Assessment of the implantation window and embryonic factor impact to the treatment of recurrent implantation failure (RIF). A prospective study

Oleksandra Kozyra, Mykhailo G. Medvediev
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Abstract

The aim: to study of the prognostic value of endometrial receptivity and preimplantation genetic diagnosis of embryos, and their influence on the effectiveness of in vitro fertilization (IVF) programs. We also evaluate the importance of this factor in comparison with other potential causes of infertility. Materials and methods: This prospective cohort study included 123 infertile women who underwent in vitro fertilization (IVF) treatment. 93 patients had repeated unsuccessful implantation attempts and were divided into three groups: group 1 - patients who were treated using genetically untested embryos according to a standard fixed stimulation protocol, group 2 - patients who were treated using euploid embryos after preimplantation genetic screening according to standard fixed protocol; group 3 - patients who underwent treatment using euploid embryos after pre-implantation genetic screening and determination of the implantation window with subsequent modification of the stimulation protocol, according to the endometrial examination result. 30 patients had a first attempt at IVF, which was carried out using genetically untested embryos, according to a standard fixed protocol, and made up the control group (CG). Determination of the window of implantation was carried out by triple aspiration biopsy of the endometrium during the luteal phase of the menstrual cycle since the endometrium is most susceptible to implantation during this period. Samples were analyzed using scanning electron microscopy. Based on the results obtained, the endometrial preparation protocol was individualized for the next attempt. preimplantation genetic testing (PGT) of embryos was carried out by the next generation (NGS) method. Statistical analysis was performed using IBM SPSS V25.0 for Windows software. Results: According to the obtained results, patient characteristics, screening rates, IVF cycle characteristics, and the number, quality, and stage of transferred embryos were compared between groups. The rate of clinical pregnancy was 46.7 % among patients of group 1.70 % among patients of group 2, 82.8 % among patients of group 3 and 50.0 % of the control group and statistically significantly different between groups (χ2=10.955, p= 0.012). The rate of live birth was 43.3 % among patients of group 1, 53.3 % among patients of group 2, 72.4 % among patients of group 3 and 43.3 % - of the control group, however, it did not differ statistically significantly between groups (χ2=6,639, р=0,084) Conclusions: The unique window of implantation and the embryonic factor are among the main reasons for multiple failed implantation attempts. Personalization of the endometrial preparation protocol and preimplantation embryo diagnosis are effective methods to improve IVF outcomes
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评估植入窗口期和胚胎因素对治疗复发性植入失败 (RIF) 的影响。前瞻性研究
目的:研究子宫内膜容受性和胚胎植入前遗传学诊断的预后价值,以及它们对体外受精(IVF)计划有效性的影响。我们还评估了这一因素与其他潜在不孕原因相比的重要性:这项前瞻性队列研究包括123名接受体外受精(IVF)治疗的不孕妇女。93名患者曾多次尝试植入失败,被分为三组:第1组--根据标准固定刺激方案使用未经基因检测的胚胎进行治疗的患者;第2组--根据标准固定方案使用胚胎植入前基因筛查后的优倍体胚胎进行治疗的患者;第3组--根据子宫内膜检查结果使用胚胎植入前基因筛查后的优倍体胚胎进行治疗,并确定植入窗口期,随后修改刺激方案的患者。对照组(CG)中有 30 名首次尝试体外受精的患者,他们按照固定的标准方案,使用未经基因检测的胚胎进行体外受精。确定植入窗口期的方法是在月经周期的黄体期对子宫内膜进行三吸活检,因为子宫内膜在这一时期最容易植入。样本使用扫描电子显微镜进行分析。胚胎植入前遗传学检测(PGT)采用下一代(NGS)方法进行:根据所得结果,比较了各组患者的特征、筛查率、IVF周期特征以及移植胚胎的数量、质量和阶段。第一组患者临床妊娠率为 46.7%,第二组为 70%,第三组为 82.8%,对照组为 50.0%,组间差异有统计学意义(χ2=10.955,P=0.012)。第 1 组患者的活产率为 43.3%,第 2 组为 53.3%,第 3 组为 72.4%,对照组为 43.3%,但组间差异无统计学意义(χ2=6,639,р=0,084):独特的植入窗口和胚胎因素是导致多次植入失败的主要原因之一。个性化子宫内膜准备方案和植入前胚胎诊断是提高试管婴儿成功率的有效方法。
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