Fertility and the Microbiome

Subfertility Clinical Trial

Official title:

Fertility and the Microbiome: an Observational Study and Randomized Placebo Controlled Double-blind Pilot Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05328999
• Other study ID #: Fertilitom
• Status: Recruiting
• Start date: August 10, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Medical University of Graz
• Contact: Sarah Feigl, Dr.
• Phone: 004331638580831
• Email: s.feigl[@]medunigraz.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2024
• Est. primary completion date: April 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthenozoospermia
• Infertility
• Subfertility

Intervention

Dietary Supplement:
• Probiotics (Omnibiotic (R))
As intervention in the randomized placebo controlled double blind trial, 30 males will receive either probiotics or placebo once daily for 3 months. Sperm count and microbiome analysis before and after intervention will be performed.

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz	Styria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

References & Publications (10)

Baud D, Pattaroni C, Vulliemoz N, Castella V, Marsland BJ, Stojanov M. Sperm Microbiota and Its Impact on Semen Parameters. Front Microbiol. 2019 Feb 12;10:234. doi: 10.3389/fmicb.2019.00234. eCollection 2019. — View Citation

Brusselaers N, Shrestha S, van de Wijgert J, Verstraelen H. Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis. Am J Obstet Gynecol. 2019 Jul;221(1):9-18.e8. doi: 10.1016/j.ajog.2018.12.011. Epub 2018 Dec 12. — View Citation

Depuydt CE, Donders G, Verstraete L, Vanden Broeck D, Beert J, Salembier G, Bosmans E, DhontT N, Van Der Auwera I, Vandenborne K, Ombelet W. Time has come to include Human Papillomavirus (HPV) testing in sperm donor banks. Facts Views Vis Obgyn. 2018 Dec;10(4):201-205. — View Citation

Depuydt CE, Donders GGG, Verstraete L, Vanden Broeck D, Beert JFA, Salembier G, Bosmans E, Ombelet W. Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination. Fertil Steril. 2019 Jun;111(6):1135-1144. doi: 10.1016/j.fertnstert.2019.02.002. Epub 2019 Apr 17. — View Citation

Jersoviene V, Gudleviciene Z, Rimiene J, Butkauskas D. Human Papillomavirus and Infertility. Medicina (Kaunas). 2019 Jul 15;55(7):377. doi: 10.3390/medicina55070377. — View Citation

Koedooder R, Singer M, Schoenmakers S, Savelkoul PHM, Morre SA, de Jonge JD, Poort L, Cuypers WJSS, Beckers NGM, Broekmans FJM, Cohlen BJ, den Hartog JE, Fleischer K, Lambalk CB, Smeenk JMJS, Budding AE, Laven JSE. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study. Hum Reprod. 2019 Jun 4;34(6):1042-1054. doi: 10.1093/humrep/dez065. Erratum In: Hum Reprod. 2019 Oct 2;34(10):2091-2092. — View Citation

Koedooder R, Singer M, Schoenmakers S, Savelkoul PHM, Morre SA, de Jonge JD, Poort L, Cuypers WSS, Budding AE, Laven JSE; ReceptIVFity study group. The ReceptIVFity cohort study protocol to validate the urogenital microbiome as predictor for IVF or IVF/ICSI outcome. Reprod Health. 2018 Dec 7;15(1):202. doi: 10.1186/s12978-018-0653-x. — View Citation

Moreno I, Simon C. Relevance of assessing the uterine microbiota in infertility. Fertil Steril. 2018 Aug;110(3):337-343. doi: 10.1016/j.fertnstert.2018.04.041. — View Citation

Simon C. Introduction: Do microbes in the female reproductive function matter? Fertil Steril. 2018 Aug;110(3):325-326. doi: 10.1016/j.fertnstert.2018.06.041. Epub 2018 Jul 20. — View Citation

Xiong YQ, Chen YX, Cheng MJ, He WQ, Chen Q. The risk of human papillomavirus infection for male fertility abnormality: a meta-analysis. Asian J Androl. 2018 Sep-Oct;20(5):493-497. doi: 10.4103/aja.aja_77_17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seminal microbiome	16S-RNA sequencing; shotgun metagenomic sequencing	3 months
Primary	Vaginal microbiome	16S-RNA sequencing; shotgun metagenomic sequencing	1 month
Primary	Uterine microbiome	16S-RNA sequencing; shotgun metagenomic sequencing	1 month
Primary	DNA-Fragmentation index	Rate of sperm with elevated DNA Fragmentation index	3 months
Secondary	Hormone status of males and females - LH (Luteinizing hormone)	LH status	3 months
Secondary	Hormone status of males and females - FSH (follicle stimulating hormone)	FSH status	3 months
Secondary	Hormone status of males and females - Testosterone status	Testosterone status	3 months
Secondary	Hormone status of males and females - free Testosterone	free Testosterone status	3 months
Secondary	Hormone status of males and females - Androstenedione	Androstenedione status	3 months
Secondary	Hormone status of males and females - AMH (Anti-Müllerian hormone)	AMH status	3 months
Secondary	Hormone status of males and females - DHEAS (dehydroepiandrosterone sulphate)	DHEAS status	3 months
Secondary	Hormone status of males and females - 25(OH)Vitamin D	25(OH)Vitamin D status	3 months
Secondary	Hormone status of males and females - TSH (thyroid-stimulating hormone)	TSH status	3 months
Secondary	Hormone status of males and females - fT3 (free Triiodothyronine)	fT3 Status	3 months
Secondary	Hormone status of males and females - freeThyroxine (fT4)	fT4 status	3 months
Secondary	HPV Status	HPV PCR analysis	3 months
Secondary	stool microbiome	16S-RNA sequencing; shotgun metagenomic sequencing	3 months
Secondary	oral microbiome	16S-RNA sequencing; shotgun metagenomic sequencing	3 months
Secondary	Cortisol in Saliva	cortisol analysis in saliva of females and males	3 months
Secondary	Amylase in Saliva	amylase analysis in saliva of females and males	3 months
Secondary	Metabolic parameters - Omega 3	Omega 3	3 months
Secondary	Metabolic parameters - Omega 6	Omega 6	3 months
Secondary	Metabolic parameters - low density lipoprotein	low density lipoprotein	3 months
Secondary	Metabolic parameters - high density lipoprotein	high density lipoprotein	3 months
Secondary	Metabolic parameters - triglycerides	triglycerides	3 months
Secondary	Metabolic parameters - LipoproteinA	LipoproteinA	3 months
Secondary	Time to pregnancy	Time until clinical pregnancy is achieved	24 months
Secondary	pregnancy rate	rate of clinical pregnancies	24 months
Secondary	live birth rate	follow up of pregnancies and their outcome	24 months
Secondary	Presence of sexual transmittable diseases	HBV, HCV, HIV, Syphilis, Chlamydia, Gardnerella, Trichomonas	3 months
Secondary	Sperm count	Motility, concentration, morphology	3 months