The Prevalence and Reproductive Outcome of Infertile Women With Genital Tuberculosis

NCT ID: NCT05311423

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 3000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-12-01
• Study Completion Date: 2023-08-01

Brief Summary

Female genital tuberculosis infection (FGTB) is an important cause of female infertility in TB-endemic areas. The pregnancy rate of assisted reproductive treatment (ART) in the infertile women with FGTB is still unsatisfied even after receiving standard anti-tuberculosis treatment. Moreover, recent years have witnessed an alarming increase in reports of FGTB-related maternal and neonatal complications after fertility treatments. These underscore that timely detection and treatment of FGTB before ART hold benefit for the mother and child.

Detailed Description

This project aims to recruit infertile female with high risk of tuberculosis infecton who need assisted reproductive treatment in multiple reproductive centers. The infertility-related medical history and laboratory examination results were recorded according to clinical routine, and other essential information such as tuberculosis symptoms, tuberculosis-related history and other health conditions were also recorded, and the pregnancy outcomes of these patients were followed up.

According to the results of clinical screening, they were divided into four cohorts: non-tuberculosis (non-TB) group, latent tuberculosis infection (LTBI) group, subclinical genital tuberculosis infection (SGTB) group and female genital tuberculosis infection (FGTB) group.

Non-TB group: QuantiFERON-TB test (QFT) negative, continue assisted reproductive treatment; LTBI group: QFT positive. Excluded active pulmonary tuberculosis, patients have negative endometrial histopathology, acid-fast bacilli (AFB) microscopy, Mycobacterium tuberculosis (Mtb) culture, or GeneXpert MTB/RIF Ultra test results. Then assisted reproductive treatment can be continued, but follow-up for tuberculosis-related symptoms is required; SGTB group: QFT positive. Excluded active pulmonary tuberculosis, patients have negative endometrial histopathology, AFB microscopy, Mtb culture, but GeneXpert MTB/RIF Ultra positive test results. They are recommended to receive 6-month first-line standard anti-tuberculosis treatment (ATT) regimen; FGTB group: QFT positive. Excluded active pulmonary tuberculosis, regardless of GeneXpert MTB/RIF Ultra results, at least one of these test results, including endometrial histopathologiy, AFB microscopy, Mtb culture is positive, they will receive 6-month ATT.

Patients diagnosed with SGTB and FGTB will receive 6-month first-line standard ATT before ART, and follow up their anti-tuberculosis drug-related adverse reactions (TB-ARs) according to clinical routine to prevent the occurrence of grade 3-4 adverse drug reactions.

All cohorts will be followed up for pregnancy outcomes after entering the assisted reproduction cycle, and the pregnancy outcomes of all subjects after the first assisted reproduction after enrollment were recorded. Follow-up nodes included the 2nd, 4th, 10th weeks and 37th weeks of gestation. Follow-up content includes pregnancy status. Follow-up subjects will be terminated when adverse pregnancy outcomes such as ectopic pregnancy and miscarriage occurred; follow-up of pregnant participants will be extended to 2 weeks postpartum. Participants from the SGTB or FGTB group achieve pregnant naturally after drug withdrawal, the follow-up of the natural pregnancy outcome will be started as well.

Conditions

Infertility, Female; Genital Tuberculoses, Female

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Non-TB Group

QuantiFERON-TB test (QFT) negative, continue assisted reproductive treatment

QuantiFERON-TB test & endometrial pathology & endometrial tissue GeneXpert Ultra

Intervention Type: DIAGNOSTIC_TEST

Endometrial biopsy is required to diagnose LTBI, SGTB and FGTB, which is an invasive operation and increases patients' economic burden. A screening method has been established that uses the interferon gamma release test as the primary screening test, and those who are positive undergo endometrial biopsy. Therefore, this project will use QFT to screen participants with Mtb infection, and further endometrium biopsy will be performed for QFT positive patients to diagnose LTBI, FGTB and SGTB. For participants with negative results for all diagnostic tests but QFT (defined as LTBI), close follow-up is necessary according to WHO guidelines.

Latent tuberculosis infection Group

QFT positive. Excluded active pulmonary tuberculosis, patients have negative endometrial histopathology, acid-fast bacilli (AFB) microscopy, Mycobacterium tuberculosis (Mtb) culture, or GeneXpert MTB/RIF Ultra test results. Then assisted reproductive treatment can be continued, but follow-up for tuberculosis-related symptoms is required

QuantiFERON-TB test & endometrial pathology & endometrial tissue GeneXpert Ultra

Intervention Type: DIAGNOSTIC_TEST

Endometrial biopsy is required to diagnose LTBI, SGTB and FGTB, which is an invasive operation and increases patients' economic burden. A screening method has been established that uses the interferon gamma release test as the primary screening test, and those who are positive undergo endometrial biopsy. Therefore, this project will use QFT to screen participants with Mtb infection, and further endometrium biopsy will be performed for QFT positive patients to diagnose LTBI, FGTB and SGTB. For participants with negative results for all diagnostic tests but QFT (defined as LTBI), close follow-up is necessary according to WHO guidelines.

