The standard fertility investigations do not always find a reason. Embryos look good. Hormones look normal. Transfers do not take, or pregnancies do not hold, and no one can tell you why. Clinicians will recognise that cohort. Recurrent implantation failure, recurrent pregnancy loss, and unexplained infertility remain the hardest groups to investigate productively once the standard workup returns normal.
One of the factors increasingly recognised in that space, and increasingly testable, is the microbial environment of the endometrium itself. For most of modern medicine, the uterine cavity was assumed to be sterile. Next-generation sequencing has shown it is not. The endometrium hosts its own microbial community, and its composition is associated with whether implantation succeeds and whether pregnancies are sustained. In a substantial proportion of women with otherwise unexplained fertility difficulties, that community is disrupted.
This is the first in a four-part series on the endometrial microbiome. It covers what the microbiome is, why it was missed for so long, what the evidence shows about its role in fertility, and how BioBloom's test measures it.
What the endometrial microbiome is
The endometrial microbiome is the population of bacteria, and to a lesser extent other microorganisms, that live within the uterine cavity.
The biomass is very low compared with other body sites. The gut contains trillions of bacteria. The endometrium contains only thousands to tens of thousands. That low density was, for a long time, indistinguishable from laboratory contamination, which is part of why the uterus was thought to be sterile.
In many reproductive-age women, the endometrial community is dominated by Lactobacillus species. "Dominated" has a specific meaning: Lactobacillus accounting for 90% or more of the bacterial community, with the remaining fraction made up of small amounts of other taxa. This 90% threshold, established by Moreno et al., 2016Am J Obstet Gynecol2016n=35LandmarkEvidence that the endometrial microbiota has an effect on implantation success or failureThe study that established the ≥90% Lactobacillus-dominant threshold; in IVF patients, non-dominant profiles showed implantation at 23.1% versus 60.7%, and live birth at 6.7% versus 58.8%.Read articleIn library, is the most widely used definition. Some studies apply an 80% cut-off or alternative definitions, and the field has not fully converged on a single standard.
When Lactobacillus dominance falls below this threshold, the community is described as dysbiotic. Other taxa, including Gardnerella, Atopobium, Streptococcus, Prevotella, and Staphylococcus, make up a larger share. Dysbiosis is a pattern, not a diagnosis of infection, and no single organism defines it.
Why it was missed for so long
Two reasons.
The sterile-uterus dogma
For decades, textbooks taught that the cervix acted as a barrier keeping the uterus bacterially clean, and that any bacteria found inside were sampling contaminants. That view persisted until 16S rRNA gene sequencing showed consistent, reproducible microbial signals from endometrial samples that could not be explained by contamination. Moreno et al., 2016 (Am J Obstet Gynecol, n=35)Am J Obstet Gynecol2016n=35LandmarkEvidence that the endometrial microbiota has an effect on implantation success or failureThe study that established the ≥90% Lactobacillus-dominant threshold; in IVF patients, non-dominant profiles showed implantation at 23.1% versus 60.7%, and live birth at 6.7% versus 58.8%.Read articleIn library was the landmark study that established the endometrial microbiota as a real, measurable entity with reproductive consequences.
The technical bar is high
Detecting a low-biomass community reliably requires next-generation sequencing with strict contamination controls at every step. Reagents, swabs, and the sampling route itself can introduce bacterial DNA that is not from the endometrium. Studies that fail to account for this produce inconsistent results. It is why endometrial microbiome testing remains specialised rather than routine, and why methodology varies significantly between providers.
What the evidence shows
The clinical evidence base has matured rapidly over the last decade. A few of the studies worth knowing:
Moreno et al., 2016 (Am J Obstet Gynecol, n=35)
In IVF patients with a confirmed receptive endometrium, Lactobacillus dominance was associated with significantly better outcomes: live birth rate 58.8% vs 6.7% (p=0.002), ongoing pregnancy 58.8% vs 13.3% (p=0.02), implantation 60.7% vs 23.1% (p=0.02). Small sample, large effect sizes, foundational paper.
Live birth rate, by microbiome status
Implantation 60.7% vs 23.1% · Ongoing pregnancy 58.8% vs 13.3% · All differences statistically significant at p < 0.05.
Moreno et al., 2022 (Microbiome, n=342)
A multicentre prospective observational study across four continents confirmed that a dysbiotic endometrial profile was associated with unsuccessful outcomes, and that the association held in a large, asymptomatic-for-infection population.
Study scale
342 patients across 13 ART centres on four continents
Hiratsuka et al., 2025 (Sci Rep, n=73)
In a RIF cohort, endometrial dysbiosis prevalence was 53.4% on sequencing. Dysbiosis, chronic endometritis on hysteroscopy (56.2%), and CD138-positive CE (49.3%) identified largely non-overlapping patient populations, suggesting each test captures a different clinical signal.
Diagnostic prevalence in 73 RIF patients
Post-treatment clinical pregnancy was 88.9% in dysbiosis-positive patients versus 56.0% without (p=0.021); in multivariate analysis, treatment of dysbiosis was associated with clinical pregnancy (OR 6.29, p=0.031).
