Ovarian Stimulation for IVF, My Call: One Size Fits All

Assisted reproduction technology is increasingly applied as a treatment mode for couples with both explained and unexplained infertility. The first step in this treatment is the creation of multiple follicles with the purpose of obtaining the oocytes held within these follicles, creating embryos in the IVF laboratory and replacing the embryos into the uterine cavity. Controlled ovarian stimulation is mostly applied by using exogenous FSH. The response of the ovaries to this exogenous FSH exposure demonstrates a high degree of variation.
From a clinical significance point of view the poor ovarian response defined as the yield of less than 4 oocytes is related to a clearly unfavorable prognosis for live birth, although much of this poor prognosis is in fact dictated by female age and not by the low egg number per se. At the other side of the spectrum excessive response arbitrarily defined as obtaining more than 15 oocytes at pick up will increase treatment risks for the patient and may even slightly limit the rates of live birth. It is therefore that many clinicians across the world try to foresee the ovarian response category in order to adjust the stimulation protocol with the expectation that the ovarian response can be brought into the normal range (5-15 oocytes) and that by doing so the prospects of pregnancy as well as the safety for the couple will improve.
Prediction of ovarian response category today is mainly applied by using the Antral Follicle Count or AntiMullerian Hormone in the early follicle phase. Both relate to the number of antral follicles present at any time and the source for the number of dominant follicles that could grow in results to the application of exogenous FSH. As such, these two ovarian response tests (ORTs) have become the standard test for response prediction, although factors such as female age and possibly body weight may add to this predictive information. It may be noted still that predictions will generally be false positive in some 15% of cases, while only 60-70% of true out of the normal range resp0nders will be identified. Basing the FSH stimulation dosage on such predictions will be imprecise practice from the start.
Recent large controlled trials have demonstrated that ORT based individualized dosing of the FSH preparation will not alter the fate of the predicted poor responder but may help in reducing the safety risk of the predicted excessive responder. Unfortunately, the promises of earlier studies that individualized dosing would also affect live birth rates in the ART program as a whole have not been fulfilled. Specifically in predicted poor responders the actual occurrence of a poor response will mean that the couple is in a prognostic unfavorable category. There, the combination of low AMH or AFC and the first cycle poor response may help to decide whether continuation of the ART treatment is really feasible.
The real gain of individualized FSH dosing could be the management of the hyper responding patient. The question then remains whether the AFC will be the prior screening test to select patients to undergo blood sampling for AMH assessment in order to confirm a sufficient risk of excessive response and apply reduced FSH dosage or antagonist co-medicated stimulation protocols. We may sincerely consider whether a standard dosage using an antagonist protocol, with the escape of GnRH agonist triggering in case of excessive ovarian response, with a freeze all strategy as second step, will not be the method to circumvene imprecise dose picking based on response tests with moderate precision.