Obesity is on the rise in the United States, with an incidence of 50% of women who are obese and 30% who are overweight. Obesity affects the reproductive system and the endocrine system. Obesity leads to infertility and repeated miscarriages.¹

Since ancient civilization, obesity has been described as a cause of infertility. Hippocrates wrote that people of such constitution cannot be prolific. Fatness and flabbiness are to blame. The womb is unable to receive the semen and they menstruate infrequently and little.²

Endocrinologically, obesity could be part of a disease process, such as polycystic ovarian syndrome, Cushing disease, and hypothyroidism. Therefore, in the evaluation of obese women, we have to take this into consideration and to order the proper endocrine testing so that treatment will be directed toward correcting these factors. Ovulatory dysfunction can be an important factor leading to infertility in obese women. In addition, there is an increased incidence of insulin resistance; these patients might develop a prediabetic or diabetic condition that will have a negative effect on fertility and pregnancy.^3,4,5

Obesity could also affect men; the result will be a low testosterone level, which will lead to sperm abnormalities. The endocrine abnormality in men might also contribute to ejaculatory dysfunction, and this will lead to infertility.⁶ Obesity in men may lead to DNA abnormalities, thus affecting the fertilization process. Also, obesity may affect the offspring, leading to obesity genetic factors.⁷ Obesity leads to increased testicular heat, which negatively affects sperm motility and function.⁸

It is estimated that obesity in women will lead to 6% of primary infertility according to a recent report by the American Society of Reproductive Medicine. Reproductive endocrinologists and infertility specialists must consider proper counseling of obese women who present for infertility evaluation because that could be the main issue. If they achieve pregnancy, there will be problems related to continuation of the pregnancy or related to the fetus and its progression in pregnancy.

One of the major effects of obesity in women is ovulatory dysfunction. These women become oligomenorrheic or amenorrheic. This is due to extragonadal estrogen synthesis, which leads to suppression of gonadotropins and of ovarian follicle development, causing anovulation. This is a major cause of infertility in obese patients.⁹

The use of fertility medications to induce ovulation may be helpful. However, the dosage of these medications may be somewhat higher that would be used for a normal-weight patient. In addition, pregnancy in obese women will subject the patient as well as the fetus to risk factors, especially if the woman develops diabetes or hypertension. For this reason, the patient would be referred to a perinatologist for prenatal counseling to understand the problems that may be present during pregnancy. Therefore, one of the goals is to counsel the patient to join a weight reduction program to avoid all these problems. Weight loss has been shown to improve ovulation and conception.^10,11,12

Obesity has also been shown to be a significant factor in male infertility. One of the major findings is abnormality in the sperm picture, with a decrease in the concentration, motility, and normal morphology. In some reports, also DNA fragmentation has been demonstrated, and this may lead to failure to achieve pregnancy or cause fetal wastage.^13,14 Furthermore, obesity in men has been associated with erectile dysfunction. This might be the result of hypogonadism and increased concentrations of inflammatory cytokines.¹⁵ Evaluation of the male factor is essential in the study of etiology of infertility because this contributes to about 30%–40% of the causes.

Obesity due to increase in subcutaneous fat increases the activity of aromatase and therefore the conversion of androgens into estrogens. The high levels of estrogens in obese women and men has a negative feedback on the hypothalamic-pituitary gonadal access, which leads to hypogonadism and subsequently to anovulation in women and decreased spermatogenesis in men. In addition, testosterone level in men decreases, causing some problems related to sperm function and erectile dysfunction in men.

Obesity is associated with an increase in insulin levels due to insulin resistance. This leads to a decrease in steroid hormone-binding globulin synthesis by the liver. The end result is the increase in free sex steroid levels, which leads to their metabolic clearance. As a result, there will be an increase in androgen synthesis that contributes to ovulatory dysfunction, irregular cycles, and infertility. Another factor in obesity is the increase in the messenger protein leptin, which in high concentrations leads to an inhibitory effect on the hypothalamic-pituitary axis. The end result is ovulatory dysfunction and infertility. The same phenomenon will affect testicular function and spermatogenesis, resulting in infertility.^16,17,18

Because of the factors mentioned, the workup of the infertile couple who have obesity as a problem in the male, female, or both needs special consideration to address all the problems and manage them properly (see Table 17-1). The female obese patient with anovulatory dysfunction requires endocrine studies in the form of thyroid studies and examination of prolactin level, total testosterone level, and cortisol and dehydroepiandrostene sulfate levels. Serum follicle-stimulating hormone (FSH) level is also recommended to evaluate ovarian reserve.^19,20 Metabolic studies in the form of liver enzymes, fasting blood sugar, and hemoglobin A_1C are also needed to help manage these patients.