The success of human reproduction is highly dependent upon the age at which women attempt to conceive. Because of a variety of social reasons this age is progressively increasing worldwide. It is well known that “natural” fertility decreases as the woman’s age advances, while the incidence of miscarriage and the prevalence of embryonic chromosomal abnormalities follow an opposite trend. This relationship is also well demonstrated in the IVF setting, where maternal age is among the strongest predictors of success. Together with a progressive reduction of the ovarian reserve (OR), the process of woman aging also involves egg compromised functional competence.
The OR is complex and is influenced by age, genetics, and environmental variables. It is challenging to predict an individual’s OR decline, but as REIs we are often asked for advice about fertility potential and/or recommendations regarding the pursuit of fertility treatment options.
Currently the OR is best determined by serum anti-Müllerian hormone (AMH) and day 3 FSH levels and/or ultrasonographic determination of antral follicular count (AFC) before controlled ovarian stimulation for IVF. By determining the OR reserve, the most appropriate stimulation protocol and gonadotropin dose can be tailored specifically to each woman enabling so-called “individualized treatment” in line with the personalized treatment concept. As in IVF the aim is to harvest an appropriate number of mature and fertilizable eggs, in a way the OR assists in giving the patient realistic expectations regarding results and to some limited extent the chance of pregnancy.
Importantly, while there is general agreement that AMH is a valid predictor of the ovarian response to controlled ovarian stimulation, so far, AMH is less optimal in prediction of natural (“spontaneous”) pregnancy and live birth after ART. There are no mathematical thresholds but typically an average response is associated with AMH levels over 1.5 ng/ml, higher levels over 3 ng/ml may identify high responders, and levels under 1 ng/ml will indicate a low or poor response.
A common challenge within the clinical scenario is: when a low OR is identified in younger patients is it also associated with accelerated reduction in oocyte quality? In other words, if patients exhibit a quantitative decline in OR earlier than expected, do they also exhibit evidence of accelerated ovarian aging i.e. a qualitative decline as well? A recent IVF study has shown that young women <38 years with evidence of accelerated follicular depletion, either by low AMH or evidence of low oocyte yield (poor response), exhibit equivalent blastulation rates, aneuploidy rates and live birth rates per euploid embryo transferred as age-matched controls with normal AMH and response. In other words, compared to normal responders, a fertilized oocyte retrieved from a young patient with low OR is no less likely to form a quality blastocyst, be euploid or produce a live birth. These interesting data provide evidence that the lower live birth rate observed in younger poor responders is due to the quantitative challenge of starting with fewer oocytes and is not due to an additional qualitative penalty of poor oocyte development in the laboratory or after transfer. Consequently, younger women with low OR can be directed to embryo accumulation strategies (banking) when considering their family building plans.
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