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Research and evidence

Published studies for each area of the test menu, with the strength of the evidence and its limits stated plainly, for fertility and gynaecology clinicians.

Article series

Four articles on the endometrial microbiome, best read in order.

  1. Part 1 · 7 min read

    The endometrial microbiome

    The microbial environment inside the uterus. What it is, why it matters for fertility, and how BioBloom Life measures it.

  2. Part 2 · 6 min read

    The microbiome and fertility

    What the evidence shows about the endometrial microbiome, implantation, and pregnancy outcomes.

  3. Part 3 · 5 min read

    Testing the endometrial microbiome

    How BioBloom Life measures the microbial environment inside the uterus, and what the test involves.

  4. Part 4 · 5 min read

    What to do with your results

    Clinical next steps after an endometrial microbiome test. Treatment options, retesting, and how results fit into a fertility care plan.

Evidence by test area

For each area of the menu: how established the evidence is, a summary, its limitations and the references.

Evidence selected by BioBloom Life. Citations from PubMed, with DOI links.

Female factor

Evidence: Well-established

Karyotyping and FMR1 (fragile-X) premutation testing are well-established, guideline-recommended parts of the premature-ovarian-insufficiency and reduced-ovarian-reserve workup; ESHRE recommends both in confirmed POI. The FMR1 premutation is among the commonest identifiable genetic causes of POI, understood as a strong risk factor rather than a deterministic predictor.

Limitations: These tests identify risk factors, not certainties. The FMR1 premutation is incompletely penetrant: it raises the risk of ovarian insufficiency but does not predict whether or when it will occur.

References (3)
  1. Panay N et al (2024). Evidence-based guideline: premature ovarian insufficiency (ESHRE update). Climacteric. (opens in a new tab)PubMed (opens in a new tab)
  2. Webber L et al (2016). ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. (opens in a new tab)PubMed (opens in a new tab)
  3. Tosh D et al (2014). Association between fragile X premutation and premature ovarian failure: case-control study and meta-analysis. Arch Gynecol Obstet. (opens in a new tab)PubMed (opens in a new tab)

Prenatal

Evidence: Well-established; prenatal exome maturing

cfDNA/NIPT is a highly accurate screening test, not a diagnostic one, for the common trisomies, outperforming traditional serum screening for trisomy 21, though positive results require confirmatory invasive testing and performance for microdeletions is more limited. Chromosomal microarray is a first-line diagnostic on invasive samples and QF-PCR gives validated rapid aneuploidy results; prenatal exome sequencing adds incremental diagnostic yield in structurally abnormal fetuses with a normal microarray.

Limitations: cfDNA/NIPT is a screening test, not a diagnosis: a high-risk result requires confirmatory invasive testing, and performance for microdeletions is more limited than for the common trisomies.

References (3)
  1. Norton ME et al (2015). Cell-free DNA analysis for noninvasive examination of trisomy (NEXT). N Engl J Med. (opens in a new tab)PubMed (opens in a new tab)
  2. Wapner RJ et al (2012). Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. (opens in a new tab)PubMed (opens in a new tab)
  3. Lord J et al (2019). Prenatal exome sequencing in fetal structural anomalies (PAGE). Lancet. (opens in a new tab)PubMed (opens in a new tab)

Male factor

Evidence: AZF and CFTR established; sperm FISH selective

Y-chromosome (AZF) microdeletion testing and CFTR analysis in CBAVD are well-established diagnostics with clear management and genetic-counselling implications. Meta-analyses link sperm DNA fragmentation with poorer assisted-reproduction outcomes, but NICE NG257 (recommendation 1.17.6) advises against the test, so it is not on our menu. Sperm aneuploidy by FISH is a helpful second-line adjunct in selected cases.

Limitations: AZF and CFTR testing are established in defined groups of men; sperm FISH is a specialist adjunct with assay-specific thresholds, and no single result determines treatment. NICE NG257 (recommendation 1.17.6) advises against sperm DNA fragmentation testing, so it is not on our menu.

