title: Chromosomal abnormalities in azoospermic and non-azoospermic infertile men: numbers needed to be screened to prevent adverse pregnancy outcomes.
abstract: OBJECTIVE
  How many infertile men who wish to conceive need to be screened for chromosomal abnormalities to prevent one miscarriage or the birth of one child with congenital anomalies (CAs)?
  
  
  CONCLUSIONS
  In azoospermic men, the prevalence of chromosomal abnormalities is 15.2% and the number needed to be screened (NNS; minimum-maximum estimate) for a miscarriage is 80-88 and for a child with CAs is 790-3951. The prevalence of chromosomal abnormalities in non-azoospermic men is 2.3% and the NNS are 315-347 and 2543-12 723, respectively.
  
  
  BACKGROUND
  Guidelines advise the screening of infertile men for chromosomal abnormalities to prevent miscarriages and children with congenital abnormalities, but no studies have been published on the effectiveness of this screening strategy.
  
  
  METHODS
  Retrospective cohort study of 1223 infertile men between 1994 and 2007.
  
  
  METHODS
  Men with azoospermia and men eligible for ICSI treatment visiting a university hospital fertility clinic in The Netherlands who underwent chromosomal analysis between 1994 and 2007 were identified retrospectively in a registry. Only cases of which at least one sperm analysis was available were included. Data were collected by chart review, with a follow-up of pregnancies and their outcomes until 2010. The chromosomal abnormalities were categorized according to their risk of unbalanced offspring, i.e. miscarriage and/or child with CAs. Multi-level analysis was used to estimate the impact of chromosomal abnormalities on the outcome of pregnancies in the different subgroups of our cohort. NNS for miscarriages and children with CAs were calculated based on data from our cohort and data published in the literature.
  
  
  RESULTS
  A chromosomal abnormality was found in 12 of 79 men with azoospermia (15.2%) and in 26 of 1144 non-azoospermic men (2.3%). The chromosomal abnormalities were categorized based on the literature, into abnormalities with and abnormalities without increased risk for miscarriage and/or child with CAs. In our study group, there was no statistically significant difference between the subgroups with and without increased risk respectively, regarding the frequency of children born with CAs (1/20; 5.0% versus 1/14; 7.1%), miscarriage (9/20; 45.0% versus 2/14; 14.3%) or unaffected liveborn children (9/20; 45.0% versus 9/14; 64.3%). The prevalence of chromosomal abnormalities with a theoretically increased risk of unbalanced progeny was 1.0% in non-azoospermic men and 3.8% in men with azoospermia. For the calculation of the NNS, the risk of an adverse pregnancy outcome in our cohort was compared with the incidence ranges of miscarriage and children with CAs in the general population. The number of azoospermic men that needs to be screened to prevent one miscarriage (80-88) or one child with CAs (790-3951) was considerably lower compared with the NNS in the non-azoospermic group (315-347 and 2543-12 723, respectively).
  
  
  CONCLUSIONS
  The prevalence of chromosomal abnormalities in infertile men is low, and although we included 1223 men, our conclusions are based on a small number (38) of abnormal karyotypes. As there are no large series on outcomes of pregnancies in infertile men with chromosomal abnormalities, our conclusions had to be partly based on assumptions derived from the literature.
  
  
  CONCLUSIONS
  Based on the NNS calculated in our study, screening for chromosomal abnormalities is recommended in all azoospermic men. In non-azoospermic infertile men, screening might be limited to men with an additional risk factor (e.g. a history of recurrent miscarriage or a positive family history for recurrent miscarriage or children with CAs). The NNS can be used in future cost-effectiveness studies and the evaluation of current guidelines on karyotyping infertile men.
authors: Department of Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen (UMCG), CB 35, PO Box 30001, 9700 RB Groningen, The Netherlands. : e.c.dul@umcg.nl
authors: E C
authors: EC
authors: Dul
authors: J
authors: J
authors: van Echten-Arends
authors: H
authors: H
authors: Groen
authors: T
authors: T
authors: Dijkhuizen
authors: J A
authors: JA
authors: Land
authors: C M A
authors: CM
authors: van Ravenswaaij-Arts
mesh_terms: D000022:Abortion, Spontaneous / Q000517:prevention & control; D000465:Algorithms; D053713:Azoospermia / Q000175:diagnosis* / Q000473:pathology*; D002869:Chromosome Aberrations; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008403:Mass Screening / Q000379:methods; D015233:Models, Statistical; D011247:Pregnancy; D011256:Pregnancy Outcome; D015995:Prevalence; D027724:Reproductive Techniques, Assisted; D012189:Retrospective Studies