A thorough medical history should be obtained from all infertile patients to detect chronic diseases such as severe anemia, autoimmune diseases, liver disease and renal disease. Debilitating disease and chronic malnutrition also may result in infertility (42). Chronic disease most likely interferes with ovulation by central mechanisms. Treatment of the disease rarely restores ovulation because such treatment is usually palliative.

The exam findings may be subtle, and include clubbing of nailbeds, poor skin turgor, subcutaneous adiposity, conjunctival pallor, thinning of hair, jaundice, cushingoid features, recent weight loss, delayed capillary refill, gum bleeds, and chelosis, Fatigue, exercise intolerance, dyspnea on exertion, peripheral edema, and cardiac murmurs are consistent with underlying cardiac disease. Splenomegaly, dilated abdominal wall collateral vasculature, and ascites or signs of anemia may represent longstanding gastrointestinal disease. Pulmonary disease is manifested by a chronic cough, diminished breath sounds, wheezing, dyspnea or simply fatigue.

In most instances, the diagnosis will already be established. Physical exam findings may indicate the patient's overall health, and nonspecific studies may be helpful such as: CBC with peripheral smear, urine dipstick for proteinuria, hematuria, pyuria and microscopic evaluation (epithelial cells, WBC casts, etc.), liver functions, and serum chemistries to include electrolytes, creatinine, BUN, magnesium, phosphate, uric acid, and protein. A sedimentation rate is a nonspecific test of inflammation, and cardiac status may be initially assessed with an ECG, CXR, echogardiaography, and stress test. Clearly, the diagnostic tests must be tailored to the individual.

Treatment of infertility associated with chronic disease requires addressing the underlying health problem and optimizing the patient's present state of health. This usually requires a multi-specialty effort specific to the patient's health needs. Special consideration should be made to assess if a relative or absolute contraindication to pregnancy exists, as the pregnancy may well exacerbate an already tenuous medical condition. Maternal surrogacy is an option in patients who are unable to tolerate the physical stresses of pregnancy, such as patients with severe hypertension, significant structural cardiac anomalies, advanced multiple sclerosis, to name a few. If premature ovarian failure has occurred, either secondary to chronic disease, or to treatments such as chemotherapy or radiotherapy, donated oocytes are an option.