Fertility and the Microbiome

Recruiting

• Conditions: Subfertility; Asthenozoospermia

• Registration Number: NCT05328999
• Lead Sponsor: Medical University of Graz

Brief Summary

With this study, the investigators want to investigate the microbiome and human papilloma virus (HPV) status of couples with subfertility. The investigators want to gain information about association of female and male microbiome and its impact on fertility. HPV prevalence is high, and its impact on fertility has not been studied intensively. The investigators want to find out whether there is an association between HPV status and subfertility, vaginal and seminal microbiome and HPV status and the prevalence among our subfertile couples.

As part of this study, the investigators will perform a randomized placebo controlled double blind pilot study to investigate the association between altered sperm quality (impaired motility and elevated DNA fragmentation index), the seminal microbiome and whether intake of probiotics alters these parameters.

Detailed Description

Observational study:

The investigators will include 150 couples within 24 months and will take samples of oral, urinary, stool, vaginal, uterine and seminal microbiome and cervical as well as seminal samples for HPV analysis. Further, the investigators will test for other sexually transmittable diseases, hormone status and metabolic status. Time to pregnancy, pregnancy rate and live birth rate will be evaluated.

Placebo controlled double blind randomized controlled trial:

30 subfertile men (Asthenozoospermia, elevated DNA fragmentation index) will be randomized in to two groups: Placebo or Probiotics for 3 months daily. Before and after these 3 months, sperm count microbiome analysis and HPV analysis will be performed to find possible associations with intake of probiotics.

Study Timeline

• Study First Submitted: 2022-04-07
• Study First Submitted QC: 2022-04-07
• Study First Posted: 2022-04-14
• Study Start: 2022-08-10
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-23
• Last Update Posted: 2024-07-24
• Primary Completion: 2025-04-11
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Couples (Males and females) with subfertility, primary or secondary infertility, or recurrent pregnancy loss.

Exclusion Criteria

• unable to consent
• diseases or conditions that might impact investigation
• intake of probiotics, antibiotics within last 3 months
• intake of nutritional supplements
• chemo therapy or radiation therapy
• excess alcohol intake
• smoking

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Vaginal microbiome	1 month	16S-RNA sequencing; shotgun metagenomic sequencing
Seminal microbiome	3 months	16S-RNA sequencing; shotgun metagenomic sequencing
Uterine microbiome	1 month	16S-RNA sequencing; shotgun metagenomic sequencing
DNA-Fragmentation index	3 months	Rate of sperm with elevated DNA Fragmentation index

Secondary Outcome Measures

Name	Time	Method
Metabolic parameters - high density lipoprotein	3 months	high density lipoprotein
Hormone status of males and females - Testosterone status	3 months	Testosterone status
Hormone status of males and females - TSH (thyroid-stimulating hormone)	3 months	TSH status
Hormone status of males and females - fT3 (free Triiodothyronine)	3 months	fT3 Status
stool microbiome	3 months	16S-RNA sequencing; shotgun metagenomic sequencing
Amylase in Saliva	3 months	amylase analysis in saliva of females and males
Hormone status of males and females - DHEAS (dehydroepiandrosterone sulphate)	3 months	DHEAS status
Hormone status of males and females - 25(OH)Vitamin D	3 months	25(OH)Vitamin D status
oral microbiome	3 months	16S-RNA sequencing; shotgun metagenomic sequencing
Metabolic parameters - Omega 3	3 months	Omega 3
Metabolic parameters - LipoproteinA	3 months	LipoproteinA
Sperm count	3 months	Motility, concentration, morphology
Hormone status of males and females - LH (Luteinizing hormone)	3 months	LH status
Hormone status of males and females - FSH (follicle stimulating hormone)	3 months	FSH status
Hormone status of males and females - Androstenedione	3 months	Androstenedione status
HPV Status	3 months	HPV PCR analysis
Cortisol in Saliva	3 months	cortisol analysis in saliva of females and males
Hormone status of males and females - free Testosterone	3 months	free Testosterone status
Hormone status of males and females - AMH (Anti-Müllerian hormone)	3 months	AMH status
Hormone status of males and females - freeThyroxine (fT4)	3 months	fT4 status
Metabolic parameters - triglycerides	3 months	triglycerides
Metabolic parameters - Omega 6	3 months	Omega 6
Metabolic parameters - low density lipoprotein	3 months	low density lipoprotein
pregnancy rate	24 months	rate of clinical pregnancies
Time to pregnancy	24 months	Time until clinical pregnancy is achieved
live birth rate	24 months	follow up of pregnancies and their outcome
Presence of sexual transmittable diseases	3 months	HBV, HCV, HIV, Syphilis, Chlamydia, Gardnerella, Trichomonas

Trial Locations

Locations (1)

Medical University of Graz; 🇦🇹 Graz, Styria, Austria