A recent study published in The Journal of Clinical Endocrinology and Metabolism, has demonstrated that low reproductive outcomes following ART in obese women may be associated with alterations in ovarian follicular environment, in particular the raised levels of C-reactive protein (CRP), metabolites, and androgen activity.
Previous studies have reported increased time to conception in obese women, although they are young and have normal menstrual cycles, thereby suggesting an alteration in the functions of ovary during the peri-conceptual period.
Rebecca Robker and coworkers from the University of Adelaide, Australia, conducted the study to determine whether changes in the pre-ovulatory follicular environment have an effect on the oocyte developmental competence in 96 women receiving infertility treatment. Based on the body mass index (BMI), the subjects were divided into 3 groups: moderate, with BMI=20 to 24.9 kg/m2 (n=33), overweight, with BMI=25 to 29.9 kg/m2 (n=31), and obese, with BMI ≥30 kg/m2 (n=32). The follicular fluid was aspirated in each patient from single follicles at oocyte retrieval followed by the pooling of the granulosa cells from the aspirates and the collection of cumulus cells after separation from the oocytes.
The researchers further analyzed the hormones and metabolites in the follicular fluid. Also, mRNA expression of insulin signaling components (IRS-2, Glut4), glucose regulated genes (ChREBP, ACC, FAS) and insulin regulated genes (SREBP-1, CD36, SR-BI) related to obesity/insulin resistance were measured in the granulosa and cumulus cells. Results showed that BMI was directly proportional to the follicular fluid insulin, lactate, triglycerides, and CRP levels, but was inversely related to sex hormone-binding globulin levels (P=0.001). Although IRS-2, Glut4, ChREBP and SREBP displayed a cell-type specific expression, they were unaffected by BMI. The scientists also noted that obese rather than moderate weight women had a modest variation in CD36 and SRBI mRNA of granulosa cells. Considering the findings, it was suggested that alterations in the ovarian follicular environment exhibited by obese women were probably linked to poor reproduction outcomes.
Recently, Bellver, et al. (Fertility and Sterility, 2009) conducted a retrospective study in women who had undergone 6,500 IVF-intracytoplasmic sperm injection (ICSI) cycles between 2001 and 2007, to analyze embryo quality and reproductive outcome based on BMI. The 4 subsets of the study subjects based on the BMI were: 16.5% lean (BMI <20 kg/m2), 60.5% normal (BMI=20-24.9 kg/m2), 16.6% overweight (BMI=25-29.9 kg/m2), and 6.4% obese (BMI≥30 kg/m2). Apart from embryo quality, reproductive outcomes, such as implantation, pregnancy, miscarriage, and live birth rates, were measured in all the study groups.
Although implantation, pregnancy, and live birth rates were lower in obese women, the scientists did not find any difference with respect to insemination procedure, fertilization rate, day of embryo transfer, mean number of transferred and cryopreserved embryos, percentage of blastocyst transfers, or embryo quality (day 2 and 3) in the 4 groups. Also, a progressive reduction in pregnancy and live birth rates occurred with each unit of BMI, with a respective odds ratio of 0.984 and 0.981. Following 4 IVF cycles, the cumulative pregnancy rate was found to be inversely proportional to BMI. It was concluded that obesity in females hinders the IVF outcome without affecting embryo quality, thereby indicating a variation in the uterine environment.
Obesity, a major risk factor for various chronic diseases such as diabetes, cardiovascular diseases, and cancer, may also compromise fertility and success rates of pregnancy. The identification of the association between altered ovarian environment and low reproductive outcomes in obese women, calls for an aggressive counseling of these patients about their enhanced obstetric risk prior to ART treatment. In addition to this, such patients should be clearly educated on employing measures to reduce obesity before initiating any ART procedure for better success rates.
References
1. Robker RL, Akison LK, Bennett BD, et al. Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared to Moderate Weight Women. J Clin Endocrinol Metab. 2009 Feb 17. [Epub ahead of print].
2. Bellver J, Ayllón Y, Ferrando M, et al. Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertil Steril. 2009 Jan 24.
