Cystic fibrosis and congenital absence of the vas deferens.
About: This article is published in The New England Journal of Medicine.The article was published on 1991-07-04. It has received 72 citations till now. The article focuses on the topics: Congenital absence of the vas deferens & Cystic fibrosis.
Citations
More filters
Book•
[...]
01 Apr 2006
TL;DR: Advances in understanding and treatment of cystic fibrosis are summarized, focusing on pulmonary disease, which accounts for most morbidity and deaths.
Abstract: Cystic fibrosis is the most common autosomal recessive disorder in white people, with a frequency of about 1 in 2500 livebirths. Discovery of the mutated gene encoding a defective chloride channel in epithelial cells--named cystic fibrosis transmembrane conductance regulator (CFTR)--has improved our understanding of the disorder's pathophysiology and has aided diagnosis, but has shown the disease's complexity. Gene replacement therapy is still far from being used in patients with cystic fibrosis, mostly because of difficulties of targeting the appropriate cells. Life expectancy of patients with the disorder has been greatly increased over past decades because of better notions of symptomatic treatment strategies. Here, we summarise advances in understanding and treatment of cystic fibrosis, focusing on pulmonary disease, which accounts for most morbidity and deaths.
4,585 citations
TL;DR: The chance of becoming spontaneously pregnant declines with the duration before conception, and the three major factors influencing the spontaneous probability of conception are the time of unwanted non-conception, the age of the female partner and the disease-related infertility.
914 citations
TL;DR: Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF, and CF mutation analysis should be recommended for them and their partners, as well as for their relatives.
Abstract: Objective. —Almost all males with cystic fibrosis (CF) have absent vasa deferentia. It has been suggested that otherwise healthy males with congenital bilateral absence of the vas deferens (CBAVD), previously considered a distinct genetic entity, have an increased frequency of CF gene mutations. This study examined the genetic commonality of these two disorders. Design. —We typed six common CF gene mutations in 25 patients with CBAVD. Additional rare mutations were sought using single-stranded conformation polymorphisms and direct DNA sequencing. When rare mutations were found, they were sought in a large sample of both CF patients and obligate CF carriers to exclude them as polymorphisms. Setting. —All the patients presented to a male infertility clinic of a teaching hospital. Subjects. —Twenty-five unselected, unrelated azoospermic men with CBAVD, most of them of Northern European ancestry. Results. —Sixteen (64%) of the 25 men with CBAVD had at least one detectable CF mutation, 16 times the expected frequency (P Conclusions. —Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF. Prior to sperm aspiration to remedy infertility, CF mutation analysis should be recommended for them and their partners, as well as for their relatives. (JAMA. 1992;267:1794-1797)
511 citations
TL;DR: The results and rationale of using testicular and epididymal spermatozoa with intracytoplasmic sperm injection (ICSI) for severe cases of male infertility are reviewed and it is now clear that even with non-obstructive azoospermia, e.g. Sertoli-cell only, or maturation arrest, there are usually some small foci of spermatogenesis which allow TESE with ICSI to be carried out.
Abstract: The results and rationale of using testicular and epididymal spermatozoa with intracytoplasmic sperm injection (ICSI) for severe cases of male infertility are reviewed. A total of 72 consecutive microsurgical epididymal sperm aspiration (MESA) cases were performed for congenital absence of the vas (CAV) and for irreparable obstructive azoospermia. ICSI was used to obtain normal embryos for transfer and fertilization in 90% of the cases. The overall fertilization rate was 46% with a normal cleavage rate of 68%. The pregnancy and delivery rates per transfer were 58 and 37% respectively. The delivery rate per cycle was 33%. In many cases, no epididymal spermatozoa were available and so testicular sperm extraction (TESE) was used for sperm retrieval. The transfer rate was lower with TESE (84 versus 96%) and the spermatozoa could not be frozen and saved for use in future cycles. However, there was little difference in pregnancy rates using epidiymal or testicular spermatozoa. The results were not affected by whether the obstruction was caused by CAV or failed vasoepididymostomy. Both fresh and frozen spermatozoa gave similar results ; the only significant factor appeared to be the age of the female. Because of the consistently good results obtained using epididymal sperm with ICSI when compared with conventional IVF, and the similarly good results with testicular tissue spermatozoa, ICSI is mandatory for all future MESA patients. All CAV patients and their partners should be offered genetic screening for cystic fibrosis ; hence pre-implantation embryo diagnosis should be available in any full service MESA programme. It is now clear that even with non-obstructive azoospermia, e.g. Sertoli-cell only, or maturation arrest, there are usually some small foci of spermatogenesis which allow TESE with ICSI to be carried out. This means that even in men with azoospermia due to absence of spermatogenesis or to a block in meiosis, there are usually a few spermatozoa available in the testes that are adequate for successful ICSI. Finally, it is likely that some forms of severe male factor infertility are genetically transmitted and although ICSI offspring have been shown to be completely normal, it is possible that the sons of these infertile couples will also require ICSI when they grow up and wish to have a family.
234 citations
TL;DR: A 14-member panel representing the fields of genetics, obstetrics, internal medicine, nursing, social work, epidemiology, pediatrics, psychiatry, genetic counseling, bioethics, health economics, health services research, law, and the public developed its conclusions based on the scientific evidence presented in open forum and the scientific literature.
161 citations
References
More filters
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Abstract: Overlapping complementary DNA clones were isolated from epithelial cell libraries with a genomic DNA segment containing a portion of the putative cystic fibrosis (CF) locus, which is on chromosome 7 Transcripts, approximately 6500 nucleotides in size, were detectable in the tissues affected in patients with CF The predicted protein consists of two similar motifs, each with (i) a domain having properties consistent with membrane association and (ii) a domain believed to be involved in ATP (adenosine triphosphate) binding A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients
6,731 citations
TL;DR: Adult males with cystic fibrosis are infertile because of failure of normal development of the vas deferens, a finding not previously recognized.
Abstract: Adult males with cystic fibrosis are infertile because of failure of normal development of the vas deferens, a finding not previously recognized. Twenty-five patients over 17 years of age ...
335 citations
TL;DR: This work attempted to determine whether human sperm that had never passed through the epididymis could fertilize eggs in vitro and whether the technique could be used for men with congenital absence of the vas deferens.
Abstract: Background. Congenital absence of the vas deferens has been considered a virtually untreatable cause of male sterility. Furthermore, sperm that have not passed through at least the head of the epididymis have been thought to be incapable of causing pregnancy. We attempted to determine whether human sperm that had never passed through the epididymis could fertilize eggs in vitro and whether the technique could be used for men with congenital absence of the vas deferens. Methods. Twenty-eight men with congenital absence of the vas deferens underwent microsurgical aspiration of sperm from the epididymis and vasa efferentia for attempted in vitro fertilization of their wives' oocytes, with subsequent transfer of embryos. Thirty-two treatment cycles were begun (four were repeat cycles). Results. The most motile sperm were found in the proximal epididymis, at or near the vasa efferentia. Embryos were obtained for transfer in 21 cases (66 percent). Ninety-three embryos resulted from 352 mature oocytes (...
195 citations
182 citations