Influence of 5-HTTLPR variants in the SLC6A4 gene over pregnancy outcomes among recipients of donated eggs.

Abstract

Serotonergic activity is regulated by serotonin transporter gene (5-HTT) that is occasionally expressed in migratory cells inside endometrial tissue during early pregnancy decidua. A serotonergic local network has been proposed to be an important key player acting locally in female genital tracts and being even more interesting target of study since it has been reported that 5-HT transporter gene (SLC6A4) is expressed in mammalian oocytes and embryos. SLC6A4 gene variation suppose an interesting target marker for assess the effect of this serotonergic activity on in vitro fertilization (IVF) treatments outcome. Recipients undergoing egg donation IVF treatment have been selected to study the influence of this polymorphism in treatment success rates and related pregnancy outcome. Results: Distribution of genotypes frequencies were in Hardy-Weinberg equilibrium except for non pregnant women. Recessive model for L allele was performed and Fisher exact test showed different genotype distribution [p=0.00698] between chemical pregnancy loss group and clinical pregnant recipients (0.79 vs 0.26). Logistic regression model showed a strong association [OR=12.89 p= 0.0007 (2.47-67.23) 95%] between chemical pregnancy loss and LL genotype. Although recipients of early spontaneous miscarriage group showed higher frequencies of LL genotype too, there were no statistical differences compared to clinical ongoing pregnancy recipients. Conclusions: A strong association between long homozygous genotype and the occurrence of early pregnancy loss has been observed. Higher transcriptional profile of L/L SLC6A4 gene variant could influence the regulation of serotonin uptake during decidualization, when the serotonin receptor is occasionally transcribed at low levels. It could affect serotonine extracellular regulation and could be related to impaired events that affects to the normal endometrial development.