Attenuated AMH signaling pathway plays an important role in the pathogenesis of ovarian hyperstimulation syndrome

The aim of this study is to investigate the potential role of attenuated anti-Müllerian hormone signaling in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). To analyze the expression of AMH and its receptors in human follicular fluid (FF) and granulosa cells (GCs), this study included consenting patients with moderate to severe OHSS (n = 83) and non-OHSS patients (control population, n = 108) undergoing IVF/ICSI treatment between March 2013 and March 2014. AMH concentrations in single FF samples from the OHSS patients were significantly lower than concentrations in samples from the control group. A negative correlation was found between the E2 level and the AMH level in single FF samples. Similarly, a negative correlation was found between the FF AMH level and the number of oocytes retrieved. Although the mRNA expression level of AMH was hardly detectable in GCs, the mRNA expression level of AMHR2 in GCs from OHSS patients was significantly lower than the AMHR2 mRNA expression level in the control population. Based on these results, we established a murine model of controlled ovarian hyperstimulation (COH) using AMHR2-down-regulated mice to demonstrate the potential role of AMH signaling in the progression of OHSS. The knockdown of AMHR2 is capable of significantly increasing the ovarian response to exogenous gonadotropins, leading to several major clinical manifestations of OHSS in the murine model. In conclusion, attenuated AMH signaling increases ovarian sensitivity to COH and the incidence of OHSS in individuals undergoes IVF/ICSI.