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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subfertile patients | Males and females between 18 and 50 years of age with subfertility presenting at the fertility center at the Medical University of Graz. | ||
| Subfertile males with elevated DNA fragmentation index and asthenozoospermia | Males between 18 and 50 years of age with elevated DNA fragmentation index and asthenozoospermia presenting at the fertility center at the Medical University of Graz. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Probiotics (Omnibiotic (R)) | Dietary Supplement | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Seminal microbiome | 16S-RNA sequencing; shotgun metagenomic sequencing | 3 months |
| Vaginal microbiome | 16S-RNA sequencing; shotgun metagenomic sequencing | 1 month |
| Uterine microbiome | 16S-RNA sequencing; shotgun metagenomic sequencing | 1 month |
| DNA-Fragmentation index | Rate of sperm with elevated DNA Fragmentation index | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Hormone status of males and females - LH (Luteinizing hormone) | LH status | 3 months |
| Hormone status of males and females - FSH (follicle stimulating hormone) | FSH status |
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Inclusion Criteria:
Exclusion Criteria:
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Couples (Males and females) with subfertility, primary or secundary infertility, or recurrent pregnancy loss.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sarah Feigl, Dr. | Contact | 004331638580831 | s.feigl@medunigraz.at |
| Name | Affiliation | Role |
|---|---|---|
| Martina Kollmann, PD Dr. | Medical University of Graz | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of Graz | Recruiting | Graz | Styria | 8036 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31311196 | Background | Jersoviene V, Gudleviciene Z, Rimiene J, Butkauskas D. Human Papillomavirus and Infertility. Medicina (Kaunas). 2019 Jul 15;55(7):377. doi: 10.3390/medicina55070377. | |
| 30550767 | Background | 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. |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| D053627 | Asthenozoospermia |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007248 | Infertility, Male |
| D005832 | Genital Diseases, Male |
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| ID | Term |
|---|---|
| D019936 | Probiotics |
| ID | Term |
|---|---|
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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Oral swabs, vaginal swabs, uterine swabs, cervical swabs, urine, ejaculate, stool samples.
|
| 3 months |
| Hormone status of males and females - Testosterone status | Testosterone status | 3 months |
| Hormone status of males and females - free Testosterone | free Testosterone status | 3 months |
| Hormone status of males and females - Androstenedione | Androstenedione status | 3 months |
| Hormone status of males and females - AMH (Anti-Müllerian hormone) | AMH status | 3 months |
| Hormone status of males and females - DHEAS (dehydroepiandrosterone sulphate) | DHEAS status | 3 months |
| Hormone status of males and females - 25(OH)Vitamin D | 25(OH)Vitamin D status | 3 months |
| Hormone status of males and females - TSH (thyroid-stimulating hormone) | TSH status | 3 months |
| Hormone status of males and females - fT3 (free Triiodothyronine) | fT3 Status | 3 months |
| Hormone status of males and females - freeThyroxine (fT4) | fT4 status | 3 months |
| HPV Status | HPV PCR analysis | 3 months |
| stool microbiome | 16S-RNA sequencing; shotgun metagenomic sequencing | 3 months |
| oral microbiome | 16S-RNA sequencing; shotgun metagenomic sequencing | 3 months |
| Cortisol in Saliva | cortisol analysis in saliva of females and males | 3 months |
| Amylase in Saliva | amylase analysis in saliva of females and males | 3 months |
| Metabolic parameters - Omega 3 | Omega 3 | 3 months |
| Metabolic parameters - Omega 6 | Omega 6 | 3 months |
| Metabolic parameters - low density lipoprotein | low density lipoprotein | 3 months |
| Metabolic parameters - high density lipoprotein | high density lipoprotein | 3 months |
| Metabolic parameters - triglycerides | triglycerides | 3 months |
| Metabolic parameters - LipoproteinA | LipoproteinA | 3 months |
| Time to pregnancy | Time until clinical pregnancy is achieved | 24 months |
| pregnancy rate | rate of clinical pregnancies | 24 months |
| live birth rate | follow up of pregnancies and their outcome | 24 months |
| Presence of sexual transmittable diseases | HBV, HCV, HIV, Syphilis, Chlamydia, Gardnerella, Trichomonas | 3 months |
| Sperm count | Motility, concentration, morphology | 3 months |
| 31119299 | Background | 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. |
| 31005311 | Background | 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. |
| 30809218 | Background | 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. |
| 30526664 | Background | 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. |
| 31367292 | Background | 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. |
| 29623908 | Background | 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. |
| 30098680 | Background | 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. |
| 30037698 | Background | 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. |
| D052801 |
| Male Urogenital Diseases |
| D019602 |
| Food and Beverages |