In 1994, more than 39,000 cycles involving ART were performed in the United States. Given the cost of approximately 8,000 per cycle, studies are needed which could improve the likelihood that ART will result in a successful pregnancy. In 1994, the investigators initiated a study of couples seeking ART that involved collect of baseline epidemiologic data, treatment variables, and biological specimens. The preliminary data collected on 927 couples, support published findings and suggest exciting new ones. Only 8 percent of women over the age of 39 years became pregnant other first ART cycle and the number of eggs retrieved during ART decline more rapidly after the age of 33 years. Key exposure examined in men and women included caffeine, alcohol, and tobacco. In women, smoking was the principal exposure that decreased number of eggs retrieved. The decrease occurred in both current and former smokers. In men, caffeine use decreased ART success. This association was not present if the ART cycle involved direct injection of sperm in eggs which suggests that caffeine (or tannins in coffee or tea) could be affecting ART success (or natural fertility) by interfering with sperm-egg penetration. Women with the primary diagnosis of endometriosis had fewer eggs retrieved, whereas diagnosis of hernia or varicocele was linked to decreased sperm concentration. Use of a gonadotropin releasing hormone agonist in a long or down regulation fashion prior to ovarian stimulation was associated with markedly better ART success and egg retrieval than used in the short or flare regimen. The joint effect of these female, male and treatment variables will be examined in discrete failure application, the investigators propose continuation of the study, anticipating that in increase in the sample size of 3,000 would allow them to examine important associations in diagnostic or treatment subgroups, as well as expand the power to study other intriguing preliminary findings. These include an association between endometriosis and a polymorphic variant, known as N314D, a key gene in galactose metabolism; evidence that acetaminophen use may lower follicle stimulating hormone levels; and evidence that alcohol use in men adversely affect sperm morphology. The investigators' ability to study male factor infertility will be enhanced by collection of a blood specimen from men and retrieval of residual semen after ART. The continued goal is to assess the effect of epidemiologic and biologic markers and treatment-related variables of ART success and to address broader aspects of reproductive physiology by examining gamete number and quality as outcomes.
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