Towards Optimal Fertility, Fathering and Fatherhood studY

Recruiting

• Conditions: Fertility Issues; Reproductive Issues
• Interventions: Other: Lifestyle and metabolic indicators

• Registration Number: NCT06293235
• Lead Sponsor: KK Women's and Children's Hospital

Brief 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.

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 Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-20
• Study First Submitted QC: 2024-02-27
• Study First Posted: 2024-03-05
• Study Start: 2024-06-21
• Last Update Submitted: 2024-10-07
• Last Update Posted: 2024-10-09
• Primary Completion: 2026-06
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 960

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subfertile couples	Lifestyle and metabolic indicators	Couples who are not able to conceive for at least 12 months with female partners without infertility diagnosis.
Fertile couples	Lifestyle and metabolic indicators	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.

Primary Outcome Measures

Name	Time	Method
Pregnancy rate	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

KK Women's and Children's Hospital; 🇸🇬 Singapore, Singapore