Comparative Study on the Vaginal Flora and Incidence of Asymptomatic Vaginosis among Healthy Women and in Women with Infertility Problems of Reproductive Age

Babu, Geethavani; Singaravelu, Balamuru Ganvelu; Srikumar, Ramakrishnan; Reddy, Sreenivasalu V; Kokan, Afraa

doi:10.7860/jcdr/2017/28296.10417

Cited by 55 publications

(55 citation statements)

References 41 publications

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“…(10) Studies have shown that the presence of certain Lactobacillus species during ART procedures may have a positive impact on outcome (4,11,12), whereas bacterial vaginosis is associated with poorer results. (13,14) The use of the vaginal microbiome as a predictor for ART outcome has not yet been investigated. We aimed to answer the following questions: First, is the presence or absence of certain vaginal bacteria associated with failure or success to become pregnant after an IVF or IVF-ICSI treatment?…”

Section: Introductionmentioning

confidence: 99%

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The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study

Koedooder¹,

et al. 2019

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STUDY QUESTION Is the presence or absence of certain vaginal bacteria associated with failure or success to become pregnant after an in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (IVF-ICSI) treatment? SUMMARY ANSWER Microbiome profiling with the use of interspace profiling (IS-pro) technique enables stratification of the chance of becoming pregnant prior to the start of an IVF or IVF-ICSI treatment. WHAT IS KNOWN ALREADY Live-birth rates for an IVF or IVF-ICSI treatment vary between 25 and 35% per cycle and it is difficult to predict who will or will not get pregnant after embryo transfer (ET). Recently, it was suggested that the composition of the vaginal microbiota prior to treatment might predict pregnancy outcome. Analysis of the vaginal microbiome prior to treatment might, therefore, offer an opportunity to improve the success rate of IVF or IVF-ICSI. STUDY DESIGN, SIZE, DURATION In a prospective cohort study, 303 women (age, 20–42 years) undergoing IVF or IVF-ICSI treatment in the Netherlands were included between June 2015 and March 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Study subjects provided a vaginal sample before the start of the IVF or IVF-ICSI procedure. The vaginal microbiota composition was determined using the IS-pro technique. IS-pro is a eubacterial technique based on the detection and categorization of the length of the 16S–23S rRNA gene interspace region. Microbiome profiles were assigned to community state types based on the dominant bacterial species. The predictive accuracy of the microbiome profiles for IVF and IVF-ICSI outcome of fresh ET was evaluated by a combined prediction model based on a small number of bacterial species. From this cohort, a model was built to predict outcome of fertility treatment. This model was externally validated in a cohort of 50 women who were undergoing IVF or IVF-ICSI treatment between March 2018 and May 2018 in the Dutch division of the MVZ VivaNeo Kinderwunschzentrum Düsseldorf, Germany. MAIN RESULTS AND THE ROLE OF CHANCE In total, the vaginal microbiota of 192 women who underwent a fresh ET could be analysed. Women with a low percentage of Lactobacillus in their vaginal sample were less likely to have a successful embryo implantation. The prediction model identified a subgroup of women (17.7%, n = 34) who had a low chance to become pregnant following fresh ET. This failure was correctly predicted in 32 out of 34 women based on the vaginal microbiota composition, resulting in a predictive accuracy of 