Association of FSHR gene polymorphisms with poor ovarian response in patients undergoing IVF: A systematic review and meta-analysis

Abstract

Background: The results of studies on the association between polymorphisms in the FSHR gene and the risk of POR undergoing IVF have been inconsistent with each other, so we conducted a meta-analysis of all the available studies to explore the association between polymorphisms in the FSHR gene and the risk of POR.

Methods: Literature that met the inclusion criteria was collected by searching six electronic databases and basic data from included studies were extracted. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between follicle-stimulating hormone receptor (FSHR) gene polymorphism and poor ovarian response (POR) risk. Begg's and Egger's tests were used to determine whether there was publication bias, and sensitivity analysis and TSA analysis were used to verify the stability and reliability of the results.

Results: We included 24 articles, 22 of which explored rs6166, including 2,206 cases and 3,897 controls. 6 articles explored rs6165, including 444 cases and 875 controls. Under additive, heterozygote, and dominant models, rs6166 was significantly associated with POR (S vs. N: OR = 1.29, 95 % CI = 1.05-1.59, P = 0.017; NS vs. NN: OR = 1.33, 95 % CI = 1.02-1.74, P = 0.038; NS + SS vs. NN: OR = 1.38, 95 % CI = 1.04-1.84, P = 0.025). In ethnicity-based subgroup analyses, the additive, homozygote, heterozygote, and dominant models increased Asian POR risk. Among the five genetic models, rs6165 was significantly associated with POR (T vs. C: OR = 1.64, 95 % CI = 1.25-2.16, P = 0.000; TT vs. CC: OR = 2.76, 95 % CI = 1.43-5.32, P = 0.003; CT vs. CC: OR = 1.58, 95 % CI = 1.19-2.10, P = 0.001; TT vs. CC + CT: OR = 2.32, 95 % CI = 1.67-3.23, P = 0.000; CT + TT vs. CC: OR = 1.80, 95 % CI = 1.22-2.65, P = 0.003). In ethnicity-based subgroup analyses, all five genetic models increased the risk of POR in Caucasians.

Conclusion: According to the current meta-analysis, the rs6166 S allele was significantly associated with an increased risk of POR, especially in Asian populations. The rs6165 T allele was significantly associated with an increased risk of POR, especially in Caucasian populations.

Keywords: FSHR; IVF; Meta-analysis; POR; Polymorphism; Rs6165; Rs6166.