The Microbiome of Infertile Couples and Its Effect on Their Reproductive Outcomes

Study Overview
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Brief Summary
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A prospective cohort study in IVF patients at 5 IVF centres in Denmark. The primary aim is to include patients positive for abnormal vaginal microbiota to an RCT (EUDRACT 2016-002385-31). Secondary aims are the prevalence of abnormal vaginal microbiota in women undergoing IVF treatment, intimate hygiene and relations to the vaginal microbiota, basic fertility work up in relation to vaginal microbiota.

Detailed Description
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At the time of the interim stage of the RCT (EUDRACT 2016-002385-31), we plan to make a first cross-sectional investigation of the intimate hygiene questionnaire at baseline as compared to abnormal vaginal microbiota. We plan to make focused interview of N=30 patients to cover any additional female hygiene details not covered in the original questionnaire. After this investigation we may include new questions after the interim analysis - given that the study proceeds. In this case we plan to publish the first results of the intimate hygiene habits of the patients enrolled until interim stage.

Official Title
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The Microbiome of Infertile Couples and Its Effect on Their Reproductive Outcomes

Conditions
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Abnormal Vaginal Microbiota, Infertility

Intervention / Treatment
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* Diagnostic Test: qPCR for abnormal vaginal microbiota


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First, second or third IVF stimulation cycle at the involved clinic. BMI<35. Written informed consent. 18-42 years old Exclusion Criteria: HIV, Hepatitis B or C positivity. Intrauterine malformations (Vaginal ultrasound) Hysterosalpinx Known severe renal or hepatic impairment. HPV CIN 2 or higher. Patients treated with vitamin K antagonists (warfarin) Known or suspected hypersensitivity to clindamycin or any other antibiotic. Myastenia Gravis Former or current inflammatory bowel disease, including Mb. Crohn and Colitis ulcerosa Any uncontrolled concomitant disease (e.g. uncontrolled diabetes, uncontrolled hypertension etc.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: qPCR for abnormal vaginal microbiota|qPCR for A.vaginae and/or G.vaginalis as developed in the pilot study (Hum Reprod. 2016 Apr;31(4):795-803. doi: 10.1093/humrep/dew026. Epub 2016 Feb 23.)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abnormal vaginal microbiota | qPCR positive diagnosis as described in intervention. | minimum 2-7 days from vaginal swab. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intimate hygiene | questionnaire | 2-5 weeks from baseline to embryo transfer | 
| Male/partner seminal microbiome | DNA sequencing of seminal samples | 2-4 weeks from baseline to oocyte pick-up | 
| Number of participants with Clinical pregnancy as measured by heartbeat | Tested by ultrasound scanning in week 7-9. | 7-9 weeks after inclusion. | 
| Number of participants achieving Live birth (defined as birth of a living child later than 23 weeks) | Tested by self-reported schemes mailed to the clinics. | 36-42 weeks after inclusion | 
| Cumulative live birth rate | The number of live births originating from one controlled ovarian stimulation. | 9 months - 24 months after inclusion |