One semen sample or 2? Insights from a study of fertile men.

ABBIE STOKES-RINER,*SALLY W. THURSTON,* CHARLENE BRAZIL,{DAVID GUZICK,{ FAN LIU,{JAMES W. OVERSTREET,{ CHRISTINA WANG,§AMY SPARKS,5 J. BRUCE REDMON,"AND SHANNA H. SWAN{From the *Department of Biostatistics andComputational Biology, University of Rochester,Rochester, New York, (Auger and Jouannet, 1997; Jorgensen et al, 2001, 2002). Center for Health and theEnvironment, Department of Obstetrics and Gynecology,University of California, Davis, California, `Departmentof Obstetrics and Gynecology, University of Rochester,Rochester, New York, §Department of Medicine,Harbor-UCLA Medical Center and Los AngelesBiomedical Research Institute, Los Angeles, California,5Departments of Urology and Obstetrics and Gynecology,University of Iowa, Iowa City, Iowa; and"Departments of Medicine and Urologic Surgery,University of Minnesota, Minneapolis, Minnesota.In clinical settings it is usually recommended that atleast 2 semen samples are obtained, because thisdecreases the error rate in classifying men as fertile,subfertile, or infertile (Berman et al, 1996; World HealthOrganization, 1999; Sharlip et al, 2002). In fact, someauthors have recommended that 3 samples be collectedbecause of the large within-man variability of semenparameters (Keel, 2006). In our prospective study of semen quality in partners ofpregnant women (the Study for Future Families, or SFF),we requested 2 semen samples from each participant inorder to reduce the variability of our estimates of semenquality. However, population studies of semen qualityfrequently collect only 1 sample from each participantIs this optimal when conducting a population study ofsemen quality when resources are limited? If the totalnumber of samples to be collected is fixed, it is preferable,from a purely statistical standpoint, to take a singlesample from as many men as possible, because a largersample size will increase the precision of the populationestimates. From an epidemiologic point of view, it isnecessary to consider whether requesting a second samplewill decrease participation or lead to a less representativestudy population. From a practical standpoint one needsto consider the cost of participant recruitment relative tothe cost of sample analysis. In SFF we found that the costof recruiting a participant far outweighs the cost ofanalyzing the semen sample(s) he provides, and the addedcost for a second sample is relatively minimal. In addition,we found that once a man has agreed to provide 1 semensample he is likely to agree to provide additional samples(88% did). However,ifmultiplesamplesarecollected,andparticularly if the number of samples per man varies, thisraises some statistical issues, which we address here.In this study, we ask 2 questions and use data fromSFF to address these. We consider the appropriatenessof (1) combining data from men who gave 1 sample anddata from men who gave 2 samples in the analysis and(2) combining data from both samples from men whogave 2. For the first question, we ask whether men whogive 1 sample and men who give 2 samples differ, onaverage, with respect to either subject characteristics orsemen parameters. For the second, we ask whethersemen parameters differed, on average, between the firstand second sample among men who gave 2 samples inour study population.