Fertility and the Microbiome

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Пищевая добавка 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.

Первичные конечные точки

• Seminal microbiome [Срок оценки: 3 months]
• Vaginal microbiome [Срок оценки: 1 month]
• Uterine microbiome [Срок оценки: 1 month]
• DNA-Fragmentation index [Срок оценки: 3 months]

Вторичные конечные точки (12)

• Hormone status of males and females - LH (Luteinizing hormone) [Срок оценки: 3 months]
• Hormone status of males and females - FSH (follicle stimulating hormone) [Срок оценки: 3 months]
• Hormone status of males and females - Testosterone status [Срок оценки: 3 months]
• Hormone status of males and females - free Testosterone [Срок оценки: 3 months]
• Hormone status of males and females - Androstenedione [Срок оценки: 3 months]
• Hormone status of males and females - AMH (Anti-Müllerian hormone) [Срок оценки: 3 months]
• Hormone status of males and females - DHEAS (dehydroepiandrosterone sulphate) [Срок оценки: 3 months]
• Hormone status of males and females - 25(OH)Vitamin D [Срок оценки: 3 months]
• Hormone status of males and females - TSH (thyroid-stimulating hormone) [Срок оценки: 3 months]
• Hormone status of males and females - fT3 (free Triiodothyronine) [Срок оценки: 3 months]
• Hormone status of males and females - freeThyroxine (fT4) [Срок оценки: 3 months]
• HPV Status [Срок оценки: 3 months]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Австрия · 1 центр

• Medical University of Graz — Graz

Публикации

• Jersoviene V, Gudleviciene Z, Rimiene J, Butkauskas D. Human Papillomavirus and Infertility. Medicina (Kaunas). 2019 Jul 15;55(7):377. doi: 10.3390/medicina55070377. PMID 31311196
• 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. PMID 30550767
• 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 PMID 31119299
• 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. PMID 31005311
• 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. PMID 30809218
• 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. PMID 30526664
• 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. PMID 31367292
• 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. PMID 29623908

Идентификаторы

NCT: NCT05328999 · Fertilitom

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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