Clinical trial NCT05166746: The Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Bacterial Vaginoses
Infertility, Female
Lead sponsor: Regionshospitalet Viborg, Skive
Sponsor class: OTHER
First posted: 2021-12-22
Enrollment: 333
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Rate of clinical pregnancy per embryo transfer
timeFrame: 7-9 weeks
Secondary outcomes:
measure: Cure of abnormal vaginal microbiota
timeFrame: 1-2 months
measure: Live birth rate
timeFrame: 25-42 weeks depending on pregnancy.
measure: Biochemical pregnancy
timeFrame: 14 days gestation
measure: Implantation rate
timeFrame: pregnancy scan at 7-9 weeks
measure: early miscarriage
timeFrame: 14 days - 12 weeks gestation
measure: Number of late miscarriage
timeFrame: 12 weeks gestation - to labour (i.e. not including still birth)
measure: Number of preterm birth
timeFrame: prior to 37 gestational weeks
measure: Birth weight
timeFrame: 25-42 weeks gestation depending on pregnancy
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
city: Copenhagen
country: Denmark
facility: Stork Fertility Clinic VivaNeo
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital, The Fertility Clinic
city: Skive
country: Denmark
facility: Fertility Clinic Skive, Skive Regional Hospital
Study officials:
References: