SubfertilityNCT05328999
Fertility and the Microbiome
An observational study of Subfertility and Asthenozoospermia, run by Medical University of Graz at 1 site in Austria.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Subfertility, Asthenozoospermia
- What is being tested?
- Probiotics (Omnibiotic (R))
- How many people
- 300 participants
- Where
- 1 siteAustria
- Study dates
- 10 Aug 2022to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Study population: Couples (Males and females) with subfertility, primary or secundary infertility, or recurrent pregnancy loss.
Who may be able to join
- Couples (Males and females) with subfertility, primary or secondary infertility, or recurrent pregnancy loss.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Graz
Graz, Styria, 8036
Sarah Feigl, Dr., 004331638580831, s.feigl@medunigraz.at
Martina Kollmann, PD Dr., 004331638584190, martina.kollmann@medunigraz.at
About this study
Official title: Fertility and the Microbiome: an Observational Study and Randomized Placebo Controlled Double-blind Pilot Trial
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.
Read the 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.
- Conditions
- Subfertility, Asthenozoospermia
- Being tested
- Probiotics (Omnibiotic (R))
- Medical subject headings
- Infertility, Asthenozoospermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: Probiotics (Omnibiotic (R)) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seminal microbiome
16S-RNA sequencing; shotgun metagenomic sequencing
Measured: 3 months
Vaginal microbiome
16S-RNA sequencing; shotgun metagenomic sequencing
Measured: 1 month
Uterine microbiome
16S-RNA sequencing; shotgun metagenomic sequencing
Measured: 1 month
DNA-Fragmentation index
Rate of sperm with elevated DNA Fragmentation index
Measured: 3 months
Secondary outcomes (27)
Hormone status of males and females - LH (Luteinizing hormone)
LH status
Measured: 3 months
Hormone status of males and females - FSH (follicle stimulating hormone)
FSH status
Measured: 3 months
Hormone status of males and females - Testosterone status
Testosterone status
Measured: 3 months
Hormone status of males and females - free Testosterone
free Testosterone status
Measured: 3 months
Hormone status of males and females - Androstenedione
Androstenedione status
Measured: 3 months
Hormone status of males and females - AMH (Anti-Müllerian hormone)
AMH status
Measured: 3 months
Hormone status of males and females - DHEAS (dehydroepiandrosterone sulphate)
DHEAS status
Measured: 3 months
Hormone status of males and females - 25(OH)Vitamin D
25(OH)Vitamin D status
Measured: 3 months
Hormone status of males and females - TSH (thyroid-stimulating hormone)
TSH status
Measured: 3 months
Hormone status of males and females - fT3 (free Triiodothyronine)
fT3 Status
Measured: 3 months
Hormone status of males and females - freeThyroxine (fT4)
fT4 status
Measured: 3 months
HPV Status
HPV PCR analysis
Measured: 3 months
stool microbiome
16S-RNA sequencing; shotgun metagenomic sequencing
Measured: 3 months
oral microbiome
16S-RNA sequencing; shotgun metagenomic sequencing
Measured: 3 months
Cortisol in Saliva
cortisol analysis in saliva of females and males
Measured: 3 months
Amylase in Saliva
amylase analysis in saliva of females and males
Measured: 3 months
Metabolic parameters - Omega 3
Omega 3
Measured: 3 months
Metabolic parameters - Omega 6
Omega 6
Measured: 3 months
Metabolic parameters - low density lipoprotein
low density lipoprotein
Measured: 3 months
Metabolic parameters - high density lipoprotein
high density lipoprotein
Measured: 3 months
Metabolic parameters - triglycerides
triglycerides
Measured: 3 months
Metabolic parameters - LipoproteinA
LipoproteinA
Measured: 3 months
Time to pregnancy
Time until clinical pregnancy is achieved
Measured: 24 months
pregnancy rate
rate of clinical pregnancies
Measured: 24 months
live birth rate
follow up of pregnancies and their outcome
Measured: 24 months
Presence of sexual transmittable diseases
HBV, HCV, HIV, Syphilis, Chlamydia, Gardnerella, Trichomonas
Measured: 3 months
Sperm count
Motility, concentration, morphology
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2022
- Study start10 Aug 2022
- Primary completion11 Apr 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for SubfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martina Kollmann, PD Dr., Principal investigator, Medical University of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05328999
- Sponsor's protocol ID
- Fertilitom
- Status last verified
- Jul 2024
- First submitted
- 7 Apr 2022
- Last updated
- 24 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Jersoviene V, Gudleviciene Z, Rimiene J, Butkauskas D. Human Papillomavirus and Infertility. Medicina (Kaunas). 2019 Jul 15;55(7):377. doi: 10.3390/medicina55070377.
