Lee Iris T, Barnhart Kurt T, Hwang Wei-Ting, Hinkle Stefanie N, Johnstone Erica, Mills James L, Caniglia Ellen C, Schisterman Enrique F, Mendola Pauline, Ryan Ginny L, Hotaling Jim, Peterson C Matthew, Van Voorhis Bradley J, Mumford Sunni L
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
Hum Reprod. 2025 Jul 2. doi: 10.1093/humrep/deaf124.
Beyond BMI, are there better predictors of the impact of high female adiposity on reproductive outcomes in patients undergoing fertility treatment or attempting unassisted conception?
Though BMI remains a predictor of fertility outcomes, alternative markers of adiposity, such as percent body fat, provide distinct information and may be more strongly associated with outcomes than BMI.
Elevated BMI is associated with a lower probability of live birth, though randomized trials have not consistently demonstrated the efficacy of weight loss for increasing live birth among patients utilizing infertility treatment.
STUDY DESIGN, SIZE, DURATION: This was a secondary analysis of data gathered from 2013 to 2017 during the Folic Acid and Zinc Supplementation Trial (FAZST). Participants in FAZST included 2370 heterosexual couples seeking infertility care at four US fertility centers. Couples were followed for 9 months while undergoing fertility treatments or attempting unassisted conception, with up to 9 additional months of follow-up if pregnancy occurred.
PARTICIPANTS/MATERIALS, SETTING, METHODS: For inclusion in the present study, female participants must have had at least one marker of adiposity measured at their baseline visit for FAZST. The primary exposure was high adiposity (defined by commonly used cutoffs in the literature) by each of five markers: BMI, percent body fat measured by dual-energy X-ray absorptiometry (DXA), serum leptin, serum adiponectin/leptin ratio, and waist circumference. Of the participants in FAZST, BMI was available for 99.6%, percent body fat for 7.3% (DXA only offered to 218 participants at two study sites between 2016 and 2017), leptin for 89.7%, adiponectin/leptin ratio for 89.7%, and waist circumference for 90.9%. Generalized linear models including age, race, parity, education, physical activity, male partner BMI ≥30 kg/m2, and Healthy Eating Index were used to estimate the relative risk of live birth.
High adiposity by BMI was associated with decreased probability of live birth (adjusted relative risk [aRR] 0.85, 95% CI 0.74-0.98). The other markers demonstrated similar associations, though a stronger effect size was seen with percent body fat (aRR 0.34, 95% CI 0.22-0.55). In an analysis by tertile, even moderately elevated percent body fat was associated with a decrease in live birth. When stratifying by infertility treatment status, associations were attenuated for most markers in the group utilizing infertility treatment, though percent body fat remained significantly associated with live birth. However, this marker was only available in a subset of participants.
LIMITATIONS, REASONS FOR CAUTION: Only a subset of participants underwent DXA scans and had data on percent body fat, limiting the generalizability of the finding that this marker was most strongly associated with live birth. There were few participants with low BMIs, limiting the ability to draw conclusions on how low adiposity may affect reproductive outcomes. Findings may not be generalizable to the non-infertility population.
The findings support prior data that high adiposity is associated with a lower probability of live birth. While most markers of adiposity performed similarly to BMI, there may be a role for percent body fat as an alternative assessment of adiposity, particularly among patients utilizing infertility treatment.
STUDY FUNDING/COMPETING INTEREST(S): The FAZST and Impact of Diet, Exercise, and Lifestyle studies were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (contracts HHSN275201200007C, HHSN275201500001C, HHSN275201300026I/HHSN27500008, and HHSN275201300026I/HHSN27500018). There are no conflicts of interest to declare.
NCT00467363 (secondary analysis).
对于接受生育治疗或尝试自然受孕的患者,除了体重指数(BMI)之外,是否有更好的指标来预测女性肥胖对生殖结局的影响?
虽然BMI仍然是生育结局的一个预测指标,但肥胖的其他标志物,如体脂百分比,能提供不同的信息,并且可能比BMI与结局的关联更强。
BMI升高与活产概率降低相关,不过随机试验并未始终证明减肥对于接受不孕症治疗的患者提高活产率的有效性。
研究设计、规模、持续时间:这是对2013年至2017年期间在叶酸和锌补充试验(FAZST)中收集的数据进行的二次分析。FAZST的参与者包括在美国四个生育中心寻求不孕症治疗的2370对异性恋夫妇。夫妇们在接受生育治疗或尝试自然受孕期间被随访9个月,如果怀孕则最多再随访9个月。
参与者/材料、地点、方法:为纳入本研究,女性参与者在FAZST的基线访视时必须至少测量过一项肥胖标志物。主要暴露因素是通过以下五种标志物中的每一种定义的高肥胖(根据文献中常用的临界值):BMI、通过双能X线吸收法(DXA)测量的体脂百分比、血清瘦素、血清脂联素/瘦素比值和腰围。在FAZST的参与者中,99.6%的人有BMI数据,7.3%的人有体脂百分比数据(2016年至2017年期间仅在两个研究地点对218名参与者进行了DXA测量),89.7%的人有瘦素数据,89.7%的人有脂联素/瘦素比值数据,90.9%的人有腰围数据。使用包括年龄、种族、产次、教育程度、身体活动、男性伴侣BMI≥30kg/m²以及健康饮食指数的广义线性模型来估计活产的相对风险。
BMI定义的高肥胖与活产概率降低相关(调整后相对风险[aRR]0.85,95%置信区间0.74 - 0.98)。其他标志物显示出类似的关联,不过体脂百分比的效应大小更强(aRR 0.34,95%置信区间0.22 - 0.55)。在按三分位数进行的分析中,即使是适度升高的体脂百分比也与活产率降低相关。当按不孕症治疗状态分层时,在接受不孕症治疗的组中,大多数标志物的关联减弱,不过体脂百分比仍与活产显著相关。然而,该标志物仅在一部分参与者中可用。
局限性、需谨慎的原因:只有一部分参与者接受了DXA扫描并有体脂百分比数据,限制了该标志物与活产关联最强这一发现的可推广性。低BMI的参与者很少,限制了就低肥胖如何影响生殖结局得出结论的能力。研究结果可能不适用于非不孕症人群。
研究结果支持先前的数据,即高肥胖与活产概率降低相关。虽然大多数肥胖标志物的表现与BMI相似,但体脂百分比可能作为肥胖的一种替代评估指标,特别是在接受不孕症治疗的患者中。
研究资金/利益冲突:FAZST以及饮食、运动和生活方式影响研究由美国国立卫生研究院尤妮斯·肯尼迪·施莱佛儿童健康与人类发展国家研究所的内部研究项目资助(合同编号HHSN275201200007C、HHSN275201500001C、HHSN275201300026I/HHSN27500008以及HHSN275201300026I/HHSN27500018)。无利益冲突声明。
NCT00467363(二次分析)