OBJECTIVE: Controlled ovarian stimulation (COS) using recombinant follicle-stimulating hormone (rFSH) is the main treatment in assisted reproduction. We performed a pharmacogenetic analysis of bone morphogenetic protein 15 (BMP15) gene using single nucleotide polymorphisms (SNPs) in COS. We also investigated the role of the BMP15 gene in ovarian hyperstimulation syndrome (OHSS). METHODS: We analysed different intragenic SNPs located within the BMP15 gene in 307 women treated with rFSH, evaluating its involvement in COS outcome. RESULTS: First, we analysed two polymorphisms, by applying different tests for genetic association, and we found a minimum P-value in patients producing > or =12 follicles in COS (high responders) in both polymorphisms of the BMP15 gene. Using bi-directional DNA sequencing, we identified two additional single nucleotide DNA variants. Second, we conducted association studies with all polymorphisms together, and noticed that none of them seemed to fully explain the association of the BMP15 gene with over-response to rFSH. However, N103S missense mutation is predicted to disrupt the secondary structure of human BMP15 protein and is weakly associated with OHSS. This coding mutation of the BMP15 gene may partially explain the results obtained during our research. Using Thesias software, we reconstructed haplotypes with the four intragenic variants and calculated their frequencies in normal and over-responders to rFSH. The haplotype TGGA was over-represented in high responders when compared with the rest of patients. Moreover, this association was higher in patients with OHSS, with a significant global haplotypic effect of the BMP15 gene. CONCLUSION: Our results suggest a direct relationship between increased follicle production during COS and BMP15 alleles in response to rFSH in humans. The use of BMP15 markers to prevent OHSS is also a possibility that requires thorough evaluation.
OBJECTIVE: Controlled ovarian stimulation (COS) using recombinant follicle-stimulating hormone (rFSH) is the main treatment in assisted reproduction. We performed a pharmacogenetic analysis of bone morphogenetic protein 15 (BMP15) gene using single nucleotide polymorphisms (SNPs) in COS. We also investigated the role of the BMP15 gene in ovarian hyperstimulation syndrome (OHSS). METHODS: We analysed different intragenic SNPs located within the BMP15 gene in 307 women treated with rFSH, evaluating its involvement in COS outcome. RESULTS: First, we analysed two polymorphisms, by applying different tests for genetic association, and we found a minimum P-value in patients producing > or =12 follicles in COS (high responders) in both polymorphisms of the BMP15 gene. Using bi-directional DNA sequencing, we identified two additional single nucleotide DNA variants. Second, we conducted association studies with all polymorphisms together, and noticed that none of them seemed to fully explain the association of the BMP15 gene with over-response to rFSH. However, N103S missense mutation is predicted to disrupt the secondary structure of humanBMP15 protein and is weakly associated with OHSS. This coding mutation of the BMP15 gene may partially explain the results obtained during our research. Using Thesias software, we reconstructed haplotypes with the four intragenic variants and calculated their frequencies in normal and over-responders to rFSH. The haplotype TGGA was over-represented in high responders when compared with the rest of patients. Moreover, this association was higher in patients with OHSS, with a significant global haplotypic effect of the BMP15 gene. CONCLUSION: Our results suggest a direct relationship between increased follicle production during COS and BMP15 alleles in response to rFSH in humans. The use of BMP15 markers to prevent OHSS is also a possibility that requires thorough evaluation.
Authors: Luciana Ochuiuto Teixeira de Resende; Alessandra Aparecida Vireque; Laura Ferreira Santana; Daniel Antunes Moreno; Ana Carolina Japur de Sá Rosa e Silva; Rui Alberto Ferriani; Carlos Alberto Scrideli; Rosana Maria Reis Journal: J Assist Reprod Genet Date: 2012-07-24 Impact factor: 3.412
Authors: Samuel Santos-Ribeiro; Nikolaos P Polyzos; Katrien Stouffs; Michel De Vos; Sara Seneca; Herman Tournaye; Christophe Blockeel Journal: J Assist Reprod Genet Date: 2015-05-17 Impact factor: 3.412
Authors: Katrien Stouffs; Sari Daelemans; Samuel Santos-Ribeiro; Sara Seneca; Alexander Gheldof; Ali Sami Gürbüz; Michel De Vos; Herman Tournaye; Christophe Blockeel Journal: J Assist Reprod Genet Date: 2018-11-27 Impact factor: 3.412
Authors: Zhen Zhen Zhao; Jodie N Painter; James S Palmer; Penelope M Webb; Nicholas K Hayward; David C Whiteman; Dorret I Boomsma; Nicholas G Martin; David L Duffy; Grant W Montgomery Journal: Hum Reprod Date: 2008-07-09 Impact factor: 6.918
Authors: Radia Boudjenah; Denise Molina-Gomes; Antoine Torre; Marianne Bergere; Marc Bailly; Florence Boitrelle; Stéphane Taieb; Robert Wainer; Mohamed Benahmed; Philippe de Mazancourt; Jacqueline Selva; François Vialard Journal: PLoS One Date: 2012-06-11 Impact factor: 3.240