Kyono et al., 2019 (Reprod Med Biol, n=92)
In IVF patients with non-Lactobacillus-dominated endometrium, a small treated cohort successfully shifted to Lactobacillus dominance after antibiotic plus Lactobacillus supplementation. Larger subsequent cohorts have reproduced the conversion at higher rates with extended protocols.
Conversion to Lactobacillus dominance
A small treated cohort with non-dominant profiles successfully shifted to Lactobacillus-dominance after combined antibiotic and Lactobacillus supplementation.
Larger subsequent cohorts have reproduced the conversion at higher rates with extended protocols.
Cicinelli et al., 2015 (Hum Reprod)
Demonstrated that antibiotic treatment for chronic endometritis in women with RIF significantly improves reproductive outcomes at subsequent IVF. The CE literature overlaps substantially with the microbiome literature, and the two investigations are complementary rather than duplicative.
IVF live birth rate after treatment
The clinical rationale for treating the endometrium as infection-addressable in RIF.
The numbers, distilled
Key findings, at a glance
of RIF patients show endometrial dysbiosis on sequencing, often missed by hysteroscopy alone.
Hiratsuka 2025IVF live birth after CE resolution with antibiotic therapy, versus 13.3% when CE persists.
Cicinelli 2015These are headline numbers; the library holds the full context, methodology, and limitations.
Browse all 16 sourcesWhat this means for you
If your workup has come back normal but transfers aren't holding, the endometrial environment may be one of the remaining modifiable factors. Testing isn't first-line - but it earns a place in the conversation after two or more failed cycles.
What "balance" means in the endometrium
A balanced endometrial microbiome is one where Lactobacillus species dominate and other taxa are present only in small amounts. Several mechanisms have been proposed:
- Lactic acid production, which lowers local pH and limits growth of other bacteria
- Modulation of the local immune environment, including reduction of pro-inflammatory signalling
- Competition with potentially pathogenic species for nutrients and binding sites
A dysbiotic endometrium shows the opposite: reduced Lactobacillus, increased diversity of other taxa, and in some studies, elevated inflammatory markers in surrounding tissue. This inflammatory state is one of the proposed mechanisms by which dysbiosis affects implantation.
The language throughout this field is associated with, not causes. The associations are strong and reproducible. Causation remains under investigation.
Why this matters clinically
The endometrium is where implantation happens. Each step of implantation, attachment, invasion, and vascular connection, depends on the endometrium being receptive. Receptivity has traditionally been assessed through endometrial thickness on ultrasound and, more recently, gene-expression profiling. The microbial environment has been largely absent from this picture despite evidence that it affects outcomes independently of embryo quality.
The clinical signal is strongest in three groups:
- Recurrent implantation failure, typically after two or more failed transfers with good-quality embryos
- Recurrent pregnancy loss, particularly early loss
- Unexplained infertility after standard workup has been unrevealing
When testing is worth considering
In each, a substantial proportion of patients, around half in some cohorts, have endometrial dysbiosis that conventional testing misses. For those patients, microbiome testing is often the first clearly modifiable finding after a long series of investigations that came back normal.
Endometrial dysbiosis is typically asymptomatic. The clinical signals that prompt consideration of testing are not physical; they are reproductive:
- Unexplained infertility after standard investigations
- Two or more failed IVF cycles with good-quality embryos
- Recurrent pregnancy loss, particularly early loss
- A history of chronic endometritis or repeated intrauterine procedures
- Planned embryo transfer in patients with any of the above
How BioBloom fits in
Where this connects to clinical practice.
BioBloom was founded to address a specific gap: the endometrial microbiome matters clinically, but most available testing was adapted from vaginal or gut microbiome protocols and is not optimised for the uterus's low-biomass environment. Inconsistent methodology has been one of the barriers to broader clinical adoption.
Built for the endometrium
Our sequencing pipeline is developed specifically for low-biomass samples. 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
The report is structured to support discussion between patient and consultant. It is ordered through partner clinics, and samples are collected by clinicians trained in the protocol. It is not a home test.
Cambridge origin, clinical partnerships
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, not only bench scientists.
Frequently asked questions
Questions, answered.
Next step
Where to go from here.
For patients
If you have had unexplained fertility difficulties and want to understand whether endometrial microbiome testing may add something to your workup, 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 the evidence base are covered in detail across this four-part series. Use it as the orientation reference when introducing endometrial microbiome testing into your fertility workup.
References
Citations & further reading
- 01
Moreno I, Codoñer FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazán J, Alonso R, Alamá P, Remohí J, Pellicer A, Ramon D, Simon C. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684-703.
- 02
Moreno I, Garcia-Grau I, Perez-Villaroya D, Gonzalez-Monfort M, Bahçeci M, Barrionuevo MJ, et al.. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome. 2022;10(1):1.
- 03
Hiratsuka D, Matsuo M, Kashiwabara K, Inoue M, Ishizawa C, Iida R, Fukui Y, 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.
- 04
Kyono 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.
- 05
Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, Marrocchella S, Greco P, Resta L. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30(2):323-330.
- 06
Chen C, Song X, Wei W, Zhong H, Dai J, Lan Z, Li F, et al.. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8:875.
Every reference above lives in our curated research library below, with ten more papers alongside.