94% (sensitivity, 26%; specificity, 97%). Additionally, the degree of dominance of Lactobacillus crispatus was an important factor in predicting pregnancy. Women who had a favourable profile as well as <60% L. crispatus had a high chance of pregnancy: more than half of these women (50 out of 95) became pregnant. In the external validation cohort, none of the women who had a negative prediction (low chance of pregnancy) became pregnant. LIMITATIONS, REASONS FOR CAUTION Because our study uses a well-defined study population, the results will be limited to the IVF or IVF-ICSI population. Whether these results can be extrapolated to the general population trying to achieve pregnancy without ART cannot be determined from these data. WIDER IMPLICATIONS OF THE FINDINGS Our results indicate that vaginal microbiome profiling using the IS-pro technique enables stratification of the chance of becoming pregnant prior to the start of an IVF or IVF-ICSI treatment. Knowledge of their vaginal microbiota may enable couples to make a more balanced decision regarding timing and continuation of their IVF or IVF-ICSI treatment cycles. STUDY FUNDING/COMPETING INTEREST(S) This study was financed by NGI Pre-Seed 2014–2016, RedMedTech Discovery Fund 2014–2017, STW Valorisation grant 1 2014–2015, STW Take-off early phase trajectory 2015–2016 and Eurostars VALBIOME grant (reference number: 8884). The employer of W.J.S.S.C. has in collaboration with ARTPred acquired a MIND subsidy to cover part of the costs of this collaboration project. The following grants are received but not used to finance this study: grants from Innovatie Prestatie Contract, MIT Haalbaarheid, other from Dutch R&D tax credit WBSO, RedMedTech Discovery Fund, (J.D.d.J.). Grants from Ferring (J.S.E.L., K.F., C.B.L. and J.M.J.S.S.), Merck Serono (K.F. and C.B.L.), Dutch Heart Foundation (J.S.E.L.), Metagenics Inc. (J.S.E.L.), GoodLife (K.F.), Guerbet (C.B.L.). R.K. is employed by ARTPred B.V. during her PhD at Erasmus Medical Centre (MC). S.A.M. has a 100% University appointment. I.S.P.H.M.S., S.A.M. and A.E.B. are co-owners of IS-Diagnostics Ltd. J.D.d.J. is co-owner of ARTPred B.V., from which he reports personal fees. P.H.M.S. reports non-financial support from ARTPred B.V. P.H.M.S., J.D.d.J. and A.E.B. have obtained patents `Microbial population analysis’ (9506109) and `Microbial population analysis’ (20170159108), both licenced to ARTPred B.V. J.D.d.J. and A.E.B. report patent applications `Method and kit for predicting the outcome of an assisted reproductive technology procedure’ (392EPP0) and patent `Method and kit for altering the outcome of an assisted reproductive technology procedure’ by ARTPred. W.J.S.S.C. received personal consultancy and educational fees from Goodlife Fertility B.V. J.S.E.L. reports personal consultancy fees from ARTPred B.V., Titus Health B.V., Danone, Euroscreen and Roche during the conduct of the study. J.S.E.L. and N.G.M.B. are co-applicants on an Erasmus MC patent (New method and kit for prediction success of in vitro fertilization) licenced to ARTPred B.V. F.J.M.B. reports personal fees from Advisory Board Ferring, Advisory Board Merck Serono, Advisory Board Gedeon Richter and personal fees from Educational activities for Ferring, outside the submitted work. K.F. reports personal fees from Ferring (commercial sponsor) and personal fees from GoodLife (commercial sponsor). C.B.L. received speakers’ fee from Ferring. J.M.J.S.S. reports personal fees and other from Merck Serono and personal fees from Ferring, unrelated to the submitted paper. The other authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER ISRCTN83157250. Registered 17 August 2018. Retrospectively registered.

