The adverse effects of obesity on fertility and pregnancy outcomes are overwhelming and indisputable. Even with fertility treatments, obesity adversely affects fertilization, embryo development, pregnancy and live birth rates, as well as increasing the rates of miscarriage. Obesity is defined as a BMI over 30 and morbid obesity is a BMI of 40 or greater. In obesity, excessive adipose tissue leads to an increase in circulating leptin, peripheral aromatization of androgens to estrogens, insulin resistance that drives hyperinsulinemia leading to hyperandrogenemia, all of which disturb the hypothalamic-pituitary-gonadal (HPG) axis leading to anovulation and infertility. Excessive adipose tissue also leads to increasing levels of circulating free fatty acids that accumulate in nonadipose tissues including the ovary. The ectopic deposition of lipids in the ovary triggers intracellular damage called lipotoxicity by increasing endoplasmic reticulum (ER) stress, mitochondrial damage and apoptosis, leading to poor oocyte quality.

Anovulation
Obesity has a negative effect on reproductive potential, primarily due to functional alteration of the hypothalamic-pituitary-ovarian (HPO) axis. Obese women often have higher circulating levels of insulin, which is a known stimulus for increased ovarian androgen production. These androgens are aromatized to estrogen at high rates in the periphery owing to excess adipose tissue, leading to negative feedback on the HPO axis and affecting gonadotropin production. This manifests as menstrual abnormalities and ovulatory dysfunction. However, many studies have shown that obese women remain subfertile even in the absence of ovulatory dysfunction and the probability of spontaneous conception declined linearly with each BMI point >29 kg/m2. These findings allude to other mechanisms in which obesity impacts fertility.

Lipotoxicity

There is overwhelming evidence in the literature that obesity has a negative impact on the oocyte. One potential mechanism for oocyte organelle damage in obesity is lipotoxicity. Obese women have higher levels of circulating free fatty acids, which damage nonadipose cells by increasing reactive oxygen species that induce mitochondrial and ER stress leading to apoptosis. This cellular damage in the cumulus oocyte complex has detrimental effects on the potential of the oocyte. It has been shown that oocytes that failed to fertilize in IVF cycles of obese women are smaller and less likely to be mature. A closer examination of these abnormal oocytes reveals high rates of meiotic aneuploidy with fragmented disorganized meiotic spindles and chromosomes not properly aligned. These oocytes that are of poor quality result in lower fertilization and poor quality embryos. These findings can explain why it takes longer for obese women to get pregnant, and why they have a higher rate of miscarriage.

Increased pregnancy complications

In addition, many studies confirm that obese women who do conceive have a significantly increased risk of pregnancy complications and adverse perinatal outcomes. These complications include pre-eclampsia, antepartum stillbirth, caesarean section, shoulder dystocia, meconium aspiration, early neonatal death, gestational diabetes, and birth defects involving the brain, heart and neural tube defects.

Weight Loss
Obese women wishing to conceive should consider a weight management program that focuses on preconception weight loss (to a BMI <35 kg/m2), prevention of excess weight gain in pregnancy, and long-term weight reduction. Weight management in all individuals is best achieved through a lifestyle modification program that combines dietary modification, physical activity, and behavioral interventions. The benefits of postponing pregnancy in women to achieve preconceptional weight loss must be balanced against the risk of declining fertility with advancing age. Current recommendations for lifestyle modification for obesity in all individuals include a weight loss of 5-10% of body weight and increased physical activity to at least 150 minutes weekly of moderate activity such as walking. Calorie restriction is a fundamental principle of successful weight loss, with dietary composition being less important. A 500–1,000 kcal/day decrease from usual dietary intake should lead to a 1–2-pound weight loss per week.

Motivation & Counseling

The take-home message from these studies is that women need to be informed that obesity seriously hampers fertility and the need to be counseled about the serious dangers associated with obesity and pregnancy complications. Obesity is a chronic but treatable condition. Simply telling a patient to lose weight does not work. The problem of obesity can be solved, but requires motivation, counseling, and behavior modification.

Conclusions
Remember that as little as a 5-10% weight loss can dramatically improve fertility treatment and pregnancy rates. For women who actively manage their obesity via good nutrition, proper exercise, and help from a Reproductive Endocrinologist or Obstetrician Gynecologist with expertise in the latest treatments, the chances of conceiving are extremely good.

Reference:
Pfeifer S., et al. Obesity and reproduction: a committee opinion. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2015 Nov;104(5):1116-26. doi: 10.1016