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.
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
OBSERVATIONAL
Enrollment
960
Socio-demographics, health history, behavioural characteristics, environmental exposures, anthropometric measurements, body fat composition, metabolic and stress biomarkers, semen physical and molecular characteristics.
KK Women's and Children's Hospital
Singapore, Singapore
RECRUITINGPregnancy rate
Defined by viable intrauterine pregnancy at gestational weeks of less or equal to 16 at the time of the study
Time frame: Up to 16 weeks of gestation
Fertility index
Defined by a composite index score derived from both male and female predictive factors
Time frame: Through study completion, an average of 3 years
Oxidative stress
Defined by oxidative status measured from blood and semen samples using the micro-NMR
Time frame: Through study completion, an average of 3 years
Semen volume
Assessed by semen analysis in ml
Time frame: Up to 2 years
Sperm concentration
Assessed by semen analysis in million/ml
Time frame: Up to 2 years
Sperm total motility
Assessed by semen analysis in percent
Time frame: Up to 2 years
Sperm progressive motility
Assessed by semen analysis in percent
Time frame: Up to 2 years
Total progressive motile sperm count
measured by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm
Time frame: Up to 2 years
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Single strand sperm DNA fragmentation
Measured by the AI-powered semen analyzer
Time frame: Up to 2 years
Double strand sperm DNA fragmentation
Measured by the AI-powered semen analyzer
Time frame: Up to 2 years
mRNA level
From blood and semen samples through transcriptomics analysis
Time frame: Through study completion, an average of 3 years
sncRNA level
From blood and semen samples through transcriptomics analysis
Time frame: Through study completion, an average of 3 years
DNA methylation
From blood and semen samples through bisulfite sequencing
Time frame: Through study completion, an average of 3 years