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Marc Goldstein

Publications and source records attributed to Marc Goldstein.

At least 19 recordsLinked to original sources

Haploinsufficiency at the protein kinase A RI alpha gene locus leads to fertility defects in male mice and men.

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxomas, and endocrine tumors. CNC is inherited as an autosomal dominant trait and is transmitted with greater frequency by women vs. men. Nearly two thirds of CNC patients are heterozygous for inactivating mutations in the gene encoding the protein kinase A (PKA) type I alpha regulatory subunit (RI alpha), PRKAR1. We report here that male mice heterozygous for the Prkar1a gene have severely reduced fertility. Sperm from Prkar1a heterozygous mice are morphologically abnormal and reduced in number. Genetic rescue experiments reveal that this phenotype results from elevated PKA catalytic activity in germ cells as early as the pachytene stage of spermatogenesis. Consistent with this defect in the male mutant mice, sperm from CNC patients heterozygous for PRKAR1A mutations were also found to be morphologically aberrant and decreased in number. We conclude that unregulated PKA activity in male meiotic or postmeiotic germ cells leads to structural defects in mature sperm and results in reduced fertility in mice and humans, contributing to the strikingly reduced transmission of PRKAR1A inactivating mutations by male patients with CNC.

Animals↗

Microsurgical reconstruction of iatrogenic injuries to the epididymis from hydrocelectomy.

PURPOSE: We determined the feasibility and outcome of microsurgical reconstruction of the excurrent ductal tract in men with obstruction secondary to iatrogenic injury to the epididymis from hydrocelectomy. MATERIALS AND METHODS: A retrospective chart review was done to identify men with iatrogenic injury to the epididymis or scrotal vas deferens and a history of hydrocelectomy. The outcome of microsurgical reconstruction was assessed by postoperative semen analysis. Pregnancy data were noted in patients actively attempting to conceive at a followup of 6 months or greater. RESULTS: Eight men were found to have iatrogenic injury to the epididymides (6) or scrotal vas deferens (2) due to previous hydrocelectomy. Injury was bilateral in 4 men and unilateral in 4 with contralateral testicular absence, dysfunction or obstruction resulting from different etiologies, rendering all patients azoospermic. The mean obstructive interval was 16 years (range 6 to 32). Bilateral and unilateral vasoepididymostomy was performed in 4 and 2 men each, and crossed vasovasostomy was performed in 2. Postoperative semen analysis data were available on 6 men. A patent microsurgical anastomosis was observed in 5 of 6 cases (83%). Four of the 5 men with patency had a followup of greater than 6 months, of whom 3 actively pursued conception. One pregnancy was achieved naturally and 1 was achieved by in vitro fertilization with intracytoplasmic sperm injection. CONCLUSIONS: Hydrocelectomy may result in inadvertent injury to the excurrent ductal tract, causing obstruction and infertility. Microsurgical reconstruction results in the restoration of spermatozoa to the ejaculate in 83% of cases. The return of spermatozoa to the ejaculate may provide the couple with an opportunity to conceive naturally or through assisted reproduction.

Adult↗

Arteriovenous malformation of scrotum causing virtual azoospermia.

We report a case of surgical correction of a scrotal arteriovenous malformation (AVM) that reversed severe oligospermia. A 31-year-old man was found to have virtual azoospermia and left scrotal swelling. The left scrotal mass was diagnosed as a varicocele, but the mass did not resolve after bilateral microsurgical varicocelectomies. Postoperative pelvic arteriography revealed a scrotal AVM that was subsequently embolized. With a microsurgical approach, the mass was excised. Surgical correction of the scrotal AVM resulted in marked improvement in his semen parameters. The effect of the AVM on spermatogenesis was most likely mediated by an elevation in scrotal temperature.

Adult↗

Microsurgical management of male infertility.

The introduction of microsurgical techniques has revolutionized the treatment of male infertility. As a result of technical advances and innovation over the past 10-15 years, previously infertile couples are now able to conceive naturally or to parent their own biological children with the aid of assisted reproductive technologies. This article reviews the indications, techniques, and outcomes of the various microsurgical procedures currently used to optimize male fertility. The most up-to-date methods of microsurgical vasal and epididymal reconstruction, sperm retrieval, and varicocele repair are discussed.

