title: Spermatogenesis in Hodgkin's lymphoma patients: a retrospective study of semen quality before and after different chemotherapy regimens.
abstract: OBJECTIVE
  Is spermatogenesis impairment caused by Hodgkin's lymphoma (HL) itself or by the various treatments?
  
  
  CONCLUSIONS
  HL is not itself the main cause of impaired spermatogenesis, which is instead affected by the treatment; the extent of impairment depends on the type of treatment and the number of cycles.
  
  
  BACKGROUND
  Data in the literature are contradictory, although most studies found poor semen quality in HL patients prior to treatment. The impact of therapy on spermatogenesis depends on the type of treatment, but the time needed to recover testicular function following treatment with chemotherapeutic agents inducing azoospermia is unknown.
  
  
  METHODS
  In a retrospective study, the semen parameters of 519 patients (504 with sperm and 15 who were azoospermic) were investigated.HL patients were analysed before therapy. A longitudinal study was also conducted of semen quality in 202 patients pre- and post-ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) at T0 (baseline) and 6 (T6), 12 (T12) and 24 (T24) months after the end of treatment, and of 42 patients pre- and post-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), COPP/ABVD (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine and dacarbazine), OPP/ABVD (vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine and dacarbazine) or MOPP (mechlorethamine, vincristine, procarbazine and prednisone) and inguinal radiotherapy at different observation times (from T0 to 16 years after treatment).
  
  
  METHODS
  Semen parameters were examined according to World Health Organization 2010 criteria, evaluating sperm concentration, total sperm number, progressive motility and morphology.
  
  
  RESULTS
  Our data, which pertain to the largest caseload reported to date, indicate that 75% of HL patients are normozoospermic prior to treatment. The results from the HL patients studied pre- and post-therapy demonstrate that spermatogenesis recovery depends on the therapeutic regimen used. After ABVD, there was a statistically significant decrease in sperm concentration and total sperm number at T6 and T12 (P < 0.001; P < 0.01, respectively). There was a significant drop in progressive motility (P < 0.001) and a significant increase in abnormal forms (P < 0.01) at T6. The differences in sperm concentration, total sperm number and abnormal forms at T0 and T24 were not statistically significant, indicating that sperm quality had returned to pre-therapy values. The most interesting data in terms of patient management arise from the study of azoospermia induced by other chemotherapeutic agents. A high number of BEACOPP, COPP/ABVD, OPP/ABVD or MOPP cycles (≥6) induced a permanent absence of sperm in the seminal fluid, while even following a low number of cycles (<6), spermatogenesis only recovered after 3-5 years and semen quality was highly impaired.
  
  
  CONCLUSIONS
  The study type (retrospective) and the low caseload and varying time of the follow-up do not permit any firm conclusions to be drawn about the recovery of spermatogenesis after BEACOPP or other combined therapies, or the identification of any risk factors for testicular function in treated patients.
  
  
  CONCLUSIONS
  The pretreatment semen parameters of HL patients in this study were better than some results reported in the literature, with a higher percentage of normozoospermic patients. Strengths of this study were the large caseload of HL patients and a high degree of consistency in semen analysis, as all parameters were assessed in the same laboratory. Following the azoospermia induced by different chemotherapeutic protocols, spermatogenesis may take several years to recover. Awareness of this issue will enable oncologists to better inform patients about the possibility of recovering fertility post-treatment and also demonstrates the importance of semen cryobanking before beginning any cancer treatment.
  
  
  BACKGROUND
  Supported by a grant from the Italian Ministry of Education and Research (MIUR-PRIN) and the University of Rome 'La Sapienza' Faculty of Medicine. The authors have no conflicts of interest.
authors.affiliation: Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome 'La Sapienza', Italy.
authors.forename: D
authors.initials: D
authors.lastname: Paoli
authors.affiliation: Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome 'La Sapienza', Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rizzo
authors.affiliation: Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome 'La Sapienza', Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fiore
authors.affiliation: Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome 'La Sapienza', Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pallotti
authors.affiliation: Department of Cellular Biotechnologies and Haematology, University of Rome 'La Sapienza', Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pulsoni
authors.affiliation: Department of Cellular Biotechnologies and Haematology, University of Rome 'La Sapienza', Italy.
authors.forename: G
authors.initials: G
authors.lastname: Annechini
authors.affiliation: Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome 'La Sapienza', Italy.
authors.forename: F
authors.initials: F
authors.lastname: Lombardo
authors.affiliation: Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome 'La Sapienza', Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome 'La Sapienza', Italy loredana.gandini@uniroma1.it.
authors.forename: L
authors.initials: L
authors.lastname: Gandini
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006689:Hodgkin Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007248:Infertility, Male / Q000139:chemically induced* / Q000150:complications; D008137:Longitudinal Studies; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D055101:Semen Analysis; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: ABVD protocol; BEACOPP protocol; Hodgkin lymphoma; chemotherapy; semen quality