Endometrial and vaginal microbiomes influence assisted reproductive technology outcomes

Objective The role of Lactobacillus-dominant microbiota in the endometrium in reproductive function is unclear. We therefore aimed to explore the impact of the balance of Lactobacillus and pathological bacteria in the endometrial and vaginal microbiomes on the pregnancy outcomes of women treated with assisted reproductive technology (ART). Methods This study included 35 women with infertility submitted to good-quality embryo transfers. The cutoff values for abundance of Lactobacillus species (spp.) and pathological bacteria in the endometrium and vagina were calculated. Women with Lactobacillus spp. and pathological bacteria abundance above the cutoff values were categorized in the high-abundance group, whereas those with abundance below cutoff values were categorized in the low abundance group. We divided the patients into four groups based on the combination of high/low abundance of Lactobacillus spp. and pathological bacteria. Results The 35 cases of good-quality embryo transfer resulted in 21 pregnancies. Pregnant women were present in significantly higher proportions in the high Lactobacillus spp. abundance and low pathological bacteria abundance group, whereas the opposite combination (i.e., low Lactobacillus spp. abundance and high pathological bacteria abundance) saw a significantly higher proportion of nonpregnant women (p=0.022). Conclusions The balance between Lactobacillus and pathological bacterial abundance in the endometrial and vaginal microbiomes is associated with pregnancy from ART.

[1]  J. Ravel,et al.  Characteristics associated with Lactobacillus iners-dominated vaginal microbiota , 2021, Sexually Transmitted Infections.

[2]  K. Ashikawa,et al.  Next-generation sequencing of 16S rRNA for identification of invasive bacterial pathogens in a formalin-fixed paraffin-embedded placental specimen: a case report of perinatal fulminant Streptococcus pyogenes infection , 2021, Medical Molecular Morphology.

[3]  D. Crosby,et al.  Probiotic therapy in couples with infertility: A systematic review. , 2020, European journal of obstetrics, gynecology, and reproductive biology.

[4]  A. Gasbarrini,et al.  Recent Insights on the Maternal Microbiota: Impact on Pregnancy Outcomes , 2020, Frontiers in Immunology.

[5]  Q. Liao,et al.  The Pathogenesis Of Streptococcus anginosus In Aerobic Vaginitis , 2019, Infection and drug resistance.

[6]  Byung-Kwan Cho,et al.  Vaginal Microbiota Profiles of Native Korean Women and Associations with High-Risk Pregnancy , 2019, Journal of microbiology and biotechnology.

[7]  T. Hashimoto,et al.  Does dysbiotic endometrium affect blastocyst implantation in IVF patients? , 2019, Journal of Assisted Reproduction and Genetics.

[8]  S. Tsui,et al.  Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method. , 2019, Fertility and sterility.

[9]  J. A. Quesada,et al.  Effect of the vaginal microbiome on the pregnancy rate in women receiving assisted reproductive treatment , 2019, Journal of Assisted Reproduction and Genetics.

[10]  R. Romero,et al.  Does the endometrial cavity have a molecular microbial signature? , 2019, Scientific Reports.

[11]  A. Di Spiezio Sardo,et al.  Unified diagnostic criteria for chronic endometritis at fluid hysteroscopy: proposal and reliability evaluation through an international randomized-controlled observer study. , 2019, Fertility and sterility.

[12]  C. Lambalk,et al.  The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study. , 2019, Human reproduction.

[13]  P. Humaidan,et al.  Reproductive outcome of patients undergoing in vitro fertilisation treatment and diagnosed with bacterial vaginosis or abnormal vaginal microbiota: a systematic PRISMA review and meta‐analysis , 2019, BJOG : an international journal of obstetrics and gynaecology.

[14]  Y. Nagai,et al.  A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium , 2018, Reproductive medicine and biology.

[15]  I. Moreno,et al.  Relevance of assessing the uterine microbiota in infertility. , 2018, Fertility and sterility.

[16]  I. Joosten,et al.  How uterine microbiota might be responsible for a receptive, fertile endometrium , 2018, Human reproduction update.

[17]  Y. Nagai,et al.  Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single‐center pilot study , 2018, Reproductive medicine and biology.

[18]  J. Passmore,et al.  Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis , 2018, Front. Public Health.

[19]  M. Herbst-Kralovetz,et al.  Uterine Microbiota: Residents, Tourists, or Invaders? , 2018, Front. Immunol..

[20]  P. Valenti,et al.  Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense , 2018, Front. Immunol..

[21]  Huijue Jia,et al.  The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases , 2017, Nature Communications.

[22]  S. Hillier,et al.  Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin. , 2017, Anaerobe.

[23]  I. Moreno,et al.  Endometrial microbiota-new player in town. , 2017, Fertility and sterility.

[24]  S. Kallapur,et al.  The Human Ureaplasma Species as Causative Agents of Chorioamnionitis , 2016, Clinical Microbiology Reviews.

[25]  J. Jimenez-Almazan,et al.  Evidence that the endometrial microbiota has an effect on implantation success or failure. , 2016, American journal of obstetrics and gynecology.

[26]  P. Humaidan,et al.  Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients. , 2016, Human reproduction.

[27]  Jens Jørgen Christensen,et al.  Aerococcus christensenii as Part of Severe Polymicrobial Chorioamnionitis in a Pregnant Woman , 2016, The open microbiology journal.

[28]  R. Fichorova,et al.  The Human Microbiome during Bacterial Vaginosis , 2016, Clinical Microbiology Reviews.

[29]  Robert J. Moore,et al.  Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites , 2015, Nature Communications.

[30]  E. Cicinelli,et al.  Chronic Endometritis Due to Common Bacteria Is Prevalent in Women With Recurrent Miscarriage as Confirmed by Improved Pregnancy Outcome After Antibiotic Treatment , 2014, Reproductive Sciences.

[31]  R. Medzhitov,et al.  The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition , 2014, Proceedings of the National Academy of Sciences.

[32]  J. Segars,et al.  Potential Influence of the Microbiome on Infertility and Assisted Reproductive Technology , 2014, Seminars in Reproductive Medicine.

[33]  P. De Sutter,et al.  Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. , 2013, Human reproduction.

[34]  O. Carmona,et al.  Posible papel de Bacteroides fragilis enterotoxigénico en la etiología de la vaginitis infecciosa. , 2012 .

[35]  Ronald W. Davis,et al.  The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer , 2012, Journal of Assisted Reproduction and Genetics.

[36]  P. Gajer,et al.  Vaginal microbiome of reproductive-age women , 2010, Proceedings of the National Academy of Sciences.

[37]  A. Mencacci,et al.  Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome , 2007, Journal of Assisted Reproduction and Genetics.

[38]  L Wildt,et al.  Physiology of Upward Transport in the Human Female Genital Tract , 2007, Annals of the New York Academy of Sciences.

[39]  L. Åhrlund-Richter,et al.  Germfree status of mice obtained by embryo transfer in an isolator environment , 2005, Laboratory animals.

[40]  R. Ness,et al.  Bacterial vaginosis and anaerobic bacteria are associated with endometritis. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[41]  Y. Sasaki,et al.  Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. , 2004, Molecular human reproduction.

[42]  R. Cox,et al.  Clinical and microbiological features of Haemophilus influenzae vulvovaginitis in young girls , 2002, Journal of clinical pathology.

[43]  E. Shalev,et al.  Bacterial colonization of the uterine cervix and success rate in assisted reproduction: results of a prospective survey. , 2002, Human reproduction.

[44]  D. Gardner,et al.  Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. , 2000, Fertility and sterility.

[45]  I. Baragetti,et al.  Vaginal colonization with group B Streptococcus (Streptococcus agalactiae) and peritonitis in a woman on CAPD. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[46]  P. Lawson,et al.  Corynebacterium riegelii sp. nov., an Unusual Species Isolated from Female Patients with Urinary Tract Infections , 1998, Journal of Clinical Microbiology.

[47]  M A Krohn,et al.  The normal vaginal flora, H2O2-producing lactobacilli, and bacterial vaginosis in pregnant women. , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[48]  N. Treff,et al.  Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit , 2015, Journal of Assisted Reproduction and Genetics.

[49]  Steven R. Head,et al.  Next-generation sequencing , 2010, Nature Reviews Drug Discovery.