References (3)
  1. Krausz C et al (2024). EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: state of the art 2023. Andrology 2024;12(3):487-504. (opens in a new tab)PubMed (opens in a new tab)
  2. Ribas-Maynou J et al (2021). Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis. Biol Rev Camb Philos Soc. (opens in a new tab)PubMed (opens in a new tab)
  3. Yu J et al (2012). CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): systematic review and meta-analysis. Hum Reprod. (opens in a new tab)PubMed (opens in a new tab)

Carrier and reproductive risk

Evidence: Carrier screening established; adjuncts developing

Expanded carrier screening is endorsed by ACMG as the equitable standard for identifying reproductive risk for recessive and X-linked conditions. Polygenic risk scoring of embryos is an active area of research and is best considered within a specialist and genetic-counselling context rather than routine use. KIR-HLA-C testing for reproductive failure remains a developing area, and the ALIFE2 randomised trial found that heparin did not improve live birth in inherited thrombophilia with recurrent loss, so thrombophilia screen-and-treat is best applied selectively.

Limitations: KIR-HLA-C is described by researchers in the field as too early for clinical intervention (Moffett 2016), and the ALIFE2 randomised trial found heparin did not improve live birth in inherited thrombophilia with recurrent loss. Embryo polygenic risk scoring has no established clinical utility and is not a routine test.

References (4)
  1. Gregg AR et al (2021). Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: an ACMG practice resource. Genet Med. (opens in a new tab)PubMed (opens in a new tab)
  2. Grebe TA et al (2024). Clinical utility of polygenic risk scores for embryo selection: an ACMG points to consider statement. Genet Med. (opens in a new tab)PubMed (opens in a new tab)
  3. Quenby S et al (2023). Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2). Lancet. (opens in a new tab)PubMed (opens in a new tab)
  4. Moffett A et al (2016). Variation of maternal KIR and fetal HLA-C genes in reproductive failure: too early for clinical intervention. Reprod Biomed Online. (opens in a new tab)PubMed (opens in a new tab)

PGT and embryo testing

Evidence: PGT-M/SR established; PGT-A used selectively

PGT-M and PGT-SR are well-established for monogenic disease and structural rearrangements. PGT-A is best used selectively: large randomised trials in unselected or good-prognosis patients have not shown improved cumulative live birth, and its role appears clearest per transfer in older patients, weighed against biopsy considerations and mosaicism interpretation. Non-invasive PGT-A from spent culture media is a promising, still-developing approach with variable concordance across labs.

Limitations: Randomised trials have not shown PGT-A to improve cumulative live birth in unselected patients: it selects between existing embryos rather than improving them. niPGT-A from spent culture medium is investigational, and its concordance with trophectoderm biopsy varies between laboratories.

References (4)
  1. Yan J et al (2021). Live birth with or without preimplantation genetic testing for aneuploidy. N Engl J Med. (opens in a new tab)PubMed (opens in a new tab)
  2. Munné S et al (2019). PGT-A versus morphology for single frozen-thawed embryo transfer (STAR). Fertil Steril. (opens in a new tab)PubMed (opens in a new tab)
  3. Cornelisse S et al (2020). Preimplantation genetic testing for aneuploidies in IVF. Cochrane Database Syst Rev. (opens in a new tab)PubMed (opens in a new tab)
  4. Yeung QSY et al (2019). A prospective study of niPGT-A using NGS on spent culture media. J Assist Reprod Genet. (opens in a new tab)PubMed (opens in a new tab)

Endometrial microbiome and implantation

Evidence: Growing evidence base

A growing evidence base associates a Lactobacillus-dominant endometrial microbiome, and the absence of dysbiosis, with better implantation and IVF outcomes, and chronic endometritis is consistently linked to recurrent pregnancy loss and infertility, though a 2024 meta-analysis found no significant association with implantation failure. Most current studies are small, low-biomass sequencing cohorts, so results are best interpreted alongside the wider clinical picture; randomised data showing that treating dysbiosis improves live birth are still maturing.

Limitations: Most evidence comes from small, low-biomass sequencing cohorts, and randomised evidence that treating dysbiosis improves live birth is not yet available. A dysbiotic result describes a bacterial pattern; it is not a diagnosis of infection.