Azoospermia↗

Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome.

PURPOSE: The aim of this study was to report the successful fertility treatment of men with Klinefelter syndrome using testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). METHODS: A total of 42 men with Klinefelter syndrome who underwent 54 TESE procedures were identified. Before TESE, patients with serum testosterone levels less than 15.6 nmol/liter were treated with an aromatase inhibitor. Sperm retrieval rates and results of ICSI, including fertilization and clinical pregnancy, were collected. RESULTS: Mean pretreatment FSH and testosterone levels were 33.2 IU/liter and 9.8 nmol/liter. During medical therapy, the mean testosterone level rose to 17.0 nmol/liter (P < 0.01). Spermatozoa were found during 39 microdissection TESE procedures, on the day before, or day of oocyte retrieval during a programmed in vitro fertilization cycle. The sperm retrieval rate was 72% (39 of 54) per TESE attempt, and 29 of the 42 different men (69%) had adequate sperm found for ICSI. Thirty-three in vitro fertilization cycles yielded embryos for transfer in the 39 (85%) cycles with sperm retrieved. Eighteen clinical pregnancies have resulted in 21 live births [18 of 39 (46%)]. All children had a normal karyotype. CONCLUSION: TESE/ICSI is a successful intervention for the majority of patients with azoospermia and Klinefelter syndrome. Sperm retrieval and ICSI success in men with Klinefelter syndrome are comparable with other men with nonobstructive azoospermia treated at our center.

Adult↗

Births using sperm retrieved via immediate microdissection of a solitary testis with cancer.

OBJECTIVE: To determine the feasibility of achieving births using sperm retrieved from a solitary testis with cancer. DESIGN: Prospective clinical study of azoospermic men with testis cancer in a solitary testis. SETTING: Infertility patients in an academic environment. PATIENT(S): Azoospermic men with previous history of orchiectomy and testis cancer in a remaining solitary testis. INTERVENTION(S): Viable sperm were retrieved by immediate microdissection of paratumor testicular tissue from orchiectomy specimen. MAIN OUTCOME MEASURE(S): Live births were achieved using sperm from immediate microdissection of orchiectomy specimen with testis cancer. CONCLUSION(S): Azoospermic men with cancer in a solitary testis have potential for fertility.

Adult↗

Inheritance of varicoceles.

OBJECTIVES: To evaluate the inheritance of varicoceles through examination of first-degree relatives of patients with known varicoceles. METHODS: A total of 44 patients with a known varicocele had available first-degree relatives (n = 62) examined for the presence of a varicocele between October 1997 and November 2003. An additional cohort of 263 men presenting for vasectomy reversal without a history of subfertility or varicocele was used as the control group. Varicocele grade and the presence of bilateral varicoceles were examined as predictive factors for inheritance. RESULTS: Of the 62 first-degree relatives of patients with a known varicocele, 35 (56.5%) had a clinically palpable varicocele on physical examination. This was significantly greater than the 18 (6.8%) of 263 men in the control group (P < 0.0001). Of the first-degree relatives, 20 (74%) of 27 brothers, 13 (41%) of 32 fathers, and 2 (67%) of 3 sons had palpable varicoceles. Neither varicocele grade nor bilaterality was predictive of inheritance in these first-degree relatives. CONCLUSIONS: The increase in varicocele prevalence is significant in the first-degree relatives (particularly brothers) of patients with known varicoceles. Given the detrimental effect of varicoceles on spermatogenesis and steroidogenesis, patients should be counseled about this increased risk in male family members.

Adolescent↗

Incidence and postoperative outcomes of accidental ligation of the testicular artery during microsurgical varicocelectomy.

