Mol. Hum. Reprod. Advance Access originally published online on May 30, 2007
Molecular Human Reproduction 2007 13(8):521-526; doi:10.1093/molehr/gam035
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Allelic estrogen receptor 1 (ESR1) gene variants predict the outcome of ovarian stimulation in in vitro fertilization
1 Department of Biotechnology, Institute of Molecular and Cell Biology, Estonian Genome Project, University of Tartu and Estonian Biocentre, 51010 Tartu, Estonia 2 Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institute, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden 3 Department of Obstetrics and Gynaecology, University of Tartu, Lossi 36, 51003 Tartu, Estonia 4 Molecular Diagnostic Centre, Tartu University Clinicum, Oru 3, 51005 Tartu, Estonia 5 Nova Vita Clinic, Centre for Infertility Treatment and Medical Genetics, Kaluri tee 5A, Haabneeme, 74001 Viimsi, Harjumaa, Estonia
6 Correspondence address. Tel: +372-5620-4004; Fax: +372-605-9608; E-mail: asalumets{at}novavita.ee
The outcome of in vitro fertilization (IVF) depends substantially on the effectiveness of controlled ovarian hyperstimulation (COH) induced by administration of follicle-stimulating hormone (FSH). In COH, endogenously produced estrogens extend the action of FSH in stimulating folliculogenesis. We determined the associations between genetic variations in estrogen receptor ESR1 and ESR2 genes and etiology of female infertility, and analysed the influence of these variations on COH outcome—the quantity and quality of oocytes retrieved. ESR1 PvuII T/C (rs2234693) and XbaI A/G (rs9340799) single-nucleotide polymorphisms (SNPs) and (TA)n microsatellite polymorphism, as well as ESR2 RsaI G/A (rs1256049) SNP and (CA)n microsatellite polymorphism were genotyped in 159 IVF patients. The ovarian response to FSH was diminished in patients with endometriosis when compared to tubal factor infertility. ESR1 PvuII and XbaI as well as ESR2 RsaI SNPs were associated with the microsatellite length of the respective genes. Shorter ESR1 (TA)n was linked with a higher risk for unexplained infertility, whereas longer ESR1 (TA)n associated with PvuII*C allele were predictive of a better COH, but not clinical pregnancy outcome in an age-independent manner. These data suggest the variations in ESR1 gene, in addition to the age of a woman, may predict the COH outcome in IVF.
Key words: estrogen receptor gene/in vitro fertilization/controlled ovarian hyperstimulation
Submitted on April 7, 2007; accepted on April 16, 2007.