in Washington DC please take a minute to read this latest installment in my effort to keep up with the 2nd Edition of 100 Questions and Answers about Infertility.

25. I have PCOS and am still not having normal cycles with metformin. What comes next?

In our experience, most patients who will resume regular cycles on metformin will demonstrate regular cycles within 4 months of starting this medication. Patients who fail to respond to metformin may require ovulation induction with either clomiphene citrate (Clomid) or injectable fertility medications (gonadotropins).

Clomid has been an FDA-approved treatment for anovulation since the late 1960s. This anti-estrogen has been used successfully in millions of women with few complications. Clomid binds to estrogen receptors in the brain, causing the pituitary gland to resume normal release of FSH, and thereby inducing follicles to grow and ultimately release an egg. Patients should take the lowest effective dose of Clomid needed to induce ovulation. With increasing doses, the anti-estrogen side effects can reduce fertility by altering the cervical mucus and leading to a thinner endometrial lining. Many physicians initially prescribe a dose of 50 mg of Clomid to be taken on cycle days 5 to 9. The physician may perform ultrasound monitoring after day 12. Most patients will ovulate around day 17. If no dominant follicle emerges by this day, then an increased dose of 100 mg should be considered in the next cycle. A dose of 150 mg is rarely prescribed, because the vast majority of Clomid-responsive patients will ovulate while taking the 50- or 100-mg dose. Patients who ovulate rarely or not at all can be given medroxyprogesterone acetate (Provera) for 10 days to induce bleeding. By convention, the first day of this bleeding is referred to as cycle day #1 (eventhough it was an induced bleed and not the result of a normal cycle) and clomiphene is prescribed as noted above.

Women with PCOS who fail to respond to Clomid can be treated with injectable fertility hormones called gonadotropins. Such hormone medications are prepared either using recombinant DNA technology (Follistim, Gonal-F) or by isolating these hormones from the urine of postmenopausal women (Bravelle, Menopur). By following a very-low-dose protocol (37.5 IU as the starting dose), approximately 90% of patients will achieve a single dominant follicle. If the treatment produces multiple follicles, however, the woman’s risk of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) may lead to cycle cancellation. Alternatives to canceling the cycle and withholding HCG include conversion to IVF or performing a follicle aspiration procedure to reduce the number of follicles to a reasonable number but without fertilizing the eggs that were removed by the aspiration procedure. Almost all of the high-order multiple pregnancies (e.g., sextuplets) born today result from PCOS patients who took gonadotropins and demonstrated an excessive follicular response (think Jon and Kate Plus Eight).

Question 24. If I have PCOS, why do I need to take metformin? Isn’t that a drug for diabetics?

2010-05-10T13:10:00.000-07:00

I must admit that I am just running on fumes today. I was in Boston yesterday so that I could visit Mom and try to raise her spirits a bit. It is tough to get old but as my Grandmother always said "it beats the alternative." Unfortunately, her poor health over these past few months has prevented her from going on the internet and I hate to ask my Dad to download these posts as he tends to get very frustrated at times with the download/print/share sequence. That means that there are now only 3 people reading this blog....

So what does any of this have to do with infertility or PCOS? Nothing. Hey, I told you I was running on fumes. But seriously, after abandoning my Special K diet yesterday in exchange for the Sunday Brunch at the Wollaston Golf Club....I feel like I have become diabetic. Now diabetes is a topic that does have something to do with today's Question of the Day so please read on....

24. If I have PCOS, why do I need to take metformin? Isn’t that a drug for diabetics?

The role of insulin resistance as the probable initiating factor in PCOS has important clinical implications. Because of the pioneering work done by Drs. John Nestler and Andrea Dunaif, the treatment of patients with PCOS has now shifted toward addressing the underlying issue of insulin resistance. Patients with PCOS are often treated with an insulin-sensitizing medication such as metformin (Glucophage). More than 20% of patients with PCOS and irregular cycles will experience a restoration of their normal cycles with metformin treatment. Because most patients who take metformin experience a diminished appetite, they may also benefit from weight loss with this therapy. Patients with PCOS also have increased rates of first-trimester miscarriage, and preliminary data suggest that there is a reduced rate of miscarriage in patients with PCOS who are treated with metformin.

In order to minimize the gastrointestinal side effects, the dose of metformin is increased gradually. Many physicians initially prescribe 500 mg a day of the extended-release preparation of metformin, to be taken at dinner. After 1 week, the dose is increased to 1000 mg; after another week, the dose is increased to the maximum of 1500 mg. Most patients can tolerate the medication, although severe gastrointestinal side effects (mainly diarrhea) arise in 10% to 15% of patients. Patients who fail to resume predictable cycles with metformin therapy alone will need to consider ovulation induction with fertility medications.

The use of metformin as a first-line medication in the treatment of ovulation problems in patients with PCOS is controversial. Some physicians believe that clomiphene should be the first medication prescribed to women with PCOS who desire pregnancy and have irregular cycles. Our preference has been to start with metformin and then add clomiphene if a women fails to resume regular menstrual cycles.

Kristin comments:
My OB suggested I try metformin to regulate my cycles. I started on 500 mg and eventually went up to 1000 mg—and it worked. I started to get regular periods. By charting my basal body temperature, I could tell that I was ovulating. I experienced major gastrointestinal issues with the drug, but they subsided after a month or so with some flare-ups on occasion. The side effects were worth it as far as I was concerned, especially if the metformin was going to help me get pregnant. When I started seeing an RE, my metformin dose was upped to 1500 mg. Once I did get pregnant through IVF, I remained on metformin for the first trimester of my pregnancy.

Question 23. What is polycystic ovarian syndrome? Where does it come from and how is it treated?

2010-05-03T13:55:00.000-07:00

So after a weekend off I found myself completely swamped this morning. How 48 hours can make such a difference is beyond me. Following two egg I rushed out to Reston and then back again. Traffic was so bad this morning that I canceled my Monday morning lecture to the residents and medical students. Too bad for them because it was supposed to be on PCOS. This is the one topic in RE that they should fully understand because it is so common. Yet, week after week I get blank stares and incomplete answers to my questions. At first I though that they were bored but now I understand they are more confused than bored.

What they all need to do is to read 100 Questions and Answers about Infertility from cover to cover. Then they will be at least as smart as my patients.....

So Happy Monday and here is today's Question of the Day!

23. What is polycystic ovarian syndrome? Where does it come from and how is it treated?

Polycystic ovarian syndrome (PCOS) is an exceedingly common reproductive disorder, affecting an estimated 10% to 15% of reproductive-age women. The diagnosis of PCOS is a clinical one. In 2003, the ESHRE/ASRM consensus conference redefined PCOS as the presence of at least two out of the three following clinical criteria:

1. Irregular menstrual cycles
2. Evidence of extra male hormones, as determined either by clinical examination or by blood tests
3. Ultrasound demonstrating ovaries with numerous small follicles (PCO-appearing ovaries)

Previously, only patients with irregular menstrual cycles were thought to have PCOS, so the expansion of this definition has led to some confusion among healthcare providers. Other features commonly associated with PCOS include obesity, insulin resistance, borderline diabetes, skin tags, and a velvety discoloration on the nape of the neck and inner thighs called acanthosis nigricans. The topic of PCOS can fill an entire book. In fact, several books have been devoted to this subject. Although this condition was originally described by Drs. Stein and Leventhal in 1935, our understanding of PCOS has advanced significantly in the last decade.

Originally, PCOS was thought to be an anatomical problem in which a thickened coating around the ovary prevented ovulation. It is now agreed that PCOS represents a hormonal imbalance. At the heart of this disorder is insulin resistance. Insulin is a hormone secreted by the pancreas that induces your body to store the sugar circulating in the bloodstream. Individuals who fail to produce insulin as a result of an autoimmune disorder require insulin therapy to maintain normal blood sugar levels. These patients are referred to as having insulin-dependent diabetes (also known as type 1 diabetes).

The majority of patients with impaired glucose metabolism actually suffer from insulin resistance rather than insulin deficiency. That is, the cells of their bodies are not sensitive to the effects of insulin, so they require ever-increasing amounts of insulin to be released from the pancreas until appropriate blood levels of glucose are obtained. These patients are commonly referred to as having non-insulin-dependent diabetes (also known as type 2 diabetes or adult-onset diabetes). Despite the name of the disease, persons with type 2 diabetes may require insulin injections to maintain normal glucose levels depending on their degree of insulin resistance.

Insulin resistance is often a genetic disorder. This explains why adult-onset type 2 diabetes is so prevalent in certain families and in certain ethnic groups. In patients who are insulin resistant, the excessive levels of insulin affect not only their metabolism, but also their reproductive system. Insulin directly affects the release of reproductive hormones from the pituitary gland and directly stimulates ovarian production of male hormones. Thus the presence of excess insulin results in a local environment that is not conducive to follicle growth. The multiple follicles that fail to grow produce excessive male hormones, resulting in acne and abnormal hair growth commonly encountered in women with PCOS. Obesity itself also increases insulin resistance, so patients can find themselves trapped in a vicious cycle of irregular cycles and worsening weight gain. Women who have always had regular periods during their entire life but suddenly gain significant weight may frequently resemble patients with PCOS. In these cases, weight loss by itself may restore normal cycles and improve fertility.

Kristin comments:
Looking back at my early menstrual cycles, it should have come as no surprise that my reproductive system was not in normal working order. I had extremely heavy periods, but they were never regular. Sometimes I would go months without a period. I didn’t think much about it until my husband and I started trying to get pregnant. I went off the pill and got a period about 2 months later. I began charting my basal body temperature and discovered that I was not ovulating. I decided to be proactive and saw my OB, who confirmed that I have PCOS. This diagnosis was further confirmed at my first RE visit. The doctor did a transvaginal ultrasound, which showed that both of my ovaries were covered with many small follicles. I did meet the clinical criteria for diagnosing PCOS, but I did not exhibit any of the outwardly apparent features—obesity, skin tags, acanthosis nigricans.

Question 22. Why are my menstrual cycles irregular?

2010-04-28T13:54:00.000-07:00

We often have residents from the Ob Gyn residency program at Georgetown rotating through our office. When they sit in on my consultations they get very familiar with my little song and dance about the normal menstrual cycle. Let's face it....if you don't understand normal reproduction then how can you figure out how to order appropriate tests on your patients to determine the problem. Yet, sometimes in spite of our attempts at education, they still can't figure it out. So here is your chance, dear reader, to become smarter than an Ob Gyn resident! Read on and ask questions as needed....

