Association between prepregnancy subnormal body weight and obstetrical outcomes after autologous in vitro fertilization cycles: systematic review and meta-analysis

Xiong, Yiquan; Liu, Yanmei; Qi, Yana; Liu, Chunrong; Wang, Jing; L, Li; Zou, Kang; Tan, Jing; Sun, Xin

doi:10.1016/j.fertnstert.2019.09.025

Cited by 12 publications

(11 citation statements)

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“…A decrease in BMI was linked to greater subfertility in women with a BMI <20 kg/m 2 , and we observed a similar tendency among men. Our results agree with previous observational studies reporting decreased fertility in underweight women who have undergone ART [6]. Low BMI values could be linked to subfertility because they are intimately related to undernutrition, which is associated with an impaired function of the reproductive system [37], defective concentrations of adipocyte-related regulators of endocrine processes such as leptin [38], and increased risk or pregnancy complications [39].…”

Section: Discussionsupporting

confidence: 91%

“…In observational studies, high body mass index (BMI) in women is associated with greater risk of subfertility, commonly defined as trying to conceive without success for ≥12 months [3,4], or a lower success of assisted reproductive technology (ART) [5]. In addition, women with BMI <18.5 kg/m 2 have a lower chance of ART success [6], supporting the hypothesis of a non-linear relationship between BMI and subfertility. In men, subfertility appears to be more prevalent among those who are overweight or obese, and obese men are also overrepresented among ART users [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

Hernáez

Rogne

Skåra

et al. 2021

Preprint

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BackgroundHigher body mass index (BMI) is associated with subfertility in women and men. This relationship is further substantiated by a few small randomized-controlled trials of weight reduction and success of assisted reproduction. The aim of the current study was to expand the current evidence-base by investigating the association between BMI and subfertility in men and women using multivariable regression and Mendelian randomization.Methods and findingsWe studied 34,157 women (average age 30, average BMI 23.1 kg/m2) and 31,496 men (average age 33, average BMI 25.4 kg/m2) who were genotyped and are participating in the Norwegian Mother, Father and Child Cohort Study. Self-reported information was available on time-to-pregnancy and BMI. A total of 10% of couples were subfertile (time-to-pregnancy ≥12 months). Our findings support a J-shaped association between BMI and subfertility in both sexes using multivariable logistic regression models. Non-linear Mendelian randomization validated this relationship. A 1 kg/m2 greater genetically predicted BMI was linked to 15% greater odds of subfertility (95% confidence interval 4% to 28%) in obese women (≥30.0 kg/m2) and 14% lower odds of subfertility (−25% to -3%) in women with BMI <20.0 kg/m2. A 1 kg/m2 higher genetically predicted BMI was linked to 23% greater odds of subfertility (6% to 43%) among obese men and 36% decreased odds (−62% to 7%) among men BMI <20.0 kg/m2. A genetically predicted BMI of 23 and 25 kg/m2 was linked to the lowest subfertility risk in women and men, respectively. The main limitations of our study were that we did not know whether the subfertility was driven by the woman, man, or both; the exclusive consideration of individuals of northern European ancestry; and the limited amount of participants with obesity or BMI values <20.0 kg/m2.ConclusionsWe observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization analysis, further supporting a potential causal role of BMI on subfertility.AUTHOR SUMMARYWHY WAS THIS STUDY DONE?Higher body mass index (BMI) in both women and men is associated with subfertility in in observational studies. A few small randomized-controlled trials of weight reduction have reported an increased success of assisted reproduction in women. In addition, women with BMI <18.5 kg/m2 have lower conception rates with assisted reproduction technologies. A non-linear relationship between BMI and subfertility is suggested.We aimed to investigate the association between BMI and subfertility using both a standard multivariable regression and a Mendelian randomization approach.WHAT DID THE RESEARCHERS DO AND FIND?We examined the relationship between BMI and subfertility (time-to-pregnancy ≥12 months) among all men and women in the Norwegian Mother, Father and Child Cohort Study with available genotype information and anthropometric data (34,157 women, 31,496 men).We observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization analysis.WHAT DO THESE FINDINGS MEAN?Together with previous observational and trial evidence, findings support a causal effect of overweight/obesity on subfertility in women and men.Our findings expand the current evidence by also indicating that individuals at the lower end of the BMI distribution (<20 kg/m2) may have an increased risk of subfertility.Current advice and support for overweight and obese subfertile couples to lose weight should continue. Additionally, clinicians should consider appropriate advice to those with low BMI on whether they should increase weight to obtain a normal BMI.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

