Abstract
PURPOSE: Ovarian stimulation (OS) is a critical component of assisted reproduction techniques (ART), in which gonadotropins are administered to induce follicular development and maturation to improve the chances of conception. It has been reported that ovarian response to OS can be affected by certain genetic factors. This study explores the relationship among SNVs of AMHR2 (c.-482A > G/rs2002555 and c.1749C > T/rs2071558), basal FSH and estradiol levels, gonadotropin dosage, and ovarian response to identify predictive indicators. METHODS: Oocytes were retrieved from 684 infertile Chinese women treated with ART. All patients were divided into three groups: low (< 6 oocytes), normal (6-14 oocytes), high response (> 14 oocytes). Genotyping of c.-482A > G and c.1749C > T were detected on the Sequenom iPlexMassARRAY platform. Transcriptional function of c.-482A > G variant in AMHR2 promoter was validated by Luciferase Reporter Assay in 293 T cells. RESULTS: Our results indicated that both c.-482A > G and c.1749C > T SNVs were associated with basal FSH levels (p = 0.047 and 0.023, respectively). Genotype and allele distribution frequencies of AMHR2 c.-482A > G were significantly different among the three ovarian response groups (p = 0.007 and 0.009, respectively). AMHR2 c.-482A > G was associated with the number of total oocytes retrieved (p = 0.011). FSH was associated with the ovarian response (p < 0.001). Validation by Luciferase Assay indicated AMHR2 c.-482A > G mutation in the promoter region affect the promoter activity. CONCLUSION: AMHR2 c.-482A > G SNVs may be involved in the mechanism of the ovarian response to OS. AMHR2 c.-482A > G SNVs can interact with basal FSH levels, and jointly serve as predictor of the ovarian response to OS.