Stimulation protocols for low response patients rationale

Women are born with a certain number of eggs, they never make any more eggs their entire life.  At the time of puberty when women start menstruating they have lost over 90% of their eggs having a few hundred thousand remaining.  Each month with menses a group of eggs start to develop, only one of which goes on to ovulate.  If multiple eggs develop a multiple pregnancy can occur. The remaining eggs that do not mature form scars in the ovary.  The whole cohort of eggs is lost each month.  Being on birth control pills does not prevent this programmed loss of eggs.  As the eggs get older they accumulate genetic/chromosomal errors in response to different environmental insults, i.e., free radicals, alcohol, caffeine, tobacco, chemotherapeutic drugs and other toxins.  As a result of the decreased number and quality of eggs fertility rates decrease over time.  At age 35 fertility rates drop significantly, by age 40 rates drop drastically.  The great majority of women older than 42 will require donor eggs to achieve healthy ongoing pregnancies.

Since the very first IVF pregnancy there have been countless different stimulation protocols to try and get women to produce more and better quality eggs.  In my reproductive medicine career spanning almost 30 years, I have reviewed at least 30 different protocols none of which have ever been shown to significantly improve the number and quality of eggs.  The only medication that has some evidence supporting a benefit to egg quality has been growth hormone, and this is questionable.  Because we have not been able to significantly improve egg number and quality in the low response patient, the stimulation strategy has changed over the last several years to stimulating patients with the least costly option, i.e. low dose gonadotropin protocols or even oral medications.  While there is a cost rational for this, in these patients it is critical to get as many eggs as possible. For that reason, in most cases, I will stimulate the patient with a high dose protocol to try and get every egg that is coming along to develop.  In the case of repeated IVF failures in the low response patient, the only real solution is that of either donor egg or donor embryo IVF whereby younger, healthier eggs are used.

Kevin L. Winslow, M.D.
Director for Florida Institute for Reproductive Medicine