title: ESR1 and ESR2 gene polymorphisms are associated with human reproduction outcomes in Brazilian women.
abstract: BACKGROUND
  Important 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).
  
  
  METHODS
  A 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.
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  ER polymorphisms have an association with the assisted reproduction outcomes in Brazilian women.
authors.affiliation: Human Reproduction and Genetics Center - Division of Sexual and Reproductive Healthcare and Population Genetics - Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil. dra.clarissa@uol.com.br.
authors.forename: Clarissa Santiago
authors.initials: CS
authors.lastname: de Mattos
authors.affiliation: Human Reproduction and Genetics Center - Division of Sexual and Reproductive Healthcare and Population Genetics - Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil. camilatrevisan22@gmail.com.
authors.forename: Camila Martins
authors.initials: CM
authors.lastname: Trevisan
authors.affiliation: Human Reproduction and Genetics Center - Division of Sexual and Reproductive Healthcare and Population Genetics - Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil. carlapeluso@yahoo.com.br.
authors.forename: Carla
authors.initials: C
authors.lastname: Peluso
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Collective Health - Faculdade de Medicina do ABC, Santo André, SP, Brazil. adamifernando@uol.com.br.
authors.forename: Fernando
authors.initials: F
authors.lastname: Adami
authors.affiliation: Human Reproduction and Genetics Center - Division of Sexual and Reproductive Healthcare and Population Genetics - Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil. emerson@embryogenesis.com.br.
authors.forename: Emerson Barchi
authors.initials: EB
authors.lastname: Cordts
authors.affiliation: Human Reproduction and Genetics Center - Division of Sexual and Reproductive Healthcare and Population Genetics - Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil. denise.morf@gmail.com.
authors.forename: Denise Maria
authors.initials: DM
authors.lastname: Christofolini
authors.affiliation: Human Reproduction and Genetics Center - Division of Sexual and Reproductive Healthcare and Population Genetics - Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil. caiopb@uol.com.br.
authors.forename: Caio Parente
authors.initials: CP
authors.lastname: Barbosa
authors.affiliation: Human Reproduction and Genetics Center - Division of Sexual and Reproductive Healthcare and Population Genetics - Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil. bianca.bianco@hotmail.com.
authors.forename: Bianca
authors.initials: B
authors.lastname: Bianco
mesh_terms: D000328:Adult; D001938:Brazil; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000628:therapy; D010062:Ovulation Induction; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D018873:Pregnancy Rate; D016896:Treatment Outcome
chemical_list: C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta