Clinical trial NCT05311423: The Prevalence and Reproductive Outcome of Infertile Women With Genital Tuberculosis
Official title: The Prevalence of Genital Tuberculosis and the Impact on Reproductive Outcomes in Infertile Women: a National Multicenter Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Infertility, Female
Genital Tuberculoses, Female
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai First Maternity and Infant Hospital
name: General Hospital of Ningxia Medical University
name: Tang-Du Hospital
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: The First Affiliated Hospital of Zhengzhou University
name: The 924th Hospital of Joint Logistics Support Force of Chinese People's Liberation
name: Shenzhen Zhongshan Urology Hospita
name: Northwest Women's and Children's Hospital, Xi'an, Shaanxi
name: Jiangxi Maternal and Child Health Hospital
name: The First People's Hospital of Yunnan
name: Tongji Hospital
name: The Second Hospital of Hebei Medical University
name: First Affiliated Hospital of Wenzhou Medical University
First posted: 2022-04-05
Enrollment: 3000
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Infertile female patients with high risk factors for tuberculosis infection who intend to undergo assisted reproduction

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.

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

Exclusion Criteria:

* 1) Co-infection with HIV;
* 2) Chromosomal abnormalities;
* 3) suspected genital tuberculosis infection symptoms (participants meet inclusion criteria 3)e in Inclusion Criteria) known to be caused only by factors part from tuberculosis, such as endocrine factors, history of ectopic pregnancy, history of uterine curettage, chronic pelvic inflammatory disease, endometriosis, malignant tumors, etc.;
* 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.

Primary outcomes:
measure: Clinical pregnancy rate of ART
timeFrame: 2 years
measure: Continued pregnancy rate of ART
timeFrame: 2 years
measure: Prevalence of SGTB among infertile women
timeFrame: 6 months
Secondary outcomes:
measure: Prevalence of FGTB/LTBI among infertile women
timeFrame: 2 years
measure: Abortion rate
timeFrame: 2 years
measure: Ectopic pregnancy rate
timeFrame: 2 years
measure: Preterm birth rate
timeFrame: 2 years
measure: Live birth rate
timeFrame: 2 years
measure: Maternal mortality rate
timeFrame: 2 years
measure: Neonatal mortality rate
timeFrame: 2 years
measure: Spontaneous pregnancy rate
timeFrame: 2 years
measure: The incidence of grade 3-4 adverse events
timeFrame: 2 years
measure: The rate of drug discontinuation due to adverse drug reactions
timeFrame: 2 years
measure: Treatment completion rate
timeFrame: 2 years
measure: Incidence of active tuberculosis of LTBI group during 1 year after enrollment
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital
state: Shanghai
Study officials:
References: