With increasingly older women striving to conceive with use of their own eggs, IVF practice – urgently - must be reconsidered
By Norbert Gleicher, MD, Medical Director and Chief Scientist, at The Center for Human Reproduction (CHR) in New York City. He can be contacted though The Reproductive Times or directly at either ngleicher@thechr.com or ngleicher@rockefeller.edu
Even our own staff at the Center for Human Reproduction (CHR) had a hard time believing our center’s recently completed 2024 IVF outcome analysis: Once again, in only one year between 2023 and 2024, the CHR’s median patient age had increased by a full year from age 44 to age 45 (in the preceding year it had advanced from 43 to 44 years). In other words, over half of our patients were above age 45. This stands in stark contrast to a steady median age of around 36 years for all U.S. IVF clinics reporting to SART and CDC over the last decade.
This article addresses the author’s believe that his center’s very rapidly increasing median age of patients undergoing autologous IVF cycles over recent years very obviously represents a national trend, which is widely overlooked because an overwhelming majority of U.S. IVF clinics after ages 42-43 years still refer patients automatically into third-party egg donation, thereby artificially maintaining the national median age of autologous IVF cycles around age 36. This interpretation of national IVF cycle data is also supported by the fact that in the same time period third-party egg donation cycle in the U.S. percentage wise increased more rapidly than autologous IVF cycles.
Building on this observation, the article then concludes that, considering the fact that this trend is likely to continue, it appears high time for IVF clinics in the U.S. (and elsewhere) to learn how to treat older patients with use of autologous oocytes and to change the current practice of advancing infertile women automatically into third-party egg donation after ages 42 to 43.
A little bit of background
Birth rates around the world, except in Africa and certain other underdeveloped regions, are declining. In some highly developed countries, like Italy, Spain, South Korea, Japan, and even mainland China, the decline is reaching economically threatening levels. Recent headlines in the U.S. press have pointed out that the U.S. is also close to missing replacement levels. However, within this overall decline in birth rates, one unique finding may come as a surprise: Birth rates in older women are on the rise. More specifically, pregnancies and deliveries among women aged 45 to 49, and even above 50, have been significantly increasing. This trend in the oldest age group is almost exclusively the result of the growing use of donor-egg cycles.
FIGURE 1. Delayed childbirth, the principal reason why women who are having children are getting older
The principal reason why the U.S. and many other countries face such contradictory demographic trends is the fact that women are delaying childbirth. The later they start trying, the more likely it is that by that time, they will have developed a fertility problem. Figure 1 demonstrates the increase in age at first birth and, cumulatively, for all births.
As is apparent from the figure, first and cumulative births since 2017 follow parallel curves. However, these societal developments not only increase infertility problems — they also contribute to obstetrical and neonatal complications, as pregnancy-related issues increase with maternal age. Caring for older women during pregnancy is, therefore, increasingly becoming a subspecialty within perinatal medicine. In major institutions, this involves teams of obstetricians and physicians from various medical specialties, depending on the needs of individual patients (1).
Why, then, haven’t ages of U.S. patients undergoing IVF cycles significantly increased?
While everyone agrees that women are having babies at more advanced ages, and that infertility is therefore on the rise (though there are, of course, other contributing factors), how is it that the median age of women undergoing IVF cycles in the U.S. (i.e., using their own eggs) has not significantly changed over the years and has remained stable at around 36 years? The CDC reported an average patient age of 36.3 years for 2022, the most recent year for which data is available (2).
This, of course, stands in stark contrast to our center’s experience, especially over the last two years. In 2023, for the first time, our median patient age surpassed 44. And, even more remarkably, as we just discovered, in 2024 — in just one year — our median age rose to 45 years (see Figure 2).
FIGURE 2. Age distribution of the CHR’s IVF patients in 2024 *
Despite two consecutive years of unusually pronounced increases in median ages, 2024 was also the second year in a row that the CHR improved ongoing pregnancy rates in this patient population: For several years until 2023, the average ongoing clinical pregnancy rate in this patient population had been around 8%. In 2023, we for the first time saw an increase to 10%, and in 2024 data we just received demonstrated that the ongoing pregnancy rate even further increased to 12%, - a 33% increase in clinical pregnancy rate over the last two years and a quite remarkable outcome improvement, considering the age of this patient population.
The extremely obvious age difference between the national U.S. and the CHR patient age data, of course, raises the question how this discrepancy can be explained? The answer is likely multifactorial, but one conclusion appears unavoidable: The CHR’s patient population going through autologous IVF cycles is radically different from the average U.S. patient population (and likely average patient populations in other countries as well).
