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PubMed1985

The relationship of semen parameters to fertilization in patients participating in a program of in vitro fertilization.

Approximately 80% of the patients in a program of in vitro fertilization (IVF) will fertilize an oocyte. The purpose of this study was to determine which parameters of the semen analysis influence fertilization in vitro. Of 120 patients participating in an in vitro fertilization program, 98 achieved fertilization of at least one mature oocyte and 22 did not. Ovulation induction was standardized and patients whose sperm was exposed to at least one mature oocyte (by light microscopy) were included in the study. Semen washing was accomplished using a "swim-up" technique. Semen parameters were assessed both before (raw) and after washing. Following insemination with 100,000 motile sperm, fertilization was determined by the presence of pronuclei or cleavage. Mean sperm count and motility were higher in patients who fertilized. However, morphology was similar. Fertilization was more likely to occur with a raw density greater than 104 million/ml and a motility greater than 64%, as well as with a density greater than 18 million/ml and a motility greater than 86% following washing. Furthermore, washing lowered sperm counts by 75% and increased motility by 25% but had no effect on morphology. This study demonstrates that sperm count and motility, but not morphology, influence fertilization in a program of in vitro fertilization and that patients with higher counts and motility have a greater probability of fertilization.

Female↗
PubMed1988

Testosterone prevents complete suppression of spermatogenesis in the gonadotropin-releasing hormone antagonist-treated nonhuman primate (Macaca fascicularis).

We studied the effects of administration of a GnRH antagonist combined with testosterone (T) as an approach to male contraception as well as the role of intratesticular androgens in spermatogenesis using a nonhuman primate model. Three groups of five adult cynomolgus monkeys (Macaca fascicularis) received daily sc injections of 420-460 micrograms/kg GnRH antagonist ([Ac-D2Nal1,D4ClPhe2,DPal3,Arg5,DGlu6(AA), DALa10]GnRH) for a period of 15 weeks. T supplementation, commencing on the first day of GnRH antagonist administration, was provided by single im injection of 40 mg (group 2) or 200 mg (group 3) of the long-acting testosterone ester testosterone-trans-4-n-butylcyclohexancarboxylate (20-Aet-1). Serum LH bioactivity was undetectable within 1 week of GnRH antagonist administration in all monkeys. GnRH antagonist administration alone (group 1) reduced serum T levels into the castrate range. Forty milligrams of 20-Aet-1 maintained serum T levels in the upper range of normal monkeys, while 200 mg 20-Aet-1 maintained serum T levels about 1.5-fold above normal. The response to electroejaculation was fully maintained in all T-treated monkeys. Sperm counts in the ejaculates dropped to zero among group 1 animals within 7-10 weeks of GnRH antagonist administration. In groups 2 and 3 consistent azoospermia could not be induced, and the sperm counts were significantly (P less than 0.05) higher in group 3 than in group 2. Histologically, spermatogenesis in group 1 was arrested at the spermatogonial level in 75% of seminiferous tubules. In group 2, spermatogenesis proceeded to spermatocytes in 50% of tubules and to elongated spermatids in 10% of tubules, while in group 3 elongation of spermatids occurred in 75% of tubules. The mean T and dihydrotestosterone concentrations in baseline testicular biopsies (n = 15) were 43.8 +/- 6.8 (+/- SE) and 5.7 +/- 1.5 ng/g, respectively. After GnRH antagonist with or without T administration, the mean (n = 15) intratesticular T and dihydrotestosterone levels were reduced to 20.3 +/- 4.9 and 3.2 +/- 0.5 ng/g, respectively, and differed little among the three groups. No correlation, however, could be established between testicular androgen levels and spermatogenic status (P greater than 0.30) or sperm counts (P greater than 0.60). These results demonstrate that administration of a GnRH antagonist in the presence of constant serum T levels does not induce consistent azoospermia, and that the supporting effects of T on spermatogenesis cannot be explained exclusively on the basis of the testicular androgen concentrations.

Androgens↗
PubMed2000

Endocrine disruptors and human health--is there a problem? An update.

It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine-active compounds may be responsible for a global decrease in sperm counts, decreased male reproductive capacity, and breast cancer in women. Results of recent studies show that there are large demographic variations in sperm counts within countries or regions, and analyses of North American data show that sperm counts have not decreased over the last 60 years. Analyses of records for hypospadias and cryptorchidism also show demographic differences in these disorders before 1985; however, since 1985 rates of hypospadias have not changed and cryptorchidism has actually declined. Temporal changes in sex ratios and fertility are minimal, whereas testicular cancer is increasing in most countries; however, in Scandinavia, the difference between high (Denmark) and low (Finland) incidence areas are not well understood and are unlikely to be correlated with differences in exposure to synthetic industrial chemicals. Results from studies on organochlorine contaminants (DDE/PCB) show that levels were not significantly different in breast cancer patients versus controls. Thus, many of the male and female reproductive tract problems linked to the endocrine-disruptor hypothesis have not increased and are not correlated with synthetic industrial contaminants. This does not exclude an endocrine-etiology for some adverse environmental effects or human problems associated with high exposures to some chemicals.

Adult↗
PubMed1995

Evaluation of reproductive capacity in germ cell tumor patients following treatment with cisplatin, etoposide, and bleomycin.

PURPOSE: To evaluate the infertility rate in patients with germ cell tumors receiving chemotherapy with cisplatin, etoposide (VP-16), and bleomycin (PVP16B). PATIENTS AND METHODS: Thirty patients were evaluated. All patients had undergone chemotherapy with two to four cycles of PVP16B. A single semen analysis was performed 24 to 78 months following initiation of chemotherapy. All 30 patients were continuously disease-free. Eight of these patients had also undergone nerve-sparing retroperitoneal lymph node dissection (RPLND). RESULTS: The median sperm concentration was 33.9 x 10(6), with a median volume of 3.2 mL. The median total sperm count was 86.4 x 10(6). Oligospermia (< 40 x 10(6) total sperm count) was found in 13 patients (43%), including six (20%) who were azoospermic. There was a high incidence of morphologically abnormal sperm, with only one patient having more than 50% normal spermatozoa. Only 13 patients (43%) had sperm motility greater than 50%. Five patients had positive semen antisperm immunoglobulin G (IgG). Eight patients fathered children, including three with document oligospermia. CONCLUSION: Patients with germ cell tumors successfully treated with PVP16B chemotherapy are at substantial risk for persistent semen abnormalities. However, some patients with oligospermia will slowly recover and others are still capable of reproductive capacity despite continued oligospermia.

Adult↗
PubMedDate not supplied

Plasma and semen ascorbic levels in spermatogenesis.

BACKGROUND: Conflicting reports on the mechanism of action of ascorbic acid level in male reproductive system exist and very little is known about the ascorbic acid status in Nigerian males with weak fertility. METHOD: Ascorbate that accumulates preferentially in the testis, the lipid and lipoprotein levels were determined in the plasma of Nigerian males. Twenty-seven (27) male with inadequate spermatogenesis (36+/-1.0) years, with mean value of 15.6+/-6.90 million/cm3 sperm count and fourteen (14) controls (34+/-0.6) years, with mean value of 108.0+/-25.42 million/cm3 sperm count were selected for this study. The anthropometric indices were also determined. RESULTS: There were highly significant decreases in sperm cell count, percentage motility and percentage vitality (p<0.001) in each case, while percentage morphologically abnormal sperm cells was significantly elevated (p<0.001) compared with the control values. There were significant decreases in the seminal and plasma ascorbic acid concentrations (p<0.001) in the males who had inadequate spermatogenesis compared with the control values. The plasma total cholesterol (TC) and body mass index (BMI) were not significantly different from the corresponding control values, but the plasma low density lipoprotein (LDLC) (p<0.001) and triglyceride (TG)(p<0.01) concentrations were significantly increased in all the patients. While the plasma high density lipoprotein cholesterol (HDLC)(p<0.001) was significantly decreased compared with the controls. The plasma lipid and lipoprotein levels did not demonstrate any definite pattern with the sperm characteristics. CONCLUSION: The decreased semen ascorbate level may play a significant role in the reduced sperm characteristics in these patients.

Adult↗
PubMed1976

Varicocle in oligospermic patients: pathophysiology and results after ligation and division of the internal spermatic vein.

We have followed for up to 32 months 51 oligospermic patients with varicoceles who underwent high ligation and division of the left spermatic vein. Of these patients 59.9 per cent had improvement in total sperm count, 47.1 per cent in sperm motility and 42.1 per cent in the morphological pattern of the spermatozoa. Pregnancies were reported by 13 patients. Improvement in sperm motility occurred first, followed by improvement in morphology. The last improvement was in total sperm count. We suggest that the observation period after a varicocele operation be restricted to 9 months, in which time about 75 per cent of the expected improvement takes place. A clinical classification for the degree of varicocele is proposed. No correlation between size of the varicocele and treatment results could be observed. A classification of sperm analysis is proposed, using a 3-digital index that might enable better comparison of sperm analysis and better communication among physicians. We could not define a specific group of oligospermic patients who might benefit more than other groups from a varicocele operation. Pathophysiological pathways leading to impaired spermatogenesis in patients with varicoceles are discussed.

Fertility↗
PubMed2003

Frequency of defective sperm-zona pellucida interaction in severely teratozoospermic infertile men.

BACKGROUND: The frequency of defective sperm-zona pellucida (ZP) interaction in teratozoospermic infertile men was investigated. METHODS: Sperm-ZP binding and the ZP-induced acrosome reaction (ZPIAR) were performed in 125 infertile men with <5% of their sperm with normal morphology (strict criteria), but with a sperm count > or =20x10(6)/ml and total motility >30% in semen. Oocytes that failed to fertilize in clinical IVF were used for the tests. Four oocytes were incubated for 2 h with 2x10(6)/ml motile sperm selected by swim-up. The number of sperm bound per ZP and ZPIAR were assessed. Under these conditions, an average < or sperm bound per ZP was defined as poor sperm-ZP binding, and a ZPIAR < or = was defined as low ZPIAR. RESULTS: Among 125 teratozoospermic men, 31% (39/125) had poor sperm-ZP binding. Of those without poor ZP binding, 48% (41/86) had low ZPIAR. Some 64% (28/44) with sperm counts between 20 and 60x10(6)/ml had low ZPIAR. Only 36% (45/125) had normal sperm-ZP binding and ZPIAR. CONCLUSIONS: Defective sperm-ZP interaction was present in 64% of teratozoospermic infertile men: 31% had defective sperm-ZP binding, and 33% low ZPIAR. The frequency of low ZPIAR was higher in men with sperm counts between 20-60x10(6)/ml.

Acrosome Reaction↗
PubMed1985

Variation of semen measures within normal men.

Variation in semen measures was assessed bimonthly in 15 healthy men over a 6-month period. Average within-subject coefficients of variation for sperm count, morphologic features, motility, and semen volume demonstrate considerable variation. Each day of abstinence increased the volume by an increment of 0.62 ml, the count by 17.6 X 10(6)/ml, and motility by 1.2%. Sperm count and semen volume correlated positively within subjects. Intraclass and serial correlations of semen measures provided an empirical clinical guide to the number and spacing of specimens. Three specimens spaced no more than 2 weeks apart established a reliable semen profile. Findings can be applied to basic research and clinical practice.

Adult↗
PubMedDate not supplied

Exploration of the testis in infertile men. Relationships among serum levels of FSH, LH, 17-alpha-OH-progesterone and testosterone.

A considerable body of evidence is available indicating a paracrine relationship between the seminiferous tubules and the Leydig cells. In 113 adult subjects in basal conditions the blood levels were determined of FSH (follicle stimulating hormone), LH (luteinizing hormone), 17-alpha-OH-P (17-alpha-OH-progesterone) and T (testosterone) either as a whole or as a free fraction. According to the sperm counts and the FSH levels, the studied subjects were divided into three groups: a group N (Normozoospermia) with sperm counts greater than 20 million/ml and FSH levels of 2.5 +/- 1.5 (mean +/- SD, mIU/ml), a group MO (moderate oligozoospermia) with mild degree of oligozoospermia (5-10 mill) and FSH levels in the range found in group N, a group SO (severe oligozoospermia) with severe degree of oligozoospermia (sperm count less than 5 mill/ml) and FSH levels greater than 2 SD the mean value in the N. Serum levels of LH, 17-alpha-OHP, total T, free T and FSH/LH, LH/T, 17-alpha-OHP/T ratios in group MO and SO were compared with those found in the group N.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1980

The combined use of oral medroxyprogesterone acetate and methyltestosterone in a male contraceptive trial programme.

A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyltestosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control - 3 months, treatment - 6 months, follow-up - 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently. Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg,MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size. We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive, purposes and that higher doses may induce severe and undesirable side-effects.

Clinical Trials as Topic↗
PubMed1985

Effect of intranasal administration of norethisterone and progesterone on pituitary and gonadal function in adult male and female bonnet monkeys (Macaca radiata).

The effect of intranasal spray of norethisterone (NET) and progesterone (P) on serum testosterone (T) and total sperm count in adult male bonnet monkeys and the effect of NET spray on the menstrual cycle in female monkeys has been studied. Whereas NET spray resulted in a drastic decrease in serum T levels and sperm count, P spray caused a decrease in total sperm count only. Intranasal spray of NET in adult cycling female monkeys between days 5 and 14 resulted in shortening of the menstrual cycle; this could be ascribed to a decrease in serum follicle-stimulating hormone, luteinizing hormone, 17 beta-estradiol, and P levels. Nasal spray of only solvent in male or female monkeys, however, had no effect on any of the parameters tested.

Administration, Intranasal↗
PubMed1985

Reduction in sperm levels after testicular irradiation of the mouse: a comparison with man.

The potential and limitations of applying extrapolation factors (EFs) to the results of animal studies to predict effects of toxic agents on human male fertility were evaluated using radiation data. The EF is the ratio of the dose to produce a given effect in the mouse to that necessary to produce the same effect in man. Sperm counts in mouse testes were compared to those in the ejaculates of human males (D. K. Clifton and W. J. Bremner, J. Androl. 4, 387-392 (1981)) at several different times after irradiation. EFs of between 2.6 and 7 were obtained at the time when minimum counts occur. However, it must be noted that the sperm being measured arose from different cell types: differentiating spermatogonia in the mouse vs stem spermatogonia in man. Sperm counts performed at times at which the sperm develop from irradiated stem cells in both species yielded EFs between 11 and 44. However, if sufficient time was allowed for maximum recovery in both species, the EF was less than 1.7. These results indicate that man appears to be much more sensitive than the mouse to the testicular effects of irradiation at 2 to 9 months postexposure, but both species are comparable in their sensitivity to irreversible damage. The use of EFs may be appropriate, but since the EF is very dependent on the time at which the comparison was made, different values must be used for prompt and permanent testicular injury.

Animals↗
PubMed2004

Decreased serum inhibin B/FSH ratio as a marker of Sertoli cell function in male survivors after chemotherapy in childhood and adolescence.

OBJECTIVE: Inhibin B produced by Sertoli cells may be an important marker of seminiferous tubule function in patients treated with chemotherapy (CT). The aim of this study was to evaluate the inhibin B/FSH ratio to detect male gonadal dysfunction in cancer survivors treated in childhood and adolescence. PATIENTS: Twenty-one male patients (group A) treated with 6-10 courses of CT for Hodgkin's disease during childhood and adolescence were examined 3-11 years after the conclusion of treatment. Twenty healthy young men (18-23 years old) were used as controls (group B). METHODS: Serum samples for the determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), sex hormone-binding globulin (SHBG) and semen for analysis were collected. RESULTS: The median testicular volume of patients of group A was lower than those of group B (p = 0.001) and a positive correlation was found between testicular size and sperm count (r = -0.5, p = 0.01). Semen analysis revealed azoospermia in 11 patients, severe oligospermia in four and normal sperm count in three. No significant difference was found in the median of T, LH, SHBG, inhibin B concentrations and T/LH ratio between the groups. Serum inhibin B was correlated with the serum FSH levels (r = -0.5, p = 0.02). Median FSH was significantly higher (p = 0.0001), and median inhibin B/FSH ratio was significantly lower in group A than in controls (p = 0.0002), but the inhibin B/FSH ratio was higher in the patients with normal sperm count than in those with oligospermia (p = 0.00004). CONCLUSIONS: These results show that the cytotoxic effects of CT cause severe damage to the germinal epithelium with subtle effects on Sertoli cells. To assess Sertoli cell function in men with primary testicular damage after treatment with CT in childhood and adolescence, the inhibin B level needs to be interpreted in the context of the circulating FSH, especially when normal FSH levels are observed.

Adult↗
PubMed1995

A randomized study of intracytoplasmic sperm injection (ICSI) versus subzonal insemination (SUZI) for the management of severe male-factor infertility.

OBJECTIVE: Our objective was to compare the fertilization rates achieved by ICSI versus SUZI in couples with severe male infertility. DESIGN: This was a randomized, prospective study. SETTING: The study took place at the In-Vitro Fertilization-Embryo Transfer Unit, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center. MATERIALS AND METHODS: Oocytes of 12 patients were randomly allocated to either ICSI or SUZI procedures. Each woman thus served as her own control. All 12 patients had undergone at least two previous in vitro fertilization cycles with no fertilization or had a very low sperm count, i.e., a total motile sperm count of less than 0.5 x 10(6). RESULTS: A total of 117 oocytes was obtained for fertilization. Of these oocytes, 16% (10/63) were successfully fertilized by SUZI, compared to 33% (18/54) treated by ICSI. This difference was statistically significant (P < 0.05). Of the 12 cycles, ICSI provided embryos in 10 cycles (83%), while SUZI was successful in only 6 cycles (50%). Four pregnancies were achieved: 33% per attempt, or 40% per transfer.

Adult↗
PubMed1987

[Chromosome anomalies and male infertility. A study of 1,444 subjects].

Chromosomal anomaly was detected in 7.6% of a cytogenetic survey of 1,444 infertile male azoospermia or oligozoospermia with a sperm count below 20 million/ml. Anomalies are especially of the sex-chromosome and of autosomal robertsonian translocation type. Distribution of these subjects on account of the sperm count has pointed out an increase of chromosomal anomalies in inverse ratio to the sperm count.

Chromosome Aberrations↗
PubMedDate not supplied

Dominant lethal studies in male mice after exposure to 2.45 GHz microwave radiation.

Adult male mice had the lower halves of their bodies exposed in a waveguide system to 2.45 GHz microwave radiation for 30 min. The half body dose-rate of 43 W kg-1 had been shown in a previous study [7] to deplete severely the heat-sensitive stages of sperm production. The males were mated at intervals to adult hybrid females over the following 8-10 weeks. There was no significant reduction in post-implantation survival, suggesting that the microwave exposure did not have a mutagenic effect on the male germ cells. However, pregnancy rate was significantly reduced in weeks 3, 4, 5 and 6; reaching a minimum of about 10% of the control value in weeks 4 and 5. The occurrence of low values in weeks 4 and 5 correlated well with the expected reductions in sperm count due to the pattern of depletion of the spermatogenic epithelium of the testes. Thus it was concluded that the reduced pregnancy rate resulted from reduced male fertility. Pre-implantation survival can also be affected by reduced sperm count [8] and was significantly reduced in this study but it correlated less well with the anticipated heat response. A further study is in progress looking at the contribution of sperm count and sperm abnormality to the results.

Animals↗
PubMed2003

Testicular toxicity of dibromoacetonitrile and possible protection by tertiary butylhydroquinone.

Dibromoacetonitrile (DBAN) is known to be water disinfectant by-product. Its broad-spectrum toxicity in different test systems in vivo and in vitro has been reported. Oxidative damage induced by DBAN may be partially responsible for its toxicity. Herein, the ability of DBAN to induce oxidative stress in mouse testis and possible protective effect of an antioxidant tertiary butylhydroquinone (TBHQ) were addressed. Male albino mice were injected with a single dose of DBAN (50mg/kg i.p.), and killed after 3h of treatment. Control animals received 10ml/kg body weight i.p. of the vehicle DMSO. In both experiments, cauda epididymis were dissected and sperm count and motility were investigated. Also, testicular activity of lactic dehydrogenase-x (LDH-x) isozyme and histopathological changes were examined. Furthermore, testicular content of malonyldialdehyde (MDA) and reduced glutathione (GSH) were determined. A single i.p. dose of DBAN caused decrease in sperm count and motility to approximately 88 and 84%, respectively, compared with control animals. A 46% decrease in testicular activity of LDH-x, compared with control animals, was observed. A significant accumulation of MDA in DBAN-treated animals was increased to 99% while testicular content of GSH was decreased by 56% compared to control animals. Compared to DBAN-treated animals, treatment with TBHQ (100mg/kg p.o.) prior exposure to DBAN showed a remarkable degree of protection as indicated by enhancement of sperm count and motility, testicular activity of LDH-x, and GSH. Accumulation of testicular content of MDA significantly decreased following TBHQ treatment compared to DBAN-treated animals. In conclusion, results presented here indicate that DBAN is capable to induce oxidative stress in mouse testis. TBHQ may play a protective role against DBAN-induced testicular cellular damage.

Acetonitriles↗
PubMed1988

Selenium, rubidium and zinc in human semen and semen fractions.

The levels of selenium, rubidium and zinc were determined in samples of semen, seminal plasma and spermatozoa from men with suspected infertility, together with several parameters of semen quality. The proportion of whole semen selenium present in sperm increased with increasing sperm count from 0 to 40%. For rubidium 98 +/- 4% and for zinc 95 +/- 8% of the total amount in semen was contained in seminal plasma. In seminal plasma a positive correlation was found between the levels of zinc and selenium, and between the levels of zinc and rubidium, indicating that, like zinc, selenium and rubidium in seminal plasma also derive mainly from the prostate gland. Semen quality parameters, such as sperm motility, vitality, speed and morphology, were not correlated with the contents of the three elements in either whole semen or seminal plasma. As the seminal content of selenium is dependent on the proportion of prostatic secretion in seminal plasma and on the sperm count, and both factors can vary considerably, the selenium level of whole semen does not appear to be a suitable parameter for investigation of the relationship between selenium and semen quality. Provisional measurements suggest lower sperm selenium levels at abnormally low or high sperm counts.

Humans↗