Here is today's Question of the Day from the upcoming 2nd Edition of 100 Questions and Answers about Infertility!

22. Why are my menstrual cycles irregular?

In a typical reproductive cycle a single follicle (containing a single egg) reaches maturity after 2 weeks culminating with the release of that egg a process called ovulation. Once ovulation has occurred menstrual flow will appear 12-14 days later unless pregnancy supervenes. Thus, most women cycle every 28 days (14 days to grow the egg and 14 days after ovulation until period returns).

Understandably, if a woman has irregular and unpredictable cycles, then logic suggests that she is probably not ovulating normally. Ovulatory problems are usually divided into two main categories: problems with the ovary and problems with the signals from the brain to the ovary. If the irregular cycles result from a lack of follicles within her ovary, then the failure of the ovary to respond will cause the pituitary gland to secrete increased amounts of follicle-stimulating hormone (FSH). Women with elevated levels of FSH are described as having diminished ovarian reserve; if their periods cease entirely, then they are described as having premature ovarian failure (POF). Different laboratories may vary as to how they define an “elevated” level of FSH, so a discussion with your physician is crucial to correctly assess the results of this test. In most cases, however, an FSH level of more than 15 IU/L is evidence of diminished ovarian reserve; FSH levels exceeding 30 IU/L usually signify POF.

If a woman has a normal complement of follicles but still does not have normal cycles, then the problem must lie elsewhere. Most such women suffer from a communication mismatch between the brain and ovary, disrupting the carefully coordinated hormone signals that induce the growth of ovarian follicles. The causes of this disruption can be further classified, with most patients being found to have polycystic ovarian syndrome (see Question 22) as opposed to other hormonal imbalances.

Question 21. Will my insurance pay for my fertility treatments?

2010-04-21T13:37:00.000-07:00

Obviously healthcare reform has been a hot topic here inside the beltway this past year. No doubt that trying to navigate the insurance coverage jungle is confusing to say the least. Most plans cover diagnostic testing for infertility. Some plans cover treatment for infertility. Some plans only cover certain treatments and dictate a specific order to those treatments. Some plans cover a certain dollar amount and couldn't care less what treatments you do....and on and on and on.

Sometimes patients ask us to code visits using non-infertility codes. In other words, a patient is sent to me by her Ob Gyn for infertility and we spend 35 minutes discussing only infertility. Then she asks me to code the visit as endometriosis because her sister has endometriosis and so perhaps maybe she also has endometriosis and that is what is causing her infertility. There is a term for this request....insurance fraud. As much as I love my patients (especially those that read this blog....both of them), I am not prepared to go to the "big house" on their behalf. Sorry but no. I am not prepared to spend a few years behind bars. It may have done wonders for Martha Stewart's career but I have no interest in that type of life experience.

So here is today's Question of the Day:
21. Will my insurance pay for my fertility treatments?

Insurance coverage for infertility varies widely across the United States. Several states, including Massachusetts, Illinois, and Maryland, have passed legislative mandates for infertility coverage. In these states, access to fertility treatment is guaranteed through the patient’s employer. In the vast majority of states, however, fertility coverage is inconsistent. Some companies may offer extensive fertility benefits, while others offer no coverage at all to their employees.

It is important that you understand your specific benefits before you seek out any kind of fertility treatment. Insurance plans may provide a specific dollar amount to spend on fertility treatments or cover a certain number of cycles of either IUI or IVF. You should work with your fertility provider’s billing staff to determine which benefits are available to you before launching into a treatment plan. Given that some insurance plans may cover infertility more extensively than others, it is always appropriate to examine your insurance options during periods of open enrollment for health benefits. Many insurance companies will not cover fertility treatments in patients who have been voluntarily sterilized (e.g., vasectomy, tubal ligation). Plans may also have specific requirements in terms of duration of fertility and exclusion criteria for IVF concerning ovarian reserve testing or age.

Rebecca comments:
One of the biggest mistakes I made in my family building journey was making ‘assumptions’ about my husband’s and my insurance plans. These assumptions, NOT FACTS, guided some of our initial decision making processes regarding treatment. Those errors in judgment wasted precious time, and most likely were financially costly. As a wiser and more seasoned patient, I would advise that one take as much precaution and care in learning about her/his insurance coverage, as one does with obtaining information about her/his treatment options. Work with the fertility provider’s billing staff regarding your plan and benefits as soon as you begin consulting with your RE.

Question 20. How expensive are infertility treatments?

2010-04-16T13:46:00.000-07:00

Children are not cheap. Unfortunately, those patients with infertility are having to invest in a bit more than dinner and a movie in order to have the privilege of spending thousands of dollars to house, feed and entertain the little monsters. But seriously, when contemplating the array of treatment options one must consider the economic aspects when making a plan. Unfortunately, the fertility treatments that work the best tend to be the most expensive and most invasive options. So let's look at the options available and a range of what these treatments cost in most clinics. Your experiences may vary from clinic to clinic and these are typical not recommended prices....

Also, many clinics offer IVF Guarantee Programs which refund a portion or all of the cost if a couple fails to deliver a baby. Many patients really embrace this concept and I certainly understand the attraction but I still recommend that you read the fine print and make sure that you fully understand what specific costs are included in such arrangements.

Good luck to all and have a great weekend as you peruse today's Question of the Day:

20. How expensive are infertility treatments?

Some insurance plans may cover the cost of a fertility evaluation but not cover any fertility treatments per se. Other plans may stipulate a certain lifetime benefit for fertility case and still other plans may provide a specific number of treatment cycles.

In those patients without insurance coverage, the cost of fertility treatments varies widely depending on the specific treatment utilized. For example, a cycle of ultrasound monitoring without the use of fertility medications, culminating with intrauterine insemination (IUI), may cost $1300 to $1500 in many clinics. Compare this with the cost of IVF with intracytoplasmic sperm injection, freezing of extra embryos, and assisted embryo hatching, for which the price tag can total $14,000 to $16,000 (not including the cost of injectable fertility medications ($2000 to $4000)). The use of donor-egg IVF, although extremely successful, is also very expensive, because the donor must be reimbursed for her time and effort as part of the treatment and also because of the extreme screening tests mandated by the FDA. The price for donor-egg IVF typically ranges between $25,000 and $30,000, depending on the clinic. Unstimulated or Natural Cycle IVF may represent an economically attractive option since it may cost a fraction of stimulated cycle IVF (e.g. $4400 per cycle in our clinic).

In most patients, the more expensive, more invasive fertility treatments usually result in the highest pregnancy rates. Couples are advised to carefully consider the proposed course of treatment and the costs that may be involved.

Many IVF centers in the United States offer “money back” (refund) programs. A couple accepted into such a program pays a premium that covers several fresh IVF cycles as well as frozen embryo transfers (FET). If they fail to conceive or are deemed to no longer be appropriate candidates for treatment, then all or a percentage of their initial payment is refunded. These programs have remained somewhat controversial but can allow couples to pursue other options if IVF proves unsuccessful.

According to the ASRM Ethics Committee Statement of June 2006, the controversy surrounding such programs relates in part to the concern that such arrangements appear to violate long-standing ethical prohibitions against paying contingency fees in medicine. This concern is based on Opinion 6.01 of the AMA Code of Medical Ethics, which states, “a physician’s fee should not be made contingent on the successful outcome of a medical treatment.”

Furthermore, the 2006 Committee Statement (which can be found on the ASRM website at http://www.asrm.org/Media/Ethics/ethicsmain.html) concludes, “the risk-sharing form of payment for IVF is an option that might be ethically offered to patients without health insurance coverage for IVF if certain conditions that protect patient interests are met. These conditions are that the criterion of success is clearly specified, that patients are fully informed of the financial costs and advantages and disadvantages of such programs, that informed consent materials clearly inform patients of their chances of success if found eligible for the risk-sharing program, and that the program is not guaranteeing pregnancy and delivery. It should also be clear to patients that they will be paying a higher cost for IVF if they in fact succeed on the first or second cycle than if they had not chosen the risk-sharing program, and that, in any event, the costs of screening and drugs are not included.

“The Committee was especially concerned about the incentives that risk-sharing programs create for providers to take actions that might harm patients in order to achieve success and avoid a refund. For risk-sharing programs to be ethical, it is imperative that patients be aware of this potential conflict of interest, and that risk-sharing programs not overstimulate patients to obtain a large supply of eggs or transfer more embryos than is safe for the patient, fetus, and prospective offspring. Patients should be fully informed of the risks of multifetal gestation for mother and fetus, and have had ample time to discuss and consider them prior to egg retrieval.”

Question 19. What are Natural Cycle fertility treatments and am I a candidate for them?

2010-04-14T13:04:00.000-07:00

Given the interest in organic food, environmentally friendly energy and "green" buildings, I guess it was only a matter of time until Natural Cycle fertility treatments became more attractive to all of us. Remember those Promise margarine commercials that would end with "It's not nice to fool Mother Nature!" Well, sometimes Mother Nature may in fact know best and that is the idea behind Natural Cycle fertility treatments.

I think that one has to be creative when considering the infertile couple and using Natural Cycles for fertility treatment may make a great deal of sense for a variety of patients. So without further delay, here is the Question of the Day for the upcoming 2nd Edition of 100 Questions and Answers about Infertility:

19. What are Natural Cycle fertility treatments and am I a candidate for them?

Natural Cycle Fertility treatments are based entirely on a woman’s normal natural menstrual cycle. In other words, no ovarian stimulating drugs are used. Rather, the doctor attempts to produce pregnancy using the woman’s naturally produced egg and/or hormones. In order to use any form of Natural Fertility treatment, the patient must have fairly regular menstrual cycles. Highly irregular cycles do not allow the use of natural fertility treatment. Three different types of Natural Fertility treatments currently exist and they are Natural Cycle IUI, Natural Cycle IVF, and Natural Cycle FET.

Natural Cycle IUI

Natural Cycle IUI is an extremely simple infertility treatment. Generally speaking, the patient is monitored during a menstrual cycle to determine the timing of ovulation using either urine LH, blood estradiol and progesterone or sonography. Once the egg has been determined to be mature ovulation can be induced by a single injection of human chorionic gonadotropin (hCG) followed by a well timed artificial insemination(IUI). Sometimes IUI is performed without the use of hCG if it appears that an LH surge has already begun based upon hormone testing. See Question xxx for more information about IUI.

