Reproductive IssuesTOFFFYNCT06293235
Towards Optimal Fertility, Fathering and Fatherhood studY
An observational study of Reproductive Issues and Fertility Issues, run by KK Women's and Children's Hospital at 1 site in Singapore.
Trial summary
This case-control study involving fertile and subfertile couples aims to identify male factors related to pregnancy likelihood, create a fertility index measure combining male and female factors to predict pregnancy likelihood, and examine how male factors relate to the semen physical and biological characteristics. Read more about this study
- Who is it for?
- Ages 21 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Reproductive Issues, Fertility Issues
- What is being tested?
- Lifestyle and metabolic indicators
- How many people
- 960 participants
- Where
- 1 siteSingapore
- Study dates
- 21 Jun 2024to Sep 2027
- 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 21 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: The subfertile couples will be recruited from the infertility clinics, while the fertile couples will be recruited from the antenatal clinics. Both groups will also be recruited from on-going preconception and pregnancy programs in the hospital.
Who may be able to join
- Subfertile couples:
- men aged ≥21-49 years
- men with a female partner aged 21-39 years
- couples who are not able to conceive for at least 12 months
- couples who are Singapore citizen or permanent resident
- Fertile couples:
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- men aged 21-49 years
- men with a female partner aged 21-39 years
- men with proven fertility defined as those female partners who are currently pregnant and with viable intrauterine pregnancy at gestational weeks of less or equal to 16 at the time of the study
- couples with attempted time to conceive within 12 months to achieve this pregnancy or with unplanned pregnancy
- couples who are Singapore citizen or permanent resident
Who cannot join
- Subfertile couples:
- male infertility of a known aetiology including azoospermia, retrograde ejaculation, genetic disorders, cancer treatment, or testes trauma
- female infertility diagnosis as confirmed by diagnostic imaging or having severe endometriosis
- female partners with irregular menstrual cycle >35 days
- couples with known chromosomal abnormalities
- Fertile couples:
Show all 9Show fewer
- couples who achieve pregnancy after oocyte or spermatozoa donation
- couples with known chromosomal abnormalities
- female partners with known uterine abnormalities
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
KK Women's and Children's Hospital
Singapore, 229899
Benjarat Oh, +6583684641, benjarat.oh@kkh.com.sg
About this study
Official title: Investigating Male Factors and Their Relationships With Reproductive Health Outcomes in Singapore: Towards Optimal Fertility, Fathering and Fatherhood studY
This case-control study involving fertile and subfertile couples aims to identify male factors related to pregnancy likelihood, create a fertility index measure combining male and female factors to predict pregnancy likelihood, and examine how male factors relate to the semen physical and biological characteristics.
Read the detailed description
Paternal contributions to fertility and reproductive health outcomes have been understudied, despite promising evidence from animal studies. This study aims to investigate the male contribution to pregnancy likelihood and explore the underlying biological mechanisms. Specifically, the investigators aim to (1) identify male factors associated with pregnancy rate; (2) develop a fertility index combining modifiable factors for both males and females to predict pregnancy rate; and (3) explore the relationship of male modifiable factors with semen physical and molecular characteristics. This is a case-control study with 480 fertile and subfertile males (along with their female partners), recruited from KK Women's and Children's Hospital. The investigators will use questionnaires to collect data on socio-demographic characteristics, clinical, lifestyle, and environmental factors; analyze metabolic and stress biomarkers from blood samples; and measure semen parameters including sperm motility, density, morphology, volume, DNA fragmentation, DNA methylation, gene expression, and seminal plasma oxidative status. Findings from this proposed study will pave the way for developing lifestyle-based or medical interventions to enhance male and couple reproductive health, and potentially benefiting future offspring health.
