Clinical trial NCT05328999: Fertility and the Microbiome
Official title: Fertility and the Microbiome: an Observational Study and Randomized Placebo Controlled Double-blind Pilot Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Subfertility
Asthenozoospermia
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2022-04-14
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Couples (Males and females) with subfertility, primary or secundary infertility, or recurrent pregnancy loss.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Seminal microbiome
timeFrame: 3 months
measure: Vaginal microbiome
timeFrame: 1 month
measure: Uterine microbiome
timeFrame: 1 month
measure: DNA-Fragmentation index
timeFrame: 3 months
Secondary outcomes:
measure: Hormone status of males and females - LH (Luteinizing hormone)
timeFrame: 3 months
measure: Hormone status of males and females - FSH (follicle stimulating hormone)
timeFrame: 3 months
measure: Hormone status of males and females - Testosterone status
timeFrame: 3 months
measure: Hormone status of males and females - free Testosterone
timeFrame: 3 months
measure: Hormone status of males and females - Androstenedione
timeFrame: 3 months
measure: Hormone status of males and females - AMH (Anti-Müllerian hormone)
timeFrame: 3 months
measure: Hormone status of males and females - DHEAS (dehydroepiandrosterone sulphate)
timeFrame: 3 months
measure: Hormone status of males and females - 25(OH)Vitamin D
timeFrame: 3 months
measure: Hormone status of males and females - TSH (thyroid-stimulating hormone)
timeFrame: 3 months
measure: Hormone status of males and females - fT3 (free Triiodothyronine)
timeFrame: 3 months
measure: Hormone status of males and females - freeThyroxine (fT4)
timeFrame: 3 months
measure: HPV Status
timeFrame: 3 months
measure: stool microbiome
timeFrame: 3 months
measure: oral microbiome
timeFrame: 3 months
measure: Cortisol in Saliva
timeFrame: 3 months
measure: Amylase in Saliva
timeFrame: 3 months
measure: Metabolic parameters - Omega 3
timeFrame: 3 months
measure: Metabolic parameters - Omega 6
timeFrame: 3 months
measure: Metabolic parameters - low density lipoprotein
timeFrame: 3 months
measure: Metabolic parameters - high density lipoprotein
timeFrame: 3 months
measure: Metabolic parameters - triglycerides
timeFrame: 3 months
measure: Metabolic parameters - LipoproteinA
timeFrame: 3 months
measure: Time to pregnancy
timeFrame: 24 months
measure: pregnancy rate
timeFrame: 24 months
measure: live birth rate
timeFrame: 24 months
measure: Presence of sexual transmittable diseases
timeFrame: 3 months
measure: Sperm count
timeFrame: 3 months
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
state: Styria
Study officials:
affiliation: Medical University of Graz
name: Martina Kollmann, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
citation: 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.
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.
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.
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.
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.
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.