5q21 deletion is often heterogeneous in prostate cancer.

Cancer heterogeneity represents a challenge for the analysis of prognostic molecular markers but can be used to study the evolution of molecular events in tumors. To assess the degree of heterogeneity of 5q21 deletions and their relationship with TMPRSS2:ERG status and 6q15 deletions in prostate cancer, a heterogeneity tissue microarray including 10 tissue spots from 10 different areas of 317 cancers was analyzed by fluorescence in situ hybridization for 5q21 deletion. Data on 6q and ERG were available from earlier studies. Deletions of 5q21 were found in 23% of 265 interpretable cancers and showed marked intratumoral heterogeneity. In the subset of 246 cancers with at least 3 interpretable spots, 23% had a 5q21 deletion. Heterogeneous 5q21 deletions were found in 71% and homogeneous in 29% of these cancers. The likelihood of 5q21 deletion was twice as high in ERG-negative (28%) than in ERG-positive cancers (16%, P = .024). In all 21 cases harboring both alterations, the tumor area containing a 5q21 deletion was smaller or equally large than the ERG-positive area but never larger. Deletions of 5q and 6q were significantly linked. However, the analysis of 32 tumors harboring both deletions did not suggest a specific order of appearance of these deletions. The 5q21 deletion preceded 6q15 in 10 tumors and 6q15 preceded 5q21 in 14 tumors. In summary, our study identifies 5q21 deletion as a highly heterogeneous aberration in prostate cancer that usually occurs late during cancer progression. This is a severe limitation for using 5q21 testing as a prognostic tool.

Novel frameshift variant in the IDUA gene underlies Mucopolysaccharidoses type I in a consanguineous Yemeni pedigree.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive storage disorder that result as a consequence of a deficiency in the lysosomal hydrolase, a-L-iduronidase enzyme encoded by IDUA gene. Over a hundred causative variants in IDUA have been identified, which result in a progressive multi-systemic disease with a broad range of severity and disease progression reported across affected individuals. The aim of this study was the detection and interpretation of IDUA mutation in a family with two children affected with lethal MPS I. The IDUA gene was sequenced in the parents of two deceased children who had a clinical diagnosis of MPS I, to assess their carrier status and to help inform on risk in future children. The sequencing analysis was performed by PCR and bidirectional Sanger sequencing of the coding region and exon-intron splice junctions at Labor MVZ Westmecklenburg molecular diagnostics laboratory. A heterozygous c.657delA variant in exon 6 was identified in each parent, which is the most likely explanation for disease in their children. This report represents the first Yemeni family to have a molecular diagnosis for MPS I.

A review of the contemporary evidence on rescue cervical cerclage.

BACKGROUND: Rescue cervical cerclage (RCC) is essentially a salvage procedure to prolong pregnancy in women with advanced cervical changes and prolapsed membranes in the second trimester. However, its effectiveness and safety remain controversial. OBJECTIVES: To provide a comprehensive review of the contemporary evidence on RCC and evaluate which treatment modalities can be offered to pregnant women based on the best available evidence. SEARCH STRATEGY: A PubMed search of published studies on RCC and perinatal outcome was conducted using defined keywords. SELECTION CRITERIA: Clinical studies were included with priority for level I evidence (randomized controlled trials [RCTs]) followed by other evidence levels. DATA COLLECTION AND ANALYSIS: Abstracts of 141 articles were screened and 40 articles were selected. MAIN RESULTS: Evidence from retrospective and nonrandomized prospective trials shows a benefit of RCC. It may prolong pregnancy by an average of 4-5 weeks, with a 2-fold reduction in the chance of preterm birth before 34 weeks. A higher chance of failure is expected if cervical dilatation exceeds 4 cm or if membranes are bulging into the vagina. CONCLUSIONS: The decision for an RCC should be individualized after comprehensive counseling by a senior obstetrician. Further research in the form of robust RCTs is recommended.

DPY19L2 deletion as a major cause of globozoospermia.

Globozoospermia, characterized by round-headed spermatozoa, is a rare (< 0.1% in male infertile patients) and severe teratozoospermia consisting primarily of spermatozoa lacking an acrosome. Studying a Jordanian consanguineous family in which five brothers were diagnosed with complete globozoospermia, we showed that the four out of five analyzed infertile brothers carried a homozygous deletion of 200 kb on chromosome 12 encompassing only DPY19L2. Very similar deletions were found in three additional unrelated patients, suggesting that DPY19L2 deletion is a major cause of globozoospermia, given that 19% (4 of 21) of the analyzed patients had such deletion. The deletion is most probably due to a nonallelic homologous recombination (NAHR), because the gene is surrounded by two low copy repeats (LCRs). We found DPY19L2 deletion in patients from three different origins and two different breakpoints, strongly suggesting that the deletion results from recurrent events linked to the specific architectural feature of this locus rather than from a founder effect, without fully excluding a recent founder effect. DPY19L2 is associated with a complete form of globozoospermia, as is the case for the first two genes found to be associated with globozoospermia, SPATA16 or PICK1. However, in contrast to SPATA16, for which no pregnancy was reported, pregnancies were achieved, via intracytoplasmic sperm injection, for two patients with DPY19L2 deletion, who then fathered three children.

