Use of Bone Morphogenetic Protein 15 Polymorphisms to Predict Ovarian Stimulation Outcomes in Infertile Brazilian Women.

Aims: Polymorphisms in the gene encoding bone morphogenetic protein 15 (BMP15) can result in inhibited secretion or lowered bioactivity of the BMP15 protein. BMP15 levels are associated with follicle-stimulating hormone receptor (FSHR) action on granulosa cells, wherein FSHR increases the sensitivity of ovarian follicles to follicle-stimulating hormone (FSH). In this study we evaluated the BMP15 polymorphisms A905 > G/rs3897937, C901 > T/rs17003221, and C-9 > G/rs3810682 in infertile Brazilian women in terms of anti-Mullerian hormone (AMH), FSH, and estradiol serum levels, as well as controlled ovarian hyperstimulation response and assisted reproduction outcomes.

Methods: A cross-sectional study comprising 186 infertile women who underwent the first cycle of high complexity assisted reproduction treatment was conducted using the TaqMan assay for quantitative polymerase chain reaction genotyping. Serum AMH, FSH, and estradiol levels were measured by enzyme-linked immunosorbent assay.

Results: For C901 > T (rs17003221) carriers, there was a statistically significant difference among carriers of a polymorphic BMP15 genotype (TT) and the estradiol concentration. These women had higher estradiol levels than women who had homozygous wild type or heterozygous genotypes. There was also a positive correlation between serum AMH and the C-9 > G (rs3810682) polymorphism, wherein women carrying both polymorphic alleles (homozygous, GG) had higher average AMH levels than heterozygous women. However, none of the three polymorphisms studied showed a statistically significant correlation with assisted reproduction outcome.

Discussion: Oocytes are known to secrete factors that regulate follicular development and oocyte maturation. Abnormal expression of these factors may thus be involved in follicular development disorders. A recent study highlighted the importance of BMP15 in regulating ovulation rates in sheep and that heterozygous deletions in the -9C > G polymorphism reduced BMP15 concentrations, increased granulosa cell FHSR mRNA levels, elevated estrogen secretion, and activated production of stem cell factors. In this study we found that BMP15 polymorphisms affected estrogen and AMH levels.

Conclusion: BMP15 polymorphisms are not correlated with ovarian stimulation and assisted reproduction outcomes in infertile Brazilian women.