Beyond the reproductive tract: gut microbiome and its influence on gynecological health.

PURPOSE OF REVIEW: The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS: The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY: The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.

[Vaginal microbiota abnormalities in women with unexplained infertility and its treatment].

The vaginal microbiota is a complex and dynamic environment that plays an important role in the healthy reproduction of women. The mechanism of unexplained infertility is not yet clear, and the imbalance and low stability of vaginal microbiota may be related to unexplained infertility. Taking probiotic composite preparations to restore normal vaginal microbiota may be a safe and natural method for treating unexplained infertility. This article reviews the probiotic composite preparations used in the treatment of unexplained infertility both domestically and internationally, including the isolation site of the bacterial species, the use method of the composite preparation, the course of treatment, and the final therapeutic effect, aiming to provide a basis for the clinical application of probiotic composite preparations in the treatment of unexplained infertility.

Analysis of the microbiota composition in the genital tract of infertile patients with chronic endometritis or endometrial polyps.

Background: The previous researches show that infertile patients have a higher incidence of endometritis and endometrial polyps, and the occurrence of these two diseases is related to changes in the microbiota of the genital tract. We aim to determine the composition and changing characteristics of the microbiota in the genital tract (especially the endometrium) of infertile patients with chronic endometritis or endometrial polyps, and find the correlation between it and the occurrence of diseases. Methods: This is a prospective study. We collected genital tract biopsy samples from 134 asymptomatic infertile patients receiving assisted reproductive therapy before embryo transfer. Through pathological examination and 16S ribosomal RNA(16S rRNA) sequencing, we determined the distribution of chronic endometritis and endometrial polyps in these patients, as well as their distribution of reproductive tract microorganisms. Results: Compared with the normal control group, the microbial group of reproductive tract in patients with chronic endometritis and endometrial polyps is changed, and there are significant species differences and relative abundance differences in the vagina, cervix and uterine cavity. Lactobacillus, the dominant flora of female genital tract, showed a change in abundance in patients with endometrial diseases. Endometrial microbiota composed of Staphylococcus, Gardnerella, Atopobium, Streptococcus, Peptostreptococcus, Chlamydia, Fusobacterium, Acinetobacter, etc. are related to chronic endometritis and endometrial polyps. Conclusion: The results showed that, compared with the normal control group, the endometrial microbiota of infertile patients with chronic endometritis or endometrial polyps did have significant changes in the relative abundance distribution of species, suggesting that changes in local microecology may be an important factor in the occurrence of disease, or even adverse pregnancy outcomes. The further study of endometrial microecology may provide a new opportunity to further improve the diagnosis and treatment strategy of chronic endometritis.

Forty years of development of salpingitis animal modeling.

This review summarizes and examines research in the area of salpingitis animal modeling in the last 40 years, focusing primarily on Chlamydia trachomatis animal models, which are the most numerous in the literature. Early animal models are examined, followed by a discussion of study parameters and their impact on modeling success, subsequent considerations of fertility measures in modeling, explorations of treatment options, and finally exploring recent directions with a brief discussion of models using other bacterial pathogens.

Evaluation of Ureaplasma urealyticum, Chlamydia trachomatis, Mycoplasma genitalium and Neisseria gonorrhoeae in infertile women compared to pregnant women.

Infertility is one of the major health problems of patients suffering from bacterial infections. Given the high percentage of infertility, the aim of this study was to investigate the prevalence of Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae and Ureaplasma urealyticum in fertile and infertile women. In the prospective study, 65 infertile patients and 54 pregnant women referred to Mahdieh Hospital in Tehran were included. After transferring of vaginal swabs to the laboratory, DNA extraction and Polymerase Chain Reaction (PCR) were performed using specific primers. Of the 65 vaginal swab specimens, the prevalence of U. urealyticum, M. genitalium, C. trachomatis and N. gonorrhoeae were as 15 (23.1%), 11 (16.9%), 9 (13.8%) and 4 (6.2%), respectively; However, these rate in fertile group was as 6 (11.1%), 3 (5.5%), 5 (9.2%) and 1 (1.8%), respectively. Bacterial infections were higher in infertile group; therefore, these bacterial agents may be associated with female infertility. Timely control and treatment of infections caused by these organisms, together with other factors, can be important in prevention and treatment of the women's infertility and thereby community health.Impact StatementWhat is already known on this subject? Infertility is one of the most common reproductive health issues in Iran. Female reproductive system is a suitable environment for the growth of many pathogens, which may disrupt any stage of foetal formation, implantation or growth. Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma urealyticum are the most important microorganisms that have been considered in the infertility.What do the results of this study add? The prevalence of C. trachomatis, M. genitalium, N. gonorrhoeae, M. genitalium and U. urealyticum were higher in infertile women, but there was no statistically significant compared to pregnant women. These results suggest that timely control and treatment of infections caused by these organisms, along with other factors, can be used to prevent and treat women infertility and community health.What are the implications of these findings for clinical practice and/or further research? Based on the results, designing and implementing national control programs to prevent subsequent complications is thought to be necessary. Comprehensive analyses of the overall prevalence of these bacteria, particularly in developing countries (including Iran), may help to carry out such a strategy.