Read the article series

References (3)
  1. Moreno I et al (2016). Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. (opens in a new tab)PubMed (opens in a new tab)
  2. Kitaya K et al (2018). Endometritis: new time, new concepts. Fertil Steril. (opens in a new tab)PubMed (opens in a new tab)
  3. Ticconi C et al (2024). Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis. Front Immunol. (opens in a new tab)PubMed (opens in a new tab)

Reading low-biomass studies

The endometrium carries a fraction of the bacterial load found in the vagina or gut. At those biomass levels, contamination from reagents, swabs, the cervix, or the lab itself can swamp the real signal. Studies that don’t account for this can produce misleading taxonomies.

When comparing studies, the questions worth asking are: was sampling transcervical or at hysterectomy, was a double-lumen catheter used, were negative controls sequenced, and was contamination partitioning applied?

Our method runs negative controls alongside patient samples, subtracts known reagent contaminants and flags low-biomass samples rather than reporting them.

Paper library

Peer-reviewed studies and reviews relevant to endometrial microbiome testing. Each entry links to its source and opens to show the finding and, where reported, the sample size.

Last reviewed April 2026

Inclusion criteria

We include peer-reviewed primary studies or systematic reviews published in indexed journals with original data or synthesis relevant to endometrial microbiome testing in fertility. We exclude commentaries, conference abstracts, and non-indexed sources. The library is selective, not exhaustive, and reviewed periodically as the field evolves. If you think we’ve missed something important, contact us.

Topic

18 papers

Am J Obstet Gynecol · 2016 · n=35

Evidence that the endometrial microbiota has an effect on implantation success or failure

Moreno et al.

Topics: Foundational, Implantation and IVF

Microbiome · 2022 · n=342

Endometrial microbiota composition is associated with reproductive outcome in infertile patients

Moreno et al.

Topics: Implantation and IVF, Foundational

Sci Rep · 2025 · n=73

Comparison of diagnostic tests for chronic endometritis and endometrial dysbiosis in recurrent implantation failure: impact on pregnancy outcomes

Hiratsuka et al.

Topics: Recurrent failure, Methodology

Reprod Med Biol · 2019 · n=92

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

Kyono et al.

Topics: Recurrent failure, Implantation and IVF

Hum Reprod · 2015

Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy

Cicinelli et al.

Topics: Recurrent failure

Am J Obstet Gynecol · 2018 · n=113

The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology

Moreno et al.

Topics: Recurrent failure, Methodology

Nat Commun · 2017

The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases

Chen et al.

Topics: Foundational, Methodology

PeerJ · 2016

Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene

Verstraelen et al.

Topics: Methodology, Foundational

Biol Reprod · 2019

Uterine microbiome: low biomass and high expectations

Garcia-Grau et al.

Topics: Methodology

Hum Reprod · 2016

Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients

Haahr et al.

Topics: Implantation and IVF

Hum Reprod · 2019

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

Koedooder et al.

Topics: Implantation and IVF

Sci Transl Med · 2023

Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts

Muraoka et al.

Topics: Endometriosis, Mechanism and immunity

Ann Clin Microbiol Antimicrob · 2024 · n=80

Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure

Zhang et al.

Topics: Recurrent failure, Methodology

BMC Med · 2024 · n=1000

Gut microbiome in endometriosis: a cohort study on 1000 individuals

Pérez-Prieto et al.

Topics: Endometriosis, Methodology

Arch Gynecol Obstet · 2022

Genital tract dysbiosis in infertile women with a history of repeated implantation failure and pilot study for reproductive outcomes following oral enteric coating lactoferrin supplementation

Kitaya & Ishikawa

Topics: Recurrent failure, Methodology

BJOG · 2020

Endometriosis and the microbiome: a systematic review

Leonardi et al.

Topics: Endometriosis, Reviews

Hum Reprod Update · 2018

How uterine microbiota might be responsible for a receptive, fertile endometrium

Benner et al.

Topics: Mechanism and immunity, Reviews

Am J Obstet Gynecol · 2015

Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women

Mitchell et al.

Topics: Methodology, Foundational

Not sure which tests fit your clinic?

Tell us about your clinic and the indications you see most, and we will map the menu to them on a short onboarding call.