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

NCT ID: NCT01322971

Last Updated: 2021-12-20

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2012-06-30

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:

1. 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.
2. 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.
3. 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.
4. All randomized patients will continue with routine monitoring and insemination as planned by their treating physician.
5. 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.
6. Primary and secondary outcomes will be followed for 2 years after date of enrollment for all patients.

Conditions

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Vaginosis, Bacterial Infertility Miscarriage

Keywords

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Bacterial Vaginosis Infertility Miscarriage Metronidazole

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Metronidazole

Patients randomized to the metronidazole arm will receive metronidazole 500mg orally twice daily for seven days.

Group Type ACTIVE_COMPARATOR

Metronidazole

Intervention Type DRUG

Metronidazole 500mg orally twice daily for seven days

Placebo

Patients randomized to the placebo arm will receive placebo orally twice daily for seven days(control arm

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered orally twice daily for seven days

Interventions

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Metronidazole

Metronidazole 500mg orally twice daily for seven days

Intervention Type DRUG

Placebo

Placebo will be administered orally twice daily for seven days

Intervention Type DRUG

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).
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Ruth Bunker Lathi

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ruth Bunker Lathi

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Ruth Lathi

Stanford, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 11592272 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10684911 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10942482 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8124116 (View on PubMed)

Hay PE. Bacterial vaginosis and miscarriage. Curr Opin Infect Dis. 2004 Feb;17(1):41-4. doi: 10.1097/00001432-200402000-00008.

Reference Type BACKGROUND
PMID: 15090889 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7491137 (View on PubMed)

Korn AP, Bolan G, Padian N, Ohm-Smith M, Schachter J, Landers DV. Plasma cell endometritis in women with symptomatic bacterial vaginosis. Obstet Gynecol. 1995 Mar;85(3):387-90. doi: 10.1016/0029-7844(94)00400-8.

Reference Type BACKGROUND
PMID: 7862377 (View on PubMed)

Liversedge NH, Turner A, Horner PJ, Keay SD, Jenkins JM, Hull MG. The influence of bacterial vaginosis on in-vitro fertilization and embryo implantation during assisted reproduction treatment. Hum Reprod. 1999 Sep;14(9):2411-5. doi: 10.1093/humrep/14.9.2411.

Reference Type BACKGROUND
PMID: 10469722 (View on PubMed)

McDonald HM, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000262. doi: 10.1002/14651858.CD000262.pub3.

Reference Type BACKGROUND
PMID: 17253447 (View on PubMed)

Nelson DB, Bellamy S, Nachamkin I, Ness RB, Macones GA, Allen-Taylor L. First trimester bacterial vaginosis, individual microorganism levels, and risk of second trimester pregnancy loss among urban women. Fertil Steril. 2007 Nov;88(5):1396-403. doi: 10.1016/j.fertnstert.2007.01.035. Epub 2007 Apr 16.

Reference Type BACKGROUND
PMID: 17434499 (View on PubMed)

Platz-Christensen JJ, Brandberg A, Wiqvist N. Increased prostaglandin concentrations in the cervical mucus of pregnant women with bacterial vaginosis. Prostaglandins. 1992 Feb;43(2):133-4. doi: 10.1016/0090-6980(92)90082-5.

Reference Type BACKGROUND
PMID: 1542740 (View on PubMed)

Platz-Christensen JJ, Mattsby-Baltzer I, Thomsen P, Wiqvist N. Endotoxin and interleukin-1 alpha in the cervical mucus and vaginal fluid of pregnant women with bacterial vaginosis. Am J Obstet Gynecol. 1993 Nov;169(5):1161-6. doi: 10.1016/0002-9378(93)90274-m.

Reference Type BACKGROUND
PMID: 8238178 (View on PubMed)

Wilson JD, Ralph SG, Rutherford AJ. Rates of bacterial vaginosis in women undergoing in vitro fertilisation for different types of infertility. BJOG. 2002 Jun;109(6):714-7. doi: 10.1111/j.1471-0528.2002.01297.x.

Reference Type BACKGROUND
PMID: 12118653 (View on PubMed)

Other Identifiers

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IRB Protocol Number 20103

Identifier Type: OTHER

Identifier Source: secondary_id

SU-03212011-7604

Identifier Type: -

Identifier Source: org_study_id