Welcome to 2018: How CHR Differs from Most IVF Practices

Now that most of us have made our annual New Year’s resolutions, we also have to acknowledge that most are, unfortunately, as quickly forgotten as they were made. Since the start of a new year often involves decisions surrounding family planning, we in this first 2018 issue of the VOICE want to take our readers on a little journey through some of the basic realities of contemporary fertility care, as CHR sees them.

Regular readers of these pages, of course, by now know that fertility treatments at CHR often differ from approaches followed by other centers to significant degrees. We here at CHR see this less as “being different” but, more so, as “being ahead of the curve.” Since its founding, CHR (originally in Chicago) has in many ways always been a little ahead of most other centers.

To name just a few major innovations in the fertility field that originated at CHR, this center was the first IVF center in the world to perform and publish ultrasound controlled vaginal egg retrievals, when the routine still was to retrieve eggs surgically in the operating room [Gleicher et al., Lancet 1983;2(8348):508-509], and the first to open obstructed fallopian tubes with transvaginal tubal catheterizations [Confino et al., Am J Obstet Gynecol 1988;159(2):370-375 and JAMA 1990;264(16):2079-2082)]. CHR investigators greatly contributed to reproductive immunology [Gleicher and Friberg, JAMA 1985;253(22):3278-3281], and were the first to report animal models for uterine transplantation [Confino et al., Int J Gynecol Obstet 1986;24(4):321-325], only now a very “hot” topic in the field. CHR brought androgen supplementation of women with poor ovarian reserve into clinical practice [Barad and Gleicher, Fertil Steril 2005;84(3):756 and Hum Reprod 2006;21(11):2845-2849], now utilized all over the world, and CHR investigators were the first to point out the potential importance of the fragile X mental retardation (FMR1) gene for ovarian function [Gleicher et al., Fertil Steril 2009;91(5):1700-1706], now widely acknowledged and intensively investigated in a number of laboratories.

In more recent years, CHR has pioneered the treatment of older women with use of their own eggs, who at most other centers usually are automatically referred into egg donation. CHR was recently, indeed, able to report the healthy birth of a daughter to a woman who, at 47 years and 10 months at time of her embryo transfer, likely, was the oldest IVF patient ever in the world to achieve a successful delivery after using her own eggs.

CHR’s remarkable progress in treating older women [and younger women with premature ovarian aging (POA)] has been a slow but consistent process, based on two principles: By investigating the basic molecular physiology of aging follicle in the laboratory, CHR investigators learned important clues about what damages oocytes (eggs) in older follicles. This knowledge then could be applied to highly individualized cycle management of patients, for which CHR has coined the term Highly Individualized Egg Retrieval or HIER (for further detail see the article on HIER in this issue).

What CHR refused to subscribe to, while other centers embraced it, may, however, have been even more responsible for CHR’s clinical successes than the center’s quite remarkable research achievements. By not jumping on the bandwagon with every “fashion of the moment,” often more propagated by economic interests than scientific evidence, CHR has also become a worldwide-recognized force in correcting some very important “wrongs” in the fertility field. The, likely, most prominent example has been preimplantation genetic screening (PGS), now also called preimplantation genetic testing for aneuploidy (PGT-A), likely the most frequent target of CHR’s wrath over the last few years.

Though at times pretty viciously attacked by proponents of the procedure, CHR is proud to have stood its grounds, as the pendulum is quickly moving into the right direction. We were especially gratified to recently learn that one of the biggest commercial genetic laboratories and manufacturer of genetic testing equipment, in recognition of the shortcomings of the procedure, has quietly decided to deemphasize PGS/PGT-A in its marketing efforts. We wish, others exhibited he same honesty!

Another area where in CHR’s opinion many “wrongs” require corrections, is the rapidly growing “egg freezing industry.” We addressed this concern in last month’s VOICE, and are also raising again some important issues in our journey through the field of infertility in this issue. But before we do so, a more prosaic point, namely time: New Year’s resolutions involving fertility must consider the importance of time in human reproduction. Female age is, in principle, the most important predictor of pregnancy chances, whether in spontaneous conceptions or in fertility treatments.

The importance of not wasting time

Nothing makes us prouder than the trust patients express in CHR when, after (often repeatedly) failing elsewhere, they still muster the will and strength to give it one more chance at CHR. Over 90% of CHR’s new patient have failed IVF previously at other centers (CHR also serves the by far oldest patient population of any U.S. IVF center, reporting to national data banks at CDC and SART).

At the same time, we, however, also always wonder how much more effective we could have been, had these patients presented to CHR only six months or a year earlier. Time is of great importance when it comes to fertility treatments, and the beginning of a new year is a good moment in time to be reminded of that. Especially at older ages or in women with significant POA, even just a few months can make a big difference.

Egg freezing

Nowhere is time, however, of more importance than when women freeze eggs for fertility preservation purposes because, as we in last month’s VOICE in detail reviewed, the earlier eggs are frozen, the better can they be expected to thaw out, and the more likely will they lead to pregnancies. For those readers whose New Year resolutions included the potential of egg-freezing during 2018, the message, therefore, is this: The earlier you do it, the better!

Also, where you freeze your eggs matters; but where you thaw them once you need them, matters even more! Freezing of eggs is not a social event, as it is marketed at “egg freezing parties” by some. It is a costly and serious medical and laboratory procedure, where patients potentially entrust their future fertility to either a serious and reputable IVF center or a fly-by-night commercial outfit. When it comes to choose where to freeze your eggs, making the right choices matters!

CHR’s newly expanded Egg Freezing Program started on January 2 with a bang, offering the services of CHR’s world-renowned clinical and laboratory staff at remarkably low packaged cycle costs. As we also noted in last month’s VOICE, CHR decided to expand its Egg Freezing Program after noticing during 2016/17 a considerable increase in women who reported very disappointing thawing rates for their eggs frozen elsewhere. We know that we can do better!

What’s My Fertility?: Diagnosing POA early

Thinking ahead, the beginning of a new year is also a good time to remind young women (and parents of young women) that ca. 10 percent of all women, independent of race and ethnic background, end up suffering from POA. This means that, often starting at quite young ages, so-affected women have fewer eggs left in their ovaries than the other 90 percent. Since POA is an insidious (i.e., asymptomatic) condition, these young women have usually no way of knowing that they are in the process of developing POA. Especially if they are on hormonal contraception of any kind, they will not even notice menstrual irregularities, which often are the only clinical symptoms of POA. At younger ages, a diagnosis of POA may not matter much since, even though affected women will have fewer eggs, they still are well above a threshold that denotes infertility. But once they get into their 30s, this threshold is often reached, and expensive fertility treatments become the only option.

As offered here at CHR and online, What’s My Fertility? is a second opinion program, which allows for definition of whether young women are or are not at risk for POA or already demonstrate evidence of POA. Most women, of course, are not at risk and, mostly, can stop worrying once they have been cleared by What’s My Fertility?.

Roughly 20-25% of women will, however, demonstrate risk factors. This does not mean that they all will develop POA (only ca. 10% do); it, however, does mean that, going forward, these young women need to be monitored longitudinally, so those who really are on the verge of developing POA are diagnosed as early as possible. They then at still young ages can be given the choice of either completing their families early or freezing their eggs. As noted above, the younger eggs are at time of freezing, the higher their pregnancy chances. With better pregnancy chances per egg, fewer also need to be frozen.

DISCLOSURE: CHR investigators developed this program and received a U.S. patent for the diagnostic algorithm feeding it.

Some of CHR’s physicians, indeed, screened their own daughters through this program. If you have daughters or granddaughters in their late teens or early 20s, you should, too! CHR sees almost daily new patients with POA who almost uniformly report stories like this: They initiated oral contraceptives during those late teens to early 20s, and never went off until recently, now in the mid- to late 30s, after reaching the conclusion that they wanted to conceive. When conception did not happen, their gynecologist’s testing to everybody’s surprise revealed high follicle-stimulating hormone (FSH) and/or low anti-Müllerian hormone (AMH). In other words, a diagnosis of POA was made. Their uninterrupted long-term use of hormonal contraceptive had covered up even the occasional symptom that, otherwise, might have led to earlier diagnosis.

Before placing young women onto hormonal contraceptives, we, therefore, always advise colleagues, either on their own or through What’s My Fertility?, to assess their young patients for risk toward POA. Once a young woman is identified as “at risk,” we generally advise against hormonal contraceptives since they hide the even minimal symptoms of the condition. If there is no good alternative to hormonal contraceptives in a given patient, then her contraceptive coverage should be interrupted annually by a two-month wash-out period, and retesting of the woman’s ovarian reserve to make sure her values have not fallen off her age-specific curve, should be performed.

CHR offers physicians access to this program for free. Gynecology, adolescent medicine and general practice medical offices all around the world are welcome to apply at no cost for designation as What’s My Fertility? centers by calling 646-882-0800 or writing to [email protected]

This is a part of the January 2018 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.