CHR Update

The following articles represent an update on CHR activities. If you want further information on any of these articles, please contact us. CHR is a comprehensive fertility center in New York, NY.

February 2012

Amongst many reasons for publishing these monthly pages, we use this format, intermittently, to discuss clinical issues that "bug us" in our daily practice. In this issue of UPDATE, we want to discuss two such issues. Let's start with:

Treatment delays

Regular readers of these pages, of course, already know that CHR's patient population is very different from what most other fertility centers come to see. For us, here at CHR, it is rare to see new patients who have not already received extensive fertility treatments at other centers. We also see a large number of patients who have, simply, been refused treatment because of, allegedly, too low pregnancy chances.

If our center were practicing oncology instead of infertility, the perfect analogy to what we do here at CHR would be only treating almost exclusively patients with end-stages of cancer--those who are often refused further treatments and sent off into hospice care.

On first glance, this analogy may sound somewhat harsh, but it is absolutely correct as an example; nowhere more appropriate than in documenting the importance of time!

Everybody knows and understands the importance of quick and reliable diagnosis, followed by speedy therapy in treating cancers. It is also widely understood that time is of essence if best possible outcomes are strived for. The same principles apply to the treatment of infertility, especially in older women!

Like cancer patients, infertile women do not have time on their side. This is nowhere more obvious than here at CHR, and in its patient population. When a patient is young with occluded tubes as the cause of her infertility, a few months--or even years--rarely matter much. But when patients are older (CHR patients' mean age, for the first time, exceeded 40 years in 2011), time becomes of essence because the ovarian aging process after age 40 speeds up, and every fertility treatment, therefore, quite rapidly loses efficacy.

Let us also not forget that a second large patient pool CHR serves are women with premature ovarian aging (POA), also called occult primary ovarian insufficiency (OPOI) by some. Like older women, POA patients do not have time on their side because nobody can tell them how quickly their POA will progress, further reducing their ovarian reserve (OR). Just very recently, we saw a woman with POA, who, within 3-4 months, went from almost normal OR to almost menopausal levels of ovarian function tests. Fortunately, such rapid progression of POA is rare, but because it can occur and because we cannot select who is at risk for such rapid progression among POA patients, time has to be of concern in all of POA patients.

Time is, therefore, of essence here at CHR! There isn't a day when we don't hear from one of our patients, "doctor, I wish I had known about CHR months (or years) ago, when I was doing so and so …"

We, of course, are delighted when patients come to us at CHR. And we are especially delighted when we still end up succeeding in helping them conceive with use of their own eggs (approximately one-third of women who come to CHR for first consultation after having been told that their only chance of pregnancy was with donor eggs, leave CHR pregnant with use of their own eggs). We, however, often wish they had come to CHR a little earlier because so much time had been wasted unnecessarily before. The earlier we can start treatment, the better, of course, our chances!

Here are, therefore, a few general recommendations for infertile women with diminished ovarian reserve (DOR) because of advanced age (over 40):

  • Above age 40, recognize the urgency of aggressive treatment;
  • Insist on rapid diagnosis and a structured treatment plan;
  • Insist on specific treatment goals that meet your expectations: i.e., for example, do not agree to treatment with clomiphene citrate and intrauterine inseminations (IUI) if the offered pregnancy chance sounds ridiculously low.
  • Do not agree to endless testing to "wait for the right results;" Time is not on your side! Test results will only get worse!
  • It never hurts to get a second opinion!

And here are a few general recommendations for younger women with DOR, especially if the cause of their infertility has not been clearly articulated (the so-called "unexplained infertility"):

  • Insist on OR-testing with FSH and AMH!
  • If under age 40, and either your FSH and/or AMH values are abnormal, suggesting DOR, you, likely, suffer from POA.
  • If that is not clearly spelled out to you, your physician, likely, has little experience with diagnosis and treatment of POA, and it may be time for a second opinion.
  • Remember that with a diagnosis of POA time is of essence since nobody can predict how quickly your OR will continue to decline.
  • It never hurts to get a second opinion!

In summary, for older women and women with POA, time is a very valuable commodity. Don't waste it because the earlier you get started with the right treatment, the more successful that treatment will be in helping you conceive.

Considering how successful CHR is in helping many women after, unfortunately, unnecessarily wasting a lot of time, imagine how much more successful we could be, if given the opportunity to start treatment a little earlier!

Have IVF pregnancy rates plateaued?

Dr. Gleicher founded CHR in Chicago in 1981. It then was one of the first IVF centers in the country, and the first in the Midwest. He still likes to tell the tale of how it took him and his embryologist almost two hours to identify under the microscope the first egg he retrieved (by laparoscopy) in the operating room.

Did you know that the first vaginal egg retrieval in the world was performed by Dr. Gleicher in 1983 at CHR, and reported in The Lancet [Gleicher et al., Egg retrieval for in vitro fertilization by sonographically controlled culdocentesis. 1983;2 (8348): 50809]?

Not only has vaginal egg retrieval become the routine, but things have, of course radically changed since, in many other important ways. IVF, which started as a highly controversial and experimental procedure, has resulted in the birth of over 4.6 million human beings who, otherwise, would not share the world with us--an accomplishment acknowledged by the 2010 Nobel Prize in Physiology and Medicine for Robert Edwards, Ph.D.

