This proposal identifies whether certain kinds of stressors are more likely to lead to some forms of infertility. Given the role of the hypothalamus in maintaining physiologic homeostasis, infertility disorders involving the neuroendocrine system [e.g., functional abnormalities of the hypothalamic-pituitary-ovarian (HPO) axis] are relatively likely to be caused by stress. By contrast, infertility disorders that have an anatomic etiology (e.g., tubal disease) are relatively unlikely to be caused by stress, and tend to be irreversible without surgical intervention. Infertile women seeking treatment are assumed to be experiencing emotional distress as a result of their infertile condition, regardless of their particular etiology. However, if psychosocial stress were an important cause of neuroendocrine, but not anatomic, forms of infertility, infertile women with neuroendocrine disorders should report higher levels of psychosocial stress than do infertile women with anatomic disorders. Similarly, controls--women with the same neuroendocrine disorders as in the neuroendocrine infertility group, but who do not wish to become pregnant--should report levels of psychosocial stress comparable to women in the neuroendocrine infertility group. This latter prediction would not be expected if stress resulting from infertility were the only stress associated with infertility since such stress should be absent in controls. A battery of questionnaires and structured interviews measuring a variety of psychosocial and other stress constructs will be given to all consenting women when in the follicular phase of their cycle, just prior to their first clinical visit. Husbands also will receive an interview at this time to corroborate the responses of their spouse. A 24 hour urine sample will be collected from the subject beginning with her first urination after completing the questionnaires and interview. A second 24 hour urine sample will be collected during the follicular phase, 1 month following the subject's first clinic visit. The urine samples will be analyzed for cortisol and catecholamine (norepinephrine, epinephrine and dopamine) concentrations. Following a complete infertility evaluation, two physicians will independently classify the etiology of each infertile woman as being of functional, anatomic or intermediate origin, based on pre-established criteria and a formal chart review. Controls will be similarly evaluated. A multivariate analysis of variance will be used to determine which stress and endocrine measures best discriminate the 3 infertility groups as well as the controls.
