Lauri D. Black

Response to varicocelectomy in oligospermic men with and without defined genetic infertility

OBJECTIVES To compare the clinical characteristics of infertile men who have varicocele with and without a genetic anomaly, and report the results of varicocelectomy in these two cohorts of men. METHODS Study subjects included 33 men who underwent genetic counseling and testing for a diagnosis of oligospermia with varicocele. Seven men were diagnosed with coexisting genetic infertility (genetic [+]; abnormal karyotype in 4, Y chromosome microdeletion in 3), and 26 men with varicocele and no genetic abnormality (genetic [-]). Five patients (Y chromosome microdeletions in 2, abnormal karyotype in 3) in the genetic (+) group and 14 patients in the genetic (-) group underwent microsurgical subinguinal varicocelectomy. Semen and hormonal parameters, physical examination findings, as well as the response to varicocele repair were compared between the two groups. Varicocele response was defined as a 50% increase in total motile sperm count in the ejaculate. RESULTS Mean preoperative seminal and hormonal parameters were not statistically significantly different between the two groups. Significant differences were observed in the volume of the right and left testicles between the two groups (left: P = 0.007; right: P = 0.04). Although 7 of 13 evaluable patients (54%) in the genetic (-) group had a seminal response to varicocelectomy, none of 5 patients in the genetic (+) group showed improvement in semen quality. CONCLUSIONS From this early experience, men with varicocele and genetic lesions appear to have a poorer response to varicocele repair than men without coexisting genetic lesions. These data may have implications for counseling male factor infertility patients contemplating varicocele treatment.

Birth after intracytoplasmic sperm injection with use of testicular sperm from men with kartagener/immotile cilia syndrome

OBJECTIVE To describe two cases of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with testicular sperm in men with immotile cilia syndromes. DESIGN Case report. SETTING A university-based male infertility clinic and assisted reproduction unit. PATIENT(S) Two couples with male factor infertility due to Kartagener/immotile cilia syndrome. INTERVENTION(S) IVF/ICSI with testicular sperm. MAIN OUTCOME MEASURE(S) Semen characteristics, sperm viability, fertilization rate, and pregnancy. RESULT(S) With testicular sperm, the two pronuclear fertilization rates were 63% and 60% in two cases. One case resulted in the birth of normal healthy girl. CONCLUSION(S) With testicular sperm, successful oocyte fertilization after ICSI in couples with male Kartagener/immotile cilia syndrome is possible despite the lack of sperm motility.

Ring 21 chromosome and a satellited 1p in the same patient: novel origin for an ectopic NOR.

Nucleolus organizer regions (NORs) are present on the satellite stalks located on the short arms of the acrocentric chromosomes. NORs present on non‐acrocentric chromosomes (ectopic NORs) are rare and were reported in both phenotypically normal and abnormal individuals. We describe a patient, ascertained prenatally, with an ectopic NOR on 1p and a ring 21 chromosomes. Amniocentesis was performed at 27‐weeks gestation on a 19‐year‐old woman after identification of intrauterine growth retardation (IUGR) by ultrasound. Cytogenetic analysis of amniocytes from the fetus showed a mos 46,XX,1ps,r(21) (p11.2q22.3)[44]/45,XX,1ps,‐21[6] karyotype. Parental karyotypes were normal, indicating a de novo origin for these rearrangements in the fetus. Molecular cytogenetic characterization of the 1ps showed no loss of euchromatin and retention of the telomeric repeats. Characterization of the r(21) using array comparative genomic hybridization (CGH) identified that the deletion was approximately 5 Mb encompassing most of chromosome band 21q22.3. The ectopic NOR (1ps) was most likely derived from the acentric 21p fragment generated by the chromosome breakage event that lead to formation of the r(21) chromosome. This represents a novel mechanism for the origin of ectopic NORs. In addition, this study illustrates the importance of FISH analysis with telomeric and subtelomeric probes for characterization of chromosomes with ectopic NORs.

Initial findings using gene sequence analysis for CFTR mutations in at risk fertility patients

Objective: Detection rates with DNA analysis for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene mutations vary widely depending on patient ancestry. In addition to routine common mutation testing and conformation-sensitive gel electrophoresis (CSGE) of specific exons, gene sequencing is now clinically available. We studied the ability of gene sequence analysis to define mutations in an at risk population of infertile couples. Design: Prospective study of CFTR mutations in infertile men with congenital bilateral absence of the vas deferens (CBAVD) and their partners referred for genetic counseling and testing. Materials/Methods: Genetic counseling was provided and informed consent was obtained prior to genetic testing for CFTR mutations. Six couples who presented with CBAVD were studied. A combination of two mutation analysis techniques were used to determine CFTR mutations, including common mutation analysis (variable detection rate based on ancestry) and CSGE analysis (variable detection rate based on ancestry). Gene sequence analysis was also offered (approximately 99% detection rates regardless of ancestry). Indications for sequencing were: a) negative CFTR mutation analysis results by other methods, b) assumed low detection rates with other methods due to patient ancestry, and c) patient choice. Results: See table.