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.

中文翻译：

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催产素拮抗剂诺拉西班在健康女性志愿者ART中的作用机制

研究问题

催产素受体 (OTR) 拮抗剂诺拉西班对子宫收缩、子宫内膜灌注和子宫内膜 mRNA 表达有何影响？

设计

诺拉西班的随机、双盲、平行组、作用机制研究。45 名健康的绝经前妇女在囊胚移植当天接受安慰剂、900 毫克或 1800 毫克诺拉西班治疗。评估了超声子宫收缩频率和子宫内膜灌注，并通过下一代测序分析了子宫内膜活检。

结果

根据评估的时间点，两种剂量的 nolasiban 均显示收缩频率降低和子宫内膜灌注增加。在 1800 mg 时，10 个子宫内膜基因（DPP4、CNTNAP3、CNTN4、CXCL12、TNXB、CTSE、OLFM4、KRT5、KRT6A、IDO2）显着差异表达（调整后的P < 0.05）。其中，OLFM4、DPP4和CXCL12在植入窗口期间与参与植入的基因方向相同。此外，三个基因（DPP4、CXCL12和IDO2）与蜕膜化和子宫内膜容受性相关。

结论

这些数据扩展了我们对 nolasiban 在增加胚胎移植后妊娠率的作用机制的认识。结果表明，与 900 mg 剂量相比，1800 mg nolasiban 的效果更显着，支持在 IVF 患者中进行更高剂量的测试。