Efficacy Study of Preconception Treatment of an Asymptomatic Bacterial Infection in an Infertility Population
Primary Purpose
Vaginosis, Bacterial, Infertility, Miscarriage
Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Metronidazole
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Vaginosis, Bacterial focused on measuring Bacterial Vaginosis, Infertility, Miscarriage, Metronidazole
Eligibility Criteria
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).
Sites / Locations
- Ruth Lathi
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Metronidazole
Placebo
Arm Description
Patients randomized to the metronidazole arm will receive metronidazole 500mg orally twice daily for seven days.
Patients randomized to the placebo arm will receive placebo orally twice daily for seven days(control arm
Outcomes
Primary Outcome Measures
Biochemical Pregnancy Rate (Positive Pregnancy Test)
Biochemical pregnancy rate was defined as number of participants who had a positive pregnancy test
Secondary Outcome Measures
Pregnancy Rate (Pregnancy Visible on Ultrasound)
Miscarriage Rate (Loss of a Clinically Recognized Pregnancy)
Infectious Morbidity (i.e. Chorioamnionitis, Neonatal Sepsis)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01322971
Brief Title
Efficacy Study of Preconception Treatment of an Asymptomatic Bacterial Infection in an Infertility Population
Official Title
Pregnancy Outcomes Following Preconception Treatment of Asymptomatic Bacterial Vaginosis in an Infertility Population: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
Disease prevalence lower than expected in population.
Study Start Date
February 2011 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vaginosis, Bacterial, Infertility, Miscarriage
Keywords
Bacterial Vaginosis, Infertility, Miscarriage, Metronidazole
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metronidazole
Arm Type
Active Comparator
Arm Description
Patients randomized to the metronidazole arm will receive metronidazole 500mg orally twice daily for seven days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients randomized to the placebo arm will receive placebo orally twice daily for seven days(control arm
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Intervention Description
Metronidazole 500mg orally twice daily for seven days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered orally twice daily for seven days
Primary Outcome Measure Information:
Title
Biochemical Pregnancy Rate (Positive Pregnancy Test)
Description
Biochemical pregnancy rate was defined as number of participants who had a positive pregnancy test
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Pregnancy Rate (Pregnancy Visible on Ultrasound)
Time Frame
up to 2 years
Title
Miscarriage Rate (Loss of a Clinically Recognized Pregnancy)
Time Frame
up to 2 years
Title
Infectious Morbidity (i.e. Chorioamnionitis, Neonatal Sepsis)
Time Frame
up to 2 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ruth Bunker Lathi
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruth Lathi
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11592272
Citation
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. (Replaces Technical Bulletin number 206, June 1995; Committee Opinion number 172, May 1996; Committee Opinion number 187, September 1997; Committee Opinion number 198, February 1998; and Committee Opinion number 251, January 2001). Obstet Gynecol. 2001 Oct;98(4):709-16.
Results Reference
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PubMed Identifier
10684911
Citation
Carey JC, Klebanoff MA, Hauth JC, Hillier SL, Thom EA, Ernest JM, Heine RP, Nugent RP, Fischer ML, Leveno KJ, Wapner R, Varner M. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med. 2000 Feb 24;342(8):534-40. doi: 10.1056/NEJM200002243420802.
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PubMed Identifier
10942482
Citation
Donders GG, Van Bulck B, Caudron J, Londers L, Vereecken A, Spitz B. Relationship of bacterial vaginosis and mycoplasmas to the risk of spontaneous abortion. Am J Obstet Gynecol. 2000 Aug;183(2):431-7. doi: 10.1067/mob.2000.105738.
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PubMed Identifier
8124116
Citation
Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C, Pearson J. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ. 1994 Jan 29;308(6924):295-8. doi: 10.1136/bmj.308.6924.295.
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PubMed Identifier
15090889
Citation
Hay PE. Bacterial vaginosis and miscarriage. Curr Opin Infect Dis. 2004 Feb;17(1):41-4. doi: 10.1097/00001432-200402000-00008.
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PubMed Identifier
7491137
Citation
Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, Cotch MF, Edelman R, Pastorek JG 2nd, Rao AV, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med. 1995 Dec 28;333(26):1737-42. doi: 10.1056/NEJM199512283332604.
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Citation
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Citation
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Citation
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Citation
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Efficacy Study of Preconception Treatment of an Asymptomatic Bacterial Infection in an Infertility Population
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