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Biomedical subjects

Mark Sigman

Publications and source records attributed to Mark Sigman.

10 recordsLinked to original sources

Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effect of oral carnitine supplementation on the semen parameters of men with idiopathic asthenospermia. DESIGN: Prospective, randomized, double-blind placebo-controlled study. SETTING: Academic tertiary referral centers. PATIENT(S): Male patients presenting with infertility and with sperm motility of 10%-50% were selected. INTERVENTION(S): Patients were randomized to 24-week treatment arms of oral carnitine (2,000 mg L-carnitine and 1,000 mg L-acetyl-carnitine per day) or placebo. MAIN OUTCOME MEASURE(S): Sperm motility and total motile sperm counts at baseline, 12 weeks, and 24 weeks. Seminal plasma and sperm free, acetyl, and total L-carnitine levels at baseline and at week 24. RESULT(S): Twenty-one patients entered the study, with 12 patients in the carnitine arm and 9 in the placebo arm. There were no significant differences in baseline semen parameters between the carnitine and placebo arms. There was no statistically significant or clinically significant increase in motility or total motile sperm counts between baseline, 12 week, or 24 weeks in the carnitine or placebo arms. CONCLUSION(S): Carnitine supplementation demonstrated no clinically or statistically significant effect on sperm motility or total motile sperm counts in men with idiopathic asthenospermia.

Administration, Oral↗

The relationship between varicoceles and obesity.

PURPOSE: To determine if a relationship between weight and varicocele occurrence exists, the prevalence of varicoceles was determined in a population of patients presenting with infertility. MATERIALS AND METHODS: Records of 3,213 males presenting with infertility were examined. Patients underwent physical examinations for varicocele presence and grade. Body mass index was calculated. Patients were categorized as normal weight, overweight and obese using National Institutes of Health criteria. Means were compared with Student's t test. Frequencies were compared by chi-square analysis and statistical significance was considered at p < 0.05. RESULTS: A total of 1,093 (34%) patients had varicoceles. The mean body mass index of those without varicoceles was 28.5 (+/- 5.6) kg/cm2, which was greater than the body mass index of those with varicoceles (26.7 [+/- 4.0] kg/cm2) (p < 0.001). Varicocele frequency was calculated for each body mass index group. In the normal weight group (body mass index less than 25) 378 of 884 patients (43%) had varicoceles. In the overweight group (body mass index 25 to less than 30) 540 of 1,549 patients (35%) had varicoceles. In the obese group (body mass index 30 or greater) 175 of 780 patients (22%) had varicoceles (p < 0.001). Analysis comparing varicocele frequency based on varicocele grade per body mass index group was performed. Prevalence of varicocele decreased with increasing body mass index for all varicocele grades (p < 0.001). CONCLUSIONS: Prevalence of varicocele decreases with increasing body mass index. One explanation is increased adipose tissue preventing compression of the left renal vein. Another explanation is decreased detection due to adipose tissue in the spermatic cord. The decrease in varicocele prevalence as a function of body mass index regardless of varicocele grade suggests this explanation is less likely.

Body Mass Index↗

The diagnosis of azoospermia depends on the force of centrifugation.

OBJECTIVE: To determine the centrifugal force required to pellet sperm. DESIGN: Prospective, in vitro study. SETTING: Tertiary referral center. PATIENT(S): Men undergoing semen processing or postvasectomy semen analyses. INTERVENTION(S): In Phase I, postvasectomy semen samples were centrifuged at 600 x g, and the pellets were examined. Supernatants from samples with no visible sperm underwent repeat centrifugation at 1,000 x g; the supernatants were removed and centrifuged at 3,000 x g. Pellets from both centrifugations were examined. Phase II examined nonazoospermic semen that was divided into 3 aliquots and centrifuged at 500, 1,000, and 3,000 x g. The supernatants were examined for the presence of sperm. MAIN OUTCOME MEASURE(S): Sperm presence in centrifuged pellets or seminal supernatant. RESULT(S): Phase I: After centrifugation at 1,000 x g and 3,000 x g, sperm were noted in 12% and 0% of samples, respectively. Phase II: Sperm were noted in the supernatant in 100% of samples subjected to 500 x g and 1,000 x g, and in 92% of samples subjected to 3,000 x g centrifugation. CONCLUSION(S): If sperm are in the seminal plasma, they will also be present in the pellet following centrifugation at a force of 1,000 x g or greater. Semen samples that appear azoospermic upon initial wet mount microscopy should be centrifuged at a minimum of 1,000 x g for 15 minutes.

Centrifugation↗

The relationship between intravasal sperm quality and patency rates after vasovasostomy.