PURPOSE: In this study the frequency and outcomes of unintentional testicular artery ligation during microsurgical varicocelectomy were evaluated. MATERIALS AND METHODS: From 1984 to 2002, 2,102 cases of microsurgical varicocelectomy were evaluated. Accidental artery ligation was confirmed intraoperatively by observation of pulsatile twitching of the ligated vessel stump under 25x magnification. RESULTS: The complication was identified in 19 cases (0.9%) and all occurrences were unilateral, with 74% on the left side and 42% on the right side. In addition to the vasal artery at least 1 alternative artery was identified in all cases. Average testis volume before surgery was 15.8 ml. Azoospermia was found in 26% of cases. After surgery during the median followup of 19 months testicular atrophy developed in 1 patient (5%). In this cohort significant improvement was found in serum total testosterone in 80% (from 362 to 493 ng/dl) and in sperm count in 80% (from 12 to 22 x 10 per ml). Return of motile sperm to the ejaculate was found in 40% of azoospermic cases. The natural pregnancy rate was 14%, which is significantly lower than the 46% previously reported in the historical cohort of varicocelectomy cases. CONCLUSIONS: The incidence of accidental testicular artery ligation in microsurgical varicocelectomy was approximately 1%. Testicular atrophy developed in 1 patient (5%). Preservation of cremasteric and/or secondary internal spermatic arteries likely contributed to a low incidence of adverse outcomes. The natural pregnancy rate was low which may be due to the high proportion of azoospermic men before surgery. It is possible that the smaller testes usually associated with azoospermia indicate smaller testicular arteries, thus posing a greater risk of accidental ligation.

Adult↗

Outcome and late failures compared in 4 techniques of microsurgical vasoepididymostomy in 153 consecutive men.

PURPOSE: Vasoepididymostomy remains one of the most technically challenging procedures in all of microsurgery. The technique has evolved from an end-to-end, to an end-to-side technique, then to intussusception end-to-side methods. We recently reported the superiority of 2-suture longitudinal and 3-suture triangulation intussusception techniques in rats. In the present study we report our results in humans. We evaluated all vasoepididymostomies performed by 1 surgeon from January 1992 until the present for patency, pregnancy and for disappearance of sperm after initial return of sperm to the ejaculate. MATERIALS AND METHODS: We recorded the results of 153 consecutive vasoepdidymostomies done by 1 surgeon (MG) from January 1992 until February 2004. Four techniques were used, namely end-to-end (EE), end-to-side (ES), 3-suture triangulation intussusception (TIVE) and 2-suture longitudinal intussusception (LIVE). Data collected included technique, months of followup, sperm density, motility and morphology (WHO 1992 criteria), pregnancy outcome and late failures. Late failures were defined as having return of sperm to the ejaculate after vasoepididymostomy and then becoming azoospermic on at least 2 subsequent semen analyses. RESULTS: A total of 153 men underwent bilateral vasoepididymostomies. The most recent 17 were LIVE, preceeded by 38 TIVE, 32 ES and 66 EE. Mean followup for the groups were 17.2 (LIVE), 70.8 (TIVE), 116.7 (ES) and 140.2 (EE) months, respectively. Intact sperm were seen in the ejaculates of 12 men (80%) in the LIVE group, 16 in the TIVE group (84%), 20 in the ES group (74%) and 30 men in the EE group (73%). Motile sperm were found in the ejaculates of 10 of 15 (67%) in the LIVE group, 13 of 19 (68%) in the TIVE group, 10 of 27 (37%) in the ES group and 20 of 41 (49%) in the EE group (p =0.2). Mean times for return of sperm to the ejaculate were 2.9, 2.8, 2.8 and 3.5 months, respectively. Pregnancies were reported by 4 men in the LIVE group all before 12 months, 6 in the TIVE group and 3 were by 12 months, and 4 each by the ES and EE groups with 3 and 2 by 12 months (p =0.07). Thus far, there have been no late failures in the LIVE group, only 1 in the TIVE group (8%), 5 in the ES group (50%) and 6 in the EE group (30%) (p =0.04). CONCLUSIONS: Although vasoepididymostomy remains a technically demanding microsurgical procedure, recent technical innovations of TIVE and LIVE offer better or comparable outcomes compared with EE and ES procedures with the use of fewer sutures, which simplifies the performance of the anastomosis. In addition, the late failure rate is lower with the use of the intussusception techniques (LIVE and TIVE) with only 1 late failure in 22 men with return of sperm to the ejaculate procedures (4%) compared with 11 of 30 (37%) in the nonintussusception groups (p =0.006).

Anastomosis, Surgical↗

Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis.