Imaging Spectrum of Female Genital Tuberculosis: A Comprehensive Review.

Female genital tuberculosis is a relatively uncommon form of extrapulmonary tuberculosis that is under-reported and under-recognized. The early course of the disease has fewer manifestations, resulting in late presentation with grave complications like infertility and ectopic pregnancy. Also, difficulty in isolation of the causative bacteria further delays the diagnosis. The radiologist should be well versed with imaging findings of female genital TB to help the clinicians to initiate prompt treatment. This review shall cover imaging findings of female genital TB involving fallopian tubes, uterus, ovaries, cervix, vagina, and vulva on different imaging modalities. Fallopian tubes are almost always involved in genital TB followed by uterus and ovaries. Hysterosalpingogram and ultrasound can best detect tubercular changes in fallopian tubes and uterus whereas cross-sectional imaging is essential for the diagnosis of ovarian or peritoneal TB as they closely mimic malignancy. Cervical, vaginal, or vulval TB produces nonspecific changes and histopathological diagnosis is required for confirmation of the diagnoses. Close differential diagnosis on imaging like malignancy or pelvic inflammatory disease, are also discussed with a brief discussion of the pathogenesis.

Fallopian tubal infertility: the result of Chlamydia trachomatis-induced fallopian tubal fibrosis.

Chlamydia trachomatis is one of the most common pathogens of sexually transmitted diseases, and its incidence in genital tract infections is now 4.7% in south China. Infertility is the end result of C. trachomatis-induced fallopian tubal fibrosis and is receiving intense attention from scientists worldwide. To reduce the incidence of infertility, it is important to understand the pathology-related changes of the genital tract where C. trachomatis infection is significant, especially the mechanism of fibrosis formation. During fibrosis development, the fallopian tube becomes sticky and occluded, which will eventually lead to tubal infertility. At present, the mechanism of fallopian tubal fibrosis induced by C. trachomatis infection is unclear. Our study attempted to summarize the possible mechanisms of fibrosis caused by C. trachomatis infection in the fallopian tube by reviewing published studies and further providing potential therapeutic targets to reduce the occurrence of infertility. This study also provides ideas for future research. Factors leading to fallopian tube fibrosis include inflammatory factors, miRNA, ECT, cHSP, and host factors. We hypothesized that C. trachomatis mediates the transcription and translation of EMT and ECM via upregulating TGF signaling pathway, which leads to the formation of fallopian tube fibrosis and ultimately to tubal infertility.

Host Genetic Risk Factors for Chlamydia trachomatis-Related Infertility in Women.

BACKGROUND: Chlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap. METHODS: We identified infertility genome-wide association study (GWAS) loci using deoxyribonucleic acid from Ct-seropositive cisgender women in a tubal factor infertility study and Ct-infected cisgender women from a longitudinal pelvic inflammatory disease cohort with known fertility status. Deoxyribonucleic acid and blood messenger ribonucleic acid from 2 additional female cohorts with active Ct infection and known endometrial infection status were used to investigate the impact of infertility single-nucleotide polymorphisms (SNPs) on Ct ascension. A statistical mediation test examined whether multiple infertility SNPs jointly influenced ascension risk by modulating expression of mediator genes. RESULTS: We identified 112 candidate infertility GWAS loci, and 31 associated with Ct ascension. The SNPs altered chlamydial ascension by modulating expression of 40 mediator genes. Mediator genes identified are involved in innate immune responses including type I interferon production, T-cell function, fibrosis, female reproductive tract health, and protein synthesis and degradation. CONCLUSIONS: We identified Ct-related infertility loci and their potential functional effects on Ct ascension.