PURPOSE: Most surgeons examine the intravasal fluid at vasectomy reversal. Vasovasostomy is performed when sperm are identified in the intravasal fluid or when sperm are absent but the fluid is copious and clear. When sperm are absent and the intravasal fluid is not copious and clear, vasoepididymostomy is often performed. Frequently the intravasal fluid contains only fragments of sperm. This study examines patency rates after microsurgical vasovasostomy as a function of the quality of sperm in the intravasal fluid. MATERIALS AND METHODS: The records of patients who had undergone microsurgical vasovasostomy were reviewed. The intravasal fluid was examined and sperm quality was recorded as no sperm, sperm heads, sperm with short tails or whole sperm. Results of postoperative semen analyses were recorded. Patency rates and postoperative semen parameters were compared. RESULTS: A total of 53 patients satisfied the entrance criteria. Ages ranged from 25 to 53 (mean age 39). Mean obstructive interval was 9.9 years (range 1 to 20). Overall patency was 98% (52 of 53 cases). Patency rates were 95% for the group with sperm heads and 100% for whole sperm, sperm with short tails and absent sperm groups. Patency rates did not vary significantly as a function of intravasal sperm quality. CONCLUSIONS: Modern microsurgical techniques yield excellent patency rates. The presence of sperm parts compared to whole sperm does not adversely affect patency rates after vasovasostomy. Vasovasostomy should be performed if any sperm parts are identified in the intravasal fluid.

Adult↗

A new look at the medical management of infertility.

Effective therapies are available for the treatment of infertility owing to specific causes. Most hormonal imbalances can be readily identified and successfully treated. The treatment of men with unexplained idiopathic infertility remains difficult. The availability of a multitude of agents ranging from hormones to nutritional supplements emphasizes the fact that none are consistently effective. There is no good way to predict which patients will respond to a specific treatment. Idiopathic infertility may result from multiple discrete defects in sperm generation and maturation that are as yet unidentified. A better understanding of these defects will yield more effective treatment options and appropriate triage of patients to specific therapeutic regimens. Assisted reproductive techniques remain an option for patients with idiopathic male infertility; however, they are expensive and treat the female partner for a male problem. Multiple gestations and other complications are not infrequent. Initial management should be directed at improving the quality of semen to facilitate natural conception. Specific abnormalities should be corrected. If empiric pharmacologic therapy is to be used, treatment should last at least 3 to 6 months to incorporate a full 74-day spermatogenic cycle. The infertile couple should be advised of the inconsistent response to therapy and the low conception rate that may follow when compared with the results of ART. When empiric therapy is decided upon, antiestrogens may be used and are effective in a subset of patients. The authors prefer to use clomiphene citrate, 25 mg per day. The dose may be increased to 50 or 75 mg to raise testosterone levels to the upper normal range. Lack of a significant improvement in semen parameters or of a pregnancy after a 3- to 6-month treatment period may be an indication to proceed with ART.

Fertility Agents, Male↗

Gonadotropin-releasing hormone antagonist (Cetrorelix) therapy fails to protect nonhuman primates (Macaca arctoides) from radiation-induced spermatogenic failure.

Treatment of men of reproductive age with radiation or alkylating agents often produces prolonged azoospermia. We previously demonstrated that suppression of testosterone (T) with gonadotropin-releasing hormone (GnRH) analogs restored spermatogenesis following atrophy induced by radiation or chemotherapy in rats. This study tested whether GnRH antagonist therapy could reverse radiation-induced testicular injury in primates with a similar protocol. Adult male stump-tailed macaques were given either 6.7 Gy radiation to the testis alone, 6.7 Gy radiation combined with GnRH-antagonist treatment starting on the day of exposure, or daily injections of the GnRH antagonist Cetrorelix for 3 months alone and were monitored for 18 months. Cetrorelix alone produced a 20-40-week fully reversible suppression of serum T, but although spermatogenic recovery was incomplete, 40%-90% of tubules contained differentiating germ cells. Following radiation alone, testis volumes were reduced to approximately 28% and sperm counts to less than 1% of pretreatment values. A biopsy at 18 months after radiation showed that only 3.0% of seminiferous tubule cross sections had germ cells. In irradiated animals that received GnRH antagonist, testis volumes were reduced to 18% of pretreatment volume, and at 18 months, only 1.9% of seminiferous tubule cross sections contained germ cells. Inhibin B values were reduced to 10% and 3% of pretreatment levels in the radiation-only and the radiation plus GnRH antagonist groups, respectively. Species differences exist in the testicular response to radiation, GnRH antagonist therapy, or both, so that rescue protocols that were successful in rodents might not work in primates.

Animals↗