Key message
The evidence that the endometrial microbiome affects fertility outcomes is now substantial, consistent across cohorts, and strongest in women with recurrent implantation failure, recurrent pregnancy loss, and unexplained infertility. The effects are associations, not certainties. The size of the effects, and their independence from other known factors, is why microbiome testing has moved from research interest into clinical use.
For decades, fertility medicine focused on a familiar checklist: egg and sperm quality, hormones, anatomy, embryo grading. When all of these looked normal, many patients were given the diagnosis of unexplained infertility, a label that, in practice, meant standard workup had not found the reason.
Over the last decade, a new variable has entered the picture. Research using next-generation sequencing has shown that the endometrium hosts its own microbial community, and that the composition of this community is associated with whether IVF cycles succeed, whether pregnancies establish, and whether they are carried to term.
This article summarises what the evidence shows. It is written to be readable by patients and useful to clinicians. The first half covers the foundational studies and effect sizes in detail. The second half covers how the evidence maps onto clinical practice and where the limits of the evidence currently lie.
The foundational evidence
The paper that established the field is Moreno et al., 2016 (Am J Obstet Gynecol, n=35).
The study enrolled 35 IVF patients and assessed both endometrial receptivity (using gene-expression analysis) and endometrial microbiome composition (using 16S rRNA sequencing). The design was important: by restricting analysis to patients with a confirmed receptive endometrium, the study isolated the contribution of the microbiome from other receptivity factors.
The outcome differences between Lactobacillus-dominant (LD) and non-Lactobacillus-dominant (NLD) groups were substantial:
- Implantation rate: 60.7% (LD) vs 23.1% (NLD), p = 0.02
- Pregnancy rate: 70.6% vs 33.3%, p = 0.03
- Ongoing pregnancy rate: 58.8% vs 13.3%, p = 0.02
- Live birth rate: 58.8% vs 6.7%, p = 0.002
The study was small, and small studies tend to produce large effect sizes that attenuate on replication. But the direction and consistency of the signal prompted a much larger follow-up.
Moreno et al., 2022 (Microbiome, n=342) was a multicentre prospective observational study across four continents. It confirmed that a dysbiotic endometrial profile, characterised by Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus, and Streptococcus, was associated with unsuccessful outcomes. All patients in this cohort were asymptomatic for infection. The dysbiosis was silent.
Together, the 2016 and 2022 Moreno studies form the evidence spine of the field. They establish that endometrial microbiome composition is independently associated with reproductive outcomes and that this association holds in a large, multicentre, asymptomatic population.
Recurrent implantation failure
RIF, typically defined as failure to achieve pregnancy after two or more embryo transfers with good-quality embryos, is where the microbiome signal is most clinically relevant and most studied.
Hiratsuka et al., 2025 (Sci Rep, n=73) is one of the most rigorous recent analyses. Seventy-three RIF patients underwent three parallel diagnostic tests: hysteroscopy, CD138 immunohistochemistry for chronic endometritis, and endometrial microbiome sequencing. The prevalence findings:
- Chronic endometritis on hysteroscopy: 56.2%
- Chronic endometritis on CD138: 49.3%
- Endometrial dysbiosis on sequencing: 53.4%
Two findings are clinically important. First, the three tests identified largely different patient populations; they were not redundant. Second, among patients with dysbiosis who received antibiotic and probiotic treatment, 88.9% achieved clinical pregnancy post-treatment, significantly higher than in patients without dysbiosis.
Other RIF cohorts have reported dysbiosis prevalence ranging from 30% to 60%, with the variation largely explained by differences in RIF definition, sampling method, and the Lactobacillus threshold used. The consistent signal across these studies is that a substantial proportion of women with RIF have endometrial dysbiosis that conventional investigations miss.
Recurrent pregnancy loss
The RPL evidence is less mature than the RIF evidence.
Cohort studies have reported lower Lactobacillus abundance and higher microbial diversity in women with recurrent miscarriage compared with controls, but the available studies are small, heterogeneous, and not yet replicated at scale. The field is still working out whether microbial differences in RPL reflect a cause, a consequence, or a co-factor.
Chronic endometritis: the related condition
Chronic endometritis (CE) is a low-grade inflammatory condition of the endometrium, diagnosed histologically by the presence of plasma cells (typically identified by CD138 staining). It is related to, but not the same as, endometrial dysbiosis. Some patients have CE without dysbiosis, some have dysbiosis without CE, and many have both.
The clinical significance of CE is well-established. Cicinelli et al., 2015 (Hum Reprod) showed that CE is present in a substantial proportion of women with recurrent implantation failure, and that antibiotic treatment significantly improves reproductive outcomes in subsequent IVF cycles.
Vitagliano et al., 2018 (Fertil Steril), a systematic review and meta-analysis, confirmed the signal. Antibiotic treatment for CE in women with reproductive failure was associated with improved outcomes, particularly when CE was confirmed as cured on follow-up endometrial biopsy.
Zhang et al., 2024 (Ann Clin Microbiol Antimicrob) characterised the endometrial microbiota in 80 RIF patients (40 with CE, 40 without) and found CE patients carried a distinct community - reduced Lactobacillus, enrichment of Proteobacteria, and altered immune-related metabolic pathways - supporting the view that CE and dysbiosis are biologically linked rather than independent.
CE matters here because it overlaps with dysbiosis conceptually and clinically. Microbiome testing does not replace CE diagnosis. They are complementary investigations that together give a fuller picture of the endometrial environment.
