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Customizing Ovarian Stimulation in “Poor Responders”
by Geoffrey Sher, M.D.
It is age rather than FSH level which is the predominant determinant of egg/embryo quality. At age 30 yrs, approximately 30% mature eggs/embryos will have structural and numerical chromosome abnormalities (aneuploidy) at age 40yrs the incidence is about 60%, at age 43yrs-+/- 75% and at 45yrs, about 85%. So, if four (4), “healthy looking” embryos were to be transferred to the uterus of a woman of say 43yrs, only about one could be expected to be chromosomally normal. A progressive increase in the incidence of embryo aneuploidy lies at the root of declining IVF success rates, increasing miscarriage rates and the increase in the incidence of birth defects such as Trisomy 21 (Down's syndrome) with advancing age. As an example, at age 43ys, under the very best circumstances, the IVF birth rate would be 10- 20% per cycle. Contrast this with a 50-60% success rate in a woman of similar age, who undergoes embryo transfer with embryos derived from a young fertile egg donor.
Often, in spite of this realization, the desire to give birth to progeny that carry the mother’s own genetic code drives many women to try with their own eggs as long as the opportunity still avails itself to them.
In an attempt to increase the number of follicles/eggs produced by older and sometimes younger women with “ovarian resistance”, some practitioners advocate the use of the so-called GnRHa (e.g. Lupron) “microflare (MCF) protocol”. The MCF protocol involves the administration of GnRHa therapy along with gonadotropins, virtually at the same time. The stated benefit of this approach is that it causes the woman’s own pituitary gland to release large amounts of FSH immediately, adding to the injected dosage of FSH and augmenting or even synergizing the follicular response. The problem is that there is no way to cause the administered GnRHa to selectively elicit an FSH response. LH is unfortunately also released along with FSH, in high concentrations in the pelvic blood system.
The target of LH is largely the connective tissue (stroma/theca) in the ovaries which responds to LH by producing male hormones (predominantly, testosterone).