Chronic Endometritis and Benefits of Antibiotics in Women With Recurrent Miscarriage

The Prevalence of Chronic Endometritis and Therapeutic Benefits of Antibiotics in Women With Unexplained Recurrent Miscarriage

The aim of the study is to estimate the incidence of CE, evaluate the endometrial microorganism of CE, and investigate the therapeutic benefits of antibiotics for women with unexplained recurrent miscarriage and CE.

Eligible women, based on the inclusion and exclusion criteria, will be recruited from the miscarriage clinic in the Prince of Wales Hospital. Endometrial sampling (ES) will alternatively be conducted during mid-luteal phase. In natural cycles, all the subjects will have a daily urine test from day 9 of the menstrual cycle to identify the Luteinizing Hormone (LH) surge. The ES will be obtained precisely 7 days after LH surge. Endometrial samples will be obtained using a Pipelle sampler as an outpatient procedure. The endometrium will be divided into three aliquots. One will be fixed in 4% formalin for 24 hours, routinely processed and embedded in paraffin wax. One will be investigated by microbial culture for infectious agents and one will be sequenced to reveal the endometrial microbiota.

CE will be diagnosed either by the presence of plasma cells and changes in endometrial stromal cells identified using HE and IHC, or by the finding of infectious agents using microbial culture. The selection of antibiotics will be based on the type of infectious agents or empirical, doxycycline 100mg BD po. for 14 days, for women with negative microbial culture. Endometrial biopsy will be repeated at the same time point after antibiotic treatment for women with CE. For persistent subjects with negative culturing, ciprofloxacin 500mg, BD po., and metronidazole 400mg TDS po. for 14 days will be used. The treatment will be repeated for three courses at maximum for women with persistent CE according to their willingness.

Inclusion Criteria:

• Women with a history of 2 or more consecutive miscarriages before 24 weeks of gestation
• Women aged 20-45 years old

Exclusion Criteria:

• Uncorrected uterine anomalies, such as the septate or bicornuate uterus, fibroids (submucous/intramural)
• Untreated hydrosalpinx
• Antiphospholipid syndrome
• Known clinical autoimmune disease
• Undergoing immunotherapy
• Abnormal thyroid function
• Abnormal karyotyping of couples
• Known immunodeficiency pathologies such as diabetes or HIV
• Currently taking other antibiotics or other trial medications or TCM;
• Currently or previously involved in other clinical trials with medication intake;
• Those with active pelvic inflammatory disease or suspicion of infection etc.