title: Shedding Light on the Nature of Seminal Round Cells.
abstract: BACKGROUND
  In this investigation we assess the incidence of round cells (RCs) in semen samples in our infertile patient population and their significance on intracytoplasmic sperm injection (ICSI) cycle outcomes. We also evaluate the usefulness of RCs as indicators of bacterial infection and highlight the origin of this cell-type, as well as its role in the human ejaculate.
  
  
  METHODS
  In a prospective fashion, a total of 4,810 ejaculated samples were included in the study during a period of 24 months. RCs were characterized for white blood cell (WBC) components versus exfoliated germ cells by testing for multiple markers of ploidy as well as protamine assays. Cases displaying ≥ 2 x 106/ml RCs were screened for bacteria. Raw specimens containing RC were processed by peroxidase and other leukocyte assays, specific stains for protamines were used to identify spermiogenic stage, aneuploidy (FISH) assessment was carried out, and the presence of various Sertoli-cell cytoplasmic remnants was analyzed to identify and characterize immature germ cells. The effect of RC on clinical outcome was assessed in specimens used for ICSI.
  
  
  RESULTS
  The average age of the men involved was 39.2 ± 7 years. Semen samples had a mean concentration of 40.7 ± 31 x 106/ml, motility of 42.6 ± 35%, and morphology of 2.3 ± 2%. RCs were identified in 261 specimens, representing a proportion of 5.4%. Men with RCs had comparable age but lower sperm concentration and morphology than the control group (P<0.001). The aneuploidy rate of 4.3% in RCs group was remarkably higher than the control group (2.3%; P<0.001). Sperm aneuploidy rate positively correlated with the number of RCs (P<0.001). Of 44 men, 17 of them in 18 cycles had up to 1.9 x 106/ml RCs without affecting fertilization and clinical pregnancy rates when compared to controls (n = 365 cycles). In 27 men undergoing 33 ICSI cycles with ≥ 2 x 106/ml RCs, the fertilization rate trended lower and the miscarriage rate was significantly increased (P = 0.05). There was lack of correlation between RC and bacteriological growth. Specific markers indicated that seminal RCs are mostly immature germ cells encased in the remnants of Sertoli cell cytoplasm. Moreover, their modest protamine content and their haploid status confirm that they are post-meiotic. Sequential observation in the same man showed that RC episodes were followed by an amelioration of semen parameters, and interestingly, the episodic occurrence of RCs often coincides with flu season peaks.
  
  
  CONCLUSIONS
  Seminal RCs are not a marker of infectiousness but rather a transient indicator of spermatogenic insult that possibly occurs in most men following a mild and transient ailment such as the flu.
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Gianpiero D
authors.initials: GD
authors.lastname: Palermo
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Queenie V
authors.initials: QV
authors.lastname: Neri
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Tyler
authors.initials: T
authors.lastname: Cozzubbo
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cheung
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Nigel
authors.initials: N
authors.lastname: Pereira
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Zev
authors.initials: Z
authors.lastname: Rosenwaks
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000150:complications / Q000175:diagnosis; D002843:Chromatin / Q000378:metabolism; D006801:Humans; D007248:Infertility, Male / Q000150:complications / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008540:Meiosis; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D011446:Prospective Studies; D012661:Semen / Q000166:cytology* / Q000382:microbiology; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism
chemical_list: D002843:Chromatin