Invited commentary: a single nucleotide polymorphism in BMP15 is associated with high response to controlled ovarian hyperstimulation

A report has been published which shows a connection between single nucleotide polymorphisms (SNP) in the bone morphogenetic protein 15 (BMP15) gene and ovarian hyperstimulation syndrome (OHSS) in women, similar to reported effects of heterozygous BMP15 point mutations in sheep. The report also describes the near-significant presence of another BMP15 gene SNP correlated with a low response to ovarian stimulation. Previous studies associated two SNP with anovulation or infertility in women with polycystic ovary syndrome, and heterozygosity for another BMP15 SNP resulted in ovarian dysgenesis and hypergonadotrophic failure. In sheep, homozygous point mutations or immunization against BMP15 led to follicular developmental arrest, ovarian dysgenesis and streak ovaries. In mammalian (including human) ovaries BMP15 and its three receptors were shown to be expressed from primary or primordial follicular stages, suggesting that BMP15 might also be involved in activating primordial follicles, and could possibly serve as a marker of follicular reserve. BMP15 also inhibited follicle stimulating hormone receptor expression, was associated with cumulus expansion and its high follicular-fluid concentration was correlated with improved oocyte and embryo quality. Thus, BMP15 seems to be an important regulator of ovarian function. Further studies are needed to clarify its roles in human female fertility.