Abstract
BackgroundImportant candidate genes involved in the ovarian response to exogenous FSH are the estrogen receptor genes (ESRs), since the effects of estrogens on follicle growth, maturation and oocyte release. It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, thus preventing excessive wear of the patient. Inspired on this information we aimed to analyze four different polymorphisms in the estrogen receptor genes ESR1: rs2234693/T-397C (PvuII) and rs9340799/A-351G (Xbal) and ESR2: rs4986938/G1082A (RsaI) and rs1256049/A + 1730G (AluI), and their association with assisted reproduction outcomes in Brazilian women that underwent in vitro fertilization (IVF).MethodsA cross-sectional study was performed involving 136 infertile women less than 39 years of age with normal ovarian reserve. Patients were divided according to the same COH protocol for statistical analysis. The Taqman assay was used for PvuII and XbaI of ESR1, and RsaI and AluI of ESR2 genotyping. Serum estradiol and FSH were measured by Elisa assay.ResultsThe PvuII (ESR1) TT and RsaI (ESR2) GG genotypes were associated with a longer induction period and higher doses of medication (p < 0.03). The XbaI (ESR1) AA genotype was associated with better COH results, including a larger number of follicles, mature oocytes, embryos, and good quality embryos (p < 0.05). The AluI GG genotype showed an association with the Ovarian Hyperstimulation Syndrome (OHSS) (p = 0.03). According to the haplotype analysis of ER1 (PvuII/XbaI), we demonstrated that the CA combination increases by 0.68 the number of good quality embryos while the TG decreases it by 0.71 (p = 0.04).ConclusionER polymorphisms have an association with the assisted reproduction outcomes in Brazilian women.
Highlights
Infertility is a health problem that affects 15–20% of couples at a reproductive age [1], with several medical, emotional, and social implications
With regard to the controlled ovarian stimulation response, we considered as Poor response < 3 growing follicles or less than 4 collected oocytes according to the European Society of Human Reproduction and Embryology (ESHRE) consensus (2011) on the definition of poor responders by Ferraretti et al [18], Satisfactory response between 4 to follicles, Hyperresponse between to follicles, and Ovarian Hyperstimulation Syndrome (OHHS) with or more follicles or/and clinical symptoms such as ascites, hematological changes, pleural effusion, and liver abnormalities according to the classifications proposed by Golan et al [19]
Characteristics of patients and controlled ovarian hyperstimulation (COH) outcome A total of 136 women were included in this study once they meet the inclusion criteria
Summary
Infertility is a health problem that affects 15–20% of couples at a reproductive age [1], with several medical, emotional, and social implications. Low response rates can lead to cycle cancellation, high responses are troublesome as they can trigger a serious medical iatrogenic condition – the ovarian hyperstimulation syndrome (OHSS) This unpredictable de Mattos et al Journal of Ovarian Research (2014) 7:114 individual variability in the ovarian response to COH represents one of the most challenging issues of IVF treatment safety. It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, preventing excessive wear of the patient Inspired on this information we aimed to analyze four different polymorphisms in the estrogen receptor genes ESR1: rs2234693/T-397C (PvuII) and rs9340799/A-351G (Xbal) and ESR2: rs4986938/G1082A (RsaI) and rs1256049/A + 1730G (AluI), and their association with assisted reproduction outcomes in Brazilian women that underwent in vitro fertilization (IVF)
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