Ovulatory Dysfunction: A Leading Cause of Infertility

Women who report regular menstrual cycles that are about twenty-three to thirty-nine days in length with her bleeding proceeded with some weight gain, breast tenderness, and mood changes are usually ovulatory. Complete lack of ovulation (anovulation) is very common and can present as lack of menstrual bleeding (amenorrhea), dysfunctional uterine bleeding (irregular vaginal bleeding in the absence of any anatomical pathology), and excess facial or body hair (hirsutism). A common form of ovulatory dysfunction is polycystic ovarian syndrome which is associated with abnormal menses, excess body hair, very commonly but not necessarily associated with obesity and increased body mass index, cardiovascular complications, insulin resistance, and increased risk for development of endometrial hyperplasia and endometrial cancer. Other forms of ovulation dysfunction which is associated with decreased ovarian hormone production and hypogonadism, can increase the risk of developing early osteoporosis. Normal ovulation requires hypothalamic-pituitary-gonadal axis coordination and ovulation dysfunction can result from disruption at any level. Many factors such as emotional, nutritional (eating disorders and weight loss), or excessive exercise can affect the brain and hypothalamus function leading to ovulation dysfunction. These situations are commonly associated with lack of menstrual bleeding (amenorrhea), however lesser degrees of stress may be associated with ovulation dysfunction and occasional uterine bleeding. Brain or pituitary tumors may interrupt hypothalamic and pituitary function resulting in menstrual irregularities and ovulation dysfunction. Prolactinomas are pituitary tumors producing the hormone prolactin and may be associated with menstrual irregularities and ovulation dysfunction resulting in infertility. Enlargement of these tumors (prolactinoma) at times could compress optic nerve and result in visual disturbances and/or headaches. In addition, excess prolactin secretion as a result of pituitary or hypothalamic tumors, hypothyroidism, or intake of neuropsychotrope drugs may at times be associated with milky or clear breast discharge (galactorrhea). As a result, breast examination with gentle compression of breast and nipples looking for evidence of milky breast discharge and measurement of serum prolactin concentration are important parts of evaluation of ovulation dysfunction. Hyperthyroidism (excess production of thyroid hormones) or hypothyroidism (diminished production of thyroid hormones) can cause chronic anovulation providing the rationale for measuring thyroid function related hormones in the evaluation of women with ovulation dysfunction and menstrual irregularities. Women with chronic anovulation and polycystic ovaries have a higher prevalence of obesity ranging between thirty-five to sixty percent. Polycystic ovarian syndrome (PCOS) is the most common and obvious condition associated with ovulation dysfunction affecting about four to six percent of reproductive aged women. Patients with PCOS have increased daily production of androgens (male hormones) and estrogens. A common feature in obese and, to a lesser degree, lean women with PCOS is the overall prevalence of insulin resistance ranging between fifty and seventy-five percent. Impaired glucose tolerance has been reported in up to thirty-five percent of women with PCOS of which seven to ten percent meet criteria for Type II diabetes mellitus. On the other hand, in women with established diagnosis of type II diabetes, the likelihood of having PCOS is six-fold more than non-diabetic women of similar age and weight. Increasing obesity in women is associated with rising risk for PCOS as well as insulin resistance, ovulatory dysfunction, and prevalence of metabolic syndrome with glucose intolerance and risk factors for cardiovascular disease and sleep apnea. Approximately thirty-five percent of all adult women and sixty percent of women with PCOS in the United States are obese. These observations indicate that obesity is a common but not essential feature of PCOS. Testosterone levels are elevated in most but not all women with PCOS. The increased testosterone level in these patients is associated with excess facial and body hair (hirsutism), acne, and male pattern alopecia. Almost fifty percent of sisters of women with PCOS and thirty-five percent of their mothers show an elevated level of serum testosterone. These observations are suggestive of a genetic predisposition or susceptibility for PCOS. This possibility is further strengthened through several reports suggestive of a heritable x-linked or autosomal dominant inheritance for PCOS. Approximately sixty to eighty-five percent of women with PCOS exhibit menstrual irregularities. In patients with PCOS, ovaries are enlarged and sonographically exhibit increased volume and increased number of small follicles, hence the name polycystic ovaries. It should be noted, however, that eight to twenty-five percent of normal women and even fourteen percent of women using oral contraceptives may exhibit sonographic criteria for PCOS. It should be emphasized that sonographic findings of PCOS do not necessarily establish and are not required for diagnosis of PCOS. In addition to insulin resistance and abnormal glucose metabolism, dyslipidemia, (abnormal levels of cholesterol and triglycerides) is perhaps the most common metabolic abnormality observed in women with PCOS. This is basically associated with low HDL (good cholesterol) and elevated levels of triglycerides and elevated LDL (bad cholesterol) concentration in some of the patients. In summary, diagnosis of PCOS is based primarily on the clinical history and physical examination. The major clinical features of PCOS include excess male hormones and menstrual irregularities. Evaluation of patients with PCOS should include evaluation of the thyroid, serum prolactin level, and consideration of two-hour oral glucose tolerance test especially in younger patients, fasting lipid profile, serum testosterone level, and evaluation of other hormones including 17-alphahydroxyprogesterone. In some patients with PCOS, endometrial sampling should be considered to rule out the possibility of malignancy in the endometrial lining. As mentioned above, patients with PCOS in addition to ovulation dysfunction, menstrual abnormalities, and infertility are at higher risk for development of endometrial malignancies, development of excess facial and body hair, and increased risk for developing type II diabetes as well as increased risk for developing cardiovascular disease. As a result, these patients should be counseled regarding lifestyle changes. For patients seeking to conceive, ovulation induction with oral or injectable medications can be considered. In patients who have no immediate desire for pregnancy, treatment with oral contraceptive pills provides management of menstrual irregularities and protects them against the risk for development of endometrial malignancies. This treatment also helps patients to prevent or control and decrease their excess male hormone levels or male hormone action. At times, treatment with insulin sensitizing agents may also be required. The most important aspects of lifestyle change is diet, exercise, and weight loss. For obese patients with PCOS, weight reduction is the first and best treatment to consider. Benefits of significant overall decrease in caloric intake and exercise for improving diabetes, insulin resistance, and decreasing cardiovascular disease risk have been repeatedly demonstrated in general population.

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