Study question Is specific microbiota in the endometrial fluid (EF) associated with pregnancy outcome in a frozen embryo transfer (FET) cycles? Summary answer Lactobacillus had high abundance in the microbiota of endometrial fluid of patients with successful pregnancy after FET treatment. What is known already Recently, the relationship between endometrial microbiota and repeated implantation failure (RIF) has been reported. While Lactobacillus-dominated microbiota (LDM, defined as > = 90 % Lactobacillus species) in the EF of the receptive phase was reported to be associated with favorable reproductive outcome, non-LDM (< 90 % Lactobacillus species) was found to decrease implantation, clinical pregnancy, ongoing pregnancy, and live birth rates. However, it is still unclear the effect of the microbiota on pregnancy outcome of the patients with the assisted reproductive technology, especially a frozen embryo transfer (FET) treatment. Study design, size, duration We included 802 cycles with clinical results of pregnancy outcome after FET treatment at our clinic from December 2018 to January 2021. Endometrium fluid was collected before FET and microbiota was examined. We examined the relationship between endometrial microbiota and pregnancy outcome in 463 cycles in which the endometrial microbiome test results were available, pregnancy outcome was known, CD138 negative, and less than 38years (229 cycles were positive pregnancy and 234 cycles were negative pregnancy). Participants/materials, setting, methods Sampling was performed carefully avoiding contamination before FET treatment. Extracted genomic DNA was sequenced for the region of 16S ribosomal RNA using next-generation sequencer (Endometrial microbiome test, Varinos, Japan). The sequencing data was assigned to bacterial taxonomy and the background-contaminated bacteria were excluded from the microbiome profile. Lactobacillus abundance was calculated. After concordance of patient background, Lactobacillus abundance between successful and unsuccessful pregnancy group was compared. Main results and the role of chance We investigated the effect of microbiota in EF, especially Lactobacillus, for the infertile female with frozen embryo transfer (FET) as an assisted reproductive treatment with large amount of cycles (802 cycles). First, all of cycles were divided into a successful pregnancy group (305/802) and an unsuccessful pregnant group (497/802), and then the abundance of Lactobacillus was analyzed (the pregnancy ratio was 38.0%). The mean abundance of Lactobacillus in EF was significantly higher in the successful pregnant group than in the unsuccessful pregnant group (70.2% 40.5 versus 63.5% 43.1, p = 0.007). To further refine the conditions of each cycle, patient backgrounds of each cycle were compared. There was a significant difference in age and CD138 results between the successful pregnant group and unsuccessful pregnant group, so the analysis was performed with the limited cycles with CD138-negative and under 38 years (229/463 versus 234/463, respectively). However, even under this strict condition, the mean abundance of Lactobacillus was significantly higher in the pregnant group than in the unsuccessful pregnant group (72.1% 39.7 versus 61.1% 44.4, p = 0.003). These results suggest that the endometrial environment with high Lactobacillus abundance is more conducive to pregnancy in FET treatment. Limitations, reasons for caution The limitation of this study is that the design is not a randomized controlled one, although it is prospective. Wider implications of the findings The results of this study suggest that the endometrial microbiota at the time of embryo implantation, especially Lactobacillus genus, is highly relevant to pregnancy outcome, implying that disruption of the intrauterine microbiota may cause infertility. We need further studies to improve the endometrial microbiota of infertile women. Trial registration number not applicable

中文翻译：

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O-256 子宫内膜微生物群对冷冻胚胎移植 (FET) 周期妊娠结局的影响