Subclinical genital tuberculosis Group

QFT positive. Excluded active pulmonary tuberculosis, patients have negative endometrial histopathology, AFB microscopy, Mtb culture, but GeneXpert MTB/RIF Ultra positive test results. They are recommended to receive 6-month first-line standard anti-tuberculosis treatment (ATT) regimen

QuantiFERON-TB test & endometrial pathology & endometrial tissue GeneXpert Ultra

Intervention Type: DIAGNOSTIC_TEST

Endometrial biopsy is required to diagnose LTBI, SGTB and FGTB, which is an invasive operation and increases patients' economic burden. A screening method has been established that uses the interferon gamma release test as the primary screening test, and those who are positive undergo endometrial biopsy. Therefore, this project will use QFT to screen participants with Mtb infection, and further endometrium biopsy will be performed for QFT positive patients to diagnose LTBI, FGTB and SGTB. For participants with negative results for all diagnostic tests but QFT (defined as LTBI), close follow-up is necessary according to WHO guidelines.

Female genital tuberculosis Group

QFT positive. Excluded active pulmonary tuberculosis, regardless of GeneXpert MTB/RIF Ultra results, at least one of these test results, including endometrial histopathologiy, AFB microscopy, Mtb culture is positive, they will receive 6-month ATT

QuantiFERON-TB test & endometrial pathology & endometrial tissue GeneXpert Ultra

Intervention Type: DIAGNOSTIC_TEST

Endometrial biopsy is required to diagnose LTBI, SGTB and FGTB, which is an invasive operation and increases patients' economic burden. A screening method has been established that uses the interferon gamma release test as the primary screening test, and those who are positive undergo endometrial biopsy. Therefore, this project will use QFT to screen participants with Mtb infection, and further endometrium biopsy will be performed for QFT positive patients to diagnose LTBI, FGTB and SGTB. For participants with negative results for all diagnostic tests but QFT (defined as LTBI), close follow-up is necessary according to WHO guidelines.

Interventions

QuantiFERON-TB test & endometrial pathology & endometrial tissue GeneXpert Ultra

Endometrial biopsy is required to diagnose LTBI, SGTB and FGTB, which is an invasive operation and increases patients' economic burden. A screening method has been established that uses the interferon gamma release test as the primary screening test, and those who are positive undergo endometrial biopsy. Therefore, this project will use QFT to screen participants with Mtb infection, and further endometrium biopsy will be performed for QFT positive patients to diagnose LTBI, FGTB and SGTB. For participants with negative results for all diagnostic tests but QFT (defined as LTBI), close follow-up is necessary according to WHO guidelines.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 1) Female, aged ≥20 years and <43 years old;
• 2) In line with conventional assisted reproduction indications;
• 3) Meet any of the following:

1. with tuberculosis infection history;

2. with a history of close contact to tuberculosis patients;

3. exact positive IGRA results in the past or chest imaging indicated a past history of pulmonary tuberculosis;

4. suspected symptoms of tuberculosis, including fever, night sweats, fatigue, cough and sputum;

5. suspected symptoms of genital tuberculosis, including lower abdominal pain, abnormal menstruation, fallopian tube stenosis, obstruction, thickening, beading changes, uterine cavity adhesions, deformation, pelvic adhesions, etc.;

• 4) Voluntarily join the study and sign the informed consent

• 4) There are other serious physical or mental illnesses that are not suitable for selection;
• 5) Participate in other clinical studies that would affect this study at the same time.

Exclusion Criteria

• 1) Co-infection with HIV;
• 2) Chromosomal abnormalities;

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 43 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Shanghai First Maternity and Infant Hospital

OTHER

Sponsor Role: collaborator

General Hospital of Ningxia Medical University

OTHER

Sponsor Role: collaborator

Tang-Du Hospital

OTHER

Sponsor Role: collaborator

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

The 924th Hospital of Joint Logistics Support Force of Chinese People's Liberation

UNKNOWN

Sponsor Role: collaborator

Shenzhen Zhongshan Urology Hospita

UNKNOWN

Sponsor Role: collaborator

Northwest Women's and Children's Hospital, Xi'an, Shaanxi

OTHER

Sponsor Role: collaborator

Jiangxi Maternal and Child Health Hospital

OTHER

Sponsor Role: collaborator

The First People's Hospital of Yunnan

OTHER

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: collaborator

The Second Hospital of Hebei Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wen-hong Zhang

director of department of infectious diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai First Maternity and Infant Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Qiaoling Ruan, Dr.

Role: CONTACT

qlruan07@fudan.edu.cn

021-52887946

Xiaoming Teng, Dr.

Role: CONTACT

tengxiaoming@51mch.com

021-54035206

Facility Contacts

Xiaoming Teng, Dr.

Role: primary

tengxiaoming@51mch.com

021-54035206

Other Identifiers

KY2021-840

Identifier Type: -

Identifier Source: org_study_id