Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome: a preliminary report

REPRODUCTIVE BIOMEDICINE ONLINE

卷:18

Article

Altmaee, Signe^1,2  Haller, Kadri³  Peters, Maire³  Saare, Merli³  Hovatta, Outi²  Stavreus-Evers, Anneli^2,4  Metspalu, Andres¹  Salumets, Andres^1,3 

[1] Univ Tartu, Dept Biotechnol, Inst Mol & Cell Biol, Estonian Genome Fdn, Tartu, Estonia

[2] Karolinska Univ, Dept Clin Sci Intervent & Technol, Div Obstet & Gynaecol, Karolinska Inst,Hosp Huddinge, Stockholm, Sweden

[3] Univ Tartu, Dept Obstet & Gynaecol, Tartu, Estonia

[4] Uppsala Univ, Dept Womens & Childrens Hlth, Akad Sjukhuset, Uppsala, Sweden

关键词: aromatase;    female infertility;    IVF;    ovarian stimulation;   

DOI  :  10.1016/S1472-6483(10)60009-0

来源: Elsevier

【 摘 要 】

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.

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