What treatment evidence exists
The intervention evidence is less mature than the observational evidence, but it is growing.
Kyono et al., 2019 (Reprod Med Biol, n=92) treated a small subset of patients with non-Lactobacillus-dominant endometrial profiles using a combination of antibiotics and Lactobacillus supplementation. The treated cohort successfully shifted to Lactobacillus dominance, and larger subsequent cohorts have reproduced the conversion at higher rates with extended protocols.
The evidence base does not yet include large randomised controlled trials specifically comparing treated versus untreated dysbiosis on live birth outcomes. This is an important limit. What the evidence does show is that dysbiosis is often treatable, and that treatment followed by retesting can confirm whether Lactobacillus dominance has been restored before embryo transfer.
What the evidence supports, and what it doesn't
What the evidence supports
- Lactobacillus dominance (≥90%) in the endometrium is associated with higher implantation, pregnancy, and live birth rates across cohorts
- Dysbiosis is present in a substantial proportion, often around half, of women with recurrent implantation failure and unexplained infertility
- The dysbiosis-outcome association is independent of age, embryo quality, and other known receptivity factors in multivariable analyses
- Dysbiosis is typically asymptomatic and missed by conventional investigations
- Targeted antibiotic and probiotic therapy can restore Lactobacillus dominance in the majority of treated patients
- Chronic endometritis, a related condition, responds to antibiotic therapy with improved subsequent IVF outcomes
What the evidence does not yet support
Honest framing matters. The association is strong. The causal pathway is biologically plausible. The intervention evidence is promising but not yet definitive. For patients with recurrent implantation failure, recurrent pregnancy loss, or unexplained infertility, the evidence is sufficient for many clinicians to consider testing. For patients earlier in their fertility journey, it is not yet part of standard workup.
- That treating dysbiosis causes better live birth outcomes in a randomised-trial sense
- That any single Lactobacillus threshold (80% vs 90%) is the correct one
- That microbiome testing should be part of first-line fertility investigation for all patients
- That lifestyle, dietary, or over-the-counter interventions meaningfully alter the endometrial microbiome
Where the evidence points clinically
The patient groups where the evidence base is strongest, and where clinicians most commonly consider endometrial microbiome testing, are:
- Recurrent implantation failure after two or more transfers of good-quality embryos
- Recurrent pregnancy loss, particularly early loss
- Unexplained infertility where standard investigations have not identified a cause
- History of chronic endometritis or repeated intrauterine procedures
- Prior evidence of pelvic inflammatory disease or other conditions associated with altered reproductive tract microbiology
For clinicians, the decision to test usually comes down to whether the result will change management. In RIF, a dysbiotic finding typically prompts targeted treatment and retesting before the next transfer. In RPL, it contributes to a workup that is often weighing multiple potential contributors. In unexplained infertility, it can be the first clearly modifiable finding after a long series of investigations that came back normal.
The next article in this series covers testing itself: what the sample involves, what the report shows, and how results are interpreted in clinical practice.
How BioBloom fits in
Where this connects to clinical practice.
BioBloom provides DNA-based profiling of the endometrial microbiome, designed specifically for the clinical decisions fertility teams actually need to make.
Built for the endometrium
Our sequencing pipeline is developed for the low-biomass environment of the uterine cavity, not adapted from vaginal or gut microbiome protocols. Contamination controls are applied at every stage, from sampling through bioinformatic analysis, with negative-control subtraction and minimum-biomass thresholds that prevent over-interpretation of low-signal samples.
Species-level resolution
The report distinguishes between Lactobacillus species rather than reporting Lactobacillus as a single block. L. crispatus and L. iners have different clinical associations in the published literature, and this distinction supports more informed treatment decisions.
Clinician-facing reports
Structured to support the discussion between patient and consultant, and the decisions around treatment and embryo transfer timing. The test is ordered through partner clinics, and samples are collected by clinicians trained in the protocol. It is not a home test.
Cambridge origin, UK clinical network
BioBloom was founded out of Cambridge and works with fertility clinics across the UK. The test development has been shaped by direct input from practising fertility consultants and embryologists.
Frequently asked questions
Questions, answered.
Next step
Where to go from here.
For patients
If any of the clinical situations described above apply to you, the next step is a conversation with a fertility specialist familiar with microbiome-guided care. BioBloom works with partner clinics across the UK who can order the test and interpret results in the context of your history.
For clinicians
Methodology, sample specifications, and evidence summaries are covered across the four-part series - use Parts 3 and 4 in particular when planning how to integrate testing and act on a result.
References
Citations & further reading
- 01Moreno I, Codoñer FM, Vilella F, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684-703.
- 02Moreno I, Garcia-Grau I, Perez-Villaroya D, et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome. 2022;10(1):1.
- 03Hiratsuka D, Matsuo M, Kashiwabara K, et al. Comparison of diagnostic tests for chronic endometritis and endometrial dysbiosis in recurrent implantation failure: impact on pregnancy outcomes. Sci Rep. 2025;15:8272.
- 04Cicinelli E, Matteo M, Tinelli R, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30(2):323-330.
- 05Vitagliano A, Saccardi C, Noventa M, et al. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis. Fertil Steril. 2018;110(1):103-112.
- 06Kyono K, Hashimoto T, Kikuchi S, Nagai Y, Sakuraba Y. 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. Reprod Med Biol. 2019;18(1):72-82.
- 07Zhang H, Zou H, Zhang C, Zhang S. Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure. Ann Clin Microbiol Antimicrob. 2024;23(1):49.