title: Muckle-Wells syndrome and male hypofertility: a case series.
abstract: OBJECTIVE
  Muckle-Wells syndrome (MWS) is a rare autoinflammatory disorder associated with NLRP3 gene mutations, which cause excessive caspase-1 activation and processing of interleukin (IL)-1β and IL-18. Here we investigated whether MWS disease may be associated with impaired fertility in male patients.
  
  
  METHODS
  Medical records of all male MWS patients with NLRP3 mutations followed in our tertiary center for inherited autoinflammatory diseases were reviewed retrospectively for data indicating fertility problems.
  
  
  RESULTS
  Six of 9 patients were unable to have children despite regular sexual activity during at least 2 years; 3 succeeded in having children through in vitro fertilization. Infertility was the main reason for divorce in 1 patient. Spermiogram analyses were available in 8 of the 9 patients. Oligozoospermia was observed in 5 patients and azoospermia in 3 patients. In 2 patients, treatment with IL-1-targeting drugs for 6 and 12 months, respectively, had a moderate or no effect on spermatozoa counts. In 2 patients testosterone levels were low and testosterone treatment significantly increased spermatozoa counts in 1 of them.
  
  
  CONCLUSIONS
  MWS may be associated with subfertility and infertility in male patients. Consequently, sexual health and fertility should be assessed systematically in adolescent and adult male patients. Additional studies are required to establish the frequency of subfertility in male MWS patients, to understand when subfertility occurs in the disease natural history, and, finally, to investigate whether early management with IL-1-targeting drugs, or testosterone treatment or early sperm cryo-conservation may help to allow procreation.
authors.affiliation: Department of Pediatrics, Pediatric Rheumatology, Reference Center for AutoInflammatory Diseases CEREMAI, Bicêtre Hospital, Assistance Publique des Hôpitaux de Paris, Université Paris Sud, Le Kremlin-Bicêtre, France. tu-anh.tran@bct.aphp.fr
authors.forename: Tu-Anh
authors.initials: TA
authors.lastname: Tran
authors.forename: Isabelle
authors.initials: I
authors.lastname: Koné-Paut
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marie
authors.forename: Jaques
authors.initials: J
authors.lastname: Ninet
authors.forename: Laurence
authors.initials: L
authors.lastname: Cuisset
authors.forename: Ulrich
authors.initials: U
authors.lastname: Meinzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D053713:Azoospermia / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D056587:Cryopyrin-Associated Periodic Syndromes / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008297:Male; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009845:Oligospermia / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D012189:Retrospective Studies; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects; D013739:Testosterone / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C541220:canakinumab; D013739:Testosterone