OBJECTIVE

To evaluate the association between the LHCGR rs2293275 (N312S) genotype and ovarian aging phenotypes in Han Chinese women, focusing on diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI).

STUDY DESIGN

This multicenter population-based study included 1,240 women aged 18-40 years diagnosed with DOR (n = 711) or POI (n = 529), alongside 72,846 ethnically and regionally matched controls from the Han Chinese Genomes Database (PGG.Han). Genotyping of rs2293275 was performed, and clinical data (menstrual history, hormonal profiles, maternal menopause age, and ART outcomes) were analyzed.

MAIN RESULTS

The AA genotype frequency in the ovarian aging cohort (1.85%) was significantly higher than in the general Han population (0.62%, OR 3.04, 95% CI 1.99-4.64, p < 0.001). AA carriers exhibited earlier POI diagnosis (25.5 ± 6.4 vs. 32.0 ± 5.1 years in GG carriers, p < 0.001) and maternal menopause (41.6 ± 3.3 vs. 47.8 ± 4.1 years, p < 0.001). In controlled ovarian stimulation cycles, AA carriers demonstrated reduced ovarian sensitivity (OSI: 3.59 vs. 1.21 in GG, p = 0.019) despite comparable gonadotropin doses.

CONCLUSIONS

The LHCGR rs2293275 AA genotype is strongly associated with accelerated ovarian aging in Han Chinese women, highlighting its potential as a biomarker for early identification of high-risk individuals. While these findings underscore genetic contributions to ovarian dysfunction, further mechanistic studies are needed to establish causality and optimize clinical translation.

TRIAL REGISTRATION NUMBER

ClinicalTrials.gov NCT05665010, registered on 2022-11-30.