Marc Goldstein

Loss of fertility in men with varicocele

OBJECTIVE To test the hypothesis that men with varicocele who have already fathered children are immune to the detrimental effect of varicocele on their fertility and will continue to be fertile. If this were the case, one would expect a very low incidence of varicocele in currently infertile men who were able to father a child in the past (secondary infertility) compared with men who have never been fertile (primary infertility). DESIGN Survey of men with male factor infertility. SETTING Tertiary care university medical center. PATIENTS One thousand ninety-nine infertile men of whom 98 (9%) met our criteria for secondary infertility. Men with prior vasectomy and men whose partners were over age 40 were excluded. MAIN OUTCOME MEASURE Difference in the incidence of varicocele in men with secondary infertility versus primary infertility. RESULTS A varicocele was palpable in 35% (352/1,001) of men with primary infertility and 81% (79/98) of men with secondary infertility. This difference in the incidence of varicocele was highly significant. Men with secondary infertility and varicocele were slightly older (37.9 versus 33.5 years), had a lower mean sperm concentration (30.2 versus 46.1 x 10(6)/mL), more abnormally shaped sperm (72% versus 40%), and higher mean serum follicle-stimulating hormone levels (17.6 versus 7.9 mIU/mL,) compared with men with primary infertility and varicocele. CONCLUSIONS The incidence of varicocele is much higher in male factor secondary infertility compared with primary infertility. These findings suggest that varicocele causes a progressive decline in fertility and that prior fertility in men with varicocele does not predict resistance to varicocele induced impairment of spermatogenesis. Men with a varicocele may benefit from early evaluation and prophylactic varicocelectomy to prevent future infertility.

Microsurgical Inguinal Varicocelectomy With Delivery of the Testis: An Artery and Lymphatic Sparing Technique

Conventional techniques of varicocele repair are associated with substantial risks of hydrocele formation, ligation of the testicular artery, and varicocele recurrence. We describe a microsurgical technique of varicocelectomy that significantly lowers the incidence of these complications. The testicle is delivered through a 2 to 3 cm. inguinal incision, and all external spermatic and gubernacular veins are ligated. The testis is returned to the scrotum and the spermatic cord is dissected under the operating microscope. The testicular artery and lymphatics are identified and preserved. All internal spermatic veins are doubly ligated with small hemoclips or 4-zero silk and divided. The vas deferens and its vessels are preserved. Initially, we performed 33 conventional inguinal varicocelectomies in 24 men without delivery of the testis or use of a microscope. Postoperatively, 3 unilateral hydroceles (9%) and 3 unilateral recurrences (9%) were detected. For the next 12 cases 2.5x loupes were used resulting in no hydroceles but another recurrence (8%). We then performed 640 varicocelectomies in 429 men using the microsurgical technique with delivery of the testis. Among 382 men available for followup examination from 6 months to 7 years postoperatively no hydroceles and no cases of testicular atrophy were found. A total of 4 unilateral recurrent varicoceles (0.6%) was identified. The differences between the techniques in the incidence of hydrocele formation and varicocele recurrence are highly significant (p < 0.001). No wound infections occurred in any men. Four scrotal hematomas (0.6%), 1 of which required surgical drainage, occurred in the group with microsurgical ligation and delivery of the testis compared to none with the conventional technique. Preoperative and postoperative semen analyses (mean 3.57 analyses per patient) were obtained on 271 men. The changes in sperm count x 10(6) cc (36.9 to 46.8, p < 0.001), per cent motility (39.6 to 45.7%, p < 0.001) and per cent normal forms (48.4 to 52.10%, p < 0.001) were highly significant. The pregnancy rate was 152 of 357 couples (43%) followed for a minimum of 6 months postoperatively. Delivery of the testis through a small inguinal incision provides direct visual access to all possible avenues of testicular venous drainage. The operating microscope allows identification of the testicular artery, lymphatics and small venous channels. This minimally invasive, outpatient technique results in a significant decrease in the incidence of hydrocele formation, testicular artery injury and varicocele recurrence.

Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia

OBJECTIVES To provide fertility for men with nonobstructive azoospermia. METHODS A retrospective review of treatment results at a university infertility center was undertaken. Sixteen couples entered an attempted in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) cycle for treatment of nonobstructive azoospermia. Each man was azoospermic, and the male factor diagnosis of nonobstructive azoospermia was made on testis biopsy for 14 men and on clinical grounds for 2 men. Sperm were retrieved by testicular biopsy on the day of oocyte retrieval. Results of testicular examinations, serum follicle-stimulating hormone levels, and testicular histology as well as evaluation of the success rates of sperm retrieval, fertilizations, and pregnancies were made. RESULTS Sperm were extracted from testis biopsies in 10 of 16 (62%) testicular sperm extraction (TESE) attempts. For cycles in which sperm were retrieved, normal fertilizations were achieved for 51 of 98 (52%) mature oocytes injected with testicular sperm in 10 couples. Biochemical pregnancies were achieved for 6 of 16 (38%) couples, with clinical pregnancies during 5 of 16 (31%) attempts at sperm retrieval, and ongoing pregnancy and subsequent live delivery for 4 of 16 (25%) attempts. CONCLUSIONS; Pretreatment clinical parameters are unable to predict which men with nonobstructive azoospermia will have spermatozoa retrieved by TESE. When sperm are found, clinical pregnancies can occur for half (5/10) of these couples using TESE with ICSI, with ongoing pregnancy and delivery for 4 of 10 (40%). Many men with nonobstructive azoospermia will have retrievable sperm with testis biopsy that are suitable for ICSI; however, 6 of 16 (38%) couples will not have sperm retrieved with TESE and may undergo an unnecessary IVF procedure.

Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe oligoasthenospermia

OBJECTIVE To characterize treatment outcome after varicocele repair in men with azoospermia and severe oligoasthenospermia. DESIGN Prospective nonrandomized study. SETTING University-based medical center. PATIENT(S) Seventy-eight men with a palpable varicocele and absolute azoospermia (n = 22) or severe oligoasthenospermia (n = 56). INTERVENTION(S) Microsurgical varicocelectomy. MAIN OUTCOME MEASURE(S) Sperm count and pregnancy rate. RESULT(S) Twelve (55%) of the 22 men with azoospermia and 35 (69%) of the 51 men with zero motile sperm before surgery had motile sperm observed in their ejaculate after varicocele repair. The total number of motile sperm per ejaculate increased from 0.08 +/- 0.02 x 10(6) before varicocelectomy to 7.2 +/- 2.3 x 10(6) afterward. Twenty-four men (31%) contributed to pregnancies leading to live births (15 unassisted [19%]), including 3 men with azoospermia preoperatively. CONCLUSION(S) Varicocele repair resulted in the induction or enhancement of spermatogenesis for most men with azoospermia or severe oligoasthenospermia. Unassisted pregnancies after varicocele repair in men with profound abnormalities of spermatogenesis are possible. Varicocele repair should be considered for all men with azoospermia and severe oligoasthenospermia.

Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia: testicular histology can predict success of sperm retrieval.

PURPOSE We present treatment results of testicular sperm extraction with intracytoplasmic sperm injection for men with nonobstructive azoospermia and reevaluate the role of testicular histology on open diagnostic testicular biopsy as a predictor of sperm retrieval success. MATERIALS AND METHODS We evaluated 75 men diagnosed with nonobstructive azoospermia. Cases were categorized into 3 groups of hypospermatogenesis, maturation arrest or Sertoli-cell-only based on the most advanced pattern of spermatogenesis seen on histology. A total of 81 testicular sperm extractions with intracytoplasmic sperm injection were performed for these 75 men. The main outcome measures reviewed included sperm retrieval, fertilization and pregnancy rates with intracytoplasmic sperm injection. Sperm retrieval success rates for men in the 3 histological categories were compared. RESULTS Spermatozoa were successfully retrieved during 47 of 81 (58%) testicular sperm extraction attempts, with subsequent fertilization of 268 of 439 (61%) injected metaphase II oocytes using intracytoplasmic sperm injection. Clinical pregnancies were obtained in 26 of 47 (55%) cycles when sperm were retrieved, with ongoing pregnancies or live deliveries for 20 of 47 (43%). Of 39 men with hypospermatogenesis on diagnostic biopsy 31 (79%) had successful sperm retrieval, compared to 9 of 19 (47%) with maturation arrest and 5 of 21 (24%) with a pure Sertolicell-only pattern. CONCLUSIONS Critical examination of the most advanced pattern of spermatogenesis from open diagnostic testis biopsy allows prediction of sperm retrieval success with testicular sperm extraction. In this study population spermatozoa were retrieved in 58% of attempts. When this testicular sperm was used with intracytoplasmic sperm injection, clinical pregnancy rate was 55% for men with nonobstructive azoospermia.

Elevation of Intratesticular and Scrotal Skin Surface Temperature in Men with Varicocele

A possible mechanism of varicocele-induced infertility is believed to be elevation of testicular temperature. Sensitive needle thermistors were used to measure directly intratesticular and bilateral scrotal surface temperatures simultaneously in anesthetized infertile men with varicocele and control subjects. We found that intratesticular temperature is elevated significantly in humans with varicocele. In addition, we have shown that scrotal skin surface temperature is elevated in men with varicocele. Furthermore, we demonstrate that unilateral varicocele is associated with bilateral elevation of scrotal surface temperature. These findings confirm the results of animal studies revealing elevation of intratesticular temperature associated with varicocele and suggest bilateral elevation in unilateral varicocele.

