A clinical trial to investigate the efficacy of Lactobacillus-containing vaginal suppository for the endometrial microbiota in the recurrent implantation failure patients.

JRCT ID: jRCTs031220184

Registered date:06/07/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Recurrent implantation failure patients with chronic endometritis and abnormal endometrial microbiot
• Date of first enrollment: 14/11/2022
• Target sample size: 60
• Study type: Interventional
• Intervention(s): The study subjects will be assigned to two groups, the unapproved drug Lactobacillus-containing vaginal suppository or placebo, to receive the vaginal suppository one capsule once a day, vaginally for 12 consecutive days.

Outcome(s)

• Primary Outcome: Amount of change in the occupancy of Lactobacillus spp. in the endometrial microbiota

Secondary Outcome

1. Improvement of chronic endometritis (change in the number of CD138 positive cells).
2. Cure rate of abnormal endometrial microbiota.
3. Amount of change in the occupancy of Lactobacillus spp.
in the endometrial microbiota at the end of the singleblind period and the open-label period in the placebo group.
4. Improvement of chronic endometritis in the placebo group at the end of the single-blind period and the open-label period (change in the number of CD138-positive cells).
5. Incidence of adverse events.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 42age old
• Gender: Female

Include criteria

1. Females between the ages of 18 and 42 years old at the time of obtaining consent
2. Those who underwent two or more previous failed cycles in which morphologically embryos were transferred.
3. Those who provide written informed consent for participation in this trial.
4. Patients who can attend outpatient clinics according to the research schedule.
5. Those with >= 1 CD138 positive cell/10 HPF in the endometrial stroma on endometrial biopsy.
6. Those with < 90% Lactobacillus spp. in the endometrial microbiota analysis.

Exclude criteria

1. Those with uterine organic causes of implantation failure.
2. Those with abnormal genital bleeding without a confirmed diagnosis.
3. Those with thrombophlebitis, pulmonary embolism, or a history of such conditions.
4. Those with estrogen-dependent malignant tumors or suspected estrogen-dependent malignant tumors.
5. Those with a history or suspected history of breast cancer or genital cancer.
6. Those with untreated endometrial hyperplasia.
7. Those with arterial thromboembolic disease or a history of such disease.
8. Those with a history of hypersensitivity to estradiol, doxycycline hydrochloride hydrate, tetracycline or new
quinolone antibiotics, or progestin preparations.
9. Those with sickle cell disease.
10. Those with Dubin-Johnson syndrome or Rotor syndrome.
11. Those with dyslipidemia.
12. Those with liver dysfunction.
13. Those with porphyria.
14. Those with allergy to gelatin.
15. Those who have taken antibiotics that affect the outcomes
16. Those who have Lactobacillus supplement regularly at the time of obtaining consent.
17. Those who do not use contraception during this trial.
18. Those who are judged by clinical research physicians to be inappropriate to participate in this trial by other
reasons.

Related Information

• Primary Sponsor: Hirota Yasushi
• Source(s) of Monetary Support: Sante Laboratories, Inc.,Japan Agency for Medical Research and Development