Towards Optimal Fertility, Fathering and Fatherhood studY

Fertility Issues Clinical Trial

— TOFFFY  

Official title:

Investigating Male Factors and Their Relationships With Reproductive Health Outcomes in Singapore: Towards Optimal Fertility, Fathering and Fatherhood studY

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06293235
• Other study ID #: 2024/2120
• Status: Not yet recruiting
• Start date: July 2024
• Est. completion date: March 2027

Study information

• Verified date: February 2024
• Source: KK Women's and Children's Hospital
• Contact: Benjarat Oh
• Phone: 63948105
• Email: benjarat.oh[@]kkh.com.sg
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 960
• Est. completion date: March 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Fertility Issues
• Infertility
• Reproductive Issues

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
KK Women's and Children's Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sperm morphology	Assessed by semen analysis	Up to 2 years
Primary	Pregnancy rate	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	Fertility index	Defined by a composite index score derived from both male and female predictive factors	Through study completion, an average of 3 years
Secondary	Oxidative stress	Defined by oxidative status measured from blood and semen samples using the micro-NMR	Through study completion, an average of 3 years
Secondary	Semen volume	Assessed by semen analysis in ml	Up to 2 years
Secondary	Sperm concentration	Assessed by semen analysis in million/ml	Up to 2 years
Secondary	Sperm total motility	Assessed by semen analysis in percent	Up to 2 years
Secondary	Sperm progressive motility	Assessed by semen analysis in percent	Up to 2 years
Secondary	Total progressive motile sperm count	measured by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm	Up to 2 years
Secondary	Single strand sperm DNA fragmentation	Measured by the AI-powered semen analyzer	Up to 2 years
Secondary	Double strand sperm DNA fragmentation	Measured by the AI-powered semen analyzer	Up to 2 years
Secondary	mRNA level	From blood and semen samples through transcriptomics analysis	Through study completion, an average of 3 years
Secondary	sncRNA level	From blood and semen samples through transcriptomics analysis	Through study completion, an average of 3 years
Secondary	DNA methylation	From blood and semen samples through bisulfite sequencing	Through study completion, an average of 3 years