This is, of course, is not a new discovery since as a “last resort center” with over 90% of patients consulting with the CHR after having failed elsewhere, and often repeatedly and at several IVF clinics. It has been apparent for many years that the CHR serves a much more adversely selected patient population than practically all U.S. IVF clinics (imagine how well we would do if patients presented to our center earlier!!!). What we, however, did not understand until very recently is that this difference in unfavourably in potential prognosis in recent years appears to have grown with increasing velocity.
And only for one reason: Most U.S. IVF clinics, by now for decades, have simply refused to change their practice pattern of - rather automatically – advancing women above ages 42 to 43 into third-party egg donation. There simply is no other explanation for the national median age of women undergoing autologous IVF cycles in the U.S. having hardly budged in so many years in the face of very obvious increases in ages of infertile women seeking treatments. In parallel IVF autologous IVF cycles numbers after age 42-43 have remained minuscule. The annual CDC report for that reason, reports on the main page only about IVF cycles up to age 42 (2).
The CHR’s plight, on the other hand, came out at the other extreme of the spectrum. As the relative percentage of patients above age 43, especially in most recent years, has been quickly growing, the CHR became known worldwide as one of the very few IVF centers where infertile women - even at more advanced ages - would still get serious treatment attempts with use of their own eggs, offering surprisingly reasonable pregnancy and live birth chances (we in 2023 for the first time reached a 10% ongoing clinical pregnancy rate for women who produced at least 1 embryo in their cycle; by 2024 – as noted above - we reached a 12% ongoing clinical pregnancy rate, considering the patient population at the center, an unimaginably excellent outcome.
This number is that more astonishing, considering the fact that many among the relatively few patients who still undergo some of those exceedingly rare autologous IVF cycles above ages 42-43 at some fertility clinics, in reality receive only “alibi cycles,” defined as exactly what the name indicates: Pressured by their patients, many colleagues who, in principle, still believe that autologous IVF cycles above age 42-43 are mostly futile, will agree to such cycles, but then really only go through the motion, unconsciously or consciously wanting to prove to the patient that they were correct in recommending third-party egg donation. Patients then end up receiving the same kind of IVF cycles the clinic uses in younger women, and that – of course – makes little sense!
Which brings us to another important question: Why has most of the IVF field stuck to the notion that autologous IVF cycles above age 42-43 are not worth it? This notion is difficult to understand, especially since it has dictated practice now for decades. As one of the last still in clinical practice remaining first-generation IVF investigators, I still remember that in the very early days of IVF, clinics refused patients over age 38 because reported pregnancy rates, which even under that age were still very low, above age 38 were basically zero. Imagine if, at that point, the IVF field had decided to send every woman above age 38 into egg donation; where would the IVF field find itself today?
The argument must, therefore, be made that the apparent lack of interest in pursuing autologous IVF cycle in women above ages 42-43 is self-defeating for the IVF field because – if one does not try – where does one learn?
Current third-party egg donation practice in this country (and in many other regions of the world where egg donation is allowed), therefore, makes little sense and one must, therefore, also ask, what other motivations may be behind this seemingly unchanging practice? And any answer to this questions – unfortunately and unavoidably – makes us dip us into the weeds of IVF as a business proposition because donor egg IVF cycles are the by far most profitable IVF cycles for IVF clinics. They also, since establishment of frozen egg banks, have become the logistically most simple cycles to manage, and last but not least, they also produce the highest satisfaction levels for treating physicians because they – of course – produce the highest pregnancy and live birth rates. They, however, also deprive infertile women of genetic motherhood!
This practice pattern also causes immense harm and pain to many patients who for religious or what they consider moral and/or ethical reasons cannot pursue donor eggs or who simply are not ready to give up on their genetic motherhood (not infrequently a sentiment even stronger expressed by the male than the female partner).
Recognizing a patient’s almost complete right to self-determination in making medical decision, it is difficult for us at the CHR to understand how patients, if they really are not yet ready to give up on their own eggs, can be intimidated and/or strong-armed to pursue egg donation or can be appeased in an “alibi cycle”.
That this is becoming an increasing problem, is no longer deniable. The time, therefore, appears to have come, to encourage a special research effort into how to improve autologous IVF cycle outcomes in women above ages 42-43. Considering above-noted demographic changes this country is undergoing and the increasing value other governments are now attributing to IVF births in their countries considering declining birth rates, it seems high time for the U.S. to offer at least this kind of research support for IVF. Mr. President we need your help!
References
1. Newman RA, Esakoff TF. Contemporary OBGYN.net. November/December 202418-21
2. CDC. 2022 Assisted Reproductive Technology (ART) Report. https://www.cdc.gov/art/php/national-summary/index.html