Clinical Relevance of Combined FSH and AMH Observations in Infertile Women

Abstract

FSH and anti-Müllerian hormone (AMH) are, individually, widely used to assess functional ovarian reserve (FOR) but demonstrate discrepancies in efficacy. How predictive they are combined is unknown. The purpose of this study was to assess predictive values of different FSH and AMH combinations on in vitro fertilization (IVF). FSH and AMH levels in patients were categorized as low, normal, and high, based on age-specific 95% confidence intervals. This allowed for establishment of nine combinations of low, normal, or high FSH/AMH patient categories. With use of various statistical methods, patients in individual categories were then compared in outcomes. We investigated 544 consecutive infertility patients in their first IVF cycles. IVF cycles were managed. Oocyte yields and implantation and pregnancy rates, adjusted for age and fragile X mental retardation 1 (FMR1) genotypes/subgenotypes, were measured. The most notable repeated finding was a strong statistical association of the FSH/AMH high/high category (characterized by abnormally high FSH and AMH levels) with favorable IVF outcomes compared with outcomes for other FSH/AMH variations (4.34 times odds of high oocyte yields and 1.93 times odds of clinical pregnancy). Addition of age to the model only minimally further improved the odds of pregnancy to 2.03 times. The positive association with high oocyte yields, however, turned negative (0.75 times lower yields) with addition of FMR1 to the model for women with FSH/AMH high/high and the het-norm/low FMR1 subgenotype compared with women with the norm FMR1 genotype and other FSH/AMH categories. In the absence of het-norm/low FMR1, abnormally high FSH and AMH, a seemingly contradictory combination, reflects highly beneficial outcomes in IVF compared with the other FSH/AMH categories, suggesting greater importance of FSH in early follicle maturation than currently recognized. The study also confirms adverse outcome effects of het-norm/low FMR1 and, therefore, the gene's importance for reproductive success.