Efficacy Study of Preconception Treatment of an Asymptomatic Bacterial Infection in an Infertility Population

Study Overview
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Brief Summary
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Bacterial vaginosis (BV) is a common vaginal infection characterized by a pathologic shift in the normal vaginal flora. BV has been associated with a number of poor reproductive outcomes, including infertility, preterm labor and premature rupture of membranes. If BV does disrupt normal embryologic development, then the treatment of BV prior to conception may improve implantation rates and other pregnancy outcomes in the infertile population. This is a prospective, randomized, double-blind, placebo-controlled trial in which infertile women undergoing intrauterine insemination or embryo transfer are screened for BV prior to treatment. Those patients who screen positive for BV will then be randomized into the treatment arm(metronidazole 500mg by mouth twice daily for 7 days) or the control arm (placebo by mouth twice daily for 7 days). The primary outcome, positive pregnancy test rate (i.e. biochemical pregnancy rate), will then be assessed. Secondary outcomes, such as clinical pregnancy rate, miscarriage rate, and live birth rate will also be examined.

Detailed Description
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The purpose of this study is to determine if preconception treatment of asymptomatic bacterial vaginosis improves pregnancy outcomes (i.e. biochemical pregnancy rate). Study protocol as follows: Patients will be notified of study via face-to-face contact at the initial clinic visit (baseline ultrasound visit, menstrual cycle day 2-5), by physician referral or the Stanford website. Patients expressing interest will be screened in person to confirm that they meet all enrollment criteria. The participant will be asked to sign informed consent documents and a brief intake questionnaire with then be administered. Enrolled patients will then be screened for bacterial vaginosis at their next visit (typically on menstrual cycle day 12), prior to transvaginal ultrasound. The screening will require that a speculum be inserted into the vagina and a vaginal smear be collected with a swab from the posterior fornix. A microscopic slide will be prepared by rolling the swab on the surface of a glass slide. The diagnosis of bacterial vaginosis will be established clinically using the Amsel criteria to confirm 3 of the following 4 signs: clue cells; vaginal pH ≥4.5; fishy odor before or after the addition of 10% potassium hydroxide solution to a wet-mount side; and a homogeneous, off-white, discharge. For validation of clinical diagnosis, 100% of screen positive slides, and 10% of screen negative slides, will be sent for to the Department of Pathology for Gram staining. The patients with a positive screen for bacterial vaginosis will then be randomized to receive metronidazole 500mg orally twice daily for seven days (treatment arm) or placebo orally twice daily for seven days(control arm). Randomization will be performed using a computer-generated code. Those patients whose screen is negative will also be followed for outcomes, but no randomization will be performed. All randomized patients will continue with routine monitoring and insemination as planned by their treating physician. If pregnancy is confirmed at least 12 weeks after intrauterine insemination by ultrasound evidence of a fetus with heartbeat, information will then be collected regarding the pregnancy and its outcome. Primary and secondary outcomes will be followed for 2 years after date of enrollment for all patients.

Official Title
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Pregnancy Outcomes Following Preconception Treatment of Asymptomatic Bacterial Vaginosis in an Infertility Population: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

Conditions
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Vaginosis, Bacterial, Infertility, Miscarriage

Intervention / Treatment
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* Drug: Metronidazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women who are actively trying to conceive via intrauterine insemination or in vitro fertilization Exclusion Criteria: Current use of an oral or vaginal antibiotic. History of allergy or adverse reaction to metronidazole. Prior enrollment in study (patients returning for repeat cycle may not be re-enrolled).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metronidazole<br>Patients randomized to the metronidazole arm will receive metronidazole 500mg orally twice daily for seven days. | Drug: Metronidazole<br>* Metronidazole 500mg orally twice daily for seven days<br>|
| Placebo Comparator: Placebo<br>Patients randomized to the placebo arm will receive placebo orally twice daily for seven days(control arm | Drug: Placebo<br>* Placebo will be administered orally twice daily for seven days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Pregnancy Rate (Positive Pregnancy Test) | Biochemical pregnancy rate was defined as number of participants who had a positive pregnancy test | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy Rate (Pregnancy Visible on Ultrasound) |  | up to 2 years | 
| Miscarriage Rate (Loss of a Clinically Recognized Pregnancy) |  | up to 2 years | 
| Infectious Morbidity (i.e. Chorioamnionitis, Neonatal Sepsis) |  | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacterial Vaginosis, Infertility, Miscarriage, Metronidazole