Abstract and Introduction
Study Question: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women?
Summary Answer: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women.
What is Known Already: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI.
Study Design, Size, Duration: Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015–2017.
Participants/Materials, Setting, Methods: Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders.
Main Results and the Role of Chance: Compared to women with a normal BMI of 18.5–22.9 kg/m2, women with higher BMI of 23–27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25–52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6–27.2%), those in the upper two quartiles of 33.0–39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability.
Limitations Reasons for Caution: Small sample size could restrict power of analysis. The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant.
Wider Implications of the Findings: Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies.
Study Funding/Competing Interest(S): This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest.
The falling trend in global fertility has been an issue of concern in many settings, imposing significant economic and social implications on a pre-existing ageing demographic (United Nations, 2015). Compounding this problem is the ongoing rise of worldwide overweight and obesity rates, particularly among women of childbearing age (NCD Risk Factor Collaboration, 2016). In Singapore, proportion of overweight people is projected to increase from 24.6% in 1990 to 38.6% by 2050; while those obese are predicted to almost quadruple from 4.3% in 1990 to 15.9% by 2050 (Phan et al., 2014). Overweight and obesity, as measured by body mass index (BMI), has been associated with lower female fecundability—the cycle probability of conception (Wise et al., 2010, 2013; McKinnon et al., 2016). To a lesser extent, underweight has also been related to reduced fecundability (Hassan and Killick, 2004; Gesink Law et al., 2007). Both extremes of BMI are associated with reproductive dysfunctions through increasing risk of anovulation (Davies, 2006), alterations in levels of various hormones and energy metabolism (Talmor and Dunphy, 2015; Fontana and Della Torre, 2016).
BMI, however, is a crude measure of body fat and does not consider body composition and shape. Excess fat deposition in the abdominal region has been associated with oligomenorrhea (De Pergola et al., 2009) and increased androgenicity of women (Diamanti-Kandarakis and Bergiele, 2001). Evidence has been limited and inconsistent regarding the extent to which female fecundability is influenced by central adiposity and body fat distribution, as often measured by waist circumference (WC) or waist-to-hip ratio (WHR) (Wise et al., 2010, 2013; McKinnon et al., 2016). Nevertheless, the use of WC or WHR as a proxy for central adiposity is subject to key limitations. Both indicators are sensitive to body size (weight and height) and highly correlated with BMI, which make it difficult to disentangle the impacts of body shape and of body size (Krakauer and Krakauer, 2012; Vikram et al., 2016). Also, WHR has limited validity in practical risk management when changes in both WC and hip circumference (HC) are in a similar direction (Vikram et al., 2016). Evidence suggests that the waist-to-height ratio (WHtR) and A Body Shape Index (ABSI = WC (m)/[BMI (kg/m2)2/3 × Height (m)1/2]) may be better proxies of central adiposity and better predictors of health risks (Krakauer and Krakauer, 2012; Vikram et al., 2016).
Previous studies assessing adiposity in relation to fecundability were conducted among white/black women (Wise et al., 2010, 2013; McKinnon et al., 2016), but have not been performed among Asian women. Asian populations have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI (Wang et al., 1994). To clarify the role of body weight and body fat distribution on fecundability in Asian women, we examined these associations among Chinese, Malay and Indian women enrolled in a prospectively studied preconception cohort in Singapore. Using Asian specific cut-offs, we assessed BMI, WC and WHR in relation to fecundability, as measured by time-to-pregnancy (TTP) in cycles (Weinberg et al., 1989). To address existing gaps in the literature, we additionally assessed subcutaneous fat deposition based on multiple sites of skinfold thicknesses (SFT), and total body fat percentage (TBF%) using air displacement plethysmography. We examined WHtR and ABSI as indicators of central adiposity. We hypothesized that increased overall adiposity as measured by BMI, SFT and TBF%, and increased central adiposity as measured by WC, WHR, WHtR and ABSI were associated with reduced fecundability.
Hum Reprod. 2018;33(11):2141-2149. © 2018 Oxford University Press