Understanding Older Women with Diminished Ovarian Reserve (DOR)

Diminished ovarian reserve (DOR) occurs when a woman’s ovaries lose their reproductive potential, which can cause infertility. DOR usually occurs around menopause, but the rate of decrease can vary from woman to woman.  Older women with diminished ovarian reserve (DOR) present perhaps the most daunting of all patient populations that fertility specialists must deal with. All women as they age ultimately will possess very low numbers of eggs to work with, but usually prior to age 42 the egg cohort is sufficient to expect reasonable outcomes.  There are, however, women in their 40s who still experience an acceleration of ovarian aging and will manifest egg numbers lower than even they ought.

It is important to realize that not all women with hormones suggesting low egg reserve (high FSH, low AMH) will ultimately prove to be “low-responders”. These hormones are merely gauges to prognosticate egg reserve, and there is considerable wiggle room in these prognostications. I have seen women with AMH values of 0.5 ng/mL produce anywhere from 2 to 12 mature eggs.  Therefore the best indicator of response in any given monthly IVF cycle is either the current number of antral follicles present or the number of oocytes retrieved in recent previous IVF cycles, not the FSH or AMH levels.

I will now address a few questions that arise in the course of treating older DOR patients.

  1. Should I wait for a “better” month to start my IVF cycle?

This depends on several factors. If your antral follicle count is lower than it has been in the recent past by at least 50%, then it would make sense to consider this a randomly “off” month for you, and wait a month to reassess. Your count should bounce back. For this reason, I often have patients take a month off after an IVF cycle, even if there are no cysts present, because it is likely their yield will be better after a month to re-establish their baseline.  There are fertility centers that establish an arbitrary day 2 or 3 FSH cut-off value, perhaps 15 mIU/mL, to decide if they will allow a patient to cycle that particular month. There is no data to suggest that an idiosyncratic monthly FSH value holds specific prognostic value for that month, therefore I do not consider this a useful adjunct in deciding when to start. It would be much more relevant to use the monthly antral follicle count to make any such decision.  On the other hand, I do not think that one should wait too long for an “ideal” month to show up. Each month that passes is a month where egg quality and quantity can go down, so a delay of no more than one or two months at the most should be considered.

  1. What stimulation dosage should be used?

There is a general supposition, although controversial, that standard IVF stimulation places an undue amount of stress on developing eggs and can increase the rate of egg abnormality. If it’s all about getting one good egg, then wouldn’t a mini-IVF type approach be advantageous for everyone?  In short, no. I suppose this may have had more relevance many years ago when it was more common to use gonadotropin dosages twice as high as what we now consider standard. The simple truth of the matter is that a low-stimulation IVF approach, along the lines of what has been developed by Dr. Keiichi Kato in the 1990s at his Kato Ladies Clinic in Tokyo, has been demonstrated to yield significantly lower success rates across the board.  This low stimulation approach was not developed to yield better quality eggs but rather to minimize their rates of severe ovarian hyperstimulation. Low stimulation indeed works for this purpose, but the rates of ovarian hyperstimulation even with standard stimulation dosages and conventional safeguards are also very low, usually less than 1%.  Therefore, although it might be somewhat more user-friendly, for most patients…. even those with low egg reserve, appropriate stimulation with more standard dosages is optimal for success. A mini-IVF type approach, in my opinion, should be reserved for patients with truly very low egg reserve because they will likely yield the same number of eggs no matter how high or high low the gonadotropin dosages are.

In future blogs, I shall address protocol regimens, when the transfer should occur, and whether or not PGS should be done.

If you feel that you might have DOR and want to discuss this in further detail or have any questions now and would like a consultation, we are excited to announce that Sher Fertility Institute New York is offering telemedicine consultations for new and established patients.  Schedule your appointment by contacting Sher Fertility Institute New York at 646-792-7476 or click here to schedule an appointment.