Can antibiotics improve outcomes after recurrent miscarriage? A randomized trial involving 438 women with CD138-positive endometrial findings found no statistically significant difference between doxycycline and placebo: 51.5% versus 49.7% achieved live birth or an ongoing pregnancy beyond 24 weeks.
Chronic endometritis has been suspected as one possible contributor to pregnancy difficulties in women who experience recurrent miscarriage. Treating endometrial inflammation with antibiotics has therefore raised hopes of reducing miscarriage and improving the chance of birth. A large clinical trial, however, did not find that antibiotic treatment translated into a significant improvement in the measured pregnancy outcome.
Researchers from the University of Warwick, the University of Oxford and other institutions in the United Kingdom studied 438 women with recurrent miscarriage. They reported no statistically significant difference between the treatment and placebo groups. The results appeared in the October 2026 issue of Human Reproduction.
438 women across 27 UK centres
Chronic endometritis refers to persistent inflammation in the tissue lining the uterus. It may occur without obvious symptoms, and a possible relationship with recurrent miscarriage or embryo implantation failure has been proposed.
The trial enrolled 438 women from 27 UK medical centres. Participants were aged 18 to under 42, had experienced at least two consecutive early miscarriages, and had CD138-positive cells identified in an endometrial biopsy.
A total of 219 women received doxycycline for 14 days, while the other 219 received an inactive placebo. The trial was randomized and double-blind: neither participants nor treating clinicians knew which treatment had been assigned.
51.5% with doxycycline versus 49.7% with placebo
Live birth or an ongoing pregnancy beyond 24 weeks occurred in 113 women (51.5%) in the antibiotic group and 109 (49.7%) in the placebo group. The difference was only 1.8 percentage points and was not statistically significant.
Miscarriages were also similar: 69 in the antibiotic group and 72 in the placebo group. There was no clear difference in time to pregnancy or time to reaching 24 weeks of gestation.
Additional analyses accounting for age, previous miscarriage history and the degree of endometrial inflammation did not materially change the findings.
No clear improvement in the endometrial marker
There was also no significant difference in the proportion of women whose inflammation-related biopsy marker disappeared after treatment.
In the paired-biopsy comparison, 33 of 104 women (31.7%) in the antibiotic group and 26 of 98 (26.5%) in the placebo group became CD138-negative.
Thus, some women who had not received antibiotics also showed improvement in the biopsy finding. A change in an endometrial inflammation marker does not necessarily demonstrate an antibiotic treatment effect.
Why routine antibiotic treatment deserves caution
The study calls into question routinely prescribing antibiotics to women with recurrent miscarriage solely because chronic endometritis has been identified using these criteria.
It does not mean antibiotics are ineffective for every patient with endometritis. Results could differ in women with a confirmed bacterial infection or those who meet different diagnostic criteria. The trial was also stopped early after an interim analysis, which should be considered when interpreting the findings.
The researchers concluded that these results do not support routine preconception doxycycline for women with recurrent miscarriage and chronic endometritis defined by CD138-positive stromal cells.
Recurrent miscarriage can involve several factors, including embryo chromosomal abnormalities, uterine structural problems and immune or coagulation-related conditions. Before prescribing antibiotics, evaluation needs to consider the individual causes and the evidence that a proposed treatment improves the chance of birth.
Related reading
For a different reproductive outcome—repeated embryo-transfer failure—our guide to recurrent implantation failure after euploid embryo transfer explains why the evidence for additional tests and treatments matters. Implantation failure and miscarriage are distinct outcomes.
Study source
This article is based on “A double-blind multi-centre randomised placebo-controlled trial of doxycycline in women with recurrent miscarriage and chronic endometritis defined by CD138 positive stromal cells,” by researchers at the University of Warwick, the University of Oxford and collaborating institutions. It appeared in the October 2026 issue of Human Reproduction, following online publication on August 20, 2026. DOI: 10.1093/humrep/deag133. PMID: 42618515.
The image was created with generative AI (ChatGPT, OpenAI) and depicts fictional people rather than actual patients.
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