What Can Serology Tell Us About the Burden of Infertility in Women Caused by Chlamydia?

Chlamydia trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia's contribution to female infertility.

Effect of probiotics on vaginal Ureaplasma parvum in women suffering from unexplained infertility.

RESEARCH QUESTION: Does oral probiotic supplementation influence the relative abundance of different vaginal microbiota in women experiencing infertility? DESIGN: A prospective, monocentric randomized controlled trial. To study the influence of probiotics on infertility, 80 patients with primary or secondary infertility were included. Patients were assigned to either a probiotic treatment or a control group. Participants in the treatment group (n = 40) took one sachet (2 g) a day of a defined probiotic supplement limiting Lactobacillus strains. Patients in the control group did not receive any additional probiotic supplements. Vaginal samples were taken on day 20 of the menstrual cycle and 4 weeks later, on day 20, of the consecutive cycle. Subsequently, 16s rRNA gene analysis of the vaginal samples was conducted. RESULTS: After the intervention phase, no effects on alpha diversity resulting from treatment could be observed. The between sample diversity of different women (beta diversity) at baseline had no effects of age, treatment group or body mass index. Primary or secondary sterility, however, had a significant effect on community. Three clusters (Lactobacillus crispatus, Lactobacillus iners and Lactobacillus gasseri) were identified as the leading representatives. Furthermore, patients treated with probiotics showed limited growth of Ureaplasma parvum compared with the control group (P = 0.021). CONCLUSIONS: This study points to a possible protective effect of probiotic supplements on the vaginal microbiota. It is tempting to speculate that this effect assists in containing the growth of non-beneficial bacteria and helps to prevent or cure a dysbiotic vaginal flora.

Results from a large cross-sectional study assessing Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma hominis urogenital infections in patients with primary infertility.

Female and male infertility have been associated to Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma hominis urogenital infections. However, evidence from large studies assessing their prevalence and putative associations in patients with infertility is still scarce. The study design was a cross-sectional study including 5464 patients with a recent diagnosis of couple's primary infertility and 404 healthy control individuals from Cordoba, Argentina. Overall, the prevalence of C. trachomatis, Ureaplasma spp. and M. hominis urogenital infection was significantly higher in patients than in control individuals (5.3%, 22.8% and 7.4% vs. 2.0%, 17.8% and 1.7%, respectively). C. trachomatis and M. hominis infections were significantly more prevalent in male patients whereas Ureaplasma spp. and M. hominis infections were more prevalent in female patients. Of clinical importance, C. trachomatis and Ureaplasma spp. infections were significantly higher in patients younger than 25 years. Moreover, Ureaplasma spp. and M. hominis infections were associated to each other in either female or male patients being reciprocal risk factors of their co-infection. Our data revealed that C. trachomatis, Ureaplasma spp. and M. hominis are prevalent uropathogens in patients with couple's primary infertility. These results highlight the importance of including the screening of urogenital infections in the diagnostic workup of infertility.

How prevalent are symptoms and risk factors of pelvic inflammatory disease in a sexually conservative population.

BACKGROUND: Pelvic inflammatory disease (PID) is the inflammation of the adnexa of the uterus, that mainly manifests in a subclinical/chronic context and goes largely underreported. However, it poses a major threat to women's health, as it is responsible for infertility and ectopic pregnancies, as well as chronic pelvic pain. Previous studies in Jordan have not reported PID, attributed mainly to the social structure of the country which largely represents a sexually conservative population. Our study aims to report the clinical symptoms that point towards PID and investigate the major risk determinants for the Jordanian population, in a cross-sectional study, using our scoring system based only on clinical data and examination. METHODS: One hundred sixty-eight consecutive adult women that came in the Outpatient Clinics of Gynaecological Department of the Jordan University Hospital were interviewed and their medical history and symptoms were registered and analysed. A Score for PID symptoms, we developed, was given to each woman. Results and correlations were then statistically tested. RESULTS: Our study population consisted of relatively young women (37.7 ± 11) that had their first child at an average age of 24.1 (± 4.8) and a mean parity of 3.1 (± 2.2). Fifty-eight women (34.5%) reported having undergone at least one CS, while the mean PID Symptom Score was 3.3 (± 2.3). The women in our study exhibited 8 symptoms of PID, namely dysmenorrhea and vaginal discharge; being the commonest (45.2% and 44.6% respectively), in addition to chronic pelvic pain, pelvic heaviness, menorrhagia, dyspareunia, urinary symptoms, and smelly urine. They also reported history of 3 conditions that can be attributed to PID, that is infertility, preterm labour, and miscarriages. CONCLUSIONS: Our PID Scoring System seems to identify the risk factors of PID and predict well the PID likelihood. This score predicts that women with higher parity, who used contraceptives and underwent any invasive medical procedure are expected to score higher in the PID Symptom Score. Our data also suggest that PID should not be ruled out in the Jordanian population when symptoms are compatible to this diagnosis.

As a sexually conservative country, Jordan is thought to have a low prevalence of pelvic inflammatory disease. The prevalence of STD pathogens is very low, however many patients present symptoms of PID, so we randomly interviewed 168 healthy participants and investigated symptoms related to PID. Surprisingly the percentage of participants who had symptoms of PID was high, reaching up to 64% for some symptoms. We then created a PID symptom score; where every symptom gets one mark (1­11), and tested it for association against independent factors. As a result, it can be predicted that a woman with higher parity, who used contraceptives, and underwent E & C, D & C, HSG, or Hysteroscopy is expected to score higher in the PID Symptom Score.This result draws the attention to PID incidence in similar conservative communities, and therefore further research is needed to confirm the prevalence of PID and identify the causative factors.

Potential biomarkers of infertility associated with microbiome imbalances.

PROBLEM: The aim of this study was to investigate the possible relationship between vaginal/rectal microbiome disbalances and miRNA expression with infertility. METHOD OF STUDY: Observational, exploratory, preliminary study. A total of 287 multiple IVF failure infertile patients were recruited. Twenty fertile women, not IVF failure, were recruited as the control group. Swab samples were collected from the vagina and rectum. Microbial composition by NGS and miRNA expression by real-time PCR of vaginal and rectal samples was measured. Immunometabolic markers from blood (insulin, vitamin D, LDL-cholesterol, ANA, TPO, Tg, and ASCA antibodies) and saliva (sIgA) were analyzed. RESULT(S): Infertile patients showed a lower bacterial richness and increased Firmicutes/Bacteroidetes ratio at rectal level and an increased Lactobacillus brevis/Lactobacillus iners ratio in vaginal samples regarding the fertile group. In the same rectal swab samples, we found that miR-21-5p, which is associated with tight junction disruption and yeast overgrowth, is upregulated and that miR-155-5p, which is associated with inflammation, is overexpressed in the unexplained infertile group (*p < .05). These deregulated miRNAs were also upregulated in the vaginal samples from the same patients (*p < .05). CONCLUSION: miRNAs could be potential biomarkers of the inflammatory impact of microbiome disbalances in unexplained infertile women.

16S rRNA long-read nanopore sequencing is feasible and reliable for endometrial microbiome analysis.

RESEARCH QUESTION: Full-length 16S rRNA gene sequencing using nanopore technology is a fast alternative to conventional short-read 16S rRNA gene sequencing with low initial investment costs that has been used for various microbiome studies but has not yet been investigated as an alternative approach for endometrial microbiome analysis. Is in-situ 16S rRNA gene long-read sequencing using portable nanopore sequencing technology feasible and reliable for endometrial microbiome analysis? DESIGN: A prospective experimental study based on 33 patients seeking infertility treatment between January and October 2019. A 16S rRNA gene long-read nanopore sequencing protocol for analysing endometrial microbiome samples was established, including negative controls for contamination evaluation and positive controls for bias evaluation. Contamination caused by kit and exterior sources was identified and excluded from the analysis. Endometrial samples from 33 infertile patients were sequenced using the optimized long-read nanopore sequencing protocol and compared with conventional short-read sequencing carried out by external laboratories. RESULTS: Of the 33 endometrial patient samples, 23 successfully amplified (69.7%) and their microbiome was assessed using nanopore sequencing. Of those 23 samples, 14 (60.9%) were Lactobacillus-dominated (>80% of reads mapping to Lactobacillus), with 10 samples resulting in more than 90% Lactobacillus reads. Our long-read nanopore sequencing revealed results similar to two conventional short-read sequencing approaches and to long-read sequencing validation carried out in external laboratories. CONCLUSION: In this pilot study, 16S rRNA gene long-read nanopore sequencing was established to analyse the endometrial microbiome in situ that could be widely applied owing to its cost efficiency and portable character.