Conservative management of triplet ICSI pregnancy on top of synechiae.

A case of complex of obstetrical complications which endangered the life of both the mother and the fetuses was presented. The dilemma the authors faced as a result of spontaneous abortion of one of the triplet was due to rupture of membranes, the remaining twins were at risk of demise. At caesarean section, the patient had severe placenta accreta and torrential haemorrhage that was managed with a Bakri balloon.

Androgen insensitivity syndrome after preimplantation genetic diagnosis for sex selection: a case report.

OBJECTIVE: To report the first case of androgen insensitivity syndrome after preimplantation genetic diagnosis (PGD) for sex selection. DESIGN: Case report. SETTING: The Farah Hospital (a private tertiary referral fertility center). PATIENT(S): A healthy woman with three daughters underwent PGD for sex selection, seeking a male baby. INTERVENTION(S): PGD was done and the woman became pregnant. Ultrasound examination showed female phenotype. Amniocentesis was performed and culture of cells confirmed XY karyotype. RESULT(S): Karyotyping confirmed the diagnosis of XY genotype and pregnancy was terminated. CONCLUSION(S): Although androgen insensitivity syndrome is very rare, it can occur in cases of PGD for sex selection.

Live birth after hysteroscopic-guided embryo transfer: a case report.

OBJECTIVE: To report a case with successful pregnancy using hysteroscopic guided embryo transfer (ET). DESIGN: Case report. SETTING: The Farah Hospital (a private tertiary referral fertility center). PATIENT(S): A healthy woman with previous ICSI trial for male factor infertility underwent a repeat ICSI trial. INTERVENTION(S): Embryo transfer was done under hysteroscopic guidance and 3 embryos were transferred. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Delivery of a healthy female baby. CONCLUSION(S): Hysteroscopic guided ET is feasible and may be of value in cases of difficult transfer.

Evaluation and treatment of familial globozoospermia in five brothers.

OBJECTIVE: To document the pathology of five siblings with complete globozoospermia and to report the effectiveness of repeated intracytoplasmic sperm injection (ICSI) treatment as therapy. DESIGN: Case report. SETTING: A tertiary center for assisted reproduction. PATIENTS(S): Five siblings with globozoospermia. INTERVENTION(S): Twenty cycles of repeated ICSI treatment. Detailed light and electron microscopy studies were performed on three of the globozoospermic brothers. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth after ICSI treatment. RESULT(S): Light and electron microscopy showed that all spermatozoa had round heads and no acrosome. Of 129 metaphase-II oocytes injected, 49 fertilized normally, giving an overall fertilization rate of 38% (range, 0-100%). No pregnancies resulted from 13 cycles in brothers 1-3. Brothers 4 and 5 had three pregnancies after seven ICSI cycles, with one live birth and two first-trimester losses. CONCLUSION(S): Despite variable fertilization rates, pregnancies and a live birth can be achieved after repeated ICSI treatment cycles in globozoospermic siblings. No apparent pattern was manifest that reflected the true pathology or determined the outcome of ICSI treatment.

Chromosomal abnormalities in embryos derived from testicular sperm extraction.

OBJECTIVE: To compare the rate of chromosome abnormalities in embryos obtained from karyotypically normal patients with nonobstructive azoospermia undergoing testicular sperm extraction (TESE) to those from patients undergoing intracytoplasmic sperm injection (ICSI) with ejaculated sperm. DESIGN: Retrospective analysis. SETTING: IVF centers. PATIENT(S): Male partners had either nonobstructive zoospermia or oligospermia. INTERVENTION(S): Preimplantation genetic diagnosis. Chromosome enumeration was performed by fluorescence in situ hybridization (FISH). Embryos classified as abnormal were reanalyzed to study mosaicism. MAIN OUTCOME MEASURE(S): Chromosome abnormalities in embryos. RESULT(S): Embryos from ICSI cycles with ejaculated sperm (group 1) were 41.8% normal, 26.2% aneuploid, and 26.5% mosaic. In contrast, the embryos from ICSI cycles with TESE for nonobstructive azoospermia (group 2) were 22% normal, 17% aneuploid, and 53% mosaic. The difference in mosaicism rate between the two groups of embryos was highly significant. CONCLUSION(S): The present study results indicate a high incidence of mosaicism in embryos derived from TESE in men with a severe deficit in spermatogenesis. Sperm derived from TESE for nonobstructive azoospermia may have a higher rate of compromised or immature centrosome structures leading to mosaicism in the embryo.