A single nucleotide polymorphism of bone morphogenic protein-15 is not associated with ovarian reserve or response to ovarian stimulation.

Abstract

Is there any effect of the -9C>G variant in the bone morphogenic protein-15 (BMP15) gene on ovarian response and/or current markers of ovarian reserve in patients undergoing in vitro fertilization (IVF) treatment? No significant associations of BMP15 genotypes with ovarian response (number of oocytes retrieved) and/or markers of ovarian reserve were detected in our cohort of women undergoing IVF treatment. There is evidence that genetic variation influences patients' response to ovarian stimulation therapy. BMP15 plays a role in the recruitment of primordial follicles. Therefore, variation in BMP15 could predict ovarian reserve and response to ovarian stimulation. Two previous studies have determined a significant correlation between the BMP15 -9C>G variant and over-response to ovarian stimulation. No studies to date have correlated this variant with ovarian reserve markers. In this prospective observational study, we genotyped the BMP15 -9C>G single nucleotide polymorphism in 239 unrelated women undergoing their first cycle of controlled ovarian stimulation for IVF and ICSI (intra-cytoplasmic sperm injection) using gonadotrophins at a tertiary referral centre for reproductive medicine between March 2009 and August 2010. Baseline pelvic ultrasound and blood tests were taken on Days 2-3 of the cycle for assessment of baseline hormones and for DNA extraction. Genotypes were determined using TaqMan allelic discrimination assay. Regression analysis was performed to assess the effect of the BMP15 genotype on the ovarian reserve markers, serum anti-Müllerian hormone (s-AMH), follicle stimulating hormone (s-FSH) and antral follicle count (AFC), with adjustment for age and body mass index (BMI), and on the primary outcomes of response (number of oocytes retrieved and gonadotrophin dose) with adjustment for age, BMI and treatment received. There was no evidence of any statistically significant (P < 0.05) difference in basal s-FSH, s-AMH and AFC between individuals with different BMP15 genotypes. The number of oocytes retrieved and gonadotrophin dose used were also comparable between the individuals with different genotypes. A larger sample size would be required in order to determine if the BMP15 genotype has a small effect on ovarian reserve or response. When considering the development of integrative clinical algorithms for individual FSH doses, our analysis suggests that the genotyping of BMP15 -9C>G does not provide additional useful information as a predictor of ovarian reserve or response to ovarian stimulation. The study was funded by the Manchester Biomedical Research Centre. The authors have no competing interests to declare.