Genital Tuberculoses, Female, Genital Tuberculosis, Latent, Infertility, Female, Recurrent Implantation Failure
Conditions
Brief summary
The purpose of this study is to assess the efficacy, safety and tolerability of the 1-month regimen of three times weekly rifapentine plus isoniazid in improving fertility outcome in recurrent implantation failure (RIF) patients with latent genital tuberculosis (LGTB), compared to no treatment and non-LGTB patients.
Detailed description
The prevalence of latent genital tuberculosis (LGTB) is relatively high in women with infertility and recurrent pregnancy loss. Whether preventive treatment of latent tuberculosis infection (LTBI) can improve the fertility outcome in women with recurrent implantation failure (RIF) remains to be explored. This is a prospective interventional cohort study.The main purpose of this study is to compare the fertility outcome between 1-month regimen of three times weekly rifapentine plus isoniazid and no treatment in RIF patients with LGTB and RIF patients without LGTB. The study will also assess the safety and tolerability and the efficacy of the preventive treatment regimen in prevention of the incidence of active female genital tuberculosis (FGTB). A total of 1050 participants will be recruited for screening of LGTB. The endometrial tuberculosis (TB) polymerase chain reaction (PCR) test will be employed for the diagnosis of LGTB. Eligible participants with negative TB PCR results will be assigned to the non-LGTB group, while those with positive TB PCR results will be assigned to the LGTB group. The LGTB group will be further assigned, according to their will to receive preventive treatment of tuberculosis, to one of the following groups: the LGTB treatment group and the LGTB no treatment group. The LGTB treatment group will receive the 1-month regimen of three times weekly rifapentine plus isoniazid, and the in vitro fertilization (IVF)/ intra cytoplasmic sperm injection (ICSI) cycle can be started after 1 month post the completion of the treatment regimen. Adverse events and side effects will be monitored at a 2-week interval during the preventive treatment and followed up once more at 4 weeks post the end of treatment. The LGTB no treatment group and the non-LGTB group will start the IVF/ICSI cycle directly after enrollment without taking any medication related to preventive treatment of tuberculosis. Eligible participants will be followed up until the end of an IVF/ ICSI cycle or pregnancy. Fertility outcomes of both groups will be recorded and compared. Secondary outcomes, including the incidence of adverse events, the adhesion of treatment and the incidence of LGTB and FGTB, ovarian reserve, embryo quality, history of infertility and tuberculosis will also be recorded and compared.
Interventions
receive the 1-month regimen of three times weekly rifapentine (450mg po) plus isoniazid (400mg po)
Sponsors
Shanghai First Maternity and Infant Hospital
Huashan Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
1. Women aged 25-40 years old 2. Infertile women failed to achieve clinical pregnancy after 4 good quality embryo transfers, with at least 3 fresh or frozen IVF cycles 3. Intended to undergo IVF/ICSI 4. Ultrasonography or hysterosalpingogram showed a normal uterus cavity, and the thickness of the endometrium was ≥8mm before implantation during last IVF/ICSI cycle 5. Patients who voluntarily signed the informed consent and agreed to be followed up as required by the study protocol
Exclusion criteria
1. Use of donor eggs/sperm 2. An abnormal uterine cavity shown on hysterosalpingogram or hysteroscopy 3. Proven tubal infertility 4. Proven preimplantation genetic abnormality 5. Proven active tuberculosis 6. Treated for active tuberculosis or used preventive treatment for LTBI within 2 years 7. Being allergic or intolerant of any study drug 8. HIV antibody positive and AIDS patients 9. Patients with impaired liver function: hepatic encephalopathy, ascites; total bilirubin is more than 2 times higher than the upper limit of normal; alanine transaminase (ALT) or aspartate aminotransferase (AST) is more than 5 times the upper limit of normal 10. Patients with diabetes mellitus 11. Critically ill patients, and according to the judgment of the research physician, it is impossible to survive for more than 16 weeks 12. Currently participating in another drug clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy rates | 6 weeks after completion of an IVF/ICSI cycle | Clinical pregnancy was defined as the presence of at least one gestational sac on ultrasound at 6 weeks. |
| Ongoing Pregnancy Rate | 10 weeks after completion of an IVF/ICSI cycle | Ongoing pregnancy was the presence of at least one foetus with heart pulsation on ultrasound beyond 10 weeks. |
| Miscarriage rate | 22 weeks after completion of an IVF/ICSI cycle | The number of miscarriages before 22 weeks divided by the number of participants with positive pregnancy test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Implantation rate | 6 weeks after completion of an IVF/ICSI cycle | The number of gestational sacs seen on scanning divided by the number of embryos replaced. |
| Incidence of LGTB | 4 weeks after enrollment | The number of participants diagnosed with LGTB devided by the number of participants screened for LGTB. |
| Incidence of FGTB | 2 years | The number of participants developed FGTB during treatment or follow-up devided by the number of participants in the LGTB treatment group. |
| Incidence of grade 3 or greater adverse events | 20 weeks after preventive treatment initiated | The number of participants reported grade 3 or greater adverse events during treatment or follow-up devided by the number of participants in the LGTB treatment group. |
| Completion rate of preventive treatment | 20 weeks after preventive treatment initiated | 11 or 12 doses of the 1-month preventive treatment regimen of three times weekly rifapentine plus isoniazid taken within 16 weeks after treatment initiated will be regarded as completion of preventive treatment. The number of participants completed treatment devided by the number of participants initiated the preventive treatment. |
| Discontinuation of treatment | 20 weeks after preventive treatment initiated | The number of participants discontinued treatment devided by the number of participants in the LGTB treatment group. |
| Discontinuation of treatment due to side effect of study drugs | 20 weeks after preventive treatment initiated | The number of participants discontinued treatment due to side effect of study drugs devided by the number of participants in the LGTB treatment group. |
Countries
China
Contacts
Primary ContactQiaoling Ruan, Dr.
Backup ContactXiaoming Teng, Dr.
Outcome results
None listed