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Section: Introductionmentioning

confidence: 99%

“…(8) Propionibacteriumand Actinomyces were also found to impair clinical outcomes (17). Bacterial vaginosis was further associated with infertility and early spontaneous abortion (13,14).…”

mentioning

confidence: 99%

The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study

Koedooder¹,

et al. 2019

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“…In a study conducted by Singaravelu, et al over a period of 6 months in 116 women with infertility problems at Sri Lakshmi Narayana Medical College and Hospital Pondicherry, it was observed that women with infertility problems showed abundance of Bacterial Vaginosis (Lactobacillus, 3.5%) compared to healthy women (Lactobacillus, 27.8%). Author of the study recommended the screening of vaginal flora as a routine for all women, especially in women undergoing infertility treatment [9]. In another study conducted by Pramanik, et al in 510 women with manifestations such as infertility, it was found that BV infection is associated with infertility and its absence leads to pregnancy, emphasizing its screening and treatment [10].…”

Section: Prevalence and Association Of Bv With Infertilitymentioning

confidence: 99%

Bacterial Vaginosis: An Underestimated Cause of Unexplained Infertility

Aa¹

2018

OAJG

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Bacterial Vaginosis (BV) characterized by symptoms of vaginal malodor and slightly too moderately increased white discharge, which appears homogeneous, with low viscosity and smoothly coats vaginal mucosa. The vaginal fluid of women with bacterial vaginosis is characterized by markedly increase prevalence and concentration of G. vaginalis, Mycoplasma hominis and several anaerobic bacteria's. The normal acidic lactobacilli is the constitute most of the normal vaginal flora and help to protect against certain cervical and vaginal infections. L. gasseri, L crispatus produce large amounts of H2O2 and inhibits the growth of G. vaginalis while L. rhamnosus increases colonization of lactobacilli and decreases the recurrence of BV. Studies have reported a high prevalence of BV in both non-tubal and unexplained infertility. The most common oral treatment for BV in both pregnant and non-pregnant women is metronidazole. Therapy with metronidazole or clindamycin alters the vaginal flora and predisposes the patient to development of vaginal candidiasis. Recurrence rate of BV remains high with use of antimicrobials and such treatments are not designed to restore the lactobacilli. Antimicrobial drug resistance remains a root cause for BV recurrence. Probiotic supplementation as part of a broader lifestyle intervention aimed at improving fertility as the potential for side effects is nearly nonexistent, and there are reasons to think that it could be helpful.

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“…It most often causes leucorrhoea with a foul odour and sometimes irritations that lead women to seek gynaecological care [2]. It is associated with the risk of preterm birth, miscarriage, and low birth weight when presenting in pregnant women [3], as well as the risk of pelvic in ammatory diseases [4]. Bacterial vaginosis predisposes women to serious health problems, including the acquisition and transmission of various pathogens such as herpes simplex virus-2 [5], human immunode ciency virus-1 [6], papillomavirus [7], Neisseria gonorrhoeae, Trichomonas vaginalis, and Chlamydia trachomatis [8,9].…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the Vaginal Microbiota Using Culturomics and Metagenomics Suggests Transplantation of Gut Microbiota Into the Vagina During Bacterial Vaginosis

Diop

Fall

Levasseur

et al. 2020

Preprint

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Background: Bacterial vaginosis is a very common vaginal disorder, with a gynaeco-obstetrical impact, but remains poorly understood. Current antibiotic treatment most often fails. Our objective was to exhaustively map the bacterial community present in bacterial vaginosis and normal flora, using not only a molecular approach but also a highly efficient culture approach, culturomics. Vaginal bacterial diversity was evaluated using both strategies for 24 Caucasian French women, including 7 cases of bacterial vaginosis, and 10 rural Senegalese women, including 5 cases of bacterial vaginosis. An additional 16 specimens (three cases of bacterial vaginosis and 13 normal flora) obtained during the follow-up visits of five French women with bacterial vaginosis were analysed using metagenomics.Results: The combination of culturomics and metagenomics reveals the richness and diversity of vaginal microbiota. Our data demonstrated that compared to healthy women, those with bacterial vaginosis present a shift in vaginal flora. The microbiota of the bacterial vaginosis group can be easily distinguished from that of healthy group by their increased bacterial diversity, abundance of Bacteroidales and Leptotrichiaeceae, and depletion of Proteobacteria and Lactobacillaceae species. In addition, a complex of 10 genera was associated with bacterial vaginosis: Gardnerella, Atopobium, Snethia, Aerococcus, Prevotella, Gemella, Facklamia, Porphyromonas, Mycoplasma, and Urinacoccus. Overall, the microbial population detected in bacterial vaginosis flora was largely similar to the bacterial communities found in gut microbiota. The two approaches showed a diverse vaginal microbiota that was largely non-overlapping, with only 146 common species. Furthermore, culturomics extends the repertoire of human-associated bacteria with the isolation of 27 new bacterial species.Conclusions: This study provides the most representative topology of the vaginal microbiota of normal flora and bacterial vaginosis and suggests the transplantation of gut microbiota into the vagina during bacterial vaginosis. Several sets of clinically relevant anaerobic bacteria and new species were also isolated from the human vagina, confirming that some previously “uncultivated” species may be cultivated using an appropriate strategy. Exhaustive characterisation of vaginal microbiota will enable a better understanding and management of bacterial vaginosis. Obtaining isolates will allow us to explore the bacterial interactions of the vaginal microbiota and will serve as a basis for the potential development of bacteriotherapy to prevent or treat vaginal dysbiosis.

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Comparative Study on the Vaginal Flora and Incidence of Asymptomatic Vaginosis among Healthy Women and in Women with Infertility Problems of Reproductive Age

Cited by 55 publications

References 41 publications

The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study

The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study

Bacterial Vaginosis: An Underestimated Cause of Unexplained Infertility

Characterisation of the Vaginal Microbiota Using Culturomics and Metagenomics Suggests Transplantation of Gut Microbiota Into the Vagina During Bacterial Vaginosis

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