The Impact of Selected Bacterial Sexually Transmitted Diseases on Pregnancy and Female Fertility.

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance.

Genital tuberculosis role in female infertility in Portugal.

INTRODUCTION: Genitourinary tuberculosis is the fourth most common cause of extrapulmonary tuberculosis, although often underestimated by clinicians due to its rare and non-specific symptoms. One of the disease's complications is infertility. Although Portugal is one of the European countries with the highest prevalence of tuberculosis, its impact on Portuguese female fertility is unknown. With this study, we intend to evaluate the prevalence of genital tuberculosis, its presenting symptoms, and pregnancy outcomes in infertile women followed in a Portuguese tertiary hospital. METHODS: Retrospective and descriptive study, performed using an electronic database and consultation of clinical files. Studied population: infertile women followed from 2000 until 2019 at the reproductive unit of a Portuguese tertiary hospital, who underwent endometrial biopsy/curettage in the context of their etiological investigation. The diagnosis of genital tuberculosis was based on histological criteria. RESULTS: Over the 19 years, 2653 endometrial specimens were analyzed. Pathological evaluation was positive for tuberculosis in 19 cases (0.72%). There was a decrease in new diagnoses throughout the observation period. CONCLUSION: Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients.

The Role of Genital Tract Microbiome in Fertility: A Systematic Review.

The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.

Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease.

Bacterial vaginosis, pelvic inflammatory disease, and endometritis are infections of the genital tract that can lead to many adverse health outcomes, including infertility. Bacterial vaginosis is characterized by a lower prevalence of lactobacilli and a higher prevalence of anaerobic bacteria, including Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae. Endometritis and pelvic inflammatory disease are caused by the ascension of pathogenic bacteria to the uterus, although the mechanisms by which they do so are unclear. Bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease have been linked to infertility in retrospective and prospective trials. Similarly, the causes of bacterial vaginosis and endometritis-related infertility are likely multifactorial and stem from inflammation, immune targeting of sperm antigens, the presence of bacterial toxins, and increased risk of sexually transmitted infections. Diagnosis and treatment of bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease before attempting conception may be important components of preconceptional care for symptomatic women to improve outcomes of natural and assisted reproduction.

Probiotics Dietary Supplementation for Modulating Endocrine and Fertility Microbiota Dysbiosis.

Human microbiota seems to play a key role in endocrine and reproductive systems. Fortunately, microbiota reproductive dysbiosis start to be treated by probiotics using typical species from genus Lactobacillus. This work presents the compiled and analysed results from the most up-to-date information from clinical trials regarding microbiota, fertility, probiotics and oral route administration, reviewing open access scientific documents. These studies analyse the clinical impact of probiotics administered on several endocrine disorders' manifestations in women: mastitis; vaginal dysbiosis; pregnancy complication disorders; and polycystic ovary syndrome. In all cases, the clinical modulation achieved by probiotics was evaluated positively through the improvement of specific disease outcomes with the exception of the pregnancy disorders studies, where the sample sizes results were statistically insufficient. High amounts of studies were discarded because no data were provided on specific probiotic strains, doses, impact on the individual autochthon microbiota, or data regarding specific hormonal values modifications and endocrine regulation effects. However, most of the selected studies with probiotics contained no protocolised administration. Therefore, we consider that intervention studies with probiotics might allocate the focus, not only in obtaining a final outcome, but in how to personalise the administration according to the disorder to be palliated.

The vaginal microbiome as a tool to predict IVF success.

PURPOSE OF REVIEW: Herein, we present an overview of the recent microbiome research and findings within the field of reproductive medicine and its relation with the outcome of Assisted reproductive technology (ART). Analyses of the microbiome composition all throughout the female reproductive trace during the process of assisted reproductive techniques are discussed. RECENT FINDINGS: Only the vaginal microbiome can be sampled without possible risks of contamination. Although this also seems to apply to the cervical microbiome, collection has to be performed with extreme caution. Because of the high risk of cross contamination, results of microbial composition of all other sites of the female reproductive tract have to be interpreted with caution. The vaginal composition prior to the start of hormonal treatment for ART seems to be predictive of in vitro fertilization/in vitro fertilization-intracytoplasmic sperm injection (IVF/IVF-ICSI) outcome, with mainly a highly negative predictive value. SUMMARY: The local microbiota, especially the absence or presence of specific microbes, within parts of the female reproductive tract seem to be associated with the outcome of ART.