Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
E-pub ahead of print

Rare genetic variants suggest dysregulation of signaling pathways in low- and high-risk patients developing severe ovarian hyperstimulation syndrome

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. Improving the maturation rate of human oocytes collected ex vivo during the cryopreservation of ovarian tissue

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Ovarian cortical follicle density in infertile women with low anti-Müllerian hormone

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Gonadotropin receptor variants are linked to cumulative live birth rate after in vitro fertilization

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

PURPOSE: To investigate if rare gene variants in women with severe ovarian hyperstimulation syndrome (OHSS) provide clues to the mechanisms involved in the syndrome.

METHODS: Among participants in a prospective randomized study (Toftager et al. 2016), six women with predicted low and six women with predicted high risk of OHSS developing severe OHSS (grades 4 and 5, Golan classification) were selected. In the same cohort, six plus six matched controls developing no signs of OHSS (Golan grade 0) were selected. Whole-exome sequencing was performed. Analysis using a predefined in silico OHSS gene panel, variant filtering, and pathway analyses was done.

RESULTS: We found no convincing monogenetic association with the development of OHSS using the in silico gene panel. Pathway analysis of OHSS variant lists showed substantial overlap in highly enriched top pathways (p value range p < 0.0001 and p > 9.8E-17) between the low- and high-risk group developing severe OHSS, i.e., "the integrin-linked kinase (ILK) signaling pathway" and the "axonal guidance signaling pathway," both being connected to vasoactive endothelial growth factor (VEGF) and endothelial function.

CONCLUSION: Rare variants in OHSS cases with two distinct risk profiles enrich the same signaling pathways linked to VEGF and endothelial function. Clarification of the mechanism as well as potentially defining genetic predisposition of the high vascular permeability is important for future targeted treatment and prevention of OHSS; the potential roles of ILK signaling and the axonal guidance signaling need to be validated by functional studies.

TidsskriftJournal of Assisted Reproduction and Genetics
StatusE-pub ahead of print - 18 sep. 2020

ID: 60880698