The Ne w E n g l a nd Jour n a l o f Me d ic i ne
SPERM MORPHOLOGY, MOTILITY, AND CONCENTRATION IN FERTILE AND INFERTILE MEN
DAVID S. GUZICK, M.D., PH.D., JAMES W. OVERSTREET, M.D., PH.D., PAM FACTOR-LITVAK, PH.D., CHARLENE K. BRAZIL, B.S., STEVEN T. NAKAJIMA, M.D., CHRISTOS COUTIFARIS, M.D., PH.D., SANDRA ANN CARSON, M.D., PAULINE CISNEROS, PH.D., MICHAEL P. STEINKAMPF, M.D., JOSEPH A. HILL,M.D., DONG XU, M.PHIL., AND DONNA L. VOGEL, M.D., PH.D., FOR THE NATIONAL COOPERATIVE REPRODUCTIVE MEDICINE NETWORK*
Background Although semen analysis is routinely
used to evaluate the male partner in infertile couples, sperm measurements that discriminate between fertile and infertile men are not well defined. Methods We evaluated two semen specimens from each of the male partnersin 765 infertile couples and 696 fertile couples at nine sites. The female partners in the infertile couples had normal results on fertility evaluation. The sperm concentration and motility were determined at the sites; semen smears were stained at the sites and shipped to a central laboratory for an assessment of morphologic features of sperm with the use of strict criteria. We usedclassification-andregression-tree analysis to estimate threshold values for subfertility and fertility with respect to the sperm concentration, motility, and morphology. We also used an analysis of receiver-operating-characteristic curves to assess the relative value of these sperm measurements in discriminating between fertile and infertile men. Results The subfertile ranges were a sperm concentration ofless than 13.5¬106 per milliliter, less than 32 percent of sperm with motility, and less than 9 percent with normal morphologic features. The fertile ranges were a concentration of more than 48.0¬106 per milliliter, greater than 63 percent motility, and greater than 12 percent normal morphologic features. Values between these ranges indicated indeterminate fertility. There was extensive overlapbetween the fertile and the infertile men within both the subfertile and the fertile ranges for all three measurements. Although each of the sperm measurements helped to distinguish between fertile and infertile men, none was a powerful discriminator. The percentage of sperm with normal morphologic features had the greatest discriminatory power. Conclusions Threshold values for sperm concentration,motility, and morphology can be used to classify men as subfertile, of indeterminate fertility, or fertile. None of the measures, however, are diagnostic of infertility. (N Engl J Med 2001;345:1388-93.)
Copyright © 2001 Massachusetts Medical Society.
EMEN analysis is routinely used to evaluate the male partner in infertile couples1,2 and to assess the reproductive toxicity of environmentalor therapeutic agents.3 Although widely used thresholds for normal semen measurements have been published by the World Health Organization (WHO),4-7 the available norms for sperm concentration, motility, and morphology fail to meet rigorous clinical, technical, and statistical standards. In recognition of these limitations, the nomenclature in the most recent WHO manual7 for semen evaluation waschanged from “normal” to “reference” values. Two recent prospective studies of semen quality and fertility concluded that the current WHO reference values should be reconsidered.8,9 In this study, we sought to determine values for semen measurements that best discriminate between fertile and infertile men and to evaluate the relative value of standard semen measurements in distinguishing betweenfertile and infertile men.
Study Population As part of a randomized clinical trial of intrauterine insemination and superovulation in the treatment of infertility at nine centers in the United States, we recruited infertile couples in which the female partners had normal results on fertility evaluation.10 All of these couples had been unable to conceive for at least 12 months; the mean...
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