Journal of Fertilization: In Vitro - IVF-Worldwide, Reproductive Medicine, Genetics & Stem Cell Biol
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Single Nucleotide Polymorphisms of BMP15 are Associated with Poor Ovarian Response in In Vitro Fertilization Programs

Rosa Vanyan, Nataliya Dolgushina, Andrey Donnikov, Ekaterina Shubina, Natalia Usman, Maria Kuznetsova and Gennady Sukhikh

Background: Poor ovarian response represents a major negative contribution to the efficacy of In vitro fertilization programs. It has been shown that specific nucleotide sequence variants of BMP15 gene, which encodes the growth factor specifically expressed by oocytes to regulate follicle development, are related to certain forms of ovarian dysfunction. The aim of the study was to search for novel variants related to poor ovarian response phenotypes by means of exon sequencing, and also to check possible relations of already known BMP15 variants to this particular form of ovarian insufficiency.

Methods: A total of 150 patients (65 women with poor ovarian response and 85 women with normal ovarian response as a control group) participated in this retrospective case-control study. All patients received ovarian stimulation according to the protocol with follicle-stimulating hormone and gonadotropin-releasing hormone antagonist. Genotyping was carried out by polymerase chain reaction with consequent readout of melting curves by means of modified kissing probes assay. Statistical tests were two-sided, with percent values compared by χ2 test and associations measured by odds ratio.

Results: Two novel single nucleotide polymorphisms of BMP15 were revealed by exon sequencing. Of these, the c.607 C>T substitution was found only in the control group. In contrast, the novel single nucleotide deletion c.-8 delC in the 5’ non-coding region of BMP15 mRNA was significantly more common in the poor ovarian response group. For the previously known sequence variants, the statistical analysis revealed associations of poor ovarian response with two single nucleotide substitutions, the exonic c.308 A>G and the intronic c.328+905 A>G.

Conclusion: Two novel variants of BMP15, both of plausible clinical relevance, were found in this study. Examination of larger patient cohorts is required to further elucidate their connection with the phenomenon of poor ovarian response in In vitro fertilization programs.