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      Vaginal microbiota are associated with in vitro fertilization during female infertility

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          Abstract

          The vaginal microbiome plays an essential role in the reproductive health of human females. As infertility increases worldwide, understanding the roles that the vaginal microbiome may have in infertility and in vitro fertilization (IVF) treatment outcomes is critical. To determine the vaginal microbiome composition of 1411 individuals (1255 undergoing embryo transplantation) and their associations with reproductive outcomes, clinical and biochemical features are measured, and vaginal samples are 16S rRNA sequenced. Our results suggest that both too high and too low abundance of Lactobacillus is not beneficial for pregnancy; a moderate abundance is more beneficial. A moderate abundance of Lactobacillus crispatus and Lactobacillus iners (~80%) (with a pregnancy rate of I‐B: 54.35% and III‐B: 57.73%) is found beneficial for pregnancy outcomes compared with a higher abundance (>90%) of Lactobacillus (I‐A: 44.81% and III‐A: 51.06%, respectively). The community state type (CST) IV‐B (contains a high to moderate relative abundance of Gardnerella vaginalis) shows a similar pregnant ratio (48.09%) with I‐A and III‐A, and the pregnant women in this CST have a higher abundance of Lactobacillus species. Metagenome analysis of 71 samples shows that nonpregnant women are detected with more antibiotic‐resistance genes, and Proteobacteria and Firmicutes are the main hosts. The inherent differences within and between women in different infertility groups suggest that vaginal microbes might be used to detect infertility and potentially improve IVF outcomes.

          Abstract

          The vaginal microbiome is crucial for reproductive health, and as global infertility rates rise, understanding its impact on in vitro fertilization (IVF) is vital. Here, we analyzed the microbiome of 1411 individuals (1255 undergoing embryo transplantation) and revealed that a moderate abundance of Lactobacillus (~80%) is most beneficial for pregnancy (pregnancy rates were 54.35% and 57.73% for community state types [CST] I‐B and III‐B respectively), outperforming higher abundances (>90%) seen in I‐A (44.81%) and III‐A (51.06%). Metagenomic analysis of 71 samples indicates more antibiotic‐resistance genes in nonpregnant women, with Proteobacteria and Firmicutes as predominant hosts. Variations among infertility groups suggest potential applications for detecting infertility and enhancing IVF outcomes using vaginal microbes. AMH, antimullerian hormones; BMI, body mass index; E2, estradiol; FSH, follicle‐stimulating hormone; LH, luteinizing hormone; P, progesterone; PRL, prolactin; T, testosterone.

          Highlights

          • Pregnancy rates vary among women with different vaginal microbiome communities.

          • Too high abundances of both Lactobacillus crispatus and Lactobacillus  iners have negative effects on in vitro fertilization (IVF) outcomes.

          • A moderate abundance (around 80%) of Lactobacillus is more beneficial for pregnancy.

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          Most cited references79

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          Fast gapped-read alignment with Bowtie 2.

          As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
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            DADA2: High resolution sample inference from Illumina amplicon data

            We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
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              fastp: an ultra-fast all-in-one FASTQ preprocessor

              Abstract Motivation Quality control and preprocessing of FASTQ files are essential to providing clean data for downstream analysis. Traditionally, a different tool is used for each operation, such as quality control, adapter trimming and quality filtering. These tools are often insufficiently fast as most are developed using high-level programming languages (e.g. Python and Java) and provide limited multi-threading support. Reading and loading data multiple times also renders preprocessing slow and I/O inefficient. Results We developed fastp as an ultra-fast FASTQ preprocessor with useful quality control and data-filtering features. It can perform quality control, adapter trimming, quality filtering, per-read quality pruning and many other operations with a single scan of the FASTQ data. This tool is developed in C++ and has multi-threading support. Based on our evaluation, fastp is 2–5 times faster than other FASTQ preprocessing tools such as Trimmomatic or Cutadapt despite performing far more operations than similar tools. Availability and implementation The open-source code and corresponding instructions are available at https://github.com/OpenGene/fastp.
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                Author and article information

                Contributors
                maorr@jxr-fertility.com
                liuyongxin@caas.cn
                lidiyan860714@163.com
                Journal
                Imeta
                Imeta
                10.1002/(ISSN)2770-596X
                IMT2
                iMeta
                John Wiley and Sons Inc. (Hoboken )
                2770-5986
                2770-596X
                19 March 2024
                June 2024
                : 3
                : 3 ( doiID: 10.1002/imt2.v3.3 )
                : e185
                Affiliations
                [ 1 ] Antibiotics Research and Re‐evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy Chengdu University Chengdu China
                [ 2 ] Jinxin Research Institute for Reproductive Medicine and Genetics, Sichuan Jinxin Xi'nan Women's and Children's Hospital Chengdu China
                [ 3 ] Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences Shenzhen China
                [ 4 ] College of Animal Science and Technology Sichuan Agricultural University Chengdu China
                [ 5 ] College of Life Sciences Wuhan University Wuhan China
                [ 6 ] College of Food and Biological Engineering Chengdu University Chengdu China
                [ 7 ] College of Agriculture Kunming University Kunming China
                [ 8 ] State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese Medicine Chengdu China
                [ 9 ] School of Biological Sciences University of the Punjab Lahore Pakistan
                Author notes
                [*] [* ] Correspondence Rurong Mao, Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, Chengdu 610000, China.

                Email: maorr@ 123456jxr-fertility.com

                Yong‐Xin Liu, Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China.

                Email: liuyongxin@ 123456caas.cn

                Diyan Li, Antibiotics Research and Re‐evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China.

                Email: lidiyan860714@ 123456163.com

                Author information
                http://orcid.org/0000-0003-1832-9835
                http://orcid.org/0000-0001-7490-3550
                Article
                IMT2185
                10.1002/imt2.185
                11183179
                38898981
                23815555-362a-418f-bf72-b670defd336d
                © 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 March 2024
                : 23 February 2024
                : 02 March 2024
                Page count
                Figures: 6, Tables: 0, Pages: 18, Words: 9829
                Funding
                Funded by: Sichuan Medical Association Grant
                Award ID: Q20055
                Funded by: Antibiotics Research and Re‐evaluation Key Laboratory of Sichuan Province, Chengdu University
                Award ID: ARRLKF23‐04
                Funded by: Sichuan Science and Technology Program Grants
                Award ID: 2018JY0353
                Award ID: 2019YFSY0047
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                June 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.4 mode:remove_FC converted:18.06.2024

                community,infertility,ivf,vaginal microbiome
                community, infertility, ivf, vaginal microbiome

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