The recent identification of mutations in the FSH receptor gene, which display an increased sensitivity to hCG and are responsible for the development of spontaneous ovarian hyperstimulation syndrome (OHSS), provides for the first time the molecular basis for the physiopathology of spontaneous OHSS.
Activating human FSHR mutants have also been described in both sexes, leading to a phenotype of normal testis function (male) or spontaneous ovarian hyperstimulation syndrome (females).
Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology.
The paper focuses on the recent identification of mutations in the FSH receptor gene that display an increased sensitivity to hCG and are responsible for the development of spontaneous OHSS occurring during pregnancy.
Beside point mutations, FSHR gene polymorphisms at specific sites (e.g., codons 307 and 680) may influence FSHR protein responsiveness to exogenous FSH, and finally affect the effectiveness of in vitro fertilization (IVF) treatment as well as the likelihood of developing a severe OHSS as a consequence of superovulation.
Gain-of-function mutations in the FSHR cause spontaneous ovarian hyperstimulation syndrome in females due to the inappropriate stimulation of the mutant FSHR by human choriogonadotropin.
Ninety-one ART patients with OHSS, eighty-eight ART patients without OHSS and ninety-seven women with assumed normal fecundity were analysed for the FSHR single nucleotide polymorphism (SNP) gene variations Asn680Ser (rs6166), Ala189Val, Ile160Thr, Thr449Ile (rs28928870) and the CYP19A1 rs10046 locus using real-time PCR.
Inferring biallelism of two FSH receptor mutations associated with spontaneous ovarian hyperstimulation syndrome by evaluating FSH, LH and HCG cross-activity.
Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women.
Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome.
In the present study, we describe the functional characterization of the two mutations Val(514)Ala (novel mutation) and Ala(575)Val in FSH receptor (FSHR) identified in women with OHSS developed during in vitro fertilization and primary amenorrhea, respectively.
Susceptibility to iatrogenic OHSS or its clinical severity may be associated with FSHR polymorphisms with slightly different activities in vivo as suggested by several studies.
We have shown that ovarian pigment epithelium derived factor (PEDF), a potent antiangiogenic factor, counteracts vascular endothelial growth factor (VEGF) expression and that OHSS is correlated with hCG-induced impaired PEDF to VEGF ratio.