In this cohort study, 1,684 couples were included, with 1,127 achieving pregnancy, constituting 67.0% of the total couples included. The observed pregnancy rate surpassed that of other NFPCP-related studies[23, 25], potentially attributed to excluding couples discontinuing efforts to conceive after the examination in our inclusion analysis. In three distinct Cox regression models, both overweight and obesity in both males and females were linked to prolonged TTP compared to normal weight. Nonetheless, no statistically significant differences in TTP were observed between underweight and normal weight individuals. The third model underwent meticulous adjustments for covariates (including age, occupation, tobacco exposure, and various lifestyle factors), underscoring the robustness of this study. Despite comprehensive adjustments, BMI remained a persistent and significant predictor of TTP, indicating an independent influence on fecundability. In the sensitivity analysis, we excluded couples with self-reported PCOS, chronic diseases, and non-viable pregnancy outcomes individually. Despite these exclusions, TTP remained prolonged for overweight and obese couples, affirming the robustness of the results. Moreover, in the Cox regression models, no multiplicative interaction effect was observed between male and female BMI. Simultaneously, we aggregated three BMI categories for women and men into nine combinations. In a Cox regression model adjusted for confounding factors, we identified that, among all BMI combinations, the fertility of overweight and obese groups decreased by 34% compared to the normal BMI combination. Currently, limited studies have delved into the concurrent examination of marital BMI and fertility. A study from the Danish National Birth Cohort suggested that the risk of low fertility is linked to overweight and obesity for both males and females, particularly in couples where both partners are overweight[26], aligning with our research findings. A retrospective cohort study from China indicates that, in comparison to women with a normal pre-pregnancy BMI, women who were overweight or obese before pregnancy experienced a prolonged TTP and an elevated risk of impaired fertility. However, no correlation was found between TTP and male BMI[21]. Another study from China focusing on couples experiencing their first pregnancy suggests that underweight, overweight, or obese status in women, and underweight status in men, were associated with prolonged TTP[27]. A cohort study from the United States revealed that, when modeled separately, the BMI of male and female partners exhibited no association with TTP. Nevertheless, in couples where both partners were classified as obese class II, fertility reduction led to a longer TTP compared to couples with a normal BMI[19–21]. A cohort study from Norway, employing logistic regression analysis, supported a J-shaped association between BMI and reduced fertility, indicating that both higher and lower BMIs are linked to a greater risk of reduced fertility[19]. Discrepancies might stem from variations in BMI classification standards, racial diversity among the study population, and differences in sample sizes compared to the aforementioned research.
In the adjusted RCS analysis, the dose-response relationship between BMI and TTP seems to exhibit a linear trend. For females with a BMI exceeding 23.65 and males with a BMI ranging from 23 to 29.4, TTP is significantly prolonged, suggesting that higher BMI negatively impacts fertility for both genders. However, when male BMI exceeds 29.4, a significant impact on fertility was not observed. This observation could be attributed to the relatively small sample size of obese males in this study.
Overweight, obesity, and infertility have always been global concerns, and their interrelationships are worth exploring. In investigating the mechanism of female infertility, some studies suggest that obesity-induced systemic and tissue-specific chronic inflammation and oxidative stress can impair the meiosis and cytoplasmic maturation of oocytes[28–30], thereby reducing their developmental ability for fertilization and pre-implantation embryo development[31]. Additionally, some studies propose that the impact of obesity on female fertility is primarily attributed to alterations in the function of the hypothalamic-pituitary-ovarian (HPO) axis. Obesity is often associated with elevated circulating insulin levels, subsequently leading to increased ovarian androgen production[32]. Excessive adipose tissue is responsible for aromatizing these androgens into estrogens, inducing a negative feedback loop in the HPO axis and affecting the production of gonadotropins[33], thereby causing ovulatory dysfunction and menstrual irregularities. In males, a meta-analysis suggests a significant correlation between increased BMI and decreased seminal volume, sperm count, concentration, and viability[34]. Additionally, in animal studies, obesity is correlated with increased sperm DNA damage, but findings in human studies are inconsistent in this regard[35]. The abnormal lipid profile in obese males may lead to testicular oxidative stress, which is a common pathway for disruption in sperm function[36]. Some studies suggest that in an obese environment, the inflammatory response triggered by excessive accumulation of abdominal fat may lead to hypothalamic inflammation, thereby influencing the release of hormones from the hypothalamus and causing dysregulation of the HPG axis[37]. Furthermore, the mechanisms linking male obesity to infertility may also involve endocrine disruptions, erectile dysfunction, and physical disorders such as high scrotal temperature[38, 39]. Despite the potential existence of these mechanisms, further research is needed to elucidate the underlying molecular pathways linking BMI to infertility. Developing effective interventions for preventing and treating infertility associated with overweight and obesity also requires additional investigation. Currently, correcting obesity is considered a potential way to reverse the impact on the male reproductive system. This is achieved through improving nutritional quality, incorporating appropriate exercise, considering micronutrients, and supplementing with light therapy[40]. Achieving optimal weight or meaningful weight loss/fat reduction before conception may be a targeted intervention to improve female fertility[41]. Lifestyle interventions for obese and infertile women can enhance female reproductive function[42]., thereby improving infertility. For couples of reproductive age, controlling preconception BMI is crucial; doctors should provide weight-related health guidance to couples preparing for pregnancy during pre-pregnancy counseling.
Strengths and limitation
Our research presents several distinct advantages. Firstly, unlike the previous NFPCP, which solely targeted rural populations, our study extended its scope beyond registered residency limitations, encompassing all permanent residents. Secondly, our investigation delved into both male and female BMI, constructing diverse models by adjusting for various variables. Moreover, we employed sensitivity analysis to assess the robustness of our findings. Thirdly, we explored the multiplicative and additive effects of male and female BMI, utilizing restrictive cubic splines to identify specific BMI thresholds associated with reduced fertility in both genders. This nuanced approach enriched our comprehension of the intricate relationship between body mass index and TTP. Lastly, in contrast to conventional NFPCP projects, our study introduced additional variables pertaining to TTP, encompassing aspects such as a woman's sleep habits, frequency of takeout consumption, nutrient intake, and exercise frequency during pregnancy preparation.
However, there are some limitations to our study. Firstly, potential selection bias could arise from participation in the NFPCP and its subsequent follow-ups, as individuals with diverse motivations for seeking prenatal care might differ from the general population. Secondly, self-reported covariates, such as lifestyle factors, may introduce recall bias, thereby potentially impacting the data's accuracy. Thirdly, our study established a correlation between BMI and fertility without delving into the underlying mechanisms, which presents an avenue for future research. Additionally, the limited geographical focus on Guangzhou may pose challenges to the study's external validity when extrapolating the findings to a broader Chinese population. Hence, caution is warranted in generalizing these results to a wider demographic.