Relationship between varicocele size and response to varicocelectomy

We studied the relationship between varicocele size and response to surgery in 86 men with a unilateral left varicocele who reported either infertility (83), pain (1) or pain and testicular atrophy (2). Varicoceles were graded according to size: grade 1--small (22 patients), grade 2--medium (44) and grade 3--large (20). Sperm count, per cent motility, per cent tapered forms and fertility index (sperm count times per cent motility) were measured preoperatively and postoperatively. Preoperatively, men with grade 3 varicocele had lower sperm counts and poorer fertility indexes compared to men with grades 1 and 2 varicocele. Sperm concentration improved significantly in men with grade 2 (33 +/- 5 million per cc preoperatively to 41 +/- 6 million postoperatively, p < 0.04) and grade 3 (18 +/- 5 million preoperatively to 32 +/- 7 million postoperatively) varicocele after microsurgical ligation of the varicocele. Motility improved significantly in men with grade 3 varicocele. Decrease in per cent tapered forms was significant in all groups. A comparison of per cent change in fertility index among the groups revealed that men with grade 3 varicocele improved to a greater degree (128%) than men with grade 1 (27%) or grade 2 (21%) varicocele. Pregnancy rates 2 years postoperatively were 40% for grade 1, 46% for grade 2 and 37% for grade 3 varicocele patients. The difference in pregnancy rates among the groups was not statistically significant. In conclusion, infertile men with a large varicocele have poorer preoperative semen quality but repair of the large varicocele in those men results in greater improvement than repair of a small or medium sized varicocele.

The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles

PURPOSE We evaluated the effect of varicocelectomy on serum testosterone. MATERIALS AND METHODS We retrospectively reviewed the effect of varicocelectomy on serum testosterone levels in 53 infertile men with varicoceles. RESULTS Mean serum testosterone increased from a preoperative level of 319 +/- 12 to 409 +/- 23 ng./dl. postoperatively (p < 0.0004). Men with at least 1 firm testis preoperatively had a greater increase in serum testosterone (p < 0.005). An inverse correlation was noted between preoperative testosterone levels and change in testosterone after varicocelectomy (r = -0.34, p < 0.013). CONCLUSIONS Varicocelectomy can increase serum testosterone for infertile men with varicoceles. Although improvement in serum testosterone does not necessarily cause a direct improvement in semen quality, varicocelectomy may improve hormonal and spermatogenic function.

Urogenital Anomalies in Men with Congenital Absence of the Vas Deferens

PURPOSE We evaluated urogenital anomalies in men with congenital absence of the vas deferens. METHODS AND MATERIALS A retrospective review was done of 104 subfertile men with congenital absence of the vas deferens (84 bilaterally and 20 unilaterally). RESULTS Of men with unilateral or bilateral congenital absence of the vas deferens 26 and 11%, respectively, had renal agenesis. Of men with unilateral congenital absence of the vas deferens and infertility 80% had genitourinary anamalies affecting the contralateral testis. No man with congenital absence of the vas deferens and renal anomalies had cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations detected. CONCLUSIONS Other urogenital anomalies are common for men with congenital absence of the vas deferens. CFTR gene mutations frequently contribute to maldevelopment of the vas deferens but vasal agenesis can occur without any evidence of CFTR defects. CFTR abnormalities are rarely detected in men with congenital absence of the vas deferens and renal anomalies.

The No-Scalpel Vasectomy

Physicians in China have developed a new technique to perform vasectomies which improves mens acceptance of vasectomy. It is called no-scalpel vasectomy. Before performing the vasectomy, the surgeon should determine whether the patient is indeed interested in permanent sterilization. The surgeon should also gather information on patients age, marital status, and medical history and perform a physical examination. Counseling should consist of clear, simple language to diminish any fears. The surgeon must inform the patient of alternative nonpermanent means of contraception and stress that vasectomy is essentially irreversible. 2 physicians recommend external spermatic fascia injection using 2-3 ml of 2% plain lidocaine to induce vasal nerve blockage. After properly fixing the vas deferens with a ring clamp, the surgeon pierces the scrotal skin, vas sheath, and vas deferens in the midline with a curved dissecting clamp held at a 45 degree angle from horizontal. The surgeon then rotates the clamp 180 degrees to prepare the vas for cutting. The surgeon cuts out a 1 cm segment and then occludes the ends of the vas. The vas is then returned to the scrotal sac via the same puncture hole. No sutures are needed for the puncture hole. The same procedure is followed for the other vas. Hands-on training requires 10-15 procedures to develop proficiency. The no-scalpel technique takes about 40% less time than conventional techniques. The complication rate for the no-scalpel technique is 0.4 events/100 procedures compared to 3.1/100 procedures for conventional techniques. Both the ring clamp and dissecting clamp were developed in China. These instruments are provided through a company in Georgia and through the Association for Voluntary Surgical Contraception (AVSC). AVSC helps medical institutions coordinate physician training of the no-scalpel technique.