Abstract

BackgroundTo determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF).MethodsThis retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015–December 2020) at Northwest Women’s and Children’s Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist–HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates.ResultsThe live birth rate in the GnRH agonist–HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P < 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist–HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381–0.926; P = 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181–0.796; P = 0.010).ConclusionsThe GnRH agonist–HRT protocol improves the live birth rate in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist–HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist–HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF.Trial registrationThis research protocol was approved by the hospital institutional ethics committee (No. 2021002).

Highlights

  • To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients with idiopathic recurrent implantation failure (RIF)

  • We hypothesize that the GnRH agonist–HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate

  • These findings are useful for further investigating the underlying mechanism of the GnRH agonist–HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF

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Summary

Introduction

To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF). Despite technical advances in in vitro fertilization (IVF), the management of idiopathic recurrent implantation failure (RIF)—the absence of implantation after repeated embryo transfers—poses a major clinical challenge in assisted reproductive technology (ART). The two interact and influence each other while the embryo enters the uterine cavity [4]. Both adequate endometrial receptivity and high embryonic quality are important for implantation. Prospective cohort studies have indicated that frozen–thawed embryo transfer (FET) might improve the reproductive outcomes in women with RIF [5]. In FET cycles, the embryos may be transferred into a more synchronous uterine environment, which can avoid the disturbed endometrial development caused by external ovarian stimulation

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