- •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
What are the effects of the oxytocin receptor (OTR) antagonist nolasiban on uterine contractions, endometrial perfusion and endometrial mRNA expression?
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.
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.
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.
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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.
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.
Published online: January 15, 2021
Accepted: January 11, 2021
Received in revised form: December 16, 2020
Received: August 19, 2020Declaration: PP, CB and SM report consulting fees from ObsEva. OP, LM and JPG are employees and stockholders of ObsEva SA. UL is an employee of Richmond Pharmacology and Principal Investigator for the trial (EudraCT No. 2018-003702-36), who provides contract research services to ObsEva and reports payments from ObsEva and Richmond Pharmacology. All of the authors made substantial contributions to the design of the trial or the acquisition, analysis or interpretation of the data and had full access to the data, drafted or critically reviewed the draft manuscript, and approved the final version. The trial was sponsored and funded by ObsEva SA.
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