Natural Cycle IVF (NC-IVF)

Natural Cycle IVF (NC-IVF) also requires that the patient have fairly regular normal menstrual cycles. NC-IVF is a very simple, patient friendly form of IVF. No ovarian stimulating drugs are used in NC-IVF. Instead , the patient’s naturally produced follicle and egg are monitored using estradiol, progesterone and ultrasound measurements. Once the egg is judged to be mature, a single injection of hCG is given and the egg easily collected in the office under transvaginal ultrasound using minimal or no sedation. It literally takes only a few minutes to collect the egg, similar to a simple in office blood draw. The egg is then fertilized usually by ICSI (as only one egg is obtained) and a single embryo is transferred 3 or 5 days later. Couples with proven previous fertility may use IVF without ICSI in many cases.

NC-IVF is extensively performed around the world in over 50 countries and the world’s very first successful IVF baby in 1978 was produced using NC-IVF. At that time, our knowledge and technology was rudimentary compared with today’s standards, so fertility drugs were used to obtain more eggs and embryos to improve the very low IVF pregnancy rates. With improved understanding and technology, many eggs and embryos are simply not necessary to produce a successful pregnancy for many couples using IVF. Also the costs for NC-IVF are about 20-25% of the cost of a single stimulated IVF cycle and NC-IVF avoids the risks associated with the use of ovarian stimulating hormones. Thus, patients who are planning on a single embryo transfer or who wish to avoid using fertility drugs often prefer NC-IVF. Other patients who fail stimulated IVF or who wish to try NC-IVF with their own egg prior to considering ova donor IVF may be candidates for NC-IVF.

Problems with NC-IVF include: premature LH surge, which occurs in 10-15% of patients, and less commonly failure to obtain an egg at the time of the follicle aspiration,. Occasionally fertilization may not occur (even with the use of ICSI) or embryo growth may suboptimal with failure of an embryo to develop to an appropriate stage prior to planned embryo transfer. When compared with stimulated IVF utilizing single embryo transfer, the pregnancy rates should be equivalent between NC-IVF and stimulated IVF. Studies comparing these 2 types of IVF are needed but our personal experience supports this notion.

Natural Cycle Frozen Embryo Transfer (NC-FET)

At Dominion Fertility, we only perform NC-FET in patients who have regular menstrual cycles. NC-FET is less expensive, simpler for the patient and the pregnancy rates are equal to medicated FET. In NC-FET, the menstrual cycle is monitored in the same fashion as described above. A single injection (hCG) is given to the patient for the entire treatment cycle. Seven days later, embryo transfer is performed. It’s just that simple! The entire treatment takes one menstrual cycle or about 4 weeks to complete.

We have been performing NC-FET for several years now and our data shows equal pregnancy rates in with NC-FET or medicated FET. In our opinion, the only draw back to NC-FET is that it requires the IVF center and patient to be flexible with respect to scheduling of the embryo transfer as this date can only be estimated. With a medicated FET, the exact date and time of the embryo transfer can be programmed before beginning the treatment.

Question 18. How will my reproductive endocrinologist determine a plan of therapy?

2010-04-13T08:00:00.000-07:00

Here in Washington we are surrounded by planners. People are available to plan your party. People are available to plan your finances. People are available to plan for your kid applying to college (or secondary school or even kindergarten). People are available to plan your attempt to lose weight and get in shape (personally I am doing the Special K diet...gotta look good for my college reunion at the end of May). So it is not surprising that patients look to their RE to plan their fertility evaluation and treatment. I am not a "me doctor - you patient" type of guy, but there is a point where I step up and say here are my recommendations. These may be negotiable but I really try to give my perspective. And yet, it doesn't matter how wonderful the plan seems to me.....if it is unacceptable to the patient then it is back to the drawing board.

Cookie cutter medicine is dangerous. One size does not fit all. I really hope that the physicians of tomorrow will still try to individualize care rather than relying upon only guidelines. My mother was diagnosed with breast cancer back in 1993. She had a very poor prognosis at that time with a <5% five year survival rate. One oncologist told my Dad that if it was his wife that he would "take her to Florida and make her ready for the end." Well, my Dad refused to take that advice and she underwent surgery, chemo and radiation therapy. Now 17 years later she has, knock on wood, never had a recurrence of her cancer. Fertility treatment can be nearly as stressful but the spontaneous cure rate is much better than with cancer. One of the best aspects of offering Natural Cycle IVF has been to allow patients with a poor prognosis to still try their hand at IVF. For some of these patients it is enough to have tried and then they can either give up or pursue donor egg IVF or adoption. For the ones that have a baby after being told that they were a hopeless case, Natural Cycle IVF seems nothing short of a miracle.

So here is today's Question of the Day.

18. How will my reproductive endocrinologist determine a plan of therapy?

In general, reproductive endocrinologists recommend a particular course of treatment only after performing a complete fertility evaluation which usually include a pelvic ultrasound, an assessment of tubal patency (hysterosalpingogram or laparoscopy), a semen analysis, and a variety of hormonal blood tests.

The therapeutic plan for any couple is unique to them. If testing has demonstrated a clear problem, such as blocked fallopian tubes or a markedly abnormal sperm count, then in vitro fertilization (IVF) may be recommended as the only reasonable alternative. However, most couples are not sterile but merely subfertile, so they may be offered a range of therapeutic options—from expectant management, to the use of insemination with or without fertility drugs, to IVF with or without intracytoplasmic sperm injection (ICSI). Furthermore, IVF can be performed using the patient’s own eggs, donor eggs, or donor sperm.

A couple’s particular therapeutic plan will be developed with their specific needs in mind. For those patients in whom IVF is not an option, whether because of religious, financial, or philosophical reasons, the physician should provide counseling about alternative treatments available to them. Not all couples are prepared to undergo extensive fertility treatments, so physicians need to consider a couple’s particular situation when proposing a course of action. Given that infertile couples can sometimes achieve spontaneous pregnancies, the desire of a couple to proceed with therapy needs to be weighed against the likelihood of success for that therapy and the cost involved. These costs may include financial, physical, and emotional considerations. We strongly urge our patients to consider ll options when dealing with infertility including alternative pathways to parenting ranging from adoption to the use of donor sperm, donor egg, donor embryo and gestational surrogacy.

Carol comments:
I feel that finding an RE who will work with you and listen to you is one of the most important factors in achieving a positive outcome. Each individual who is faced with infertility deals with the varying costs (financial, physical, and emotional) differently. For some, the financial aspect limits the number or attempts they can make. For others, the physical and emotional aspects take such a toll that they are only willing to go through a set number of attempts. Based on my discussions with other women who have faced fertility challenges, I believe that each person has a unique threshold for these costs. If you are dealing with a doctor who strictly adheres to a “one size fits all” policy and won’t take your personal situation into consideration, it will only add more stress to an already stressful situation.

Question 17. Can I choose the sex of my baby?

2010-04-09T09:50:00.000-07:00

Years ago I saw a patient that had 3 girls and wanted a boy. Their solution was to take fertility shots and have timed intercourse with the logic that even if they had a multiple pregnancy, one should be a boy. I tried to explain that their logic was not very sound and that they could end up with a real surprise. They were not to be dissuaded and went to another clinic. They followed through with that plan and ended up with triplets....all girls. Six girls under 6 years of age is hard for me to contemplate. Wow. That is a lot of squealing under one roof.

So although we are sympathetic to those who are hoping for family balancing, there still has to be consideration given to the wisdom of certain solutions to this question. As we head into a glorious weekend of weather here in DC, I leave you with the following Question of the Day:

17. Can I choose the sex of my baby?

Gender is determined at the moment of fertilization, when a sperm bearing either an X or Y chromosome penetrates the egg, resulting in formation of either a female or male embryo, respectively. The event is random, and the sex ratio of females to males conceived is fairly even.

Several techniques exist that can enhance the likelihood that a couple will conceive a child with the desired gender. The Ericsson method is a simple, noninvasive method that separates X-bearing sperm from Y-bearing sperm using centrifugation techniques. The sperm are placed on the top of a column of either albumin or Sephadex, and the specimen is centrifuged to isolate the desired gender-selected sperm. This sperm sample is then used for either intrauterine insemination or IVF. The success rates reported with this method vary from no benefit to as high as 75% for the desired gender. The Ericsson method is not associated with any known risk to either baby or mother.

Microsort is a newer experimental technique that involves the labeling of the DNA of the sperm, followed by passage of the sample through a cell-sorting machine. This process yields a smaller sperm sample than the Ericsson method, and IVF with ICSI may be required for pregnancy. Nevertheless, the results appear encouraging in terms of gender selection.

The gender of a child can also be selected using IVF and preimplantation genetic diagnosis (PGD). This technique is expensive and much more complex than the Ericsson method, but success rates for the selected gender routinely exceed 90%. Couples who elect to pursue IVF and PGD for gender selection often do so to prevent genetically inheritable medical diseases, such as Duchenne muscular dystrophy, from occurring in their children.

Many medical authorities consider gender selection to be unethical except in a few circumstances, such as when the couple runs a high risk of having a child with an inheritable medical disease. Others support the use of gender selection when a couple has at least one child but want to limit their family size and desire a child of the opposite gender.

Question 16. My friend keeps asking whether I had an endometrial biopsy or a postcoital test. Do I need these tests?

2010-04-07T13:51:00.000-07:00

As we work our way through the 2nd Edition of 100 Q&A about Infertility, I suppose it is inevitable that some blog posts may end up getting recycled. When discussing the post coital test I always think of the story that I initially related in one of my first blog posts. It may not be the most politically correct story but here it goes....

Here is a true RE urban legend. Many years ago a very trustworthy and honest infertility specialist (not yours truly although I would hope to be described in this fashion) arrived at the office for his usual consultations. He was informed that Mrs. Jones (not her real name) was waiting for Dr. James (not his real name) in the exam room. She was scheduled for a postcoital test.

