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Background  Both follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) are widely used to assess the ovarian reserve in women for in vitro fertilization (IVF). However, studies also showed that both AMH and FSH are significantly associated with age: as age increases, AMH decreases and FSH increases. This study aims to investigate the mechanism of age effect on IVF live birth rate, particularly through mediation and interaction by AMH and FSH.    Methods  We conducted a retrospective cohort study of 13970 IVF cycles collected by eIVF from 2010 to 2016. A series of logistic mixed models were used to estimate the association of live birth and AMH (or FSH). The mediation effects and proportion mediated, were quantified by our previously proposed mediation analyses. We further investigated the FSH-modified mediation effects on live birth rate through AMH, accounting for the nonlinear age effect.    Results  Our analyses showed that age effect on live birth was mediated more by AMH than by FSH (18 vs. 6%). The mediation effect through AMH can be further modified by FSH level regardless of women’s age.    Conclusions  In summary, mediation model provides a new perspective elucidating the mechanism of IVF successful rate by age. The majority of the age effect on live birth rate remained unexplained by AMH and FSH, suggesting its importance and independent role in IVF.

Age effect on in vitro fertilization pregnancy mediated by anti-Mullerian hormone (AMH) and modified by follicle stimulating hormone (FSH)