PURPOSE: We determined the standardized incidence ratio of testicular cancer in infertile men presenting with an abnormal semen analysis compared to the general population. MATERIALS AND METHODS: The charts from more than 3,800 men presenting with infertility and abnormal semen analysis during a 10-year period were retrospectively reviewed. The incidence of testicular tumors diagnosed in this group was compared to that of race and age matched controls during the same period from the general population (as reported by the Surveillance, Epidemiology and End Results [SEER] database). RESULTS: Of 3,847 men 10 (0.3%) with infertility and abnormal semen analysis were diagnosed with testicular tumors. Mean patient age was 32.6 years (range 25 to 52) and all 10 men were diagnosed with a seminomatous germ cell tumor. Two men had a history of cryptorchidism while the remaining 8 had no identifiable risk factors for testicular cancer. The SEER database reported an incidence of 10.6 cases of testicular cancer (95% CI 10.3-10.8) per 100,000 men of similar age group and racial composition during the same period. The standardized incidence ratio of testicular cancer was 22.9 (95% CI 22.4-23.5) when comparing our infertile group to the control population. Exclusion from analysis of the 2 patients with a history of cryptorchidism decreased the standardized incidence ratio to 18.3 (95% CI 18.0-18.8). CONCLUSIONS: Infertile men with abnormal semen analyses have a 20-fold greater incidence of testicular cancer compared to the general population. Patients and physicians should be aware that one of the causes of infertility could be cancer, particularly testicular cancer.

Adult↗

Herniorrhaphy with polypropylene mesh causing inguinal vasal obstruction: a preventable cause of obstructive azoospermia.

OBJECTIVE: To report a multiinstitutional experience of men presenting with infertility secondary to inguinal hernia repair using polypropylene mesh. SUMMARY BACKGROUND DATA: An estimated 80% of inguinal hernia operations involve placement of a knitted polypropylene mesh to form a "tension-free" herniorrhaphy. The prosthetic mesh induces a chronic foreign-body fibroblastic response creating scar tissue that imparts strength to the floor and leads to fewer recurrences. However, little is known about the long-term effects of the polypropylene mesh on the vas deferens, especially with regard to fertility. METHODS: Eight institutions in the United States reported a total of 14 cases of azoospermia secondary to inguinal vasal obstruction related to previous polypropylene mesh herniorrhaphy. Patient characteristics and operative findings were forwarded to 1 center for tabulation of data. RESULTS: Mean patient age was 35.5 years with an average duration of infertility of 1.8 years. Mean number of years between urologic evaluation and herniorrhaphy was 6.3 years. Types of inguinal hernia repair previously performed were: open (10), laparoscopic (2), or both (2). Nine patients had bilateral obstruction and 5 patients had unilateral obstruction with contralateral testicular atrophy or epididymal obstruction. Surgical exploration revealed a dense fibroblastic response encompassing the polypropylene mesh with either trapped or obliterated vas in all patients. Surgical reconstruction was performed in 8 of 14 men (57%). CONCLUSION: Reconstruction to restore fertility can be difficult secondary to fibrotic reaction. Before undergoing polypropylene mesh herniorrhaphy, men, especially of young reproductive age or with a solitary testicle, need to be carefully advised of potential obstruction and compromise to future fertility.

Adult↗

Managing varicoceles in children: results with microsurgical varicocelectomy.

