Best of AUA 2013: Infertility/Andrology

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Presented by Aaron Spitz, MD

University of California, Irvine

• In rats, candesartan (Atacand) lessens cisplatin-induced testicular damage of testicular podocin.

• Rats treated with lycopene, selenium, or both demonstrated resistance to cisplatin-induced testicular damage.

• Clusterin may be able to protect against injury of testicular cells induced by heat shock stress.

• Researchers developed a human testis xenotransplant model to study testicular changes in epigenetic modification and gene expression patterns after exposure to cyclophosphamide.

• Fifty percent of adolescents will have masturbated and successfully ejaculated by age 13 years, so requesting an ejaculated semen specimen may be appropriate at this age for the purposes of fertility preservation.

• Histologic examination reveals that males with Klinefelter’s syndrome experience a loss of Sertoli cells after puberty.

• Seven of nine adolescent males with Klinefelter’s treated with topical testosterone replacement therapy had successful sperm retrieval.

• Preorchiectomy azoospermia resolves after orchiectomy in men with testis cancer. Thirty-nine percent of men had return of some sperm to the ejaculate. Sperm concentration was sufficient to avoid testis sperm extraction in almost 20% of men.

• Spermatogonial stem cell propagation may allow for eventual autotransplantation for prepubertal boys exposed to chemotherapy.

• Sperm retrieval rates in men undergoing microdissection testicular sperm extraction (mTESE) were not affected by age, with the exception of older men with Klinefelter’s. A separate study found only 13% of older men with Klinefelter’s had successful sperm retrieval.

• Seventy-three percent of 41 men with complete AZFc deletions had sperm retrieved successfully through mTESE, with a clinical pregnancy rate of 59%.

• Twice-daily celecoxib (Celebrex) use started the night before TESE reduces pain and narcotic use for patients in the postoperative period without complications.

• In a study of 40 men with cryptozoospermia, 85% were able to produce sufficient sperm with serial banking for in vitro fertilization-intracytoplasmic sperm injection.

• Small numbers of sperm can be microinjected into preformed, polymerized alginate beads that can be frozen and thawed individually with no decline in viability compared with controls.

• Achievement of ultra-rapid vitrification of sperm in microcapillaries with low volumes of a nontoxic sugar instead of traditional toxic cryoprotectants holds promise for the preservation of low quantities of sperm from men with severe oligospermia or who are undergoing TESE.

• A meta-analysis showed that the use of frozen thawed testicular sperm for assisted reproduction had no clinical or statistical significance in pregnancy outcomes for patients with nonobstructive azoospermia compared with the use of fresh sperm.

• RA-GEF-2 knockout mice exhibited marked testicular atrophy and severe defects in mature sperm formation. This may be due to the downstream effect on the small GTPase Rap1, which has known diverse functions by regulating cell adhesion mediated by cadherins and integrens.

• Human ubiquitin specific protease 26 is an X-linked gene that regulates androgen receptor transcriptional activity. Mutations in this gene lead to infertility and low testosterone, and may have a role in progression of androgen-sensitive cancers such as prostate cancer.

• Detection of missense mutations in the DNA mismatch repair protein MLH1 in men with impaired spermatogenesis and recombination defects suggest a role of this gene in early meiotic arrest and as a possible cause of nonobstructive azoospermia.

• In spontaneously hypertensive rats, hypertension induces testicular alterations both in seminiferous tubule and intratesticular vessels, resulting in low spermatozoid concentration. Enalapril (Vasotec) treatment partially protected the testicle and restored normal spermatozoid production.

• Microarray analysis performed in testicular tissue in men with nonobstructive azoospermia identified several genes associated with male infertility and DNA repair and found that CtBP2, which plays a role in apoptosis and transcriptional regulation, is significantly decreased in men with Sertoli cell only.

• Sperm with abnormal protamine mRNA ratios as measured by RT-PCR leads to a decline in total motile sperm counts and fertilization rates with IVF and ICSI. Screening for protamine ratio may provide additional information over standard semen analysis.

• In 24 couples where men with elevated sperm DNA fragmentation and oligospermia had failed IVF, TESE provided sperm with normal DNA fragmentation, as measured by TUNEL assay. The harvested testicular sperm increased clinical pregnancy rates to 50%.

• Varicocele ligation in men with nonobstructive azoospermia can return sperm to the ejaculate. The results are best if the underling histology is hypospermatogenesis or maturation arrest at the spermatid stage.

• Testosterone levels improve after varicocele ligation, especially in men with sub-normal levels at baseline.

• When the 2012 AUA vasectomy guidelines were applied retrospectively to a large cohort of vasectomy patients, repeat semen analyses would have been reduced by 40% and repeat vasectomies for rare nonmotile sperm would have been avoided completely.

• A meta-analysis of 23 studies related to vasectomy reversal found a patency rate of 91.1% and a pregnancy rate of 72.6%. An obstructive interval of greater than 10 years has minimal impact on outcomes.

• Vasectomy reversal for men with previous children from the same partner shows an odds ratio of 2 with a pregnancy rate of 83%.

• Practitioners in the U.S. do more vasectomy reversals than in the United Kingdom and counsel their patients more. In both countries, they follow best practices more carefully if they’ve had formal infertility training.

• Men’s health comprehensive centers are emerging, but they’re very heterogeneous in the services they provide and their presence significantly trails those for women’s health.UT

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