研究问题 子宫内膜液 (EF) 中的特定微生物群是否与冷冻胚胎移植 (FET) 周期中的妊娠结局相关？总结回答 FET 治疗后成功妊娠的患者子宫内膜液微生物群中乳酸菌含量较高。已知情况 最近，已经报道了子宫内膜微生物群与反复植入失败 (RIF) 之间的关系。虽然据报道在接受期的 EF 中以乳酸菌为主的微生物群（LDM，定义为 > = 90% 乳酸菌）与有利的生殖结果相关，但发现非 LDM（<90% 乳酸菌）减少植入、临床妊娠、持续妊娠和活产率。然而，目前尚不清楚微生物群对辅助生殖技术，尤其是冷冻胚胎移植（FET）治疗患者妊娠结局的影响。研究设计、规模、持续时间 我们纳入了 2018 年 12 月至 2021 年 1 月在我们诊所接受 FET 治疗后妊娠结局临床结果的 802 个周期。在 FET 之前收集子宫内膜液并检查微生物群。我们检查了 463 个周期中子宫内膜微生物群与妊娠结局之间的关系，其中子宫内膜微生物组检测结果可用、妊娠结局已知、CD138 阴性和小于 38 年（229 个周期为阳性妊娠，234 个周期为阴性妊娠）。参与者/材料、设置、方法 在 FET 处理之前仔细进行采样以避免污染。使用下一代测序仪（子宫内膜微生物组测试，Varinos，日本）对提取的基因组 DNA 进行 16S 核糖体 RNA 区域的测序。测序数据被分配给细菌分类，背景污染的细菌被排除在微生物组谱之外。计算乳酸菌丰度。在协调患者背景后，比较成功和不成功妊娠组之间的乳酸菌丰度。主要结果和机会的作用 我们调查了 EF 中微生物群的影响，尤其是乳酸菌，对冷冻胚胎移植 (FET) 作为辅助生殖治疗的不孕女性的影响，该治疗具有大量周期（802 个周期）。首先，将所有周期分为成功怀孕组（305/802）和失败怀孕组（497/802），然后分析乳酸杆菌的丰度（妊娠率为38.0%）。成功怀孕组的 EF 中乳酸杆菌的平均丰度显着高于未成功怀孕组（70.2% 40.5 对 63.5% 43.1，p = 0.007）。为了进一步细化每个周期的条件，比较了每个周期的患者背景。成功妊娠组和未成功妊娠组的年龄和 CD138 结果存在显着差异，因此以 CD138 阴性和 38 岁以下的有限周期进行分析（分别为 229/463 和 234/463）。然而，即使在这种严格的条件下，妊娠组的乳酸菌平均丰度也显着高于未成功妊娠组（72.1% 39.7 对 61.1% 44.4，p = 0.003）。这些结果表明，乳酸菌丰度高的子宫内膜环境更有利于 FET 治疗中的妊娠。局限性，谨慎的理由 本研究的局限性在于该设计不是随机对照的，尽管它是前瞻性的。研究结果的更广泛意义 这项研究的结果表明，胚胎植入时的子宫内膜微生物群，尤其是乳酸杆菌属，与妊娠结果高度相关，这意味着子宫内微生物群的破坏可能导致不孕。我们需要进一步的研究来改善不孕妇女的子宫内膜微生物群。试用注册号不适用 谨慎的原因 本研究的局限性在于该设计不是随机对照的，尽管它是前瞻性的。研究结果的更广泛意义 这项研究的结果表明，胚胎植入时的子宫内膜微生物群，尤其是乳酸杆菌属，与妊娠结果高度相关，这意味着子宫内微生物群的破坏可能导致不孕。我们需要进一步的研究来改善不孕妇女的子宫内膜微生物群。试用注册号不适用 谨慎的原因 本研究的局限性在于该设计不是随机对照的，尽管它是前瞻性的。研究结果的更广泛意义 这项研究的结果表明，胚胎植入时的子宫内膜微生物群，尤其是乳酸杆菌属，与妊娠结果高度相关，这意味着子宫内微生物群的破坏可能导致不孕。我们需要进一步的研究来改善不孕妇女的子宫内膜微生物群。试用注册号不适用 这意味着宫内微生物群的破坏可能导致不孕。我们需要进一步的研究来改善不孕妇女的子宫内膜微生物群。试用注册号不适用 这意味着宫内微生物群的破坏可能导致不孕。我们需要进一步的研究来改善不孕妇女的子宫内膜微生物群。试用注册号不适用