Obesity and IVF outcome:
cohort study finds no effect of BMI on embryo ploidy

A new study has found no association between BMI and an embryo’s chromosome profile after trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A).

This study from the Weill Medical College group in New York – included 1750 women having their first IVF cycle with trophectoderm biopsy, next-generation sequencing analysis (NGS), and blastocyst freezing. The patients were classified into three BMI groups: normal-weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/ m2), obese (≥30 kg/m2) and a subgroup analysis based on patient age (<35, 35-40, >40)

Data analysis of embryo ploidy showed no statistically significant relationship between the proportion of aneuploid, mosaic, or euploid embryos and BMI when compared with the normal-weight patients. Similarly, a subgroup analysis based on patient age (<35, 35-40, >40) also failed to find any significant relationship.

Question: If embryo ploidy appears unaffected by BMI, why miscarriage rates have been found significantly higher in obese women after euploid embryo transfer than in normal-weight women?

Answer: There is evidence that increased BMI is associated with impaired ovarian folliculogenesis, abnormal oocyte mitochondria, and poor granulosa cell metabolic activity. Obesity has also been correlated with higher levels of blood insulin, androgen, estrogen, and leptin, which in the follicular fluid may contribute to poor folliculogenesis, poor cumulus cells function, and subsequently poor oocyte quality.

Impaired endometrial receptivity has also been associated with obesity, although the results obtained from recent studies on overall IVF outcomes are controversial. For example, a meta-analysis of five studies concluded that there is no association between obesity and the chance of pregnancy after IVF in egg donor recipients, while a 12-year retrospective study of almost 10,000 cycles with oocytes from normal-weight donors suggested that a recipient’s increased BMI is indeed associated with impaired reproductive outcome.

However, this latest study suggests that any negative effect of elevated BMI on IVF outcomes cannot now be explained by the ploidy status of the embryo cohort.

Ref：

1. Stovezky YL, Romanski PA, Bortoletto P, et al. Body mass index is not associated with embryo ploidy in patients undergoing in vitro fertilization with preimplantation genetic testing. Fertil Steril 2021; doi: 10.1016/j.fertnstert.2021.02.029

2. Goldman KN, Hodes-Wertz B, McCulloh DH, et al. Association of body mass index with embryonic aneuploidy. Fertil Steril 2015; 103: 744-748.

doi:10.1016/j.fertnstert.2014.11.029

3. Cozzolino M, García-Velasco JA, Meseguer M, et al. Female obesity increases the risk of miscarriage of euploid embryos. Fertil Steril 2020; doi:10.1016/j.fertnstert.2020.09.139

4. Broughton DE, Moley KH. Obesity and female infertility: potential mediators of obesity’s impact. Fertil Steril 2017; 107: 840-847. doi:10.1016/j.fertnstert.2017.01.017

5. Jungheim ES, Schon SB, Schulte MB, et al. IVF outcomes in obese donor oocyte recipients: a systematic review and meta-analysis. Hum Reprod 2013; 28: 2720-2727.

doi:10.1093/humrep/det292

6. Bellver J, Pellicer A, García-Velasco JA, et al. Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors. Fertil Steril 2013; 100: 1050-1058. doi:10.1016/j.fertnstert.2013.06.001