Two recent studies shed new light on the effects of obesity on results in ART, the first from a large 15-year cohort study and the second from a case-control comparison of fresh and frozen blastocyst transfers in obese patients.

The association between excess bodyweight and an extended time to pregnancy has long been recognised. The NICE guidelines of 2013 (and updated 2017) warned that women with a BMI of 30 or more 'should be informed that they are likely to take longer to conceive', and were recommended dietary advice and a group exercise programme. Similarly, a Practice Committee opinion from the ASRM in 2015, while recognising that 'many obese women and men are fertile', advised consideration of a weight management programme for women aiming for 'preconception weight loss (to a BMI <35), prevention of excess weight gain in pregnancy, and long-term weight reduction'. Now, two new reports, each published online by Human Reproduction, cast new light on this well accepted guidance.

The first is a large population government-funded study from Australia which, after following for 15 years a completed cohort of 6000+ women in their 20s all trying to conceive, confirms the advice that moderate and high levels of physical activity provide advantages for fertility in women with a normal BMI, but that obesity does indeed increase the risk of infertility.(1) The latter finding, say the authors, is well understood and supported; however, while the association between physical activity and sitting time is recognised in numerous health outcomes (notably cardiovascular disease), 'little is known about their effects on reproductive health, particularly in the area of infertility'.

The study was a continuation of the Australian Longitudinal Study on Womens Health which followed by survey the fertility progress of 6130 women aged 20 to 27 beginning in 2000 (ie, from the birth cohort of 1973-78), with follow-up reports every three years until 2015. These reports included information on physical activity levels, sitting time and problems with conception. BMI was calculated from their height and weight data. And follow-up did indeed show that 'problems with fertility' were inversely associated with physical activity levels and positively associated with BMI, with incidence lowest in highly active women. Thus, the incidence rate of fertility problems in highly active women was 2.65%, but 3.49% in those with low activity - an 18% lower risk. Similarly, problems were found greatest in those with the highest BMI ('obese'), and lowest in those of normal BMI or underweight (2.79%). There was no association found with the duration of sitting time per day, and the cohort's overall cumulative incidence of subfertility was calculated as 15.4% over the 15-year study period.

However, the protective effects of physical activity were only seen in women with normal BMI. This was evident in stratified models, where high levels of activity appeared only to attenuate the risk of subfertility in women who were in this normal BMI category (HR 0.64, 95% CI 0.490.82). Nevertheless, because the rates of developing fertility problems were highest in every survey interval in those who reported low levels of physical activity and who were obese, the authors conclude that 'improving physical activity levels could be an affordable strategy to reduce problems with fertility in women who are trying to conceive'. However, they add within the context of the analyses stratified for BMI that in the overweight and obese category physical activity itself did not reduced the risk or problems with fertility, suggesting that 'a high BMI is the important driver' in this association.

The second Human Reproduction study takes as its starting point the likelihood that obesity is indeed associated with lower rates of natural fertility and higher rates of miscarriage.(2) In ART, the authors add, citing a catalogue of evidence, obesity is associated with higher required doses of gonadotrophins, increased duration of stimulation, higher cancellation rates and fewer oocytes retrieved. Nevertheless, in laying the base for this study, they note that the evidence in ART is based on outcomes nearly always derived from fresh embryo transfers. How would obesity affect IVF treatments with frozen blastocyst transfers, as is increasingly practised today?

Their answer came in a retrospective case-control study conducted in all consecutive frozen-thawed blastocyst transfers between 2012 and 2017 at a single university centre in Nantes, France - a total of 1415 frozen cycles in normal weight women (BMI 18.524.9) and 252 in obese women (BMI 30). Outcome variables such as patient age, AMH levels and infertility cause were comparable between the two groups. Only endometrial thickness at baseline was significantly different - higher in the obese group. However, after analysing outcomes over the five-year study period results showed no difference in implantation rate, clinical pregnancy rate and live birth rate - and thus no association with BMI.

How could such apparently counterintuitive results be explained? The author suggest - subject to confirmation, of course - that the impairment of uterine receptivity observed in obese women after fresh embryo transfer might be associated with ovarian stimulation rather than with oocyte/embryo quality; transfer in a frozen cycle might avoid that effect.

1. Mena GP, Mielke GI, Brown WJ. Do physical activity, sitting time and body mass index affect fertility over a 15-year period in women? Data from a large population-based cohort study. Hum Reprod 2020; doi:10.1093/humrep/dez300 2. Prost E, Reignier A, Leperlier F, et al. Female obesity does not impact live birth rate after frozen-thawed blastocyst transfer. Hum Reprod 2020; doi:10.1093/humrep/deaa010

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Obesity and outcome in assisted reproduction - ESHRE