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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Human controlled ovarian hyperstimulation outcome is a polygenic trait.

This study aimed to evaluate the association between follicle-stimulating hormone (FSH) hormone efficacy and FSHR, CYP19, ESR1 and ESR2 genes using single nucleotide polymorphism analyses. One hundred and seventy women with conserved ovarian function undergoing controlled ovarian stimulation (COS) with daily exogenous recombinant FSH administration. Women were categorized as poor responders to FSH (three or less ovarian follicles observed at the end of cycle) or normal responders (more than three follicles). The outcome is the number of normal/poor responders as defined by the number of follicles obtained during COS. The DNA markers studied are located in genes related to the FSH mechanism of action (FSH receptor, CYP19 aromatase and oestrogen receptors alpha and beta genes). We conducted an association study between the COS outcome and selected DNA markers using two-point and multi-locus genetic association studies. Genotype pattern tracking in extreme phenotypes and multi-locus analysis using Sumstat and PM algorithms provided significant evidences of genetic interaction between FSHR, ESR1 and ESR2 markers in relation to COS outcome (P = 0.0015). Our results support the hypothesis that a discrete set of genes, related to the FSH hormone mechanism of action, controls the ovarian response to FSH in humans. An oligogenic model including specific FSHR, ESR1 and ESR2 genotype patterns may partially explain the poor response to FSH hormone during controlled ovarian stimulation treatments. The existence of genetic heterogeneity is also suspected.[1]


  1. Human controlled ovarian hyperstimulation outcome is a polygenic trait. de Castro, F., Morón, F.J., Montoro, L., Galán, J.J., Hernández, D.P., Padilla, E.S., Ramírez-Lorca, R., Real, L.M., Ruiz, A. Pharmacogenetics (2004) [Pubmed]
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