Clinical trial NCT06293235: Towards Optimal Fertility, Fathering and Fatherhood studY
Official title: Investigating Male Factors and Their Relationships With Reproductive Health Outcomes in Singapore: Towards Optimal Fertility, Fathering and Fatherhood studY
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Reproductive Issues
Fertility Issues
Keywords: Male
Risk factor
Lifestyle
Semen analysis
Epigenetic
Oxidative stress
DNA fragmentation
Lead sponsor: KK Women's and Children's Hospital
Sponsor class: OTHER_GOV
First posted: 2024-03-05
Enrollment: 960
Sex: ALL
Minimum age (years): 21
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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.

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

Primary outcomes:
measure: Pregnancy rate
timeFrame: Up to 16 weeks of gestation
Secondary outcomes:
measure: Fertility index
timeFrame: Through study completion, an average of 3 years
measure: Oxidative stress
timeFrame: Through study completion, an average of 3 years
measure: Semen volume
timeFrame: Up to 2 years
measure: Sperm concentration
timeFrame: Up to 2 years
measure: Sperm total motility
timeFrame: Up to 2 years
measure: Sperm progressive motility
timeFrame: Up to 2 years
measure: Total progressive motile sperm count
timeFrame: Up to 2 years
measure: Single strand sperm DNA fragmentation
timeFrame: Up to 2 years
measure: Double strand sperm DNA fragmentation
timeFrame: Up to 2 years
measure: mRNA level
timeFrame: Through study completion, an average of 3 years
measure: sncRNA level
timeFrame: Through study completion, an average of 3 years
measure: DNA methylation
timeFrame: Through study completion, an average of 3 years
Other outcomes:
measure: Sperm morphology
timeFrame: Up to 2 years
Locations:
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
Study officials:
affiliation: KK Women's and Children's Hospital
name: See Ling Loy, PhD
role: PRINCIPAL_INVESTIGATOR
References: