title: Diagnostic genetic screening for assisted reproductive technologies patients with macrozoospermia.
abstract: Macrozoospermia is characterized by a high proportion of abnormal spermatozoa with enlarged heads. So far, it has been associated with mutations only in the Aurora Kinase C gene (AURKC) in some cases. Although many publications have reported failure to conceive in couples with macrozoospermia, a few others have described successful pregnancies, thus raising questions as to whether ICSI and AURKC genetic screening should be recommended in all patients with macrozoospermia. First, we report on two monozygotic twins presenting macrozoospermia for whom the genetic status was explored (Aurora Kinase C sequencing) and whole semen and gradient-selected spermatozoa were analyzed, using Fluorescent In Situ Hybridization (FISH), Electron Microscopy and flow cytometry. Additionally, FISH analysis was performed on individually selected uniflagellate spermatozoa with normal sized heads. Second, we also provide an updated review of patients with macrozoospermia gathering the percentage of enlarged head spermatozoa, the genetic status and pregnancy outcomes. Both twins carried a homozygous mutation of AURKC. Spermocytograms showed means of 86% and 83.5% of enlarged head forms. FISH analyses showed that normal head size, uniflagellate spermatozoa had an aneuploid or polyploid nucleus despite a high level of selection. SEM analysis also showed special intranuclear inclusions in enlarged head spermatozoa. Our data together with cases reported in the literature allowed us to recommend that the AURKC gene should be sequenced when the sperm contains 30% or more of enlarged head spermatozoa, and when a mutation is found, ART should not be performed. Our analyses provide information that could greatly help practitioners in their decision-making with regard to optimal care of patients with macrozoospermia.
authors.affiliation: Equipe GAD, Génétique des Anomalies du Développement, Université de Bourgogne, Dijon, France.
authors.forename: V
authors.initials: V
authors.lastname: Carmignac
authors.affiliation: Laboratoire de Cytogénétique Constitutionnelle, Faculté de Médecine, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France.
authors.forename: J-M
authors.initials: JM
authors.lastname: Dupont
authors.affiliation: Laboratoire de Microscopie, Université Lorraine, Nancy, France.|Sciences de la Santé, Université Autonome Métropolitaine, Mexico City, Mexico.
authors.forename: R C
authors.initials: RC
authors.lastname: Fierro
authors.affiliation: Service de Biologie de la Reproduction, Hôpital François Mitterrand, Université de Bourgogne, Dijon, France.
authors.forename: J
authors.initials: J
authors.lastname: Barberet
authors.affiliation: Service de Biologie de la Reproduction, Hôpital François Mitterrand, Université de Bourgogne, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Bruno
authors.affiliation: Service de Biologie de la Reproduction, Hôpital François Mitterrand, Université de Bourgogne, Dijon, France.
authors.forename: N
authors.initials: N
authors.lastname: Lieury
authors.affiliation: Service d'Histologie-Embryologie, Biologie de la Reproduction/CECOS, Hôpitaux Universitaires Paris Centre, Paris, France.|INSERM U1016, Equipe 'Génomique, Epigénétique et Physiologie de la Reproduction', Institut Cochin, Université Paris Descartes, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Dulioust
authors.affiliation: Service d'Histologie-Embryologie, Biologie de la Reproduction/CECOS, Hôpitaux Universitaires Paris Centre, Paris, France.|INSERM U1016, Equipe 'Génomique, Epigénétique et Physiologie de la Reproduction', Institut Cochin, Université Paris Descartes, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Auger
authors.affiliation: Equipe GAD, Génétique des Anomalies du Développement, Université de Bourgogne, Dijon, France.|Service de Biologie de la Reproduction, Hôpital François Mitterrand, Université de Bourgogne, Dijon, France.
authors.forename: P
authors.initials: P
authors.lastname: Fauque
mesh_terms: D000328:Adult; D064108:Aurora Kinase C / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D027724:Reproductive Techniques, Assisted; D013077:Sperm Head; D000072660:Teratozoospermia / Q000235:genetics*; D014427:Twins / Q000235:genetics
chemical_list: D064108:Aurora Kinase C
keywords: assisted reproductive technologies; aurora kinase C gene; macrozoospermia; pregnancy outcomes