Effect of ESR1 and ESR2 polymorphisms on ovarian response in assisted reproductive technology cycles: a systematic review and meta-analysis

Abstract

Abstract Genetic factors contribute to poor ovarian response (POR) in assisted reproductive technology cycles, with estrogen receptor gene polymorphisms ( ESR1 and ESR2 ) being explored as a causative factor in many studies. However, there is no systematic review and meta-analysis conducted on these studies to assess the association of these receptor polymorphisms on POR. This systematic review and meta-analysis evaluated the association between ESR1 and ESR2 single nucleotide polymorphisms (SNPs) and ovarian response in women undergoing controlled ovarian stimulation (COS). The study was registered with PROSPERO and conducted according to PRISMA guidelines. 11 eligible studies were included. Among the various SNPs, meta-analysis focused on ESR1 rs2234693 and rs9340799, and ESR2 rs4986938. ESR1 rs2234693 C‑allele carriers showed significantly increased odds of POR in both heterozygote (pooled log odds ratio (LOR) = 0.99, standard error (SE) = 0.213; odds ratio (OR) = 2.69, p  < 0.001)) and dominant models (LOR = 1.69, SE = 0.449, OR = 5.41, p  < 0.001), with consistent findings in European populations. Associations for ESR1 rs9340799 and ESR2 rs4986938 with POR showed substantial heterogeneity. Overall, ESR1 rs2234693 may be associated with POR, in women undergoing COS. Further large-scale studies with appropriate study designs are warranted to clarify the potential role of ESR polymorphisms in COS outcomes.