Towards Optimal Fertility, Fathering and Fatherhood studY
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Lifestyle and metabolic indicators.
- Who it may be relevant to
- Registry conditions: Reproductive Issues, Fertility Issues. Basic parameters: 21 years — 49 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Singapore
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Investigating Male Factors and Their Relationships With Reproductive Health Outcomes in Singapore: Towards Optimal Fertility, Fathering and Fatherhood studY
Overview
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.
Interventions
- 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.
Primary outcome measures
- Pregnancy rate [Time frame: Up to 16 weeks of gestation]
Secondary outcome measures (12)
- 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]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Case-control
Study locations
Singapore · 1 center
- KK Women's and Children's Hospital — Singapore
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. PMID 39819913
Identifiers
NCT: NCT06293235 · MOH-001530-01