My IVF Cycle Failed – What Went Wrong? Question #6: How much could my elevated FSH and/or low AMH levels have contributed?
Why did my IVF cycle fail?
FSH and AMH levels
This is the sixth in a series of responses to common questions about Failed IVF Treatment.
Women with elevated basal (day 2-4) Follicle Stimulating Hormone (FSH) levels and/or low antimullerian hormone (AMH) levels often have diminished ovarian reserve (DOR). This means that they have a reduced number of eggs left in their ovaries and, as a consequence, are likely to be resistant to controlled ovarian stimulation (COS). Such “poor responders” often will require an aggressive protocol for COS in an attempt to make them yield more eggs at egg retrieval.
This having been said, it is important to realize that basal blood FSH/AMH levels predict the number of eggs present in the ovaries (ovarian reserve) and NOT necessarily the quality of the eggs at ovulation or egg retrieval (ER). So it is that low basal FSH and high AMH concentrations point to a normal or high ovarian reserve, and the likelihood of a high response to a modest protocol of COS. Conversely, a high basal FSH and/or a low AMH suggest a diminished ovarian reserve (DOR) and a blunted response to even high dosage COS.
In an effort to improve their yield of quality (“competent”) eggs at ER, women with DOR are often prescribed strong (high-dosage gonadotropin) protocols of COS. But here is where a word of extreme caution is appropriate: unless COS protocols that lead to increased follicular exposure to Luteinizing Hormone (LH) are avoided (e.g. “flare-agonist protocols,” clomiphene citrate/Humira and high dosages of LH-containing gonadotropins such as Menopur) in women with DOR, follicular growth and egg quality can be severely compromised by resulting high ovarian production of male hormones (androgens) such as testosterone. Moreover, in spite of best efforts, the egg retrieval (ER) will still yield fewer eggs, and this will reduce the odds of ending up with at least one “competent” (chromosomally normal) embryo for transfer. Simply stated, women with DOR require LH down-regulation in advance of initiating COS. Optimally, this requires prior suppression of LH using a combined birth control pill (BCP), followed by administration of an agonist (e.g. Lupron, Superfact, Nafarelin) initiated several days before to the onset of menstruation. This is followed by the initiation of FSH-dominant gonadotropin stimulation (e.g. Folistim, Gonal F, Puregon) as soon as the period begins. Such “Long Down-Regulation Protocols” can often be modified and improved by switching from an agonist to an antagonist (e.g. Ganirelix, Cetrotide, or Orgalutron) as soon as menstruation occurs (agonist/antagonist conversion protocol-A/ACP) and by adding low dose estrogen administration for 7-10 days prior to commencing gonadotropin stimulation (“estrogen priming”).
It is important to recognize that basal (FSH) levels will often fluctuate from month to month. A higher or lower FSH level does NOT mean that the woman will respond better if stimulated with fertility drugs in that cycle. Thus, there is no point in delaying treatment to a subsequent cycle in order to try first to bring down the basal FSH level. It simply won’t help, and will only put an extra burden on an already taxed biological clock. Remember, it is not possible to grow more eggs for recruitment by waiting for the FSH level to drop.
Some doctors advocate using low dosage gonadotropin protocols in cases of DOR, so as to put less stress on developing follicles /eggs. This is really a waste of time in my opinion. It is like saying that if five men cannot move a piano, we should take three of them away so as to put less stress on the piano. It simply makes no sense, and more importantly, it does not work.
So yes indeed, women with diminished ovarian reserve have a higher mountain to climb when it comes to IVF. However, this is more due to the fact that they yield fewer eggs, and NOT because the DOR causes poor egg quality. In addition, DOR compounds with advancing age and the older the woman, the poorer egg quality is likely to be. Dealing with DOR in a young women (under 39) is far more likely to be successful than would be the case for a woman in her mid-forties with a comparable degree of DOR.