PubMed 31311196Brusselaers 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.
PubMed 30550767Koedooder 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.
PubMed 31119299Depuydt 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.
PubMed 31005311Baud 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.
PubMed 30809218Koedooder 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.
PubMed 30526664Depuydt 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.
PubMed 31367292Xiong 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.
PubMed 29623908Moreno 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.
PubMed 30098680Simon 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.
PubMed 30037698
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fertility and the Microbiome: an Observational Study and Randomized Placebo Controlled Double-blind Pilot Trial
- ClinicalTrials.gov ID
- NCT05328999
- Acronym / sponsor ID
- Fertilitom
- Conditions
- Subfertility, Asthenozoospermia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Study start
- 10 Aug 2022 (actual)
- Primary completion
- 11 Apr 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 14 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | – | Dietary Supplement: Probiotics (Omnibiotic (R))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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Couples (Males and females) with subfertility, primary or secundary infertility, or recurrent pregnancy loss.
Key inclusion criteria (1 listed)
- Couples (Males and females) with subfertility, primary or secondary infertility, or recurrent pregnancy loss.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Dietary supplement | Subfertile males with elevated DNA fragmentation index and asthenozoospermia |
Primary outcome
Seminal microbiome
Time frame: 3 months
16S-RNA sequencing; shotgun metagenomic sequencing
Vaginal microbiome
Time frame: 1 month
16S-RNA sequencing; shotgun metagenomic sequencing
Uterine microbiome
Time frame: 1 month
16S-RNA sequencing; shotgun metagenomic sequencing
DNA-Fragmentation index
Time frame: 3 months
Rate of sperm with elevated DNA Fragmentation index
27 secondary outcomes
Hormone status of males and females - LH (Luteinizing hormone)
Time frame: 3 months
Hormone status of males and females - FSH (follicle stimulating hormone)
Time frame: 3 months
Hormone status of males and females - Testosterone status
Time frame: 3 months
Hormone status of males and females - free Testosterone
Time frame: 3 months
Hormone status of males and females - Androstenedione
Time frame: 3 months
Hormone status of males and females - AMH (Anti-Müllerian hormone)
Time frame: 3 months
Hormone status of males and females - DHEAS (dehydroepiandrosterone sulphate)
Time frame: 3 months
Hormone status of males and females - 25(OH)Vitamin D
Time frame: 3 months
Hormone status of males and females - TSH (thyroid-stimulating hormone)
Time frame: 3 months
Hormone status of males and females - fT3 (free Triiodothyronine)
Time frame: 3 months
Hormone status of males and females - freeThyroxine (fT4)
Time frame: 3 months
HPV Status
Time frame: 3 months
stool microbiome
Time frame: 3 months
oral microbiome
Time frame: 3 months
Cortisol in Saliva
Time frame: 3 months
Amylase in Saliva
Time frame: 3 months
Metabolic parameters - Omega 3
Time frame: 3 months
Metabolic parameters - Omega 6
Time frame: 3 months
Metabolic parameters - low density lipoprotein
Time frame: 3 months
Metabolic parameters - high density lipoprotein
Time frame: 3 months
Metabolic parameters - triglycerides
Time frame: 3 months
Metabolic parameters - LipoproteinA
Time frame: 3 months
Time to pregnancy
Time frame: 24 months
pregnancy rate
Time frame: 24 months
live birth rate
Time frame: 24 months
Presence of sexual transmittable diseases
Time frame: 3 months
Sperm count
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
- Background: PubMed 31311196Jersoviene V, Gudleviciene Z, Rimiene J, Butkauskas D. Human Papillomavirus and Infertility. Medicina (Kaunas). 2019 Jul 15;55(7):377. doi: 10.3390/medicina55070377.
- Background: PubMed 30550767Brusselaers 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.
- Background: PubMed 31119299Koedooder 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.
- Background: PubMed 31005311Depuydt 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.
- Background: PubMed 30809218Baud 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.
- Background: PubMed 30526664Koedooder 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.
- Background: PubMed 31367292Depuydt 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.
- Background: PubMed 29623908Xiong 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.
- Background: PubMed 30098680Moreno 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.
- Background: PubMed 30037698Simon 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Martina Kollmann, PD Dr. principal investigator
Medical University of Graz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Subfertility and Asthenozoospermia, run by Medical University of Graz at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sarah Feigl, Dr. (004331638580831, s.feigl@medunigraz.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seminal microbiome (time frame: 3 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05328999, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.