Dr. James went into the room, said hello and then sat down to perform the postcoital. As he was placing the speculum he asked Mrs. Jones the usual questions: “What cycle day are you?” “Day 14 ,”she replied. “Did you have an LH surge?” “Yes, last night,” she promptly informed the doctor. “OK, so how many hours ago did you have sex?” No answer. Dr. James asked again. The patient hesitated and then blurted out, “But Dr. James I am here for a postcoital test!” “Yes, I know, so when did you and your husband have relations?” She hesitated and then clarified her misunderstanding. “Oh my gawd, Dr. Jones, I thought I was supposed to have sex with you!” Dr. James removed the speculum. Stood up. Walked out of the room with his face blazing in embarrassment.This story was related to me by Dr. James, at a conference one year, so I have no reason to doubt its veracity. Of course, this became a huge inside joke at Dr. James’ practice as Dr. James was routinely asked after that exactly how much time he needed to perform any scheduled postcoital test!

We all want to help our patients and in the process we form some very close relationships, but clearly there are some limits that should never be crossed…even as part of the diagnostic evaluation. So here is today's Question of the Day.

16. My friend keeps asking whether I had an endometrial biopsy or a postcoital test. Do I need these tests?

In the past, the endometrial biopsy was a routine part of the fertility evaluation, but current practice has been to limit performance of this test to a minority of fertility patients. An endometrial biopsy is a simple office-based procedure that is performed just before the onset of a woman’s menses. It is usually performed without any anesthesia and is well-tolerated by most patients with the majority reporting uterine cramping that quickly resolves.

An endometrial biopsy can yield information about the hormonal status of the lining and can rule out chronic infection/inflammation in the uterus. The problem with the endometrial biopsy in terms of its usefulness as a fertility test is that abnormal biopsies are obtained in more than one-third of women with proven fertility. Therefore, the finding of an abnormal endometrial biopsy in fertility patients is of uncertain benefit. Most reproductive endocrinologists prefer simply to have their patients take extra progesterone, essentially obviating the need for the endometrial biopsy in most patients. At the present time, the endometrial biopsy is most reliable as a means to rule out endometrial cancer in those patients who are at increased risk of this disease. Patients at increased risk for endometrial cancer include those who have polycystic ovarian syndrome and infrequent, heavy periods but who do not receive the protective benefit of oral contraceptives or other progesterone-containing medications.

In patients who have experienced repeated IVF failures in spite of the transfer of good quality embryos, it is reasonable to perform an endometrial biopsy to ensure that the lining demonstrates the appropriate hormonal response, the absence of infection/inflammation or the correct expression of cell surface proteins. There is a class of cell surface proteins call integrins that play a putative role in implantation. Some physicians will perform an endometrial biopsy to ensure the proper expression of integrins on the surface of the endometrium. Abnormal integrin expression has been demonstrated in a range of clinical situations including the presence of a fluid filled fallopian tube or hydrosalpinx, but most experts consider testing for integrins to be investigational and limited to special circumstances.

The postcoital test was initially proposed as a means to evaluate the interaction of the male partner’s sperm and the female partner’s cervical mucus. This test is performed approximately 8 to 24 hours after intercourse at midcycle (around days 12 to 14 of the menstrual cycle). During a speculum exam, the physician collects a sample of cervical mucus. This sample is then placed on a slide and examined under a microscope for the presence of motile sperm. In addition to the presence or absence of sperm, the physician records the quality, quantity, and appearance of the mucus. Unfortunately, the postcoital test has very poor reproducibility and limited utility in the evaluation of infertile couples. For example, couples for whom no motile sperm were observed during the postcoital test have conceived. Although the spontaneous pregnancy rates are higher in those patients with a normal postcoital test, the information gathered in this way seldom provides any useful insight when developing a therapeutic plan.

Postcoital tests may prove more valuable in couples in whom, for social or religious reasons, the male partner is unable to provide a specimen for semen analysis. In these cases, a postcoital test reassures all parties that sperm are actually deposited in the vagina during the act of intercourse.

Question 15. After we have sex, I think that everything comes out. Is this why I am not getting pregnant?

2010-04-02T08:26:00.000-07:00

A few years ago I had a high school student spend the day with me in the office since he was considering a career in medicine. He went with me to Fairfax Hospital where I gave a lecture to the medical students and residents. He went with me to Reston to see some consultations. He went with me back to Arlington to watch some procedures including an embryo transfer (he was in the lab not in the room with the patient). I thought that he would be impressed by the depth and breadth of what I do all day long.....

At the end of the day I asked him what he thought of being a Reproductive Endocrinologist. He paused for a minute then blurted out "So basically you talk about sex and tell people when to do it." Oh well. So much for impressing him with the depth and breadth of my medical specialty. He wanted to be a heart surgeon anyway.....

But he was correct that we do have to talk about sex with our patients and that leads us to the Question of the Day just in time for the weekend! Hope all of you have a Happy Easter. He is risen indeed.

15. After we have sex, I think that everything comes out. Is this why I am not getting pregnant?

Honestly, this question is one of the most frequently asked questions that we get during new patient consultations. At the time of male orgasm, the ejaculate is composed of proteins, enzymes, and water from the seminal vesicles. The sperm represent only one to three drops of the total ejaculate volume of 1.5 to 5 mL. Following ejaculation in the vagina sperm rapidly move from the vagina into the cervical mucus, where they can live for 5 to 7 days. The cervical mucus serves as a reservoir for the sperm, from which they can subsequently travel to the upper reproductive tract and meet the egg in the fallopian tube.

It is normal for much of the ejaculate to spill out of the vagina following coitus. For most couples, this does not decrease their chances for pregnancy. Rarely, a woman may suffer from vaginal or uterine prolapse. The altered anatomic relationship may not hold enough of the ejaculate in close proximity to the cervix following coitus. Such conditions usually occur only after several previous vaginal deliveries.

Question 14. Can infertility be unexplained?

2010-04-01T14:45:00.000-07:00

Well I am back from Spring Break in beautiful Quincy, Massachusetts where it rained constantly and there was flooding on a Biblical scale....The ride back was tough but all of us survived the New Jersey Turnpike without incident. To help pass the time, my wife and I listened to an audiobook while the kids watched DVD after DVD. We listened to "The Thirteenth Tale" which is really an amazingly good Gothic-type ghost story. Early on in the book the reclusive author Ms. Vida Winter is confronted by a young man who demands that she "tell him the truth." The truth finally comes out 12 hours into the audiobook but it does make for a great listen!

Sometimes I feel that patients are confronting me in a similar way...tell us the truth. Will we ever get pregnant? Will we have success with IUI or with IVF? Can his sperm fertilize my egg? Will the Red Sox win the American League Pennant race? (well only a few special patients ask that last one...)

The truth is that sometimes we really don't understand why a couple is infertile. But that doesn't mean we can't try to treat infertile couples with unexplained infertility....and that is the topic of today's Question of the Day.

14. Can infertility be unexplained?

The etiology (underlying cause) of infertility in many couples can be determined by various tests as previously described. Yet, there still remains a sizable percentage of couples in whom no obvious cause of infertility can be identified. Some studies estimate that approximately 10% to 20% of patients fall into this category. However, “unexplained infertility” is not necessarily equivalent to “untreatable infertility.” If a couple has prolonged, unexplained infertility with no previous pregnancies, then a number of etiologies are possible.

If a woman is having normal, regular menstrual cycles, it is likely that each month a follicle is growing and that an egg is being released in an appropriate fashion. If pregnancy has never occurred, however, we cannot be sure that the woman’s fallopian tubes are able to trap the egg or that her partner’s sperm are able to swim through the cervix and uterus and find/fertilize the egg in the fallopian tube. In the absence of a previous pregnancy, the question arises as to whether fertilization can, in fact, occur. The scope of this problem is made clear when we look at the fertilization results for patients who undergo IVF with a diagnosis of unexplained infertility. Typically the rate of failed fertilization with IVF is approximately 2%, but this rate increases dramatically—to approximately 20%—in couples who have prolonged unexplained infertility with no previous pregnancies. Ultimately, failed fertilization may result from problems with either sperm or egg, or both. In such cases of prolonged unexplained infertility, the use of intracytoplasmic sperm injection (ICSI) can markedly reduce the rate of IVF fertilization failure since ICSI involves the direct injection of a single sperm in to a mature egg. If a woman produces a sufficient number of eggs, then one option that we frequently employ is to split the eggs into two groups – ICSI and regular IVF. This split provides a control group but if fertilization is poor without ICSI then IVF may ultimately prove to have been of diagnostic benefit.

One of the most significant developments in the treatment of infertile couples has been the move away from extensive diagnostic testing and toward a more rapid recommendation to undergo IVF. We often recommend that patients with prolonged unexplained infertility consider IVF with ICSI, as this combination has both diagnostic and therapeutic benefits.

Carol comments:
We were never able to diagnose the exact reason that I couldn’t become pregnant. This can be frustrating and scary because there is no clear-cut path to fixing a problem that you can’t define. I remember talking to other women who had more defined issues such as male factor or PCOS and thinking that those would be easier diagnoses to deal with. Luckily, we were able to benefit from the movement to more rapidly recommend undergoing IVF for patients whose infertility is unexplained.

Question 13. What is ureaplasma, and how did I get it?

2010-03-26T06:59:00.001-07:00

Well I am trying to keep up with my schedule of daily posts but life and work keeps getting in my way. Spring Break starts this week so my ability to post daily bits of wisdom to the 3 regular readers of this blog may be limited. My apologies in advance.

Screening for ureaplasma is like religion....some people have religion and some do not! Many REs simply treat all patients and some treat none.... However, one issue is absolutely true and that is the presence of ureaplasma does not suggest marital infidelity. On the other hand, if your spouse likes to hang out with Tiger Woods then all bets are off...

13. What is ureaplasma, and how did I get it?

Most reproductive endocrinologists routinely obtain samples from the cervix (cervical cultures) to assess their patients for gonorrhea, chlamydia, ureaplasma, mycoplasma, and other bacterial infections. Gonorrhea and chlamydia are sexually transmitted diseases that can cause tubal damage and infertility when these bacteria travel from the cervix through the uterus and out into the fallopian tubes. Sexually transmitted infections can be passed back and forth between sexually intimate partners. Patients with gonorrhea may have a yellowish discharge associated with pelvic pain and fever. Although chlamydia can be associated with these symptoms, chlamydial infections are often silent; despite their lack of symptoms, Chlamydia infections may result in significant tubal scarring and damage.

Ureaplasma and mycoplasma are bacteria that can be commonly found in the reproductive tract of both men and women. It is somewhat more problematic to label these two bacteria as reproductive tract pathogens, because they are often found in fertile, healthy couples in addition to those with infertility. Although the presence of these two bacteria have been hypothesized to play a role in both infertility and miscarriage, the specific mechanisms by which they impair fertility remains unclear. The question of whether ureaplasma or mycoplasma can cause reproductive tract damage or whether their presence increases the rate of miscarriage has not been definitively answered. As a consequence, many clinics do not test for ureaplasma or mycoplasma routinely.

If cervical cultures for ureaplasma and mycoplasma are positive, both the patient and her sexual partner are usually treated with antibiotics such as doxycycline. As these bacteria may have been present for many years without causing any symptoms, the finding of ureaplasma and mycoplasma on cervical cultures does not in any way indicate infidelity or sexual misconduct.

Question 12: What is a hysteroscopy, and do I need one? Is it the same as a water sonogram or a hysterosalpingogram?

2010-03-24T07:53:00.000-07:00

Sometimes you have to learn a new language when dealing with medical issues. Fertility treatment is no exception. Unfortunately, some of our terms sound very similar....especially those that start with HYST. So we have hysteroscopy, hysterosalpingogram, hysterosonogram and hysterectomy. The last one refers to the surgery performed to actually remove the uterus. Clearly, hysterectomy is not a fertility preserving procedure! So when filling out your new patient information, make sure that you only check off hysterectomy if you have indeed undergone a surgery that removed your uterus!

So here is today's Question of the Day! Sorry I missed posting yesterday but it was a kleenex box type of day and I was too wiped out to post.

12. What is a hysteroscopy, and do I need one? Is it the same as a water sonogram or a hysterosalpingogram?

A hysteroscopy is a simple surgical procedure that is performed either to diagnose or to treat a problem within the uterine cavity. During hysteroscopy, the physician inserts a small fiber-optic telescope through the cervix and into the uterus. Either gas or liquid can be used to distend the uterus and allow the physician to directly visualize the uterine cavity. The physician may also introduce small instruments into the uterus to cut scar tissue or remove polyps or fibroids. Although diagnostic hysteroscopy can be performed in the physician’s office under local anesthesia, operative hysteroscopy usually requires anesthesia because of the cramping that occurs during uterine manipulation. Complications of hysteroscopy are rare but may include infection, bleeding, uterine perforation, damage to adjacent structures, and even death.

A water sonogram (hysterosonogram ) is a specialized ultrasound examination performed using a transvaginal ultrasound probe. First, a small catheter is passed through the cervix and into the uterine cavity. Sterile saline is then introduced into the cavity while a transvaginal sonogram is performed allowing the physician to visualize any uterine polyps or fibroids. Usually, a hysterosonogram does not provide any information about the status of the fallopian tubes. Nevertheless, hysterosonograms are helpful in identifying the presence of an endometrial polyp seen on routine sonogram or the location of a fibroid (see Figure 3). A hysterosonogram has limited benefit in evaluating for the presence of uterine scar tissue and is a diagnostic and not therapeutic procedure.

A hysterosalpingogram (HSG) is similar to a hysterosonogram in that fluid is introduced into the uterine cavity. However, the fluid is not saline but rather is a radio-opaque dye. This dye is introduced into the uterus and under fluoroscopy the dye is observed as it sequentially fills the uterine cavity and then passes out into the fallopian tubes and ultimately spills out of the ends of the tubes and into the pelvis . The HSG can be used to diagnose polyps and fibroids and is superior to hysterosonogram in evaluating the presence of uterine scar tissue. This imaging procedure also provides information on the status of the fallopian tubes, unlike either a hysteroscopy or a hysterosonogram. Because it employs traditional x-rays, an HSG is usually performed at a hospital’s radiology department or at a radiologist’s office, since few REs have this equipment in their offices.

Question 11. What is a laparoscopy, and do I need one?

2010-03-22T11:47:00.000-07:00

When I was a medical student at Duke back in the 1980s I spent a rotation with the fertility division that was headed up by Dr. Arthur Haney. Dr. Charles Hammond was the Chairman of the Department and was also an attending in that division. Every Thursday they would have 8-12 laparoscopic surgeries scheduled. A large percentage of these laparoscopies revealed either no problems or very minimal endometriosis. Over the past 20 years the surgical approach to infertility has been replaced by a more rapid move to IVF. However, some patients still benefit from laparoscopy which leads to today's Question of the Day:

11. What is a laparoscopy, and do I need one?

A laparoscopy is an outpatient surgery usually performed under general anesthesia. Most laparoscopies are completed in a hospital, but some physicians utilize freestanding outpatient surgery centers.

During a laparoscopy, the physician inserts a small fiber-optic telescope into the abdominal cavity through an incision made in the patient’s umbilical area (belly button). Most physicians initially distend the abdomen using carbon dioxide gas with a needle (Veres needle) to create what is called a pneumoperitoneum. A trocar—an instrument with a diameter similar to that of a pencil—is then passed through the umbilicus, allowing for introduction of the telescope (called a laparoscope) into the abdomen.

Using the laparoscope, a gynecologic surgeon can inspect the uterus, fallopian tubes, and ovaries. The appendix and upper abdomen are carefully inspected as well. Additional instruments may be inserted into the abdomen through incisions (ports) made along the hairline above the pubic bone. For example, the physician may use graspers, scissors, or suction irrigators to rinse the tissue and remove blood and fluids as needed. Some physicians insert a slightly larger telescope through the umbilical port, which allows them to use a carbon dioxide laser to cut scar tissue or destroy implants of endometriosis. Besides the laser, other instruments can be used to cut or burn abnormalities such as endometriosis or scar tissue.

During a laparoscopy, the physician typically introduces a blue dye into the uterine cavity while directly visualizing the fallopian tubes. If the fallopian tubes are patent (open) but are located in an abnormal location because of scar tissue, then the surgeon may try to free the fallopian tubes to improve the patient’s fertility.

If abnormal ovarian cysts such as endometriomas are present, then the physician may remove them during the course of the laparoscopy or, if necessary, perform a laparotomy. A laparotomy is a surgery performed through a larger incision, usually made along the bikini line. It may require the patient to stay 1 to 3 days in the hospital following the surgery. In addition, a laparotomy requires a longer recovery period and may create more new scar tissue than laparoscopic surgery.

Certain abnormalities cannot be easily treated through laparoscopy, including exceedingly large ovarian cysts, ovarian cysts that are suspicious for cancer, and fibroids that are deeply embedded in the wall of the uterus. Patients with these problems are probably better served by a laparotomy.

For many years, all women who were seeking fertility care underwent laparoscopy as part of the initial evaluation. In recent times, this practice has faded with increased utilization of IVF. Although IVF has essentially replaced tubal surgery in patients with tubal factor infertility, laparoscopy is still used to correct certain problems in patients prior to undergoing IVF. For patients uninterested in IVF (for religious, financial or philosophical reasons), laparoscopy may still represent an important part of their diagnostic and therapeutic options. Complications of laparoscopy are rare but can include injury to the bowel, bladder, and blood vessels; a need for laparotomy; and even death.

Question 10. What is antimullerian hormone and what does this test tell my doctor?

2010-03-19T10:29:00.000-07:00

TGIF. Yup, it is Friday afternoon here at Dominion and I am looking forward to a free weekend. For the past 10 years it has been just myself and Dr. DiMattina and I can tell you that every other weekend on call can wear you down....especially if the other guy has vacation. Before I joined him, Dr. DiMattina never took a vacation and at one point had to remove his own appendix with a spoon immediately following an egg collection which was performed at 2 am since this was in the days before Lupron...or ultrasound...or anesthesia....or electricity (if you catch my drift). Still as long as you give the staff bagels and muffins the weekends run quite smoothly.

So what about newer tests of ovarian reserve? The use of AMH is kinda like religion..either you are a believer or you are not. We are believers in AMH here at Dominion. I find it to be very helpful in assessing patients for IVF protocols and for making a host of other treatment related decisions. However, I would not ask your Ob Gyn to check this hormone as the interpretation of the results can be tricky.

Hope all of you have a great weekend and here is the Question of the Day!

10. What is antimullerian hormone and what does this test tell my doctor?

AMH is a protein hormone produced by the cells that directly surround the egg, called the granulosa cells. Granulosa cells (GC) also produce the hormones estrogen and progesterone. Since the cells that surround each egg produce AMH, we can measure a patient’s blood AMH level and get a good determination of her total follicle pool or total egg count. If her AMH level is low, then her total follicle pool or egg count is also probably low. AMH offers additional insight into the patient’s ovarian reserve in addition to the other tests such as serum day 3 FSH, day 3 estradiol, clomiphene citrate challenge testing (CCCT), or an ovarian ìantralî follicle count (AFC) using ultrasonography. Since cycle day 3 FSH levels often fluctuate widely, a single measure of FSH may not represent a patient’s true ovarian reserve especially if AMH and antral follicle count are normal.

The advantage of serum AMH testing is that AMH can be measured on any day of the patient’s menstrual cycle. In other words, its levels are cycle day independent, so patients don’t have to worry whether or not the blood sample is collected on day 3. Also, its levels tend to be more constant and more reliable for assessing ovarian reserve than day 3 serum FSH and estradiol. We often observe patients whose day 3 FSH and estradiol levels are normal indicating normal ovarian reserve, yet their AMH level is low and consistent with an observed low antral follicle count suggesting diminished ovarian reserve. Upon performing ovarian stimulation on such patients using gonadotropins, we often find that the AMH and antral follicle count properly identified the patient’s true ovarian reserve better than using serum day 3 FSH and estradiol measurements.

At Dominion Fertility, we place much more emphasis on AMH levels than we do on the other blood markers for ovarian reserve. In Europe, AMH is also the preferred biomarker for assessing ovarian reserve in many IVF centers but the use of AMH in the United States is becoming increasingly more popular.

Question 9. What is ovarian reserve, and how is it tested?

2010-03-18T06:34:00.000-07:00

Ovarian reserve is a very important but confusing topic. I would like to share an interesting story about ovarian reserve before getting to the Question of the Day on this day after Saint Patrick's Day. For those reading this blog on Fertile Grounds, feel free to skip to the Question if you have already read this story in my post.

