title: Prediction model for obtaining spermatozoa with testicular sperm extraction in men with non-obstructive azoospermia.
abstract: Can an externally validated model, based on biological variables, be developed to predict successful sperm retrieval with testicular sperm extraction (TESE) in men with non-obstructive azoospermia (NOA) using a large nationwide cohort?
  
  
  
  Our prediction model including six variables was able to make a good distinction between men with a good chance and men with a poor chance of obtaining spermatozoa with TESE.
  
  
  
  Using ICSI in combination with TESE even men suffering from NOA are able to father their own biological child. Only in approximately half of the patients with NOA can testicular sperm be retrieved successfully. The few models that have been developed to predict the chance of obtaining spermatozoa with TESE were based on small datasets and none of them have been validated externally.
  
  
  
  We performed a retrospective nationwide cohort study. Data from 1371 TESE procedures were collected between June 2007 and June 2015 in the two fertility centres.
  
  
  
  All men with NOA undergoing their first TESE procedure as part of a fertility treatment were included. The primary end-point was the presence of one or more spermatozoa (regardless of their motility) in the testicular biopsies.We constructed a model for the prediction of successful sperm retrieval, using univariable and multivariable binary logistic regression analysis and the dataset from one centre. This model was then validated using the dataset from the other centre. The area under the receiver-operating characteristic curve (AUC) was calculated and model calibration was assessed.
  
  
  
  There were 599 (43.7%) successful sperm retrievals after a first TESE procedure. The prediction model, built after multivariable logistic regression analysis, demonstrated that higher male age, higher levels of serum testosterone and lower levels of FSH and LH were predictive for successful sperm retrieval. Diagnosis of idiopathic NOA and the presence of an azoospermia factor c gene deletion were predictive for unsuccessful sperm retrieval. The AUC was 0.69 (95% confidence interval (CI): 0.66-0.72). The difference between the mean observed chance and the mean predicted chance was <2.0% in all groups, indicating good calibration. In validation, the model had moderate discriminative capacity (AUC 0.65, 95% CI: 0.62-0.72) and moderate calibration: the predicted probability never differed by more than 9.2% of the mean observed probability.
  
  
  
  The percentage of men with Klinefelter syndrome among men diagnosed with NOA is expected to be higher than in our study population, which is a potential selection bias. The ability of the sperm retrieved to fertilize an oocyte and produce a live birth was not tested.
  
  
  
  This model can help in clinical decision-making in men with NOA by reliably predicting the chance of obtaining spermatozoa with TESE.
  
  
  
  This study was partly supported by an unconditional grant from Merck Serono (to D.D.M.B. and K.F.) and by the Department of Obstetrics and Gynaecology of Radboud University Medical Center, Nijmegen, The Netherlands, the Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, Den Bosch, The Netherlands, and the Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands. Merck Serono had no influence in concept, design nor elaboration of this study.
  
  
  
  Not applicable.
authors.affiliation: Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, PO Box 90153, 5200 ME 's-Hertogenbosch, The Netherlands Department of Obstetrics and Gynaecologie, Center for Reproductive Medicine, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Cissen
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Meijerink
authors.affiliation: Department of Urology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: K W
authors.initials: KW
authors.lastname: D'Hauwers
authors.affiliation: Department of Obstetrics and Gynaecologie, Center for Reproductive Medicine, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands Department of Urology, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Meissner
authors.affiliation: Department of Obstetrics and Gynaecologie, Center for Reproductive Medicine, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: van der Weide
authors.affiliation: Department of Obstetrics and Gynaecologie, Center for Reproductive Medicine, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Mochtar
authors.affiliation: Department of Obstetrics and Gynaecologie, Center for Reproductive Medicine, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: de Melker
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Ramos
authors.affiliation: Department of Obstetrics and Gynaecologie, Center for Reproductive Medicine, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Repping
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: D D M
authors.initials: DD
authors.lastname: Braat
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Fleischer
authors.affiliation: Department of Obstetrics and Gynaecologie, Center for Reproductive Medicine, Academic Medical Center, PO Box 22660, 1100 DE Amsterdam, The Netherlands m.vanwely@amc.uva.nl.
authors.forename: M
authors.initials: M
authors.lastname: van Wely
mesh_terms: D000328:Adult; D000367:Age Factors; D053713:Azoospermia / Q000097:blood / Q000473:pathology*; D000066491:Clinical Decision-Making; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007713:Klinefelter Syndrome / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008954:Models, Biological; D012189:Retrospective Studies; D053625:Sperm Retrieval; D013094:Spermatozoa / Q000473:pathology*; D013737:Testis / Q000473:pathology*; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: ICSI; azoospermia; prediction model; sperm injections; sperm retrieval