Cohort study underlines association between BMI and live birth and pregnancy loss in euploid FET cycles

Cohort study underlines association between BMI and live birth and pregnancy loss in euploid FET cycles

Published 21 August 2023

Large cohort study based on SART data finds increasing BMI associated with decreasing pregnancy and live birth rates following the transfer of frozen euploid embryos; while the pattern was evident among the entire cohort and among patients with a sole diagnosis of PCOS, it was not similarly evident in those with a sole male factor indication.

Back in 2016 a review of almost 250,000 fresh IVF cycles reported to the SART registry between 2008 and 2010 found a direct association between pregnancy rate and BMI, notably that success rates in fresh non-donor cycles were highest in those with low and normal BMIs.(1) Indeed, the study found a progressive and statistically significant worsening of outcomes in groups with higher BMIs.

The conclusion seemed simple enough, at least in fresh cycles, and lent support to the standard preconceptional advice that normalisation of bodyweight would encourage improved outcomes. Indeed, at a time when obesity represents ‘an increasingly higher percentage of our patients’, the SART authors felt able to ‘recommend weight loss’ in obese patients, but remained cautious about a strict interpretation of their results. ‘Despite live birth rates as much as 10% lower in the highest BMI groups,’ they cautioned, ‘IVF success rates in the highest BMI group are still higher than for some of our poor-prognosis patients with diagnoses such as diminished ovarian reserve.’

The study has now been updated to reflect a more contemporary scenario of frozen non-donor euploid embryo transfers.(2) This time the analysis comprised more than 55,000 FETs reported to SART between 2016 and 2019, with sub-analyses now included for PCOS and male factor only. Nearly 10,000 of the cohort were defined as obese. Again, as before with fresh transfers, outcomes were most favourable among those with normal BMI and progressively
worsened with increasing BMI. Thus, when BMI was analysed as a continuous variable, the odds of clinical pregnancy decreased by 2% with every one unit increase in BMI. This trend was similarly apparent in the PCOS sub-group for all study endpoints (CPR, pregnancy loss, LBR) but not in the male factor group. In the former, CPRs decreased from 65.6% in those with normal BMI to 51.3% among those with BMI 45-49.9 kg/m2 and 52.6% in those with BMI ≥50 kg/m2.

These sub-group analyses prompted two key observations: first, the trends in the PCOS group mirrored those of the entire cohort, but second, there was no such association in the male factor group. Collectively, these results suggest that the association between BMI and euploid FET outcomes may be mediated at least in part by associated female infertility diagnoses, and not by obesity alone. By way of further explanation, the authors add that obese women having IVF have been shown to have higher levels of insulin and other metabolic markers in follicular fluid, as have women with PCOS. While recognising that the inclusion of only euploid blastocysts in this study may control for some of these factors, ‘it is possible,’ the authors propose, ‘that embryos from women with PCOS are particularly sensitive to obesity-induced inflammatory milieu which may impact downstream implantation and pregnancy outcomes’. And of course, there may be explanatory factors beyond the oocyte or embryo affecting uterine receptivity. Thus, while the overall negative effect of obesity on IVF outcome may be generally explained by increased rates of anovulation, this study suggests that other factors may well contribute.

For example, a similarly recent study in egg donors and recipients correlated outcomes with donor and recipient BMIs.(3) Results showed that LBR per blastocyst SET showed no significant association with donors’ BMI, but there were associations of both LBR and miscarriage with recipient BMI. ‘Obesity mostly affects the uterus,’ the authors concluded, ‘especially due to higher miscarriage rates.’

Despite the similar results of the two cohort studies (in fresh and frozen transfers), and subsequent meta-analyses, not all studies have always been so consistent. However, a recent review - of 21 eligible studies - found a decreased probability of live birth following IVF in obese (BMI ≥30 kg/m2) women when compared with normal weight (BMI 18.5-24.9 kg/m2) women. Subgroup analyses found poorer prognosis when obesity was associated with PCOS.(4)

Nevertheless, despite the overall trends of lower pregnancy and higher miscarriage rates with increasing BMI, the authors emphasise that ‘IVF among women with obesity and infertility is highly likely to result in a live birth’ and thus represents a ‘viable treatment option’ with appropriate pre-conception counselling, even among women in the highest BMI categories. Indeed, data analysis revealed a LBR above 48% in every BMI category, and a generally higher rate than found in US national averages for women aged 38-40.

It's for these reasons and the ambivalent results of other studies of BMI and IVF outcome that the authors argue against universal BMI cut-offs in treatment eligibility scales and more in favour of counselling and a broader approach. Many of those studies find greater effect on IVF ‘outcome’ in miscarriage rate than in pregnancy rate. And it’s worth noting that there’s no mention in the study’s public health recommendations of preconceptional weight loss, though that would surely be included in any counselling programme.

So no mention of the emerging appetite-suppressing drugs as IVF pretreatment for the obese, but an important recognition that BMI itself, as a calculation based on height and weight, ‘is likely to oversimplify the obesity experience’ while ignoring such factors as nutrition, activity and insulin resistance. A recent follow-up study on more than 500,000 US adults found that BMI alone was a poor predictor of future death, and that BMI should not drive clinical decisions.(5) And in line with the general unease about BMI, the American Medical Association has recently adopted a new policy suggesting that BMI be used only along with other ‘valid measures’ of risk, including visceral fat, waist circumference and genetic/metabolic factors.

1. Provost MP, Acharya KS, Acharya CR, et al. Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008–2010 Society for Assisted Reproductive Technology registry. Fertil Steril 2016; 105: 663-669.
2. Bakkensen J, Strom D, Boots C. Frozen embryo transfer outcomes decline with increasing female body mass index with female but not male factor infertility: analysis of 56,564 euploid blastocyst transfers. Fertil Steril 2023;
3. Fabozzi G, Cimadomo G, Maggiulli T, et al. Association between oocyte donors’ or recipients’ BMI with clinical outcomes after first single blastocyst transfers. The uterus is the mostly affected. Fertil Steril 2023;
4. Sermondade N, Huberlant S, Bourhis-Lefebvre V, et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Hum Reprod Update 2019; 25: 439-451.
5. Visaria A, Setoguchi S. Body mass index and all-cause mortality in a 21st century U.S. population: A National Health Interview Survey analysis. PLoS ONE 2023; 18: e0287218.

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