DK is a 38 year old who came to see me in September 2008. She and her husband had undergone fertility treatment 3 years earlier at another center and conceived with CC/FSH/IUI but had a quintuplet pregnancy that ultimately ended up as twins. They were very worried about having another multiple pregnancy and wished to discuss options.

However, as part of the evaluation her FSH was found to be 14 with a normal E2 but an AMH of<0.1 and an antral follicle count of 2-3. Although they had originally considered stimulated IVF with single embryo transfer that option seemed unlikely given her diminished ovarian reserve. After failing a few natural cycle IUIs they decided to try Natural Cycle IVF in 2009. Their first Natural Cycle IVF was a biochemical pregnancy. They tried Natural Cycle IVF again in June 2009 and were successful. She was sent off to her Ob Gyn with a normal looking pregnancy.

But the roller coaster was just getting cranked up....

She underwent a CVS given her age and the results showed that some of the cells were normal but some were trisomy 9 (not compatible with life). Her Ob Gyn was suggesting a D&C so she called me just to let me know what was going on. I fired off an email to Dr Mark Hughes (the world's smartest geneticist). Since we know that the 8 cell human embryo can contain both normal and abnormal cells (limiting the usefulness of PGS) I was thinking that maybe the CVS results represented a case of placental mosaicism where the baby is normal but the placenta has both normal and abnormal cells. Dr. Hughes confirmed that was indeed possible.

The couple elected to continue the pregnancy and undergo amniocentesis. The amnio was totally normal and all sonograms were normal. She went full term and just went home from the hospital today after delivering a healthy 9 pound baby!

So this case demonstrates many interesting points. First of all, is Natural Cycle IVF appropriate in a couple with normal tubes, normal sperm and previous pregnancy? The answer was a resounding "yes" in this case. Secondly, can ovarian reserve drop dramatically in just a few years? The answer is "yes" and although this case is a bit unusual in that the patient went from quints to diminished ovarian reserve in just 3 years. Thirdly, this case does demonstrate again the limitations of PGD/PGS and even CVS in cases of mosaicism. Finally, this case shows how important it is to consider all options especially when confronted with an unexpected result (like mosaicism on CVS).

I am so happy for this family and considering that I am not a big lover of roller coasters, all I can say is a few more wild rides like that one and I probably wont have any hair left at all!

9. What is ovarian reserve, and how is it tested?

During a woman’s reproductive cycle, each month a single follicle is selected out of a group of potential follicles, reaches maturity, and ovulates a single egg. Many fertility treatments use medications to “rescue” other follicles from that group, so that multiple eggs are released during ovulation as opposed to just a single egg. If physicians could predict which patients would respond well to fertility treatments, then those women predicted to produce a low number of eggs with a poor chance of success with stimulated cycle IVF could defer this treatment and consider other options including unstimulated or Natural Cycle IVF. Those women who respond well to fertility medications are described as having normal ovarian reserve. Those patients who have a poor response to fertility medications are described as having diminished ovarian reserve. Although those patients with diminished ovarian reserve are likely to demonstrate suboptimal numbers of eggs during a stimulated IVF cycle, they may still conceive spontaneously, or with non-IVF treatments or with Natural cycle IVF.

Ovarian reserve consists of two separate components, both of which determine a woman’s chance of conceiving a child with IVF. The first component is the number of extra follicles that are available to undergo recruitment with treatment using fertility medications. This number depends on several factors, including the woman’s chronological age (as discussed below), previous ovarian surgery, genetics, and exposure to environmental toxins (most notably, tobacco usage).

The second component is the actual health of the follicles and the eggs within those follicles. First and foremost, egg quality is determined by a woman’s chronological age. Peak female fertility occurs when a woman is in her twenties and then drops significantly with age, especially following age 35. This fact has been conclusively demonstrated in many ways but is especially obvious when we look at IVF pregnancy rates. In patients who undergo IVF, studies have shown that around the age of 35 years old a marked decrease occurs in the chance of an embryo implanting successfully. In addition, the miscarriage rate rises with age, especially in those women older than age 40, in whom this rate exceeds 50%. Therefore, the age component of ovarian reserve is essentially immutable. In other words, unless she uses eggs from an egg donor, a woman cannot change her chronological age—and with increasing age, the number of normal eggs inevitably falls sharply. Although it is true that the percentage of normal eggs within an ovary is specific to the individual woman, even the most fertile women possess very few normal eggs after age 40.

The concept of ovarian reserve testing, therefore, represents a means by which the physician attempts to evaluate a woman’s reproductive potential both in terms of the number of follicles that remain and the health of those follicles. There are several ways in which one can assess ovarian reserve. First, the woman’s follicle-stimulating hormone (FSH) level can be measured on day 2 or 3 of a normal menstrual cycle. An estradiol level should be obtained at the same time, because the FSH level can be misleadingly low in women who have a high estrogen level early in the menstrual cycle. Alternatively, ovarian reserve can be assessed by performing a transvaginal ultrasound and counting the antral follicles present. In women with a slightly elevated FSH level, a transvaginal ultrasound may reveal a large number of follicles—somewhat reassuring the patient and her physician that perhaps her ovarian reserve is more normal than might otherwise be expected.

Unfortunately, normal FSH and estradiol levels do not guarantee a normal response to fertility medications. The clomiphene citrate challenge test (CCCT) was initially described as a means to identify those women with normal FSH and estradiol levels on day 3 of the menstrual cycle (day-3 hormones) who may demonstrate a suboptimal response to injectable fertility medications and poor IVF pregnancy rates. In the CCCT, the patient takes 100 mg of clomiphene citrate on cycle days 5 through 9. An FSH level is checked on days 3 and 10. If both of these levels are less than 10 IU/L (international units), then this represents a normal response. If the FSH level is greater than 10 IU on day 3 but less than 10 IU on day 10, then this represents a borderline situation, but potentially reassuring based on the response of the ovary to stimulation with clomiphene citrate. If the FSH level is normal on day 3 but more than 10 IU on day 10, however, the woman is likely to exhibit a suboptimal response to fertility medication, along with high IVF cancellation rates and poor pregnancy rates.

Antimullerian hormone (AMH) is another blood hormone test that is often used to assess ovarian reserve. Many experts believe that AHM is a better indicator of ovarian reserve than serum FSH as it has less cycle to cycle variability. See Question XX for more information on AMH.

A word of caution is in order regarding ovarian reserve testing, including the CCCT: Virtually all physicians have patients who have successfully delivered a child following an abnormal CCCT. An abnormal CCCT or elevated FSH levels on cycle day 3 do not preclude spontaneous pregnancy and delivery. Nevertheless, the miscarriage rate and the incidence of Down syndrome may be increased in such pregnancies. Patients with diminished ovarian reserve may have successful treatment with the combination of fertility drugs and intra-uterine insemination (IUI), or even with IUI alone. More recently, unstimulated or Natural Cycle IVF has gained increased popularity in treating patients with diminished ovarian reserve. A recent paper from Italy described 500 Natural Cycle IVF cycles in patients who had previously failed to respond to ovarian stimulation medications. In spite of having such a poor history, over 10% of the women under 40 years of age achieved a pregnancy. Considering that in the United States, most of these women would have only been offered donor egg IVF, we consider that pregnancy rate to be very remarkable.

The real benefit of the CCCT is its ability to identify often those patients in whom stimulated IVF is markedly less likely to be successful, allowing them to focus on other options such as unstimulated IVF, donor-egg IVF, adoption, or less invasive office-based fertility treatments. Overall, ovarian reserve testing represents an important factor when considering various fertility treatments and may be the final arbitrator in selecting the specific treatment plan.

Rebecca comments:

I first walked into my RE's office at the age of 39. I had just suffered the loss of a pregnancy that had taken me 8 months to conceive. I was very aware of the proverbial 'biological time clock' and was concerned that my husband and I may have run out of time. I was panic stricken about the tests that would evaluate my ovarian reserve, however my desire to have children was greater than the fear I had about the test results. Fortunately, we found an RE who did not rely solely on my chronological age when he discussed our treatment options with us. He reviewed all my medical tests with me and offered an individualized plan that included a number of family building options that might address my infertility issues (most likely age related). Looking back, I realize how important our choice of RE was. It is important for women of advanced maternal age (AMA) to quickly identify an RE that is willing to work with, and is experienced in working with, women of AMA. An AMA woman must find a fertility clinic that offers a variety of fertility treatment options; one size (or one treatment) does NOT fit all. And finally, an AMA woman must find an RE who is willing to be aggressive in her treatment, but is also capable of being honest about the limitations of those treatment options for an AMA woman.

Question 8: What tests will we have to undergo as part of a fertility evaluation?

2010-03-17T05:57:00.000-07:00

Happy Saint Patrick's Day from Dr. G and the rest of the staff here at Dominion Fertility. Let me tell you that Dr. DiMattina's outfit today puts mine to shame! If only all of you could see his day-glo green shoes, belt, tie and hat. Oh well. Perhaps I will post some photos of him this week so you can see what you missed by not hanging out at Dominion Fertility.

Most patients are anxious about coming to see the fertility specialist because they just don't know what to expect in terms of testing and treatment. In general, most REs approach the testing phase in a similar fashion as detailed below. The women are usually quite easy to work with while the men are usually pretty resistant. I think that getting reduced down to a number is problematic for many of us. Yes it can be embarrassing to have to do a semen analysis but that's just the way it is!

Happy Saint Patrick's Day!

8. What tests will we have to undergo as part of a fertility evaluation?

The basic infertility evaluation consists of a handful of tests. The woman typically undergoes a transvaginal ultrasound, hormone blood tests, an assessment of the fallopian tubes and uterus (by x-ray or by laparoscopic surgery). The man gets off relatively easily as he usually only undergoes a semen analysis.

Transvaginal ultrasound allows the physician to assess the appearance of the uterus and the ovaries. During this examination, the physician may discover uterine abnormalities such as fibroids (benign growths of the muscle of the uterus) or uterine polyps (benign growths of the lining of the uterus). Ultrasonography can also identify the location of the ovaries and determine the number of follicles present (antral follicle count), which correlates with the woman’s response to fertility medications. In addition, examination of the ovaries may reveal the presence of abnormal ovarian cysts such as endometriomas, dermoid cysts, or—in rare cases—precancerous and cancerous lesions.

