We examined the associations of BMI and short term weight change with embryological and clinical outcomes in a contemporary cohort of women undergoing infertility treatment with ART. As expected, BMI was associated with reduced peak E2 levels and live birth rates. Losing weight prior to initiation of ART was related to higher yield of MII oocytes, particularly among women who were overweight or obese at baseline. Short term weight change, however, was not related to clinical outcomes among women who underwent an embryo transfer.
An understanding of the strengths and limitations of our study is necessary to properly interpret the results. Assessing the relation between short-term weight change is both the most innovative aspect of our study and an important limitation. We assessed weight change as the difference in weight on the last clinical appointment preceding an ART cycle and weight upon study entry. Since we used data across multiple ART cycles whenever these data was available and a substantial proportion of participants had undergone IUI and/or ART cycles prior to joining the study, follow-up body weight will represent both real pre-treatment changes in body weight during the specified period as well as any residual effects that treatment may have on body weight during and after the completion of the previous treatment cycle. However, since ovarian stimulation does not result in lasting weight gain despite statistically significant weight gain during an ovarian stimulation cycle (15
), this potential limitation is unlikely to affect our results. A second limitation with our approach is that we did not assess whether short-term weight change was voluntary or not. Unintentional weight loss could be present in women with undetected chronic wasting conditions. However, the demographic profile of these women along with the fact that the majority of women who lost weight were overweight or obese at baseline strongly suggests that weight loss in this study was most likely intentional. Conversely, weight gain in this study is most likely unintentional and, as discussed above, unrelated to treatment. A related problem was that the magnitude of weight loss among women who lost weight was modest. The median weight change among all women who lost weight was −3.1 kg and the median in among women in the group of women who lost at least 3kg was −4.6 kg. Therefore our data may not be generalizable to women with a greater amount of weight change.
Our findings regarding the association of BMI with ART outcomes are consistent with the existing literature on this topic. Peak E2 levels decreased linearly with increasing baseline BMI. This finding is in agreement with 5 previous studies (7
), collectively representing 4,175 ART cycles, where a statistically significant inverse relation between BMI and peak E2 levels was documented and consistent with an additional 8 studies (16,778 ART cycles) (6
) documenting an inverse relation that failed to reach statistical significance. Equally consistent with the literature is the lack of association of BMI with fertilization rate and embryo quality. Although, three previous studies have reported an association between BMI and decreased fertilization rate (8
), another eleven studies, collectively representing more than 25,000 ART cycles, have found no association between BMI and fertilization rate (6
). Likewise, the majority of studies that have so far assessed the relation between BMI and morphology-based embryo quality scores have reported no association between them (6
) with only two studies suggesting an adverse association of obesity with embryo quality (9
). Our findings are also consistent with the preponderance of data on the association of BMI with clinical outcomes. Of the twelve studies that have examined the association between BMI and live birth rate, only the two smallest ones (30
) did not document linear decrease in live births with increasing BMI. In all the remaining studies (5
) there was an absolute reduction in live birth rates of approximately 5% to 10% when the leanest and heaviest women within each study are compared. The largest study conducted to date found that, compared to normal weight women (BMI 18.5–24.9 kg/m2
), the odds of failing to achieve a live birth was 18% higher in overweight (BMI 25–29.9 kg/m2
) women, 36% higher among class I (BMI 30–34.9 kg/m2
) and class II (BMI 35–39.9 kg/m2
) obese women and 48% higher among class III (BMI ≥40 kg/m2
) obese women using their own eggs (5
We found that short-term weight loss was associated with a higher yield of MII oocytes, particularly among women who were overweight or obese at baseline, but it was unrelated to embryo development or clinical outcomes among women who reached embryo transfer. Results of a recent animal experiment suggest that the observed association may reflect a true biological effect of short term weight change. Adult female mice reared on chronic caloric restriction that are put on an ad libitum
diet for 1 month (resulting in weight gain) produce fewer MII oocytes and a lower number of embryos reaching blastocyst stage than female mice that are kept on caloric restriction (36
). In addition, despite the effects on MII oocyte yield, there were no statistically significant differences in pre-implantation embryonic development following IVF between the mice kept under caloric restriction and the mice allowed to feed ad libitum
). Embryo transfer and evaluation of pregnancy outcomes was not performed in this animal study and thus there is no animal data to compare with our results. However, it is not entirely surprising that, despite the observed positive effect on oocyte quality, weight change was unrelated to clinical outcomes among women who underwent an embryo transfer given that the best embryos available are usually selected for transfer which may, to some extent, minimize any effects short term weight gain may have on clinical ART outcomes.
We also found that short-term weight loss was related to a lower fertilization rate in ICSI cycles. There is not, to our knowledge, previously published data to compare these results with. We do not have a satisfactory explanation for this finding and believe it may be a chance finding. Similarly, we believe that our finding that weight loss may be detrimental for clinical outcomes among women with PCOS is also likely a chance finding since only 2 women with PCOS lost weight in this study. While interesting, this finding is at odds with previous literature showing a beneficial effect of weight loss on reproductive performance of women with PCOS (37
). Nevertheless, given the paucity of data in this area it is important that other studies examine these associations.
Contrary to our expectation, we did not observe any beneficial effect of short term weight loss in relation to clinical outcomes. To our knowledge, two previous studies examined the relation between short term weight change and clinical outcomes of women undergoing infertility treatment with ART. Clark and colleagues compared the pregnancy rates between obese women who underwent a lifestyle program with women who dropped out of this program. Among the women who failed to conceive spontaneously during the program and went on to receive infertility treatment, 26 of the 47 women who completed the program and underwent IVF became pregnant compare to none of the 35 women who dropped out of the program and underwent IVF (39
). More recently, Moran and collaborators completed a pilot randomized trial of weight loss among obese women undergoing ART. There were no differences in pregnancy or live births between women randomized to lifestyle intervention (n=18) and women randomized to control (n=20) (40
). Clearly, the data available to date does not clarify whether losing weight prior to initiating ART has any beneficial effects on clinical outcomes.
In summary, we found an association of BMI with lower peak E2 levels and live birth rates. This is consistent with the current literature. In addition, we found that short term weight loss has a beneficial effect on MII oocyte yield (particularly among overweight or obese women) but was unrelated to clinical ART outcomes. Thus, our results are not consistent with recommendations to either limit access of obese women to ART or to delay their treatment until weight loss is achieved. However, given the limitations of this study and the paucity of data on the relation between short term weight change and ART outcomes it is important that this question is addressed further, ideally in randomized trials.