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Long-Acting GnRH Agonist Improves IVF Outcomes of Young Patients with Diminished Ovarian Reserve by Increasing Endometrial Receptivity.


 Background: Up to now, there is not sufficient evidence to recommend a treatment optimizing in vitro fertilization (IVF) outcomes for diminished ovarian reserve (DOR). This study is aimed to investigate whether long-acting gonadotrophin-releasing hormone (GnRH) agonist long protocol in follicular phase could improve the IVF cycle outcomes for young patients with DOR when compared with GnRH antagonist and mild ovarian stimulation protocols. Methods: This retrospective cohort study was carried out from June 2015 to March 2019. 338 patients aged 20-40 years with DOR who underwent first IVF between were enrolled. These patients were assigned to three groups depending on the ovarian stimulation protocols. The outcome parameters of IVF were compared in each group. The demographic and reproductive characteristics were calculated by Mann-Whitney, Kruskal-Wallis or chi-square test as appropriate. We evaluated the clinical outcomes of IVF cycle between the three groups using univariate and multivariate logistic regression analyses. In addition, we evaluated the morphology and coverage of pinopode and expression of HOXA10 in endometrium during implantation window between three groups by scanning electron microscope and qRT-PCR.Results: Patients who received long-acting GnRH agonist long protocol had significantly higher clinical pregnancy rates (66.67%, 42.17% and 39.02%, respectively; P=.010 and .005), implantation rates (46.15%, 29.71%, and 28.57%, respectively; P=.041 and .025) and ongoing pregnancy rates (60.00%, 34.94%, and 36.59%, respectively; P=.018 and .004). They also had significantly higher duration of stimulation, total dose of gonadotrophins and endometrial thickness than the other two groups (P＜.001). However, serum luteinizing hormone (LH) and estradiol (E2) level on gonadotrophins initiation day, serum LH level on human chorionic gonadotropin (hCG) day, the embryos transferred cancellation rate and abnormal endometrium rate were significantly lower among women who received long-acting GnRH agonist (P＜.001). In addition, we found that long-acting GnRH agonist could improve the development of pinopode and mRNA of HOXA10 (P＜.05).Conclusions: To our knowledge, this is the first time that the benefit of long-acting GnRH agonist long protocol in follicular phase in young DOR patients has been reported. Though this novel protocol may have further suppressed response, it can increase endometrial receptivity, reduce cycle cancellation rate and improve IVF cycle clinical outcomes for these patients compared with mild stimulation and GnRH antagonist protocols.