In addition to the routine vaginal ultrasound, an assessment of the fallopian tubes and the uterine cavity is appropriate when the woman is having trouble conceiving. This examination is usually accomplished through a hysterosalpingogram (HSG: see Figure 2), an x-ray test that is performed under fluoroscopy by a gynecologist, a reproductive endocrinologist or a radiologist. Although it may sometimes cause mild uterine cramping, the vast majority of patients tolerate this procedure without difficulty. The individual physician performing this test can make a huge difference in the experience for a typical patient. For example, we utilize a soft catheter which is held in place against the cervix but is not actually passed into the uterine cavity. The use of this instrument rather that a balloon type catheter that must be introduced through the cervix and into the uterus can markedly reduce patient discomfort with this test. Similarly, only a small volume of dye is needed to fill the uterus and fallopian tubes. Excessive pressure and volume of dye can lead to much greater cramping and rarely improves the diagnostic accuracy of the test.
Alternatives to the hysterosalpingogram include laparoscopy and hysteroscopy; these outpatient surgical procedures are described in Questions 10 and 11.

Laboratory tests on the female partner of an infertile couple usually include routine screening tests such as those for blood type, blood count, and rubella immunity. In addition, most physicians perform tests that check the woman’s prolactin and thyroid-stimulating hormone (TSH) levels. Additional reproductive hormone testing for ovarian reserve is usually part of the routine evaluation as well (see Question 9).

Routine testing of the male partner of an infertile couple includes a basic semen analysis evaluating the volume of semen, the concentration of sperm (sperm count), the percentage of moving sperm (sperm motility), and the percentage of normally shaped sperm (sperm morphology). (See Table 2.) Although some clinics perform additional sperm function tests, such as the acrosome reaction and hypo-osmotic swelling test, the overall benefit of these two tests remains somewhat controversial. Both of these tests attempt to predict the functional ability of the sperm in terms of its ability to fertilize an egg. Ultimately, however, the best evidence of normal sperm function is a recent pregnancy or normal fertilization during a cycle of IVF.

Tests to detect the presence of antisperm antibodies in the blood of the female partner or coating the individual sperm may sometimes be recommended. Female antisperm antibodies may cause infertility that is best treated by IVF. Antisperm antibodies present on the sperm themselves may inhibit normal fertilization. In such cases, collecting a semen sample in media for use in artificial insemination may be considered, but these patients are usually recommended to pursue IVF with intracytoplasmic sperm injection (ICSI).

Kristin comments:

Despite having a diagnosis of PCOS when I was referred to an RE, I still had to go through the regular battery of blood tests, ultrasounds, and an HSG. It was a really scary time because none of my friends had ever gone through any of the tests and I really felt like a pincushion. Besides the physical toll of the tests, it was definitely emotionally draining. I think the initial tests in some ways prepare you for the weeks of daily blood draws and ultrasounds that accompany IUI [intra-uterine insemination] and IVF. Before IVF I was terrified of needles, but within days I was a pro at giving myself shots.

Question 7: What are typical causes of infertility?

2010-03-16T08:09:00.000-07:00

Being a fertility specialist is a bit like being a detective. You gather the evidence and then work on a hypothesis. Once you have the hypothesis, then you can test it out and see if the problem is resolved. Today I saw a new patient that was very frustrated with her situation and the response that she had gotten from her previous physicians. I listened carefully to her story and then explained carefully what I thought explained her particular problem. We now have a plan to test my hypothesis. If I am right then we will all be very happy, but I think that even if I am wrong then at least the couple understood how I approached the problem in a logical fashion.

Ultimately there are not that many fertility issues and common things are common. But every patient has their own story to tell and we need to listen in order to make sound decisions. So what types of problems do we deal with? Good question and the topic of today's Question of the Day from the upcoming 2nd Edition of 100 Questions and Answers about Infertility.

7. What are typical causes of infertility?

The causes of infertility are wide ranging but can be examined in light of the reproductive cycle described in Question 1. (See Table 1.) In general, the causes of infertility can be equally divided between the male and female partners in a couple.

Half of all infertility cases, therefore, involve problems with the sperm of the male partner. Unfortunately, functional tests for sperm competence (the ability of sperm to fertilize an egg) are not available leaving us to rely upon the descriptive components of the semen analysis. A complete semen analysis should include the total number of sperm (concentration), the percentage of those sperm that are moving (motility), and the shape of those sperm (morphology).

Many factors can reduce the female partner’s ability to conceive. For example, a woman may have anatomical problems related to the fallopian tubes, uterus, and peritoneal structures within the pelvis such as adhesions or endometriosis. Problems with ovulation are very common in infertile patients, and women with irregular periods may suffer from a common disorder such as polycystic ovarian syndrome (PCOS). Another major fertility factor is reproductive aging. Peak fertility occurs when a woman is in her twenties, and it declines significantly during her thirties and forties. The rate of decline increases after the age of 35 as is evident in decreased IVF pregnancy rates and decreased embryo implantation rates in this age group.

Question 6: How do I choose a fertility clinic?

2010-03-15T13:35:00.000-07:00

Well Washingtonian magazine has published its annual "Top Docs" issue and I was pleased to report to my parents that I made the cut again (as did Dr. DiMattina). Yet, several excellent Ob Gyn physicians that I know were not on the list this year. Did they suddenly become terrible doctors? No. However, probably they will lose some patients because of the fact that they were not voted in this year.

Popularity contests are probably not the ideal way to choose a physician. Neither is the internet. So how should a patient make such an important decision.? I would go with whatever clinic has the best candy at the front desk...but seriously, this is an important question to consider. So important that it is the Question of the Day for this rainy Monday in March.

6. How do I choose a fertility clinic?

Choosing a fertility doctor for your care may be the single most important factor that leads to a successful pregnancy, so choose carefully.

Many patients are referred to us by their OB/GYN, friends, relatives, former patients, news articles, or through the Internet. But the one common denominator we have routinely observed with the sophisticated patient is that she is well prepared before coming for her initial office visit or she quickly becomes informed and knowledgeable before we begin any treatments. Patients often say to us, “I checked you out before making this appointment.” Of course, we are always flattered by such comments, and we anticipate that this patient will ask all of the important questions and make an intelligent decision regarding her treatment options. She will also probably experience less stress during the evaluation and treatment process, as she has developed a better knowledge base and understanding of what to expect.

All fertility clinics come with a unique flavor of their own. Some are run by a solo practitioner, others by 2 to 6 member groups, while others are clinics with over 15 doctors. Regardless of the size of the group, be sure you are getting the attention and treatments you desire and deserve. You should never feel like a number with a revolving door of doctors.

Of course, patients are not doctors and will not have the knowledge or experience of a reproductive endocrinologist, but a caring doctor will always welcome any and all questions and will take the time to answer them in a way that you can understand. We view patients as our partners, and once we understand what they are willing or not willing to do, we can devise a treatment plan that offers hope without subjecting them to any unnecessary additional stress.

Other things to consider.
Statistics, statistics, statistics: You want a baby, so choose a fertility clinic with good success rates. However, a wise man once said: “There are lies, damn lies, and statistics.” So, how does one determine what to make of these statistics? In truth, there is no easy answer. Clinics that are more selective can inflate their success rates, while those that have a different philosophy may suffer the consequences even though they have an excellent program. For example, clinics that encourage elective single embryo transfer (eSET) or that offer unstimulated or Natural Cycle IVF may demonstrate lower clinical pregnancy rates as fewer embryos are transferred. Yet, in fact, such clinics that routinely transfer one or two embryos may have the best IVF programs. When considering a clinic, it is important to know what your specific chances for success will be within that clinic.

If there is one yardstick with which to compare clinics, then we recommend examining the pregnancy rate using donor eggs. In this patient population, the pregnancy rates should be very high. A low donor egg pregnancy rate may be concerning. All clinics should have a good pool of young egg donors and a recipient population that is fairly similar allowing for better comparison of clinics.

Advertising may be misleading. Obviously, a practice with 10 to 20 doctors will produce more total babies than a medical practice with only 2 to 6 fertility doctors, but the pregnancy rates may be equivalent (as can be seen in Figure 37 of Appendix B). Individuals should evaluate the clinic statistics and obtain a good understanding and feel for what their specific chances for pregnancy will be per treatment. Patients may also evaluate the clinic success by reviewing IVF statistics at the Centers for Disease Control and Prevention (www.cdc.gov/ART/index.htm/).

Experience: Experience of the clinic, in our opinion, may be one of the most important factors when deciding which doctor and which clinic to seek for fertility care. One should ask how long the doctors have been performing various treatment procedures. It is also important to know whether or not cutting edge procedures are either being offered or are being developed in the practice.

Subspecialty board certification: Most doctors practicing in the field of in vitro fertilization and infertility are subspecialty board certified in reproductive endocrinology and infertility. Evidence of this certification can be found by going to the Society for Reproductive Endocrinology’s Web site, which lists doctors who are subspecialty certified in reproductive endocrinology and infertility. Additionally, patients may find it beneficial to check if their doctor has a faculty position at one of the local medical universities or actively participates in the teaching of the medical students and residents in their locality.

Availability and accessibility of doctors: It is important that you have access to your doctor in order to have your questions answered and needs addressed. Evaluate whether or not the availability and accessibility of the doctor is an easy process or a difficult one when making decisions as to where to seek care. The friendliness and helpfulness of the staff will also give you a feel for the character of the practice.

Cost: It is always important to get the total cost. Factor in extra expenses such as the fertility drugs, which can cost thousands of dollars; intracytoplasmic sperm injection (ICSI); assisted embryo hatching; embryo cryopreservation; and preimplantation genetic diagnosis (PDD). These drugs and procedures can quickly increase the overall cost for treatment.

A word of caution: In general, Internet chat rooms may be a dangerous place for seeking advice regarding finding an infertility doctor. Be careful what you hear online, as it always represents just one half of the story. It is far better for you to do your own homework and research than to rely on information provided from others, which may be based on misleading impressions or experiences. Patients reporting on their experience with a given clinic or doctor may represent both extremes of the spectrum.

Question 5: Who should evaluate the infertile couple?

2010-03-13T10:56:00.000-08:00

I was never sure if I had all my shots as a child. With a father who was a general surgeon all of my camp forms were filled out at home. My Dad would pretty much just make up dates that seemed reasonable. I bet that many of these forms had me getting shots on major holidays and weekends but no one ever seemed to care.

