"Is it worth the ''weight'' to delay in vitro fertilization until BMI decreases?", Study answers
Knowing the fact that obesity has been demonstrated to impair reproduction in men and women, it is necessary to comprehend the relationship between obesity and reproductive outcomes. It has been proven that obesity can cause changes in the hypothalamic-pituitary ovarian axis leading to menstrual irregularities and ovulatory dysfunction in females.
Additionally, women with obesity have a longer time to conception, decreased fecundity ratios, increased rates of miscarriage, and decreased live birth rates. Obesity also has been associated with reduced live birth rates after in vitro fertilization (IVF), suggesting that factors beyond ovulatory dysfunction affect reproductive success. Despite this knowledge, it remains unclear why obesity is associated with impaired reproductive outcomes. Proposed etiologies fall into three main categories: effects on the oocyte, the embryo, and the endometrium.
In Fertility and Sterility, Stovezky et al. evaluated whether increases in aneuploidy may be the cause of impaired reproductive outcomes in women with obesity. They examined whether there was an association between body mass index (BMI) and embryonic aneuploidy and mosaicism in women undergoing IVF with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A).
In this retrospective cohort study of 1,750 women undergoing their first cycle of IVF with PGT-A, no relationship between BMI and number or proportion of aneuploid, mosaic, or euploid embryos was found in an age-adjusted model. These results were supported further when the investigators did a subgroup analysis, stratifying women by age (<35, 35–40, and >40 years), and found no association between BMI and ploidy status of embryos.
If embryonic aneuploidy is not increased and, therefore, cannot be deemed responsible for increased miscarriage rates in women with obesity, altered endometrial receptivity may offer an alternative explanation.
This well-designed study by Stovezky et al. has a number of strengths. The large size of the cohort allows for meaningful comparisons between groups with different BMIs. Further, the investigators only studied women undergoing their first IVF attempt, which should have limited selection bias toward patients with a history of reproductive failure.
The findings presented by Stovezky et al. raise important clinical questions regarding how to best counsel and manage patients with obesity who desire to conceive. If BMI does not appear to be associated with ploidy status, is the cause of impaired reproductive outcomes treatable with lifestyle modifications or not. Although there is some evidence that individuals who are able to achieve and sustain weight loss have improved rates of conception, require fewer treatment cycles, and have increased live birth rates, the data are not conclusive.
"Given the absence of clear evidence, it is not possible to simply counsel patients that weight loss will reverse the impact of obesity on reproductive success. Going a step further, instead of focusing on weight loss, we believe that there should instead be a promotion of ''well-being.'' Women should be encouraged to address their ''well-being'' by improving nutrition, increasing physical activity and workingto treat their medical comorbidities that contribute to higher BMIs. With these measures, weight loss is likely to occur, but even if weight loss is not profound, it seems inevitable that a healthier maternal state will lead to improved outcomes."
The data on euploidy rates among women with obesity suggest maternal age remain the strongest predictor of embryo ploidy status. Given this, perhaps there should be a focus on cryopreserving oocytes or embryos at younger ages despite elevated BMIs and then working to optimize health before pregnancy.
Many practices require patients to achieve a certain BMI before starting the IVF process. However, knowing that healthy weight loss can require significant time and that aneuploidy rates increase with maternal age but not with increasing BMI, then perhaps the aim instead should be to retrieve oocytes in women with obesity at as young an age as possible.
"There may not be a reason for women with obesity to wait to conceive at all, but certainly these data suggest that holding to retrieve oocytes until an optimal BMI is achieved will lead to increased aneuploidy rates from increasing maternal age. Ultimately, is it worth the ''weight'' to delay IVF in women with obesity? Perhaps as a field we should reconsider this and prioritize oocyte or embryo cryopreservation as an initial step while focusing on improvement of ''well-being'' before embryo transfer is performed."