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The mechanism of action of oxytocin antagonist nolasiban in ART in healthy female volunteers

Published:January 15, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.01.003

      Highlights

      • Uterine contractions at embryo transfer (ET) negatively correlate with pregnancy rates
      • Uterine blood flow at ET is a predictor of uterine receptivity
      • Oxytocin receptor antagonists, such as nolasiban, increase pregnancy rates after ET
      • Nolasiban lowers contractions, alters endometrial genomics and increases perfusion

      Abstract

      Research question

      What are the effects of the oxytocin receptor (OTR) antagonist nolasiban on uterine contractions, endometrial perfusion and endometrial mRNA expression?

      Design

      Randomized, double-blind, parallel-group, mechanism-of-action study with nolasiban. Forty-five healthy, pre-menopausal women were treated with placebo, 900 mg or 1800 mg nolasiban on the day corresponding to blastocyst transfer. Ultrasonographic uterine contraction frequency and endometrial perfusion were assessed, and endometrial biopsies analysed by next-generation sequencing.

      Results

      Both doses of nolasiban showed decreased contraction frequency and increased endometrial perfusion depending on the time point assessed. At 1800 mg, 10 endometrial genes (DPP4, CNTNAP3, CNTN4, CXCL12, TNXB, CTSE, OLFM4, KRT5, KRT6A, IDO2) were significantly differentially expressed (adjusted P < 0.05). Of these, OLFM4, DPP4 and CXCL12 were regulated in the same direction as genes involved in implantation during the window of implantation. In addition, three genes (DPP4, CXCL12 and IDO2) were associated with decidualization and endometrial receptivity.

      Conclusions

      These data expand our knowledge of the mechanism of action of nolasiban in increasing pregnancy rates after embryo transfer. The results suggest more marked effects of nolasiban 1800 mg compared with the 900 mg dose, supporting testing at higher doses in IVF patients.

      KEYWORDS

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      Biography

      Piotr Pierzynski is Associate Professor, co-owner and consultant in reproductive medicine at an independent IVF and research centre ‘OVIklinika’ in Warsaw, Poland. His scientific interests are embryo implantation and the role of the oxytocin receptor system in human assisted reproduction.
      Key message
      The oxytocin receptor antagonist ‘nolasiban’ reduced uterine contractions at certain time points depending on the treatment group, increased endometrial blood flow and changed the expression of some endometrial genes involved in endometrial receptivity. It may, therefore, increase pregnancy rates after embryo transfer.