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Role of passive smoke on sperm, ICSI and IVF

Institution: University of California, San Diego
Investigator(s): Hillary Klonoff-Cohen, Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0014 Award: $628,862
Subject Area: Epidemiology
Award Type: Research Project Awards

Initial Award Abstract
Infertility, the inability to achieve a pregnancy, currently affects 2.5 million couples in the United States. Many factors for infertility have been identified in the woman, such as anatomical, hormonal, genetic and psychological problems. However, the causes of male infertility (e.g., ability of the sperm to fertilize the egg) remain unclear. While the field of obstetrics and gynecology is advanced, male infertility lags 20 years behind. There are a number of causes for male infertility, including varicose veins in the scrotum, obstruction of the seminiferous tubes that carry the sperm from the testicle to the penis, ejaculatory problems and problems in sperm quantity and quality. Over the past 30 years, sperm quality has declined markedly. This decrease has been attributed to changes in lifestyle habits, such as smoking. It is well known that tobacco smoke has many negative effects on human health, but little is known about its impact on male infertility. In infertile men, smoking may affect sperm in several ways: it decrease sperm number and movement, reduces the lifespan of the individual sperm, decreases the ability to penetrate the egg and alters male sex hormones. Assisted reproductive technologies (ART) have been developed in recent years to treat male infertility. Two methods that have significantly improved pregnancy rates in couples experiencing male infertility are in vitro fertilization (IVF) which involves placing the sperm and egg together in a laboratory dish to fertilize in vitro, and intracytoplasmic injection (ICSI), which consists of injecting a single mature sperm into an egg. While technical aspects of the procedures are important for a successful outcome, it is very likely that other factors, such as parental exposure to active and passive tobacco smoke, may negatively impact a successful healthy, live birth delivery. Cigarette smoke contains several hundred substances including nicotine, carcinogens, and heavy metals. Tobacco smoke can be directly or indirectly inhaled through the environment. Men who smoke have abnormally high levels of DNA damage in their sperm. This damage can lead to an increased risk of birth defects and cancer in their offspring. The sperm of infertile men are even more susceptible to the detrimental effects of tobacco smoke than the sperm of fertile men. This study will examine the effect of passive and direct tobacco smoke on the sperm of infertile men, and reproductive outcomes of those men undergoing IVF and ICSI. A total of 500 men of all racial backgrounds (Caucasian, African-American, Hispanic and Asian) will be recruited at seven different centers in Southern California over a 23- month period. Men with either primary or secondary infertility will be included in the study. The men will complete three confidential questionnaires: at the first office visit, during semen collection and at the pregnancy outcome. There will be questions on medical, surgical and lifestyle habits (e.g., smoking, alcohol, illicit drugs, caffeine, nutrition, and psychosocial stress) and occupational and environmental exposures. In addition, men will provide two urine samples and one sperm sample which will be measured for cotinine, a breakdown product of nicotine, to quantify tobacco exposure. This is a unique opportunity to view the impact of passive tobacco exposure on the sperm, as well as the reproductive endpoints of ICSI and IVF through a "physiologic window." This study may identify that smoking cessation and/or avoidance will ultimately ameliorate or even prevent male infertility in some instances, as well as increase the overall success rates of ICSI and/or IVF (livebirths).