Association of estrogen receptor and progesterone receptor genetic polymorphisms with recurrent pregnancy loss: A systematic review and meta-analysis

Abstract

ObjectiveEstrogen and progesterone play key roles in the maintenance of pregnancy, and their function is mediated via estrogen receptor 1 (ESR1)/estrogen receptor 2 (ESR2) and progesterone receptor (PGR), respectively. It has been suggested the genetic variations in ESR1, ESR2, and PGR may contribute to recurrent pregnancy loss (RPL); however, the available evidence remains controversial. This meta–analysis aimed to explore the relation of various polymorphisms in ESR1, ESR2, and PGR genes to the risk of RPL. MethodsA systematic literature search was conducted using PubMed and Scopus up to August 2023 to obtain relevant studies. The odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed and pooled with the use of random–effects models to test the associations. ResultsA total of 31 studies with 12 different polymorphisms, including 5 polymorphisms for ESR1, 3 polymorphisms for ESR2, and 4 polymorphisms for PGR, were analyzed in this meta-analysis. Overall, no significant relationship was found between various polymorphisms of ESR1 and ESR2 with RPL in any of the genetic analysis models. PGR rs590688 (C > G) polymorphism was significantly related to the elevated risk of RPL under the dominant (OR = 1.67; 95 %CI: 1.15–2.44), allelic (OR = 1.55; 95 %CI: 1.13–2.12), and GC vs. CC (OR = 1.55; 95 %CI: 1.07–2.23) models. No significant association was identified for other variants of PGR gene. ConclusionUnlike estrogen receptors, variations in PGR rs590688 (C > G) may be linked to the increased risk of RPL. More studies are required to confirm this finding.