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The Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota

Phase 2
Recruiting
Conditions
Bacterial Vaginoses
Infertility, Female
Interventions
Other: Placebo
Registration Number
NCT05166746
Lead Sponsor
Peter Humaidan
Brief Summary

Study question: Does antibiotic alone or in combination with live biotherapeutic treatment of an abnormal vaginal microbiota improve the reproductive outcomes of IVF couples?

Study hypothesis:

The investigator hypothesize that treatment of the reproductive tract pathogens and restoration of vaginal Lactobacillus will improve the reproductive outcomes of IVF patients.

What is known already? Ultra-deep sequencing methods enable the refinement of reproductive tract microbiology in infertile patients. A recent meta-analysis reported that 19% of infertile patients had abnormal vaginal microbiota Moreover, someone have detected the presence of a Gardnerella (G.) vaginalis dominated endometrial biofilm in 50% of non-infertile patients with abnormal vaginal microbiota undergoing curettage; thus the treatment of such an endometrial biofilm might play an important role for the endometrial receptivity and subsequently the clinical pregnancy rate.

Pilot study: In a recent pilot study it was observed that an abnormal vaginal microbiota negatively affects the clinical pregnancy rate in IVF patients. In this study the prevalence of abnormal vaginal microbiota was 28% (36/130) and only 9% of patients with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (p=0.004). This association remained significant in an adjusted analysis. Furthermore, the invetigators have preliminary results demonstrating that vaginal bacteria such as G. vaginalis can be found in the endometrium of IVF patients, which is also supported by recent publications

What is the novelty of this study? To the investigators knowledge, no previous treatment study of abnormal reproductive tract microbiota has been performed in IVF patients; this relatively small intervention holds the potential to increase the baby-take-home rate after IVF treatment.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
333
Inclusion Criteria
  • Abnormal vaginal microbiota.
  • The screening swab should be repeated if more than 3 months old.
  • HIV, Hepatitis B or C positivity.
  • First, second or third IVF stimulation cycle or embryo transfer therefrom.
  • BMI<35
  • Written informed consent.
Exclusion Criteria
  • Known or suspected hypersensitivity to clindamycin.
  • HPV CIN 2 or higher.
  • Former or current inflammatory bowel disease
  • Severe concomitant disease, including diabetes.
  • MAX 2 embryos may be transferred
  • Artificial heart valve
  • Intrauterine malformations with operation indication as determined by treating physician (Polyps, Septum, fibroma)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Clindamycin + placebo LACTIN-VClindamycinOral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V placebo (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.
Clindamycin + LACTIN-V (L.crispatus)ClindamycinOral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.
Placebo clindamycin + placebo LACTIN-VPlaceboMatching clindamycin placebo 2 times per day for 7 days followed by LACTIN-V placebo (Osel Inc.) until completion of the clinical pregnancy scan at week 7-9.
Primary Outcome Measures
NameTimeMethod
Rate of clinical pregnancy per embryo transfer7-9 weeks

Ultrasound scan detection of intrauterine fetal heartbeat in gestational week 7-9

Secondary Outcome Measures
NameTimeMethod
Implantation ratepregnancy scan at 7-9 weeks

The number of embryos implanting

Number of late miscarriage12 weeks gestation - to labour (i.e. not including still birth)

The of pregnancy in late pregnancy

Live birth rate25-42 weeks depending on pregnancy.

The birth of a live born child after 25 gestational weeks.

Biochemical pregnancy14 days gestation

positive hCG blood test

Cure of abnormal vaginal microbiota1-2 months

A vaginal swab and qPCR-validated diagnostics for abnormal vaginal microbiota

early miscarriage14 days - 12 weeks gestation

The loss of an hCG positive pregnancy

Number of preterm birthprior to 37 gestational weeks

birth of a liveborn

Birth weight25-42 weeks gestation depending on pregnancy

weight at birth

Trial Locations

Locations (4)

Stork Fertility Clinic VivaNeo

🇩🇰

Copenhagen, Denmark

Hvidovre Hospital, The Fertility Clinic

🇩🇰

Hvidovre, Denmark

Fertility Clinic Skive, Skive Regional Hospital

🇩🇰

Skive, Denmark

Copenhagen University Hospital, Rigshospitalet

🇩🇰

Copenhagen, Denmark

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