The aim of the study is to investigate the confounding factors of chronic endometritis and therapeutic benefits of antibodies targeting plasma cells in women with reproductive failure.

Eligible women, based on the inclusion and exclusion criteria, will be recruited from the IVF and/ or miscarriage clinic in the Prince of Wales Hospital/ CUHK medical centre (CUMC). 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. In artificial cycles, 6mg estradiol will be given daily orally from day 2 of the menstrual cycle for 14+/-1-2 days. Transvaginal ultrasound will be performed on day 14 of the estrogen therapy to assess the endometrial thickness and to exclude ovarian activity. If endometrial thickness is ≥8 mm, plasma progesterone level is < 4nmol/L, progesterone will be commenced using either Endometrin (Ferring, Saint-Prex, Switzerland) 100 mg TDS vaginally. ES will be obtained using a Pipelle sampler as an outpatient procedure. The ES will be obtained precisely 5 days after progesterone supplementation.

Immunohistochemical staining will be used to determine plasma cells by using a mouse antihuman monoclonal primary anti-CD138 antibody and anti-CD38 antibody. The total number of plasma cell present in the stroma of the entire specimen will be determined and expressed as plasma cell count per unit area of the specimen. If CE is present, antibiotics will be given following the guideline from the Hospital Authority (HA). Then ES will be taken again to be re-examined by histology and microbiology.

Inclusion criteria:

1. Age 20-45 years;
2. Women with a history of 2 or more consecutive miscarriages before 24 weeks of gestation12; or
3. Women who failed to conceive after unprotected intercourse for one year; or
4. Women who failed failure to achieve a clinical pregnancy after two consecutive cycles of IVF, ICSI or frozen embryo replacement cycles where the cumulative number of transferred embryos is no less than four for day-2 embryos and no less than 2 for day-5 embryos (blastocysts), with all embryos being of good quality.

Exclusion criteria

1. Uncorrected uterine anomalies, such as the septate or bicornuate uterus, fibroids (submucous/intramural);
2. Untreated hydrosalpinx;
3. History of antiphospholipid syndrome;
4. Known clinical autoimmune disease;
5. Undergoing immunotherapy;
6. Abnormal thyroid function;
7. Abnormal karyotyping.
8. Those with active pelvic inflammatory disease or suspicion of infection etc.

Please kindly see the inclusion criteria. The endometrics sampling is only done for female patients.

Subjects will be identified and recruited from the IVF and miscarriage clinic by clinicians and research nurse.