- Conditions
- Reproductive Issues, Fertility Issues
- Being tested
- Lifestyle and metabolic indicators
- Keywords
- Male, Risk factor, Lifestyle, Semen analysis, Epigenetic, Oxidative stress, DNA fragmentation
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lifestyle and metabolic indicatorsOther
Also called Semen quality and characteristics
Socio-demographics, health history, behavioural characteristics, environmental exposures, anthropometric measurements, body fat composition, metabolic and stress biomarkers, semen physical and molecular characteristics.
| Study group | Role | What they receive |
|---|---|---|
| Subfertile couples | Couples who are not able to conceive for at least 12 months with female partners without infertility diagnosis. Receives: Other: Lifestyle and metabolic indicators | |
| Fertile couples | Couples with attempted time to conceive within 12 months to achieve this pregnancy or with unplanned pregnancy, with female partners who are currently pregnant with viable intrauterine pregnancy. Receives: Other: Lifestyle and metabolic indicators |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pregnancy rate
Defined by viable intrauterine pregnancy at gestational weeks of less or equal to 16 at the time of the study
Measured: Up to 16 weeks of gestation
Secondary outcomes (12)
Fertility index
Defined by a composite index score derived from both male and female predictive factors
Measured: Through study completion, an average of 3 years
Oxidative stress
Defined by oxidative status measured from blood and semen samples using the micro-NMR
Measured: Through study completion, an average of 3 years
Semen volume
Assessed by semen analysis in ml
Measured: Up to 2 years
Sperm concentration
Assessed by semen analysis in million/ml
Measured: Up to 2 years
Sperm total motility
Assessed by semen analysis in percent
Measured: Up to 2 years
Sperm progressive motility
Assessed by semen analysis in percent
Measured: Up to 2 years
Total progressive motile sperm count
measured by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm
Measured: Up to 2 years
Single strand sperm DNA fragmentation
Measured by the AI-powered semen analyzer
Measured: Up to 2 years
Double strand sperm DNA fragmentation
Measured by the AI-powered semen analyzer
Measured: Up to 2 years
mRNA level
From blood and semen samples through transcriptomics analysis
Measured: Through study completion, an average of 3 years
sncRNA level
From blood and semen samples through transcriptomics analysis
Measured: Through study completion, an average of 3 years
DNA methylation
From blood and semen samples through bisulfite sequencing
Measured: Through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2024
- Study start21 Jun 2024
- Primary completionMar 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Reproductive IssuesStudies of the same condition, open and under way.
- More trials run by KK Women's and Children's HospitalThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 960 participants (estimated)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Loy See Ling, KK Women's and Children's Hospital
- Investigators
- See Ling Loy, PhD, Principal investigator, KK Women's and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06293235
- Sponsor's protocol ID
- MOH-001530-01
- Acronym
- TOFFFY
- Status last verified
- Mar 2026
- First submitted
- 20 Feb 2024
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ku CW, Pek JW, Cheung YB, Tharmalingam Durgahshree MD, Chan M, Lee YH, Godfrey K, Yap F, Chan JKY, Loy SL. Investigating male factors and their relationships with reproductive health outcomes: a case-control study protocol for Towards Optimal Fertility, Fathering, and Fatherhood studY (TOFFFY) in Singapore. BMJ Open. 2025 Jan 15;15(1):e088143. doi: 10.1136/bmjopen-2024-088143.
PubMed 39819913
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Male Factors and Their Relationships With Reproductive Health Outcomes in Singapore: Towards Optimal Fertility, Fathering and Fatherhood studY
- ClinicalTrials.gov ID
- NCT06293235
- Acronym / sponsor ID
- TOFFFY / MOH-001530-01
- Conditions
- Reproductive Issues, Fertility Issues
- Keywords
- Male, Risk factor, Lifestyle, Semen analysis, Epigenetic, Oxidative stress, DNA fragmentation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 960 participants (estimated)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Study start
- 21 Jun 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 5 Mar 2024 (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.
This case-control study involving fertile and subfertile couples aims to identify male factors related to pregnancy likelihood, create a fertility index measure combining male and female factors to predict pregnancy likelihood, and examine how male factors relate to the semen physical and biological characteristics.
