Purpose

Does controlled ovarian stimulation (COS) and progesterone (P) luteal supplementation modify the vaginal and endometrial microbiota of women undergoing in vitro fertilization?

Methods

Fifteen women underwent microbiota analysis at two time points: during a mock transfer performed in the luteal phase of the cycle preceding COS, and at the time of fresh embryo transfer (ET). A vaginal swab and the distal extremity of the ET catheter tip were analyzed using next-generation 16SrRNA gene sequencing. Heterogeneity of the bacterial microbiota was assessed according to both the Bray-Curtis similarity index and the Shannon diversity index.

Results

Lactobacillus was the most prevalent genus in the vaginal samples, although its relative proportion was reduced by COS plus P supplementation (71.5 ± 40.6% vs. 61.1 ± 44.2%). In the vagina, an increase in pathogenic species was observed, involving Prevotella (3.5 ± 8.9% vs. 12.0 ± 19.4%), and Escherichia coli-Shigella spp. (1.4 ± 5.6% vs. 2.0 ± 7.8%). In the endometrium, the proportion of Lactobacilli slightly decreased (27.4 ± 34.5% vs. 25.0 ± 29.9%); differently, both Prevotella and Atopobium increased (3.4 ± 9.5% vs. 4.7 ± 7.4% and 0.7 ± 1.5% vs. 5.8 ± 12.0%). In both sites, biodiversity was greater after COS (p < 0.05), particularly in the endometrial microbiota, as confirmed by Bray-Curtis analysis of the phylogenetic distance among bacteria genera. Bray-Curtis analysis confirmed significant differences also for the paired endometrium-vagina samples at each time point.

Conclusions

Our findings suggest that COS and P supplementation significantly change the composition of vaginal and endometrial microbiota. The greater instability could affect both endometrial receptivity and placentation. If our findings are confirmed, they may provide a further reason to encourage the freeze-all strategy.

中文翻译：

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控制性卵巢刺激和孕酮补充影响IVF周期的阴道和子宫内膜微生物群：一项试点研究。

目的

受控卵巢刺激（COS）和黄体酮（P）黄体补充剂是否会改变接受体外受精的女性的阴道和子宫内膜微生物群？

方法

15名妇女在两个时间点进行了菌群分析：在COS之前的周期的黄体期进行的模拟转移过程中，以及在进行新鲜胚胎移植（ET）时。使用下一代16SrRNA基因测序分析了阴道拭子和ET导管尖端的远端。根据Bray-Curtis相似指数和Shannon多样性指数评估细菌菌群的异质性。

结果

乳酸菌是阴道样本中最普遍的属，尽管通过添加COS和P可以降低乳酸菌的相对比例（71.5±40.6％对61.1±44.2％）。在阴道中，观察到的致病菌种有所增加，包括普雷沃氏菌（3.5±8.9％比12.0±19.4％）和大肠杆菌-志贺氏菌属。（1.4±5.6％与2.0±7.8％）。在子宫内膜中，乳酸杆菌的比例略有下降（27.4±34.5％对25.0±29.9％）；以不同的方式，普雷沃特氏菌和拟南芥都增加了（3.4±9.5％对4.7±7.4％和0.7±1.5％对5.8±12.0％）。在两个地点，COS后生物多样性都更大（p 小于0.05），尤其是在子宫内膜微生物群中，如Bray-Curtis对细菌属间系统发生距离的分析所证实的那样。Bray-Curtis分析证实，每个时间点配对的子宫内膜-阴道样本也存在显着差异。

结论

我们的发现表明，补充COS和P会显着改变阴道和子宫内膜微生物群的组成。较大的不稳定性可能会影响子宫内膜的接受性和胎盘形成。如果我们的发现得到证实，它们可能会提供进一步的理由来鼓励“冻结所有人”战略。