Dataset Information

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia.

ABSTRACT:

Objective

To identify gene dosage changes associated with nonobstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH).

Design

Prospective study.

Setting

Medical school.

Patient(s)

One hundred ten men with NOA and 78 fertile controls.

Intervention(s)

None.

Main outcome measure(s)

The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy number variations (CNVs); Taqman CNV assays to validate CNVs; mutation identification by Sanger sequencing; and histological analyses of testicular tissues.

Result(s)

A microduplication at 20q11.22 encompassing E2F transcription factor-1 (E2F1) was identified in one of eight men with NOA analyzed using aCGH. CNVs were confirmed and in an additional 102 men with NOA screened using Taqman CNV assays, for a total of 110 NOA men analyzed for CNVs in E2F1. Eight of 110 (7.3%) NOA men had microduplications or microdeletions of E2F1 that were absent in fertile controls.

Conclusion(s)

E2F1 microduplications or microdeletions are present in men with NOA (7.3%). Duplications or deletions of E2F1 occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset of NOA men. These results recapitulate the infertility phenotype seen in mice lacking or overexpressing E2f1.

SUBMITTER: Jorgez CJ

PROVIDER: S-EPMC4282601 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia.

Jorgez Carolina J CJ Wilken Nathan N Addai Josephine B JB Newberg Justin J Vangapandu Hima V HV Pastuszak Alexander W AW Mukherjee Sarmistha S Rosenfeld Jill A JA Lipshultz Larry I LI Lamb Dolores J DJ

Fertility and sterility 20141024 1

<h4>Objective</h4>To identify gene dosage changes associated with nonobstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH).<h4>Design</h4>Prospective study.<h4>Setting</h4>Medical school.<h4>Patient(s)</h4>One hundred ten men with NOA and 78 fertile controls.<h4>Intervention(s)</h4>None.<h4>Main outcome measure(s)</h4>The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy number variations (CNVs); Taqman CNV assays to validate ...[more]

PMID: 25439843

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Project description:The objective of this systemic review was to evaluate the benefit of repairing clinical varicocele in infertile men with nonobstructive azoospermia (NOA). The surgically obtained sperm retrieval rate (SRR) and pregnancy rates following assisted reproductive technology (ART) with the use of retrieved testicular sperm were the primary outcomes. The secondary outcomes included the presence of viable sperm in postoperative ejaculate to avoid the testicular sperm retrieval and pregnancy rates (both assisted and unassisted) using postoperative ejaculated sperm. An electronic search to collect the data was performed using the MEDLINE and EMBASE databases until April 2015. Eighteen studies were included in this systematic review and accounted for 468 patients who were diagnosed with NOA and varicocele. These patients were subjected to either surgical varicocele repair or percutaneous embolization. Three controlled studies evaluating sperm retrieval outcomes indicated that in patients who underwent varicocelectomy, SRR increased compared to those without varicocele repair (OR: 2.65; 95% CI: 1.69-4.14; P< 0.001). Although pregnancy rates with the use of testicular sperm favored the varicocelectomy group, results were not statistically significant (clinical pregnancy rate OR: 2.07; 95% CI: 0.92-4.65; P= 0.08; live birth rate OR: 2.19; 95% CI: 0.99-4.83; P= 0.05). The remaining fifteen studies reported postoperative semen analysis results. In 43.9% of the patients (range: 20.8%-55.0%), sperm were found in postoperative ejaculates. Pregnancy rates for unassisted and assisted (after IVF/ICSI) were 13.6% and 18.9% in the group of men with sperm in postoperative ejaculates, respectively. Our findings indicate that varicocelectomy in patients with NOA and clinical varicocele is associated with improved SRR. In addition, approximately 44% of the treated men will have enough sperm in the ejaculate to avoid sperm retrieval. Limited data on pregnancy outcomes with both postoperative ejaculated sperm and harvested testicular sperm preclude any firm conclusion with regard to the possible increased fertility potential in treated individuals. In conclusion, the results of our study indicate that infertile men with NOA and clinical varicocele benefit from varicocelectomy. Given the low/moderate quality of evidence available, it is advisable that doctors discuss with their patients with NOA the risks and benefits of varicocele repair.

Dataset Information

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia.

Objective

Design

Setting

Patient(s)

Intervention(s)

Main outcome measure(s)

Result(s)

Conclusion(s)

Publications

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia.

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