Detailed description
Paternal contributions to fertility and reproductive health outcomes have been understudied, despite promising evidence from animal studies. This study aims to investigate the male contribution to pregnancy likelihood and explore the underlying biological mechanisms. Specifically, the investigators aim to (1) identify male factors associated with pregnancy rate; (2) develop a fertility index combining modifiable factors for both males and females to predict pregnancy rate; and (3) explore the relationship of male modifiable factors with semen physical and molecular characteristics. This is a case-control study with 480 fertile and subfertile males (along with their female partners), recruited from KK Women's and Children's Hospital. The investigators will use questionnaires to collect data on socio-demographic characteristics, clinical, lifestyle, and environmental factors; analyze metabolic and stress biomarkers from blood samples; and measure semen parameters including sperm motility, density, morphology, volume, DNA fragmentation, DNA methylation, gene expression, and seminal plasma oxidative status. Findings from this proposed study will pave the way for developing lifestyle-based or medical interventions to enhance male and couple reproductive health, and potentially benefiting future offspring health.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subfertile couples | – | Other: Lifestyle and metabolic indicatorsCouples who are not able to conceive for at least 12 months with female partners without infertility diagnosis. |
| Fertile couples | – | Other: Lifestyle and metabolic indicatorsCouples with attempted time to conceive within 12 months to achieve this pregnancy or with unplanned pregnancy, with female partners who are currently pregnant with viable intrauterine pregnancy. |
Who may qualify
- Ages
- 21 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- The subfertile couples will be recruited from the infertility clinics, while the fertile couples will be recruited from the antenatal clinics. Both groups will also be recruited from on-going preconception and pregnancy programs in the hospital.
Key inclusion criteria (11 listed)
- men aged ≥21-49 years
- men with a female partner aged 21-39 years
- couples who are not able to conceive for at least 12 months
- couples who are Singapore citizen or permanent resident
- men aged 21-49 years
Key exclusion criteria (9 listed)
- male infertility of a known aetiology including azoospermia, retrograde ejaculation, genetic disorders, cancer treatment, or testes trauma
- female infertility diagnosis as confirmed by diagnostic imaging or having severe endometriosis
- female partners with irregular menstrual cycle >35 days
- couples with known chromosomal abnormalities
- couples who achieve pregnancy after oocyte or spermatozoa donation
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 |
|---|---|---|
| Lifestyle and metabolic indicatorsAlso: Semen quality and characteristicsSocio-demographics, health history, behavioural characteristics, environmental exposures, anthropometric measurements, body fat composition, metabolic and stress biomarkers, semen physical and molecular characteristics. | Other | Fertile couples, Subfertile couples |
Primary outcome
Pregnancy rate
Time frame: Up to 16 weeks of gestation
Defined by viable intrauterine pregnancy at gestational weeks of less or equal to 16 at the time of the study
12 secondary outcomes
Fertility index
Time frame: Through study completion, an average of 3 years
Oxidative stress
Time frame: Through study completion, an average of 3 years
Semen volume
Time frame: Up to 2 years
Sperm concentration
Time frame: Up to 2 years
Sperm total motility
Time frame: Up to 2 years
Sperm progressive motility
Time frame: Up to 2 years
Total progressive motile sperm count
Time frame: Up to 2 years
Single strand sperm DNA fragmentation
Time frame: Up to 2 years
Double strand sperm DNA fragmentation
Time frame: Up to 2 years
mRNA level
Time frame: Through study completion, an average of 3 years
sncRNA level
Time frame: Through study completion, an average of 3 years
DNA methylation
Time frame: Through study completion, an average of 3 years
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 20 Mar 2026.
- Derived from this study: PubMed 39819913Ku CW, Pek JW, Cheung YB, Tharmalingam Durgahshree MD, Chan M, Lee YH, Godfrey K, Yap F, Chan JKY, Loy SL. Investigating male factors and their relationships with reproductive health outcomes: a case-control study protocol for Towards Optimal Fertility, Fathering, and Fatherhood studY (TOFFFY) in Singapore. BMJ Open. 2025 Jan 15;15(1):e088143. doi: 10.1136/bmjopen-2024-088143.
- 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.
See Ling Loy, PhD principal investigator
KK Women's and Children's Hospital
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 Reproductive Issues and Fertility Issues, run by KK Women's and Children's Hospital at 1 site in Singapore.
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 11 inclusion and 9 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 20 Mar 2026. 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 Singapore. 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 Benjarat Oh (63948105 ext. 65, benjarat.oh@kkh.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pregnancy rate (time frame: Up to 16 weeks of gestation). 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 NCT06293235, which also lists 1 linked publication.
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 20 Mar 2026.