title: Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome: a preliminary report.
abstract: Progress has been made towards ascertaining the genetic predictors of ovarian stimulation in IVF. Aromatase cytochrome P450, encoded by the CYP19A1 gene, catalyses a key step in ovarian oestrogen biosynthesis. Hence, the aromatase gene is an attractive candidate for genetic studies. This study aimed to examine the genetic influences of CYP19A1 TCT trinucleotide insertion/deletion (Ins/Del) and (TTTA)(n) microsatellite intronic polymorphisms on ovarian stimulation outcome and aetiology of female infertility. IVF patients (n = 152) underwent ovarian stimulation according to recombinant FSH and gonadotrophin releasing hormone antagonist protocol. Del/Del homozygous patients with shorter TTTA repeats exhibited decreased ovarian FSH sensitivity in ovarian stimulation, which may reflect variations in aromatase gene expression during early antral follicle development. Accordingly, this study demonstrates correlations between Del allele and shorter (TTTA)(n) repeat sizes with smaller ovaries (r = -0.70, P = 0.047) and fewer antral follicles (r = 0.21, P = 0.018) on days 3-5 of spontaneous menstrual cycle, respectively. Furthermore, Del variation linked with low-repeat-number (TTTA)(n) alleles are involved in enhanced genetic susceptibility to unexplained infertility (adjusted OR = 4.33, P = 0.039) and endometriosis (r = -0.88, P = 0.026), which corroborates evidence on the overlapping patient profiles of ovarian dysfunction in both types of female infertility.
authors: Department of Biotechnology, Institute of Molecular and Cell Biology, Estonian Genome Foundation, University of Tartu, Estonia.
authors: Signe
authors: S
authors: Altmäe
authors: Kadri
authors: K
authors: Haller
authors: Maire
authors: M
authors: Peters
authors: Merli
authors: M
authors: Saare
authors: Outi
authors: O
authors: Hovatta
authors: Anneli
authors: A
authors: Stavreus-Evers
authors: Agne
authors: A
authors: Velthut
authors: Helle
authors: H
authors: Karro
authors: Andres
authors: A
authors: Metspalu
authors: Andres
authors: A
authors: Salumets
mesh_terms: D001141:Aromatase / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004957:Estonia; D005260:Female; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D007247:Infertility, Female / Q000235:genetics*; D016014:Linear Models; D018895:Microsatellite Repeats / Q000235:genetics; D010062:Ovulation Induction / Q000379:methods*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D016896:Treatment Outcome
chemical_list: D017931:DNA Primers; D001141:Aromatase