The male biological clock is ticking: a review of the literature.

The term biological clock is usually used by physicians and psychologists to refer to the declining fertility, increasing risk of fetal birth defects and alterations to hormone levels experienced by women as they age. Female fecundity declines slowly after the age of 30 years and more rapidly after 40 and is considered the main limiting factor in treating infertility. However, there are several scientific reports, chapters in books and review articles suggesting that men may also have a biological clock. The aim of our study was to conduct a review of the literature, based on the Medical Literature Analysis and Retrieval System Online (Medline), to evaluate the male biological clock. After adjustments for other factors, the data demonstrate that the likelihood that a fertile couple will take more than 12 months to conceive nearly doubles from 8% when the man is < 25 years old to 15% when he is > 35 years old. Thus, paternal age is a further factor to be taken into account when deciding on the prognosis for infertile couples. Also, increasing male age is associated with a significant decline in fertility (five times longer to achieve pregnancy at the age of 45 years). Patients and their physicians therefore need to understand the effects of the male biological clock on sexual and reproductive health, in that it leads to erectile dysfunction and male infertility, as well as its potential implications for important medical conditions such as diabetes and cardiovascular diseases.

Testicular growth, sperm concentration, percent motility, and pregnancy outcome after varicocelectomy based on testicular histology.

OBJECTIVE: To evaluate the outcome following surgery in two different patterns of testicular histology in patients with varicocele. DESIGN: Prospective study. SETTING: Academic medical center. PATIENT(S): Sixty patients underwent varicocelectomy and had a testicular histology diagnosis of germ-cell aplasia (group I, n = 28) or maturation arrest (group II, n = 32). INTERVENTION(S): Varicocelectomy. MAIN OUTCOME MEASURE(S): Preoperative hormone levels, testicular size, and sperm parameters. After varicocelectomy, variations in testicular size, semen parameters, and pregnancy rates were evaluated. RESULT(S): The mean volume of the right and left testicle was smaller in group I patients than in group II. In addition, the mean sperm concentration before treatment was lower in group I than in group II. The mean volume of the left and right testicle increased in group I after the intervention. The mean postoperative sperm concentration and motility in group II showed no increase, whereas the mean sperm concentration in group I did increase. The pregnancy rate was higher in group II (14/26, 53.8%) than in group I (4/16, 25%) (P=.02). CONCLUSION(S): Patients with germ-cell aplasia present a postoperative increase in testicular size but the pregnancy rate is higher in patients with maturation arrest following surgery.

Semen profile, testicular volume, and hormonal levels in infertile patients with varicoceles compared with fertile men with and without varicoceles.

OBJECTIVE: To assess semen analysis, testicular volume, and hormone levels in fertile and infertile patients with varicoceles and fertile men without varicoceles. DESIGN: Retrospective study. SETTING: Academic medical center. PATIENT(S): Patients were divided into three groups: fertile men with varicoceles (n = 79), infertile men with varicoceles (n = 71), and fertile men without varicoceles (n = 217). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of LH, FSH, and total T and testicular volume in fertile and infertile men with varicoceles and fertile controls without varicoceles. RESULT(S): LH (IU/L) and T (ng/dl) levels were not statistically different across the three groups. FSH levels were significantly higher in infertile men with varicoceles (7.8 +/- 7.6 IU/L) than in the fertile men with varicoceles (3.5 +/- 2.1 IU/L) or in fertile men without varicoceles (3.5 +/- 1.9 IU/L). The right testicle was smaller in infertile patients with varicoceles (18.7 +/- 8.3 cm(3)) than in fertile men with varicoceles (25.2 +/- 13 cm(3)) or in fertile men without varicoceles (24.9 +/- 10.7 cm(3)). In addition, the left testicle was smaller in infertile men with varioceles (17.6 +/- 8.9 cm(3)) than in fertile men with varicoceles (21.6 +/- 7.8 cm(3)) or in fertile men without varicoceles (23.4 +/- 8.3 cm(3)). Sperm concentration was lower in infertile men with varicoceles (33.7 +/- 23.3 x 10(6)/mL) than in fertile men with varicoceles (101.8 +/- 76.6 x 10(6)/mL) or in fertile men without varicoceles (111.8 +/- 74.2 x 10(6)/mL). In addition, sperm motility was lower in infertile men with varicoceles (37.2% +/- 23.9%) than in fertile men with varicoceles (53.9% +/- 17.4%) or fertile men without varicoceles (58.9% +/- 15.8%). CONCLUSION(S): Infertile patients with varicoceles have higher levels of FSH, smaller testes, and lower sperm concentration and motility compared with controls with or without varicoceles. No statistical differences were seen in the variables evaluated among the fertile men with incidental varicoceles detected at physical examination and those without varicoceles.

Current concepts and future trends in male germ cell cryobanking.

While the idea of freezing human male gametes has been experimented since the late 1700's, it was not until 50 years ago that human sperm were frozen, and later thawed in such a way that they could fertilize an egg and initiate development. In the past several decades the technology of cryopreservation, or maintaining life in a frozen state, has advanced considerably. With the use of modern techniques, cryopreservation of sperm to preserve an individual's ability to reproduce has become successful, safe, and widely available. In the past several decades the technology of cryopreservation, or maintaining life in a frozen state, has advanced considerably preserving the ability of sperm to maintain its fertilizing potential.

The role of enzymatic antioxidants detected in the follicular fluid and semen of infertile couples undergoing assisted reproduction.

The follicular fluid environment surrounding the oocytes may play a critical role in fertilization and subsequent embryo development. The goal of our study was to evaluate the oxidative stress markers in the semen, blood serum, and follicular fluid of couples undergoing Intracytoplasmic Sperm Injection (ICSI). Two hundred and eight infertile couples underwent ICSI and the levels of superoxide dismutase (SOD) and catalase and lipid peroxidation (LPO) were evaluated. Semen Catalase was highly correlated with fertilization and cleavage rates, but not with pregnancy rates. Fertilization and cleavage rates were correlated with the levels of SOD and Catalase in the follicular fluid. After adjusting for age, a negative correlation was detected between LPO levels in follicular fluid and pregnancy rates. Follicular fluid LPO levels may be a marker as a metabolic activity within the follicle need for establishing a pregnancy.

Azoospermia after treatment with clomiphene citrate in patients with oligospermia.

OBJECTIVE: To describe three cases of azoospermia in patients with oligospermia after clomiphene citrate (CC) intake. DESIGN: Case report. SETTING(S): Academic medical center. PATIENT(S): Three patients with oligospermia. INTERVENTION(S): Three oligospermic men used CC, resulting in azoospermia. MAIN OUTCOME MEASURE(S): Semen analysis after CC use and after discontinuation of CC. RESULT(S): Three patients were sent to our clinic for investigation of their azoospermia after use of CC. They had severe oligozoospermia (sperm concentrations of 3.4, 2.8, and 4.1 x 10(6)/mL, respectively) before treatment with CC. These patients were re-evaluated with two new semen analyses, showing azoospermia. After 3 months without use of the drug, the mean sperm concentration was 2.5 +/- 1.1 x 10(6)/mL. CONCLUSION(S): The benefits of empiric treatment with CC must be balanced with the possible undesirable effects, such as azoospermia.

Effect of cigarette smoking on antioxidant levels and presence of leukocytospermia in infertile men: a prospective study.

OBJECTIVE: To evaluate the effect of cigarette smoking on antioxidant levels and the presence of leukocytospermia in infertile men. DESIGN: Prospective study. SETTING: Academic medical center. PATIENT(S): Ten fertile donors and 112 infertile patients were included in the study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis was performed according to the World Health Organization guideline. The activity of the superoxide dismutase was based on the adrenochrome concentration, and the catalase activity was determined by the velocity of hydrogen peroxide consumption. RESULT(S): Lower levels of superoxide dismutase and catalase were seen in infertile patients compared with fertile donors. Superoxide dismutase was significantly correlated with sperm concentration and negatively correlated with leukocytospermia. In addition, leukocytospermia was inversely correlated with sperm motility. Superoxide dismutase levels were negatively related to cigarette smoking. CONCLUSION(S): Cigarette smoking may impair sperm motility and decrease the antioxidant activity (negative correlation with superoxide dismutase) in the seminal plasma.

Induction of spermatogenesis in azoospermic men after varicocelectomy repair: an update.

OBJECTIVE: To assess the treatment outcome after varicocele repair in azoospermic men and to correlate this outcome with the testicular histology patterns. DESIGN: Prospective study. SETTING: Academic medical centers. PATIENT(S): Medical records of 27 azoospermic men, who underwent testis biopsy and microsurgical repair of clinical varicocele between July 1999 and May 2004, were reviewed. INTERVENTION(S): Twenty-seven azoospermic men underwent testis biopsy and microsurgical repair of clinical varicocele. All patients had at least two semen analyses showing azoospermia taken before the surgery and two semen analyses postoperatively. MAIN OUTCOME MEASURE(S): Semen analysis after varicocelectomy. RESULT(S): Hypospermatogenesis was identified in 9, maturation arrest in 8, and germ cell aplasia in 10 men. Induction of spermatogenesis was achieved in nine men (33.3%). Of these, four had germ cell aplasia, three had maturation arrest, and two had hypospermatogenesis. The improvement in sperm concentration and motility ranged from 1.2 x 10(6)/mL to 8.9 x 10(6)/mL, and from 24% to 75.7%, respectively. Of these nine patients with improvement in semen quality, five relapsed into azoospermia 6 months after the recovery of spermatogenesis (four germ cell aplasia and one maturation arrest). One patient with maturation arrest established pregnancy. CONCLUSION(S): Azoospermic patients may have an improvement in semen quality after varicocelectomy. Semen samples may be cryopreserved after an initial improvement after varicocelectomy.

Clinical diagnosis in men undergoing infertility investigation in a university hospital.

INTRODUCTION: It was the aim of this study to assess whether the changes in the diagnostic techniques and treatment modalities have altered the epidemiology of male factor infertility in the last decade. MATERIAL AND METHODS: From September 1999 to July 2003, 822 patients were evaluated for infertility in a University Hospital. We divided our infertility patients according to the clinical diagnosis. RESULTS: Most of the patients presented with varicocele (n = 282, 34.3%), idiopathic infertility (n = 260, 31.6%), or had had seminal tract obstruction (n = 85, 10.34%). Least common but equally important causes found were mumps (n = 43, 5.23%), pyospermia (n = 37, 4.5%), systemic diseases (n = 36, 4.37%), testicular failure (n = 34, 4.13%), cryptorchidism (n = 14, 1.7%), ejaculatory dysfunction (n = 11, 1.3%), genetics (n = 9, 1.1%), endocrinopathies (n = 4, 0.5%), testicular cancer (n = 4, 0.5%), and testicular torsion (n = 3, 0.36%). CONCLUSIONS: Even with the changes in reproductive healthcare in the last years, varicocele and seminal tract obstruction remain the leading causes of male infertility. However, clinicians should not forget other treatable causes of male infertility such as pyospermia, systemic diseases, or testicular cancer.

High percentage of abnormal semen parameters in a prevasectomy population.

OBJECTIVE: To evaluate semen characteristics, testicular volume, and hormonal levels of normal fertile men requiring vasectomy for sterilization. DESIGN: Retrospective study. SETTING(S): Academic medical centers. PATIENT(S): A total of 889 patients underwent a vasectomy for sterilization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen volume, sperm concentration, motility, and morphology according to the World Health Organization (WHO); complex motion parameters evaluated by computer-assisted semen analyzer; FSH, LH, and T levels; and both testicular volumes. RESULT(S): When compared with the WHO values, 87.2% of the patients presented normal sperm morphology below the normal level. The other semen parameters (semen volume, pH, sperm concentration, and sperm motility) differed from the WHO parameters in 6%-32.2% of patients. Semen volume and sperm concentration presented a progressive increase according to the duration of sexual abstinence. However, patients with 5 days or more of abstinence had a decrease in sperm motility. Mean testicular size had the strongest correlation with serum FSH levels, total sperm count, and sperm concentration. CONCLUSION(S): Low sperm motility and morphology were found in men who request a vasectomy for sterilization. Semen volume and sperm concentration present a progressive increase and sperm motility a decrease according to the duration of sexual abstinence. Sperm concentration had stronger correlations with testicular size than did sperm quality. Therefore, the WHO normal values need to be reconsidered.

Is it worthwhile to operate on subclinical right varicocele in patients with grade II-III varicocele in the left testicle?

PURPOSE: To determine whether repair of subclinical varicoceles in the right testicle results in significant seminal improvement in patients with clinical left varicocele. METHODS: Patients were divided into two groups: Group I (unilateral varicocelectomy) and Group II (bilateral varicocelectomy-subclinical left varicocele). The mean sperm concentration before treatment was higher in Group I (21.01 +/- 19.1) compared to Group II (5.7 +/- 10.7) (p = 0.04). RESULTS: An increase in volume was detected in the left testicle of patients in Group I (17 +/- 7.9 vs. 22.81 +/- 8.2; p = 0.04) and in the right testicle of patients in Group II (18.4 +/- 6.2 vs. 22.3 +/- 6.5; p = 0.04). Although the mean postoperative sperm concentration in Group I increased slightly (25.7 +/- 22.8), the mean sperm concentration in Group II increased significantly (30.32 +/- 9.8; p = 0.03). Pregnancy rate was higher in Group II (66.7%) compared to Group I (33.3%). CONCLUSIONS: Even a small, subclinical unrepaired varicocele continues to have a detrimental effect on bilateral testis function in a patient with grade II-III left varicocele.

Relationship between the number of veins ligated in a varicocelectomy with testicular volume, hormonal levels and semen parameters outcome.

PURPOSE: Correlate semen analysis, hormones, and testicular volume with the number of veins ligated. METHODS: Patients were divided into three groups: Group 1 (< or = 5 veins), Group 2 (6-10 veins), and Group 3 (> 10 veins). We evaluated testicular volume, hormonal levels, sperm concentration, and motility before and after the surgical procedure. RESULTS: In Group 1, even though there was an improvement in both testicular volume and sperm concentration; testosterone levels and sperm motility did not improve with surgery. In Group 2, no changes were detected in the both testicular volumes, in sperm concentration, motility, and testosterone levels. In Group 3, an improvement was seen in the right testicle volume, testosterone levels, and sperm concentration. Follicle-stimulating hormone levels decreased following the surgical procedure in all groups. CONCLUSION: Patients with more than 10 ligated veins have better chances to improve sperm concentration. FSH levels decreased in all groups of patients.

The best infertility treatment for vasectomized men: assisted reproduction or vasectomy reversal?

In men with prior vasectomy, microsurgical reconstruction of the reproductive tract is more cost-effective than sperm retrieval with in vitro fertilization and intracytoplasmic sperm injection if the obstructive interval is less than 15 years and no female fertility risk factors are present. If epididymal obstruction is detected or advanced female age is present, the decision to use either microsurgical reconstruction or sperm retrieval with in vitro fertilization and intracytoplasmic sperm injection should be individualized. Sperm retrieval with in vitro fertilization and intracytoplasmic sperm injection is preferred to surgical treatment when female factors requiring in vitro fertilization are present or when the chance for success with sperm retrieval and intracytoplasmic sperm injection exceeds the chance for success with surgical treatment.

Risks and benefits of hormone replacement therapy in older men.

The use of testosterone in older men, known as male hormonal replacement therapy or androgen replacement therapy, has become of increasing interest to both the medical and lay communities over the past decade. Even though the knowledge of the potential benefits and risks of male Androgen Replacement Therapy has increased dramatically, there is still much that needs to be determined. Although there are a number of potential benefits of male Androgen Replacement Therapy and data concerning clinical effects of such replacement have accumulated, as yet there have not been any large multicenter randomized controlled trials of this therapy. It is the purpose of this article to review what is currently known about the possible risks and benefits of male Androgen Replacement Therapy by discussing the clinical trials to date.

Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertility.

Infertility affects up to 15% of the sexually active population, and in 50% of cases, a male factor is involved, either as a primary problem or in combination with a problem in the female partner. Because many commonly encountered drugs and medications can have a detrimental effect on male fertility, the medical evaluation should include a discussion regarding the use of recreational and illicit drugs, medications, and other substances that may impair fertility. With the knowledge of which drugs and medications may be detrimental to fertility, it may be possible to modify medication regimens or convince a patient to modify habits to decrease adverse effects on fertility and improve the chances of achieving a successful pregnancy. Concern is growing that male sexual development and reproduction have changed for the worse over the past 30 to 50 years. Although some reports find no changes, others suggest that sperm counts appear to be decreasing and that the incidence of developmental abnormalities such as hypospadias and cryptorchidism appears to be increasing, as is the incidence of testicular cancer. These concerns center around the possibility that our environment is contaminated with chemicals--both natural and synthetic--that can interact with the endocrine system.

Detection of testicular cancer in men presenting with infertility.

PURPOSE: Infertility is one of the less common presenting features associated with testicular tumors. We evaluated the histologic and biochemical findings, and pregnancy outcome in patients presenting with infertility who were found to have testicular tumors. METHODS: Seven patients with infertility were found to have testicular cancer over a 15-year period. All patients had a testicular ultrasound evaluation. The indications for the ultrasound were testicular pain in 2 patients, suspicious palpable mass in 4, and to rule out the presence of germ cell neoplasia in a patient with carcinoma in situ detected on a previous biopsy. Physical exam, histological findings, hormonal levels, tumor markers, and pregnancy outcome results were recorded from the patients medical charts. RESULTS: Two men had elevated serum follicle stimulant hormone and luteinizing hormone levels, 1 of them had an abnormally low serum testosterone level. Tumor markers were normal in all patients. In 4 patients the tumor was on the right side and in 3 on the left. The histological diagnoses were seminoma (n = 5), Leydig cell tumor (n = 1), and carcinoma in situ (n = 1). Of the 7 patients, 5 underwent adjuvant radiation therapy. Two patients had sperm cryopreserved. Follow up on fertility status was available in 6 cases. One patient has established a pregnancy and 5 did not achieve a pregnancy after treatment for their cancer. CONCLUSIONS: Most of the men who have testicular cancer and male infertility have a seminona. Therefore, men who present with infertility should be thoroughly investigated to rule out such serious, concomitant diseases along with their infertility.

Trends in male contraception.

Methods that are available for male contraception, namely coitus interruptus, condoms, and vasectomy, have been used since the 19th century. With the exceptions of a few improvements of these methods, no major progress has been made with respect to introducing new male contraceptives since then. It is extremely urgent to develop new, safe, effective, and reversible male contraceptive methods. Among all male contraceptive methods that are being investigated, the hormonal approach is the closest to clinical application. Hormonal contraception provides pregnancy protection by means of spermatogenic suppression. Androgen-progestin regimens currently represent the best available hormonal combination for induction of a profound suppression of spermatogenesis. Further development of new steroids is mandatory for increasing the choices of available contraceptive formulations and to optimize long-term safety of these regimens.

Results of microsurgical anastomosis in men with seminal tract obstruction due to inguinal herniorrhaphy.

UNLABELLED: The incidence of vasal injury during inguinal herniorrhaphy is estimated at 0.5%. We sought to assess the patency rates and long-term fertility outcome after microsurgical repair of vasal obstruction related to prior inguinal herniorrhaphy. METHODS: Twenty procedures were performed on 13 men diagnosed with infertility and vasal injury secondary to previous inguinal herniorrhaphy. Eight of these men had undergone bilateral and 5 unilateral inguinal herniorrhaphy. Twelve procedures were vasovasostomies, 3 were crossover vasovasostomies, 2 were vasoepididymostomies, and 3 were crossover vasoepididymostomies. Eight patients were azoospermic, 2 were severely oligospermic (<1 M/mL), 1 was oligospermic, and 2 were asthenospermic. Patency data was obtained on all 13 patients, and pregnancy data was available for 10 couples (77%), with a mean follow-up of 69.5 months. RESULTS: The overall patency rate was 65%. In the vasovasostomy group, the patency rate was 60% (9/15), and in the vasoepididymostomy group it was 80% (4/5). Among the azoospermic patients, 13 procedures were performed. The patency rate was 42.9% for the vasovasostomy (3/7), and 100% for the vasoepididymostomy procedure (4/4). The overall pregnancy rate was 40%. Of the men who underwent vasoepididymostomy, 80% (4/5) established a pregnancy. CONCLUSIONS: Microsurgical vasovasostomy after inguinal vas injury results in a reasonable patency rate but a lower pregnancy rate than that after vasectomy reversal. When microsurgical vasoepididymostomy was possible, it resulted in high patency and pregnancy rate. Crossover vasoepididymostomy, when appropriate, can be a useful alternative to inguinal vasovasostomy.

The male biological clock is ticking: a review of the literature / O relógio biológico masculino está batendo: revisão da literatura

The term biological clock is usually used by physicians and psychologists to refer to the declining fertility, increasing risk of fetal birth defects and alterations to hormone levels experienced by women as they age. Female fecundity declines slowly after the age of 30 years and more rapidly after 40 and is considered the main limiting factor in treating infertility. However, there are several scientific reports, chapters in books and review articles suggesting that men may also have a biological clock. The aim of our study was to conduct a review of the literature, based on the Medical Literature Analysis and Retrieval System Online (Medline), to evaluate the male biological clock. After adjustments for other factors, the data demonstrate that the likelihood that a fertile couple will take more than 12 months to conceive nearly doubles from 8 percent when the man is < 25 years old to 15 percent when he is > 35 years old. Thus, paternal age is a further factor to be taken into account when deciding on the prognosis for infertile couples. Also, increasing male age is associated with a significant decline in fertility (five times longer to achieve pregnancy at the age of 45 years). Patients and their physicians therefore need to understand the effects of the male biological clock on sexual and reproductive health, in that it leads to erectile dysfunction and male infertility, as well as its potential implications for important medical conditions such as diabetes and cardiovascular diseases.

O termo relógio biológico é geralmente usado por médicos e psicólogos para se referir ao declínio da fertilidade, aumento no risco de defeitos congênitos, e níveis hormonais alterados que a mulher com o passar dos anos apresenta. A fecundidade feminina declina paulatinamente após os 30 anos e mais rapidamente após os 40 anos e é considerada como o principal fator limitante nos tratamentos da infertilidade. Entretanto, existem vários artigos científicos capítulos de livros e artigos de revisão sugerindo que o homem também apresente um relógio biológico. O objetivo do nosso estudo foi realizar uma revisão no Medline (Medical Literature Analysis and Retrieval System Online) para avaliar o relógio biológico masculino. Após ajustar para outros fatores, foi demonstrado que a probabilidade de um casal apresentar uma demora superior a 12 meses para engravidar praticamente duplica de 8 por cento quando o homem possui idade inferior a 25 para 15 por cento quando possui idade superior a 35 anos; desta forma, a idade paterna é um fator a ser levado em consideração quando se decidir sobre o prognóstico de um casal infértil. Além disso, a idade avançada está associada com um declínio significante na fertilidade (tempo para engravidar superior a cinco vezes aos 45 anos de idade), sendo independente de idade da parceira, freqüência de relação sexual e estilo de vida, assim como os efeitos de outros fatores de risco para subfertilidade. Os pacientes e seus médicos devem entender os efeitos do relógio biológico na saúde sexual e reprodutiva, levado à disfunção erétil e infertilidade, assim como às potenciais contribuições para condições médicas como diabetes e doenças cardiovasculares.