UNLABELLED: Authors from New York present their experience of elective varicocelectomy, using microsurgical techniques, in a large series of children. They found the procedure to be safe and effective, and gave a much lower complication rate than the published rate in open varicocelectomy. The results of urethroplasty in post-traumatic paediatric urethral strictures are presented by authors from Mansoura. They found the overall success of one-stage perineal anastomotic repair of such strictures to be excellent, with very little morbidity. OBJECTIVE: To report our experience of microsurgical subinguinal varicocelectomy in boys aged < or = 18 years. PATIENTS AND METHODS: Boys aged < or = 18 years treated with microsurgical varicocelectomy between 1996 and 2000 at one institution were retrospectively reviewed. Indications for surgery included ipsilateral testicular atrophy, large varicocele or pain. Microsurgery was assisted by an operating microscope (x10-25) allowing preservation of the lymphatics, and the testicular and cremasteric arteries. Patient age, varicocele grade, complications and follow-up interval were recorded. RESULTS: In all there were 97 microsurgical subinguinal varicocelectomies (23 bilateral) in 74 boys (mean age 14.7 years). Left-sided varicoceles were significantly larger (mean grade 2.9) than right-sided (mean grade 1.4) varicoceles. The mean follow-up was 9.6 months. There were four complications: two hydroceles, of which one resolved spontaneously after 4 months; one patient had persistent orchialgia that resolved after 8 months; and one developed hypertrophic scarring at the inguinal incision site. There were no infections, haematomas or intraoperative injuries to the vas deferens or testicular arteries. All boys were discharged home on the day of surgery. CONCLUSIONS: Microsurgical subinguinal varicocelectomy in boys is a safe, minimally invasive and effective means of treating varicoceles. Compared with published results of the retroperitoneal mass ligation technique, which has a 15% overall complication rate and a 7-9% hydrocele occurrence rate, the microsurgical subinguinal approach appears to offer less morbidity, with a 1% hydrocele rate. We consider that microsurgical subinguinal varicocelectomy offers the best results with lower morbidity than other techniques.

Adolescent↗

Prospective analysis of outcomes after microsurgical intussusception vasoepididymostomy.

OBJECTIVE: To prospectively analyse the outcomes of microsurgical vasoepididymostomy using the intussusception technique, as vasoepididymostomy is considered the most challenging reconstructive microsurgery in urology. PATIENTS AND METHODS: From 1998 to 2003, of 324 men with obstructive azoospermia who had undergone microsurgical reconstruction of the reproductive tracts, 68 (21%) had intussusception vasoepididymostomy bilaterally or unilaterally in a functionally solitary testis. The outcomes of these patients were analysed prospectively. RESULTS: The mean age was 39.8 years for the men and 31.8 years for their partners. The causes of obstruction were after vasectomy in 31%, infection in 22%, iatrogenic in 19%, trauma in 1.5%, and idiopathic in 27%. The median duration of obstruction was 18.8 years; 37% of patients had had previous failed attempts at reconstruction. The mean (range) follow-up was 15.2 (1-36) months. The overall patency (>10 000 sperm/mL) rate was 84% (53/63). Patency was achieved in 60% (38/63) of men at 1 month after surgery. The mean best sperm count was 12.8 (0.01-80) x 10(6)/mL, with a 21 (0-30)% motility. Among patients with a follow-up of > 1 year, the natural paternity rate was 40%. The median time to achieve a natural pregnancy was 14.3 (3-30) months. Pregnancy was achieved with in vitro fertilization or intracytoplasmic sperm injection in 31% of cases, all using fresh ejaculated sperm. CONCLUSIONS: A favourable patency and pregnancy rate can be achieved using microsurgical intussusception vasoepididymostomy. Even when assisted-reproductive technology is needed, fresh ejaculated sperm can be used without requiring a subsequent sperm retrieval procedure. Thus, microsurgical reconstruction of the reproductive tract should be primary therapeutic method in cases of azoospermia from epididymal obstruction.

Adult↗

In vitro transfection of the human vas deferens using DNA-liposome and DNA-neutral lipid complexes.

OBJECTIVE: To transfect the human vas deferens in vitro. DESIGN: Prospective study, description of a procedure. SETTING: Research center and university hospital. PATIENT(S): Seven fertile men undergoing vasectomies or vasovasostomies. INTERVENTION(S): Human vas deferens pieces were transfected in vitro using the p-GeneGrip gene construction, which codifies for the green fluorescent protein (GFP). Lipofectamine or GenePorter were employed as gene vectors. MAIN OUTCOME MEASURE(S): After vas deferens epithelium transfection, we described the vas deferens foreign gene expression. Maximum transfection occurred in 14.7% of the vas deferens epithelial cells. After using GenePorter, we observed green fluorescent protein gene expression in 40% of samples, which occupied 9.86% of the epithelial area. After Lipofectamine treatment, transgene expression occurred in 33% of the samples and occupied 9.05% of the epithelial area. CONCLUSION(S): The human vas deferens epithelium has the potential to be modified by gene transfection.

DNA↗