A Double-blind, Placebo-controlled Multicenter Trial on the Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 333
- Locations
- 4
- Primary Endpoint
- Rate of clinical pregnancy per embryo transfer
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Masking Description
Moreover, an interim analysis will be performed by blinded outcomes assessors according to the primary outcome.
Eligibility Criteria
- Ages
- 18 Years to 42 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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.
- •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)
Arms & Interventions
Clindamycin + LACTIN-V (L.crispatus)
Oral 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.
Intervention: Clindamycin (Drug)
Clindamycin + placebo LACTIN-V
Oral 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.
Intervention: Clindamycin (Drug)
Placebo clindamycin + placebo LACTIN-V
Matching 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.
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Rate of clinical pregnancy per embryo transfer
Time Frame: 7-9 weeks
Ultrasound scan detection of intrauterine fetal heartbeat in gestational week 7-9
Secondary Outcomes
- Live birth rate(25-42 weeks depending on pregnancy.)
- Biochemical pregnancy(14 days gestation)
- Implantation rate(pregnancy scan at 7-9 weeks)
- Number of late miscarriage(12 weeks gestation - to labour (i.e. not including still birth))
- Cure of abnormal vaginal microbiota(1-2 months)
- early miscarriage(14 days - 12 weeks gestation)
- Number of preterm birth(prior to 37 gestational weeks)
- Birth weight(25-42 weeks gestation depending on pregnancy)
Investigators
Peter Humaidan
Professor, MD
Regionshospitalet Viborg, Skive