Diminished Ovarian Reserve: The Sher Philosophy

Dr. Geoffrey Sher and Dr. Drew Tortoriello - December 16, 2021
Diminished Ovarian Reserve: The Sher Philosophy

 

It appears from my vantage point that the proportion of patients suffering from diminished ovarian reserve is on the increase.

This increase is likely due to several reasons:

  1. Social/lifestyle: Many women are deliberately delaying their childbearing to focus on other aspects of their life, including the furtherance of their education and their career objectives.
  2. Environmental issues: As technology advances, we are constantly being exposed to new food additives, new medications, and even potentially more radiation from perceived friendly sources.

All infertility patients have heard the mantra at one point: “We only need one good egg”. It is indeed true that the rate-limiting step to achieving success in most infertility treatment journeys is the acquisition of a healthy, or chromosomally normal, oocyte.  Each oocyte during its maturational process must discard half of its chromosomal content, going from 46 chromosomes (“diploid”) to 23 chromosomes (“haploid). The key processes involved in this transformation occur very late in the lifespan of the egg, essentially within a 36-hour time span following the mid-cycle surge of LH in natural cycles or the hCG  “trigger” shot in IVF cycles. Unfortunately, the lattice-like structures that attach and align the chromosomes in each oocyte become faulty and fragile as a woman ages, and this leads to the release of mature eggs with abnormal numbers of chromosomes. These eggs will yield poor outcomes, either no pregnancy or a pregnancy that ends with miscarriage. Given the role of aging upon egg DNA stability, it is no surprise that younger women are able to more frequently produce normal eggs. Therefore younger women in their twenties to mid-thirties, are more likely to conceive with any fertility treatment even if their egg reserve is considerably lower than their age would suggest.  

Prematurely low egg reserve, therefore, does not apparently equate to prematurely poor egg quality. In general, we know this to be true because younger DOR patients do much better than older DOR patients across all fertility treatments. But if the reason for DOR stems from ovarian injury of some sort, such as from cancer treatments (chemotherapy or radiation), one should expect a decrease in both regardless of age. There is also some evidence that the inflammation from endometriosis can exert a similar, although milder effect. In these patients, one must weigh the invasivity of surgery to remove endometriosis against a small benefit in egg quality. 

I recall a patient in her twenties who was referred to me for greatly diminished ovarian reserve with over a year of infertility. Her cycles were irregular and her serum markers for egg reserve were in the menopausal range.  At our first visit, I did a sonogram and saw a single large follicle on one ovary. Her hormone levels showed high estrogen levels, suggesting that this was a genuine follicle. That same day I asked her to take an hCG trigger shot and have well-timed intercourse with her partner. She conceived and now has a son. Obviously her egg that day was a good one! Unfortunately, women older than she would have been much less likely to get the same result. 

The problem of diminished ovarian reserve is a difficult one for fertility specialists to treat. We cannot, at least yet, help a woman running low in her egg reserve to create more eggs. We have to work with what she as yet possesses. And the fewer eggs we can work with in any given treatment, the more difficult it is to achieve success, at least in the fairly expeditious time frame that both patients and their physicians would like to have. The difficulty of the problem often leads both doctors and patients to give up. Sometimes patients are given a perfunctory attempt at IVF, and upon seeing the response is poor, are canceled and directed towards egg donation. Is this the right thing to do? Sometimes. If your menstrual pattern and your hormonal profile are clearly suggestive of menopause or a state near to it, then indeed egg donation is the only ethical and realistic method to conceive a child. Of if you are of advanced age, say 45 or more, egg donation is likely the best first step because, at this age, the quality of the oocytes is so poor that even a plethora of eggs to work with is often not enough to conceive a healthy child. But the majority of patients with DOR are in that grey zone, where the prognosis is not good, but not completely out of reach.  Such patients, in my opinion, deserve a chance. I am happy to note that more and more practices are willing to step up to the plate and work with these patients in a comprehensive and realistic manner. But unfortunately, many more practices choose not to.

We at Sher Fertility Solutions have been working with DOR patients of varying ages since our inception, and have never placed cutoffs upon them that would restrict their ability to get treated.  In other words, we will not force you to wait until you achieve a day 3 FSH value below a certain level before we would initiate a treatment cycle.  Others might.  Doing so does nothing more than to delay you in a vain attempt to reach a “better” month.  When egg reserve is very low, time is of the essence, and no data suggests that months with idiosyncratically lower day 3 FSH values prognosticate for a better outcome.   We also have realistic expectations. We do not expect women with advanced DOR to make many eggs.  Why would we?  Therefore we would not cancel a cycle if an arbitrary follicle threshold has not been reached.  This merely delays you from treatment and bypasses what may be a perfectly good egg or two.  Is it unfair to a patient to put her through an egg retrieval or the IVF process in general if her egg yield will be low, and more broadly, if her odds of success are low?   We are here to counsel you about your options and your odds of success with each option.  We attempt to make each IVF process in the DOR patient as gentle and as minimal in its medications as is possible to achieve the most number of eggs.  Usually, a maximal number of eggs in low-responding patients can be achieved with very minimal amounts of medication.  Moreover, the egg retrieval process can often be done with little to no sedation in patients who have low follicle number, and they can have a retrieval and then immediately go about their lives with no real down time.

In short, women with DOR present a challenge, and we as physicians trained in this field, need to be malleable, creative, and diligent in our approach to this challenge.


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