Male Fertility · Male Factor Causes
RRM Academy Synopsis
Singapore study protocol tests male factors linked to pregnancy
A Singapore hospital has registered a plan to study couples' fertility. The study will compare 240 couples with impaired male fertility to 240 couples with normal male fertility. Researchers will look for male factors linked to pregnancy and build a fertility index from male and female factors. Recruitment is planned for July 2024 to June 2026.
Key Findings
- The plan is an unmatched case-control study of 480 couples, recruited at KK Women's and Children's Hospital: 240 cases with impaired male fertility and 240 controls with normal male fertility.
- Cases are couples who could not conceive in at least 12 months of regular, unprotected intercourse. Controls have a viable pregnancy at 16 weeks or less after trying 12 months or less.
- Inclusion requires men aged 21 to 49 and female partners aged 21 to 39, all Singapore citizens or permanent residents. Men also give blood and semen samples.
- Semen samples will be tested for sperm DNA fragmentation, DNA methylation and gene expression, alongside standard semen measures.
- The fertility index will be scored with points and checked by 10-fold cross-validation. An AUROC value above 0.80 will count as good discrimination.
Interpretation
This paper is a study plan and reports no results. The design compares two groups at a single visit, so any finding will show association. The authors say a causal link would remain inferential, and they name recall bias in self-reported lifestyle answers as a limit. The plan recruits cases from infertility clinics and controls from antenatal clinics. All participants are Singapore citizens or permanent residents at one hospital, so the findings may apply differently elsewhere.
RRM Context
The authors cite preliminary estimates that men are solely responsible in 20–30% of cases and contribute in 50% overall. Restorative reproductive medicine evaluates both partners and looks for the cause in each. This study measures men's habits, metabolic health and semen next to women's factors. Results are still to come.
Abstract
Introduction
Despite the global prevalence of low fertility rates, male contributions to fertility and reproductive health outcomes have been understudied. This study aims to investigate the male contribution to fertility and explore the underlying biological mechanisms. Specifically, we aim to (1) identify male factors associated with successful pregnancy, (2) develop a fertility index incorporating modifiable factors for both males and females to predict pregnancy rate and (3) explore the relationship of male modifiable factors with semen parameters and molecular characteristics.
Methods and Analysis
We will conduct an unmatched case-control study involving 240 couples with impaired male fertility (cases) and 240 couples with normal male fertility (controls). Between July 2024 and June 2026, we will recruit 480 eligible couples from KK Women's and Children's Hospital, Singapore. Male and female participants will complete questionnaires on sociodemographics, general health and lifestyle factors, and their anthropometry and body fat composition will be measured. Blood and semen samples from the male participants will be collected for biochemical, molecular and semen analyses. Predictive male factors will be identified using the least absolute shrinkage and selection operator method, accounting for female factors. We will construct a logistic regression model incorporating both male and female factors to derive a fertility index, which will be evaluated using cross-validation on subsets of the study population. Multivariable linear regression will be used to explore relationships between male modifiable exposures and semen parameters.
Ethics and Dissemination
The study protocol has received approval from the Centralised Institutional Review Board of SingHealth (2024/2120), Singapore. Participants will provide written informed consent. Study results will be disseminated through conferences and peer-reviewed scientific journals.
Trial Registration
NCT06293235.