The impact of genetic variants in folliculogenesis and steroidogenesis pathways on ovarian response: a post hoc multicenter multiethnic cohort study

PURPOSE: To evaluate whether genetic variants in genes involved in folliculogenesis and steroidogenesis are associated with ovarian response in Vietnamese and Caucasian women undergoing IVF/ICSI.

METHODS: This was a post hoc analysis of a prospective multicenter study including patients < 38 years old with normal ovarian reserve markers undergoing their first or second ovarian stimulation cycle. All patients were genotyped for 67 single nucleotide variants (SNVs) and underwent ovarian stimulation with a fixed 150 IU rFSH dose. Primary outcomes were the number of oocytes retrieved, hypo-response (< 10 oocytes), follicular output rate (FORT), follicle-to-oocyte index (FOI), and steroid hormone levels on trigger day.

RESULTS: A total of 368 patients were included. Multivariable regression identified novel associations between ovarian response and SNVs in GPER (rs3808350), ATF7IP (rs3213764), YWHAZ (rs10098502), COMT (rs4680), TCN2 (rs1801198), GNA11 (rs8092), APLP2 (rs2054247), AP4E1 (rs4775912), SMARCA4 (rs1122608), IGF1R (rs2016347), DENND1A (rs2479106), and BMP15 (rs3897937). Previously reported associations with LHB rs1056917, AMH rs4807216, and AMHR2 rs2002555 were also confirmed.

CONCLUSIONS: This study supports a role for multiple genetic variants in modulating ovarian response to stimulation, providing a basis for future work toward personalized ovarian stimulation protocols. However, the post hoc design limits causal inference, and prospective validation is warranted.