In a recent study published in the journal BMC Medicine, researchers evaluate the effect of lifestyle behaviors on various fertility and reproductive outcomes.
Study: Associations between health behaviours, fertility and reproductive outcomes: triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa). Image Credit: Chinnapong / Shutterstock.com
Factors contributing to infertility
Fertility guidelines include smoking cessation, limiting the consumption of caffeine and alcohol, and weight management. Heavy smoking and increased alcohol intake reduce the likelihood of conception, whereas obesity and increased caffeine intake increase miscarriage risks.
In males, alcohol intake and smoking lower semen quality, whereas obesity increases the time to conception and lowers the probability of natural conception. However, fertility-related advice is largely based on observational studies, often analyzing data with confounding bias from diet, sleep, and physical exercise.
About the study
In the present study, researchers explore the relationships between lifestyle choices and reproductive and fertility outcomes among men and women using a Mendelian randomization (MR) approach to account for potential confounding and reverse causation.
The study utilized data from 84,705 Norwegian mother, father, and child (MoBa) study participants, 68,002 of whom were female.
Multivariate regression modeling of lifestyle choices, including caffeine and alcohol intake, smoking, and body mass index (BMI), was performed to assess the self-reported study outcomes. The assessed fertility outcomes included infertility therapy usage, miscarriage, and the time for conception, whereas the reproductive outcomes were age at first delivery and number of children.
Data were adjusted for the year of birth, attention-deficit hyperactivity disorder (ADHD) traits, and level of education. Individual-level MR was used to explore probable causal effects of lifestyle choices on reproductive/fertility outcomes among 63,376 women and 45,460 men.
In addition, summary-level multivariate MR was performed for available study outcomes among the United Kingdom Biobank participants, controlling for educational level and ADHD liability.
The study utilized measures from the first questionnaires received between weeks 13 and 17 of gestation to obtain data on previous deliveries, medical history, occupation, medications, home and workplace exposures, mental well-being, and lifestyle choices.
Questionnaire data were linked to the Medical Birth Registry of Norway (MBRN). Women and men documented their health behavior three and six months before pregnancy, respectively.
Blood samples were obtained from MoBa study parents during pregnancy. The most recently released quality-controlled genotype data for MoBa study participants were used.
The MR approach included multivariate regression analysis, followed by individual-level MR and summary-level Mendelian randomization. For individual-level MR analyses, genetic scores were constructed using genome-wide association studies (GWAS) summary statistics, whereas, for summary-level Mendelian randomization, individual single nucleotide variant (SNP) effect size data were utilized.
Multivariate regression modeling showed that elevated BMI values increased the time to conception, the need for infertility therapy, and the chances of miscarriage. In addition, the time to conception was higher among smokers. Robust evidence was obtained for the effects of smoking and elevated BMI on lower age at first delivery, as well as elevated BMI on longer time for conception.
Weak evidence was obtained for the effects of smoking on longer times to conception. Similar associations were obtained for age during the first delivery in the summary-level Mendelian randomization analyses; however, attenuated effects were observed in the multivariate MR analyses. The study outcomes did not show significant differences between men and women, except for parent age at first birth, which was greater among men.
Greater age at first delivery was related to having fewer children, longer times to conception, as well as increased chances of miscarriage and infertility therapy requirements. Having more children was related to shorter times to conception, a greater likelihood of miscarriage, and using infertility therapy.
Greater frequency of alcohol intake and binge drinking were both related to having fewer children and greater age at first delivery. Individuals with greater alcohol intake were less likely to require infertility treatment, with odds ratios (OR) for alcohol frequency and binge drinking of 0.9 and 0.8, respectively. Greater caffeine intake was related to lower age at first birth among men and a lower likelihood of requiring treatment among women (OR 1.0).
Cigarette use was related to having fewer children and lower age at first delivery. Both cigarette smoking measures were related to longer times to conception for women.
Greater BMI values were related to having fewer children. Elevated BMI was related to greater age at first birth among men and lower age at first birth among women.
Higher BMI was related to longer times to conceive, greater likelihood of requiring infertility therapy (OR 1.0), and having miscarriages (OR 1.0). In the individual-level MR analyses, genetically estimated elevated BMI values were related to lower age at first birth, as were genetic liabilities for the initiation of cigarette smoking initiation.
There was weak evidence for an association between genetically estimated greater alcohol intake and lower age at first birth among men. Genetically estimated elevated BMI was related to longer times to conception among women.
Similarly, weak evidence was presented for genetic liability to smoking initiation and genetically estimated greater alcohol intake, both related to longer times to conceive. In the summary-level Mendelian randomization analyses, strong evidence was obtained for the effects of smoking initiation on lower age at first birth for women, a greater number of children, and fewer miscarriages.
The study findings showed the most consistent associations between smoking habits and BMI values and increased time to conception and lower age during the first delivery. The positive association between the age at first delivery and time to conception indicated that the mechanisms for reproductive outcomes and fertility outcomes were distinct.
Multivariate MR analysis findings indicated that the effects of age at first delivery might be explained by underlying educational and ADHD liabilities. Taken together, the study findings could inform fertility guidance.
- Wootton, R. E., Lawn, R. B., Magnus, M. C. et al. (2023). Associations between health behaviours, fertility and reproductive outcomes: triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa). BMC Medicine 21(125). doi:10.1186/s12916-023-02831-9