When my Mother was 40 years old she stopped getting her period and felt pretty awful....tired, sick, nauseated etc. She asked my Dad what his diagnosis was and he replied "menopause." He snorted when she suggested that she might me pregnant. I arrived 7 months later! So my suggestion is to avoid getting fertility advice from general surgeons. Ob/Gyns are another story and in many cases the fertility evaluation can be initiated without a specialist. However, for patients over 35 yrs old and those with prolonged infertility or a recognized issue, it may make more sense to start with an RE.

So here is part 1 of the weekend edition of 100 Q&A about Infertility:

5. Who should evaluate the infertile couple? Do I need to see a Reproductive Endocrinologist?

In many cases, the routine fertility evaluation can be conducted by an obstetrician/gynecologist, or a family practitioner. Certain tests can easily be ordered and interpreted by physicians in the first two specialties, but a reproductive endocrinologist (RE) may be required to interpret advanced testing and provide the most accurate counseling. Women who are more than 34 years old may elect to immediately consult with a reproductive endocrinologist.

Although all physicians trained in obstetrics and gynecology are exposed to the specialty of reproductive endocrinology and infertility, this training may by cursory at best. On the other hand, a reproductive endocrinologist (RE) is a physician who specializes in the treatment of reproductive disorders and infertility. A physician specializing in reproductive endocrinology undergoes 4 years of training in general obstetrics and gynecology following his or her completion of medical school. At the end of these 4 years internship and residency (which includes exposure to normal and high-risk obstetrics, gynecology, gynecologic oncology, and reproductive endocrinology and infertility) a physician may then apply for an additional 3-year fellowship in reproductive endocrinology and infertility. There are usually only 25-35 fellowship positions available each year so competition can be intense. After completing these 7 years of training, the physician takes a series of written and oral examinations to become board certified in this specialty. Although not all practitioners of reproductive endocrinology and infertility have undergone formal fellowship-level training, the majority have, and this training includes both clinical and basic science experience.

There are several professional organizations for physicians who are interested in the treatment of the infertile couple, including the American Society of Reproductive Medicine (ASRM) and the Society for Reproductive Endocrinology and Infertility (SREI). Any physician who is interested in infertility may join ASRM, but members of SREI must be board eligible or board certified in reproductive endocrinology and infertility. Both of these organizations maintain websites that allow patients to identify local specialists (www.asrm.org; www.socrei.org).

Carol comments:

I began discussions with my gynecologist at age 34 regarding my lack of success at getting pregnant. He put me on a plan that seemed to represent a pretty standard process of elimination. First, I did the basal body temperature charting for 3 months to determine if I was ovulating; then, I spent 3 months on Clomid with no success. Looking back on it now, I question his resistance to send me directly to an RE for further evaluation given my age and what the ovulation charting had revealed. Don’t be afraid to push your doctors. I wish I would have pushed harder to get things moving.

Question 4: Is Infertility Becoming More Common?

2010-03-12T05:43:00.000-08:00

Are you familiar with those ads for "Hair Club for Men?" Well, besides the fact that I am losing my hair (which my kids think is hilarious) I have always liked the line where the owner states I am not just the owner...I am also a customer. In the mid 1940s my parents were told that they could never have children. My mother had a bicornuate uterus with one side that was abnormally small. She later found out she was missing a kidney on that same side which my Grandmother always blamed on my Dad who is/was a general surgeon. "My daughter was perfect until she married your father" she would often tell us. Yup, Nana and Dad did not have a real good relationship.

In any case, while stationed in Italy just after WWII my parents found themselves pregnant again after a number of terrible miscarriages. Instead of following the advice of the doctors, my Dad refused to have them do a D&C on my Mom once she started bleeding a bit. It was the right decision as what was happening was the bleeding was from the abnormal side of the uterus and the pregnancy was actually doing fine on the other side.

The end result was my older brother Mike (see photos of Baby Mike with 2 people who claim to be my parents). With the exception that he is also a general surgeon, he seems to have turned out OK. After 2 more successful pregnancies my parents called it quits with 3 boys.

So whenever I deal with a patient with a uterine anomaly I think of that Hair Club for Men advertisement....I'm not just a fertility doctor...I'm also the product of a couple with fertility issues...

4. Is infertility becoming more common?

A common misperception is that infertility is becoming more common. In fact, the infertility rate has held relatively stable over the years. Instead, two major factors account for the increased utilization of fertility services.

The first of these factors is simply the greater availability of the services themselves. Prior to the 1978 birth of Louise Brown, the world’s first baby conceived through in vitro fertilization (IVF), the options available to treat an infertile couple were limited to tubal microsurgery and ovulation induction with medications such as clomiphene citrate (Clomid). With the development of advanced reproductive technologies (ART), the techniques used to treat the infertile couple have become both much more successful and more accessible. Fertility providers now practice throughout nearly all urban centers in the continental United States, with more than 400 IVF clinics reporting their success rates through the Society for Assisted Reproductive Technologies (SART) and the Centers for Disease Control and Prevention (CDC). Statistics from all reporting IVF clinics are available at http://www.cdc.gov/ART/index.htm.

The second factor accounting for the increased use of fertility services is the trend toward delayed childbearing. Over the last generation, a significant number of women have deferred childbearing while they pursued advanced academic careers or entered the workplace. Unfortunately, female reproductive capacity drops from a peak in the second and third decades of life so that by the age of 40 years there is a marked reduction in fertility and an increased risk of miscarriage.

Finally, the stigma associated with fertility treatments themselves has also eased in recent years, prompting more couples to seek out such help. Previously, couples who were seeking fertility treatments often found themselves beset by a bewildering array of options and knew few other couples with whom they could discuss the range of treatments. Today, more than 100,000 cycles of ART are performed in the United States every year. Given that 1% of all U.S. births are now the result of fertility treatments, most couples probably know someone with a successful outcome from fertility treatments. The current explosion of information available through the Internet and through organizations such as the American Society for Reproductive Medicine (ASRM), RESOLVE, and the American Fertility Association has allowed patients to better understand fertility-related problems and seek appropriate care. A number of states have implemented mandates that guarantee varying levels of insurance coverage for fertility-related procedures, which has had the effect of easing the financial burden for couple who seek out this type of care.

Kristin comments:

When I started discussing my fertility problems with my mother, she opened up about her own struggles to conceive my brother and me. While she did eventually get pregnant on her own, it took her over 2 years to conceive me and about the same amount of time to conceive my brother. She said that nobody really talked about infertility when she was trying to get pregnant and the fertility options were minimal. My mother was an only child because my grandmother could never become pregnant again despite years of trying. I would guess that both my grandmother and my mother had the same infertility diagnosis as I do—PCOS [polycystic ovarian syndrome]—but in their childbearing years it was not commonly diagnosed and treatments were either nonexistent or limited.

Question 3: How Common is Infertility

2010-03-11T06:59:00.000-08:00

One of the unique features of the 100 Q&A series of books is that patients offer their view on several of the topics that are covered. As a physician it is easy sometimes to assume that patients have knowledge that they actually don't possess. We do thousands of sonograms every year and yet to the patient these images often just look like weather maps. It's kind of like that scene in the Matrix when they are all watching a stream of numbers flowing down the screen. To us we just see a flow of characters on the screen and yet to them they are watching Neo and Morpheus slug it out in a training session within the Matrix... Perhaps it is not the smartest idea to share my knowledge of science fiction with potential/existing patients.... On the other hand, I did convince my wife to date, marry and reproduce with me so go figure.

So here is the Question of the Day from the soon to be published 2nd Edition of 100 Questions and Answers about Infertility by Gordon and DiMattina...with a little help from three of our patients....

3. How common is infertility?

Infertility is an extraordinarily common disorder. An estimated 25% of all women will experience an episode of infertility during their lifetime. Infertility currently affects about 6.1 million women and their partners in the United States. The percentage of reproductive-age women who report problems successfully conceiving and maintaining a pregnancy varies with age. In the youngest segment of the population, approximately 10% to 15% are affected by this problem. Among women older than age 35, however, more than one-third report diminished fertility. The rates of pregnancy loss are also related to a woman’s age, with the rate of miscarriage exceeding 50% in women older than age 40.

Kristin comments:

When you’re in the throes of infertility, desperately wanting a child while seemingly everybody around you gets pregnant on their “first try,” you wonder if you’re the only one who can’t get pregnant. My husband and I have been very open about our fertility problems, and once I really started to share our story with friends and acquaintances I discovered I was not alone . . . far from it. I have created amazing friendships with other “infertiles” I have met through Internet communities, reading blogs, and even support groups in my area.

Question 2: What is Infertility?

2010-03-10T06:37:00.001-08:00

So how bad was the snow in Washington, DC? Let me tell you....it was epic! Seriously. I had not seen see snow that deep since the Blizzard of 1978 in Boston when I was only 12 years old (see photo below).

The roads were a complete disaster and just trying to get to work was near impossible. I remember a few years ago when we had a lesser storm that I arrived at the office to find myself the only employee who made it in. There were 18 patients waiting and no nurses, no medical assistants, no front desk. So until the rest of the crew made it in I was checking the patients in, rooming them, drawing the blood and doing the sonograms (my usual role)! So the hotel seemed a good option for this most recent storm (see other photo).

Of course, the bad weather was a perfect time for us to work on revising the book and trying to get it off to the publisher. I am pleased to say that we are doing well in terms of the timetable and I truly hope thatthe book will go to press way before I complete running through all these questions. I think that I need to talk with Jones and Bartlett about an iPad version so I have an excuse to give Steve Jobs more of my money.

2. What is infertility?

Approximately 80% to 85% of couples who are trying to become pregnant will successfully conceive within a year. Thus infertility is commonly defined as the inability to achieve a pregnancy within 12 months of unprotected intercourse. However, certain patients may have recognized factors that preclude normal conception; for them, the 12-month period of waiting makes little sense. Common examples of women with such problems include those who have extremely irregular periods, a history of severe endometriosis, a history of previous tubal pregnancies, or other anatomical factors that would clearly lead to diminished fertility. Since fertility declines significantly as a woman ages, couples are encouraged to seek evaluation for infertility after 6 months of no contraception if the woman is older than age 35.

Another problem related to reproduction is recurrent pregnancy loss. Many women can readily conceive, only to suffer repeated pregnancy losses. These women represent a special subset of those who are unable to successfully reproduce and should be evaluated by a medical professional.