Towards Optimal Fertility, Fathering and Fatherhood studY (TOFFFY)

March 17, 2026 updated by: Loy See Ling, KK Women's and Children's Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
960

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Singapore
      • Singapore, Singapore, 229899
        • Recruiting
        • KK Women's and Children's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

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.

Description

Inclusion Criteria:

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:

  • 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

Exclusion Criteria:

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:

  • couples who achieve pregnancy after oocyte or spermatozoa donation
  • couples with known chromosomal abnormalities
  • female partners with known uterine abnormalities

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Subfertile couples
Couples who are not able to conceive for at least 12 months with female partners without infertility diagnosis.
Other: Lifestyle and metabolic indicators
Socio-demographics, health history, behavioural characteristics, environmental exposures, anthropometric measurements, body fat composition, metabolic and stress biomarkers, semen physical and molecular characteristics.
Other Names:
  • Semen quality and characteristics
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.
Other: Lifestyle and metabolic indicators
Socio-demographics, health history, behavioural characteristics, environmental exposures, anthropometric measurements, body fat composition, metabolic and stress biomarkers, semen physical and molecular characteristics.
Other Names:
  • Semen quality and characteristics

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Up to 16 weeks of gestation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Fertility index
Time Frame: Through study completion, an average of 3 years
Defined by a composite index score derived from both male and female predictive factors
Through study completion, an average of 3 years
Oxidative stress
Time Frame: Through study completion, an average of 3 years
Defined by oxidative status measured from blood and semen samples using the micro-NMR
Through study completion, an average of 3 years
Semen volume
Time Frame: Up to 2 years
Assessed by semen analysis in ml
Up to 2 years
Sperm concentration
Time Frame: Up to 2 years
Assessed by semen analysis in million/ml
Up to 2 years
Sperm total motility
Time Frame: Up to 2 years
Assessed by semen analysis in percent
Up to 2 years
Sperm progressive motility
Time Frame: Up to 2 years
Assessed by semen analysis in percent
Up to 2 years
Total progressive motile sperm count
Time Frame: Up to 2 years
measured by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm
Up to 2 years
Single strand sperm DNA fragmentation
Time Frame: Up to 2 years
Measured by the AI-powered semen analyzer
Up to 2 years
Double strand sperm DNA fragmentation
Time Frame: Up to 2 years
Measured by the AI-powered semen analyzer
Up to 2 years
mRNA level
Time Frame: Through study completion, an average of 3 years
From blood and semen samples through transcriptomics analysis
Through study completion, an average of 3 years
sncRNA level
Time Frame: Through study completion, an average of 3 years
From blood and semen samples through transcriptomics analysis
Through study completion, an average of 3 years
DNA methylation
Time Frame: Through study completion, an average of 3 years
From blood and semen samples through bisulfite sequencing
Through study completion, an average of 3 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sperm morphology
Time Frame: Up to 2 years
Assessed by semen analysis
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
KK Women's and Children's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: See Ling Loy, PhD, KK Women's and Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 21, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 20, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 5, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MOH-001530-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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