A main characteristic of the uniquely successful development of IVF into a routine treatment of female as well as male infertility has been the procedure's steady improvement in pregnancy rates per cycle attempt. Now, for the first time, data suggest that IVF success rates may have plateaued.

In the September 2011 issue of Focus on Reproduction, official organ of the European Society for Human Reproduction and Embryology (ESHRE), Simon Brown reports that pregnancy rates, multiple pregnancy rates, and pregnancy rates in donor egg cycles as well as frozen-thawed cycles, appear to have leveled off, based on the preliminary 2008 data from ESHRE's European IVF monitoring. We, however, caution against automatically assuming that European data necessarily reflects what is going on in the U.S.

With over 500,000 cycles, Europe now represents 52% of all IVF activity in the world. The most cycles per country are, however, performed in Japan (ca. 160,000) and the U.S. (ca. 130,000). Pregnancy rates after IVF are still significantly lower in Europe: Europe reports clinical pregnancy rates per cycle of 32.5% for IVF cycles and 31.9% for ICSI cycles. Since Europe, in contrast to the U.S., does not report delivery rates, assuming an average miscarriage rate of 15%, (likely, a low estimate for IVF cycles) this would mean delivery rates of 26.6% and 27.1%, respectively. The average U.S. delivery rate, in comparison, was 40.7% for the same time period.

Since CHR investigators first pointed out this discrepancy between the U.S. and Europe in two reports (Gleicher et al., Hum Reprod 2006;21:1945-50 and Gleicher et al., Fertil Steril 2007;87:1301-5), our European colleagues have been trying to figure out why pregnancy rates in Europe have remained dramatically lower than in the U.S. Even they since had to acknowledge that this rather significant discrepancy in pregnancy rates cannot be explained only by the fact that U.S. programs transfer slightly more embryos. So what, then, are the real causes?

There is still evidence that the overall quality of IVF, as performed in the U.S., is superior to the overall quality in Europe. A rarely mentioned piece of evidence for this assumption is a clinical study, conducted by a European drug manufacturer, under identical conditions at centers in Europe and centers in the U.S. The U.S. centers demonstrated significantly better pregnancy rates, even though basic protocols were, allegedly, the same on both sides of the Atlantic.

One has to recognize, however, that the European experience is much less homogenous than conditions in the U.S. Undoubtedly, the U.S. also has better and poorer IVF programs; yet the U.S. does not demonstrate the significant differences in national outcomes observed in Europe. And it is this observation, probably better than others, that explains what is going on.

In our opinion, the principal reason for much poorer IVF outcomes in Europe than the U.S. is policy and politics. In many ways, Europe and the U.S., in regards to infertility treatment, reflect the same political differences, which currently consume our political discourse in this country on a much broader basis. Europe, in that regard, demonstrates what happens to medicine within a socialistic societal model, which offers wider access (note number of European IVF cycles in comparison to U.S. cycles) but also with obviously reduced outcome success.

We use the term "outcome success" on purpose rather than "quality," because our European colleagues, under their, usually government-driven, health care, perceive "quality" differently. This is probably best documented by the success of single-embryo transfer (sET) in Europe.

While sET, indisputably, reduces immediate pregnancy chances, many of our European colleagues (and many governments) consider this not only appropriate, but, indeed, "good quality of care" because sET reduces twin pregnancy rates. Since they (in our opinion incorrectly) consider twin pregnancies to cause increased risks to mother and child, "good quality of care" in their opinion warrants reduced pregnancy chances with IVF, even though innumerable articles in the medical literature, including those from European authors, very clearly demonstrate that patients on both sides of the Atlantic value pregnancy chances over everything else in deciding on their fertility treatments.

Europe, in this example, very obviously values what our colleagues and governments perceive as the "common good" over individual rights of patients. Like in other spheres of life, they, however, fail to see unintended consequences from their interventions into the physician-patient relationship: Not only do their populations have lower pregnancy chances with IVF than U.S. patients, but European populations are also forced to undergo more IVF cycles in the end, at more cost and, of course, more risks. What this example, therefore, very well demonstrates is not only the very obvious downsides of "one-size-fits-all" communal care instead of "one-on-one" medical care but also its cost-ineffectiveness.

Who, therefore, can be surprised that European IVF results have plateaued! We, indeed, would predict further declines, unless systems change, and the individual patient, once again, returns to the center of medical attention.

IVF results have continuously increased because in the U.S., IVF represents the only medical mainstream treatment, which, over the last few decades, was developed without any federal financial help whatsoever (Democrat as well as Republican administrations, in unison, have withheld federal funds for IVF research). IVF in its development was, therefore, dependent on success in the market place.

We are confident that, if we leave it that way, IVF pregnancy rates in the U.S. will continue to improve. CHR is a good example: Look what CHR has accomplished over the last 10 years in treating women with DOR, who many of our European colleagues "for the societal good" now routinely refuse to treat!

All over the Scandinavian countries, where sET has found peak acceptance, women above 40-41 are now refused IVF treatments because these treatments are considered "too inefficient." Is this the "social" administration of medicine to be proud of? We don't think so, and neither do all of the Scandinavian patients who now come to NYC (if they can afford it) to receive treatment at CHR. There is a lesson to be learned here!

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-The CHR

Last Updated: December 23, 2011