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TOPLINE
In a placebo-controlled trial, preconceptual doxycycline failed to improve cumulative live birth rates, ongoing pregnancy rates, or time to conception in women with recurrent miscarriage and chronic endometritis (CE), as defined by CD138-positive stromal cells.
METHODOLOGY
- Researchers conducted a double-blind, placebo-controlled, randomised trial to evaluate whether preconceptual doxycycline improves cumulative live birth rates or ongoing pregnancy rates and the time to conception in women with recurrent miscarriage and CE.
- The trial included 438 women with two or more consecutive first-trimester miscarriages and CE, defined as at least five CD138-positive cells per 10 mm2.
- Participants were randomly assigned to receive either doxycycline 100 mg (n = 219; mean age, 34.9 years) or placebo (n = 219; mean age, 34.4 years) twice daily for 14 days from the first day of the menstrual cycle.
- The primary outcome was cumulative live birth or an ongoing pregnancy of at least 24 weeks of gestation by trial completion; secondary outcomes included the first pregnancy outcome, time to first conception, and type of miscarriage.
- A subgroup of women underwent a second endometrial biopsy on day 10 ± 4 after ovulation or day 23 ± 3 of their menstrual cycle, 5-10 days after completing the treatment to assess whether CD138 status changed.
TAKEAWAY
- Cumulative live birth or ongoing pregnancy rates did not differ between doxycycline and placebo groups (52% vs 50%; adjusted relative risk [aRR], 1.02; 95% credible interval [CrI], 0.85-1.21).
- Doxycycline did not affect the time to first conception or time to 24 weeks of gestation. Live birth or ongoing pregnancy rates in the first pregnancy after treatment were also similar between the doxycycline and placebo groups.
- In an exploratory analysis, women without CD138-positive CE had significantly fewer live births (aRR, 0.73; 95% CrI, 0.56-0.91) and more miscarriages (aRR, 1.47; 95% CrI, 1.14-1.93) during their first follow-up pregnancy than those with CD138-positive CE in the placebo group.
- Repeated biopsies showed no meaningful effect of doxycycline on CD138-positive CE. Similar proportions of women in the doxycycline (31.7%) and placebo (26.5%) groups tested negative after treatment, and CD138 staining patterns remained unchanged in both groups.
IN PRACTICE
"The totality of our findings does not support the use of doxycycline in the management of CE as defined by CD138 staining in stromal cells in recurrent miscarriage," the authors of the study wrote.
SOURCE
This study was led by J. Odendaal, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, England. It was published online on August 20, 2026, in Human Reproduction.
LIMITATIONS
The trial was stopped early at interim analyses based on the futility criteria. The prevalence of CD138-positive CE (71%) was higher than expected. Because the second biopsy was taken within the same treatment cycle, the trial could not rule out a treatment effect that might only emerge after a subsequent menstrual cycle and endometrial regeneration.
DISCLOSURES
This study was funded by the Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health and Care Research partnership. The authors declared having no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