Hernáez

Rogne

Skåra

et al. 2021

Preprint

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“…In 2016, a meta‐analysis suggested that underweight was associated with slightly increased risk of MR (RR 1.08, 95% CI: 1.05–1.11) in the overall population; however, the association was not significant (RR 1.03, 95% CI: 0.87–1.22) for conception by ART 131 . In another meta‐analysis, authors suggested that maternal underweight had a modest association with lower CPR (adjusted OR 0.86, 95% CI: 0.74–0.998); however, it did not seem to affect LBR or MR following IVF 132 . By dividing the underweight into three levels (severe: BMI < 16 kg/m 2 , moderate: 16.0–16.99 kg/m 2 , mild: 17.0–18.49 kg/m 2 ), Kawwass et al reported no clinically significant association among the three levels of underweight and pregnancy outcomes, including CPR, MR, and LBR 15 …”

Section: Discussionmentioning

confidence: 97%

Association between maternal prepregnancy body mass index and pregnancy outcomes following assisted reproductive technology: A systematic review and dose–response meta‐analysis

et al. 2021

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Summary This systematic review investigated dose–response relationship between maternal prepregnancy body mass index (BMI) and pregnancy outcomes following assisted reproductive technology, including clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR). We searched four major databases and finally included 105 studies involving more than 271,632 pregnant women. We performed linear or nonlinear dose–response meta‐analyses using random effects models. At per‐woman level, pooling of unadjusted estimates shown an inverted J‐shaped relationship between maternal BMI and CPR; pooling of adjusted estimates showed a linear association, suggesting statistical association between higher maternal BMI and lower CPR (adjusted OR [aOR] for 5‐unit increase in BMI: 0.96, 95%CI: 0.94–0.98). At per‐cycle level, linear dose–response relationship was found between maternal BMI and CPR (crude relative risk, RR, [cRR] for 5‐unit increase in BMI 0.97, 0.96–0.98; aOR 0.96, 0.94–0.99). Linear dose–response relationship was established between maternal BMI and the outcomes of MR or LBR (higher BMI associated with higher MR [cRR 1.15, 1.08–1.22] and lower LBR [cRR 0.91, 0.88–0.94] at per‐woman level). Sensitivity analyses showed no significant changes. In conclusion, there is dose–response relationship between maternal BMI and pregnancy outcomes following assisted reproductive technology. Higher BMI values may suggest suboptimal pregnancy outcomes.

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“…Because the effect disappeared per cycle level, and miscarriage and live birth rates were similar per cycle or women level, this may have been due to a statistical artifact. As Xiong et al (5) commented, their findings should be interpreted with caution due to the small number of studies included in the adjusted analyses, the results being potentially underpowered. However, at present, this is the strongest evidence that we have, and it is in line with previous publications.…”

mentioning

confidence: 97%

“…Despite the lack of a clear consensus, it is currently generally considered that results are similar to those in normal weight women, except with regard to obstetric complications, as commented previously. The recent article by Xiong et al (5) updates and summarizes the available evidence concerning this issue through a meta-analysis of 38 cohort studies with a low risk of bias. The investigators conclude that there are no differences in terms of miscarriage or live birth rates between underweight and normal weight patients, but that clinical pregnancy rates are slightly impaired in underweight women.…”

mentioning

confidence: 99%

In vitro fertilization in underweight women: focus on obstetric outcome

Bellver

2020

Fertility and Sterility

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Association between prepregnancy subnormal body weight and obstetrical outcomes after autologous in vitro fertilization cycles: systematic review and meta-analysis

Cited by 12 publications

References 57 publications

Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

Association between maternal prepregnancy body mass index and pregnancy outcomes following assisted reproductive technology: A systematic review and dose–response meta‐analysis

In vitro fertilization in underweight women: focus on obstetric outcome

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