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Teratozoospermia influences fertilization rate in vitro but not embryo quality.

The purpose of this study was to retrospectively compare the overall results and embryo quality in 102 cycles of in-vitro fertilization (IVF)-embryo transfer using normal frozen donor semen (group D) and 94 cycles of IVF-embryo transfer using husbands' teratozoospermic sperm (group T). Donor semen was purchased from men with proven fertility and normal semen parameters. Teratozoospermia was defined in group T as the presence of <20% of normal spermatozoa in semen on the day of oocyte retrieval. Exclusion criteria were a sperm count <10 x 10(6)/ml or with <10% progressive motility. Fertilization rate, transfer rate and number of transferred embryos per cycle were significantly lower in the teratozoospermic group (45 vs 72%, 66 vs 96%, 1.7 vs 2.9%, respectively). Pregnancy rate per cycle was also lower, but not significantly (18 vs 28%). However, pregnancy rate per transfer, implantation rate per transferred embryo and take home baby rate were comparable (27 vs 30%, 15 vs 15%, 21 vs 24%, respectively). Similarly, embryo quality in terms of number of embryos displaying fragmentations or irregular cells, cleavage stages and embryo scores were comparable. When group T was divided into two subgroups according to sperm count (group T1: sperm count = 10-20 x 10(6)/ml; group T2: sperm count >20 x 10(6)/ml), there was no difference between them with regard to fertilization rate, pregnancy rate or embryo quality. This study confirms low pregnancy rate per cycle in IVF-embryo transfer using teratozoospermic semen, but demonstrates for the first time that embryo quality and viability are not impaired. It is proposed that the poor pregnancy rate per cycle obtained is due only to the poor fertilization rate, and to the subsequent limited choice of embryos to be transferred.

Cryopreservation↗

Comparison of male reproductive parameters in three rat strains: Dark Agouti, Sprague-Dawley and Wistar.

The choice of experimental animal can have a large impact on experimental results, an example is the anecdotal evidence suggesting that Dark Agouti (DA) rats have a lower reproductive capacity than other rat strains. In this paper we report on an investigation into male reproductive characteristics in three rat strains--Wistar, Sprague-Dawley (outbred strains) and DA (an inbred strain). Reproductive organ weights, blood testosterone levels and sperm counts were measured in mature age-matched male rats. DA animals had significantly smaller testis weights than the Sprague-Dawley and Wistar animals, and this did not appear to be related to the overall smaller body mass of the DAs. There were no differences between the three strains in testicular histology or sperm counts (per gram testis). Although there was also no significant difference in epididymal sperm count, the DA animals had a much greater variability in sperm count than the other strains. There were no differences in relative (to body weight) epididymal, seminal vesicle or ventral prostate weights or in the blood testosterone levels. These results suggest that differences in reproductive capacity in DAs are neither the result of morphological differences in the reproductive organs nor in circulating testosterone levels. Sperm production appears to be normal but the lowered testicular weight and variability in epididymal sperm counts suggests that there are other factors in the testicular or epididymal environment which alter male reproductive function.

Animals↗

Carbendazim-induced alterations of reproductive development and function in the rat and hamster.

We are developing a data base that will allow us to select endpoints that would be useful in the detection of reproductive toxicity in a multigenerational test. In this effort, carbendazim (MBC), a known reproductive toxicant, was administered to male and female rats from weaning, through puberty, gestation, and lactation. A similar study was conducted with hamsters. In rats, MBC was administered at 0, 50, 100, 200, or 400 mg/kg/day. Hamsters were dosed at 0 or 400 mg/kg/day. In the parent (P0) generation, landmarks of puberty were measured. In females, estrous cyclicity, litter size, the number of implants, organ weights, and histology were assessed. Our assessment of the male rat included organ weights, testicular and epididymal sperm counts, a quantitative measure of sperm motility, sperm morphology, testicular histology, and endocrine measures. The growth, viability, and reproductive function of the offspring (F1) were observed during a 4-month period of continuous breeding. In the P0 of both species. MBC did not alter pubertal development, growth, or viability. The reproductive potential of the rats treated with MBC at 200 and 400 mg/kg/day was reduced due to effects on sperm production and fetal viability. In the male rat, MBC treatment markedly altered sperm morphology, testicular and epididymal weights, and sperm numbers and testicular histology. Fertility, sperm motility, and hormonal levels were altered, primarily in the males with very low sperm counts. The ability to conceive did not appear to involve a female factor. In P0 female rats, MBC administration caused postimplantation losses in the high-dosage groups and a few malformed rat pups were found in the litters from the 100 and 200 treatment groups. MBC was less toxic to the hamster than the rat. The only reproductive effects induced by MBC treatment were on sperm measures. Fertility of the P0 generation and fetal and neonatal (F1) viability were not decreased by MBC administration. In the male rat, testis weight, sperm numbers in the cauda epididymis and testis and sperm morphology were sensitive to the effects of MBC. In females, counting implantation scars at necropsy was useful, as this information allowed us to confirm pregnancy and identify postimplantation losses induced by MBC administration.

Animals↗

Therapeutic strategy after microsurgical varicocelectomy in the modern assisted reproductive technology era.

In this study, we searched for prognostic factors at preoperative examination for the improvement in spermatogenesis of patients undergoing varicocelectomy. Eighty patients with varicocele testis underwent microsurgical varicocelectomy. Before surgery, the seminogram, testicular volume, varicocele grade, and serum FSH, LH, testosterone, prolactin, and estradiol were evaluated. Postoperatively, semen analysis was performed every 3 months. We assessed the associations between the preoperative variables and postoperative seminogram improvement. 0f 80 patients, 37 showed improvement, usually by 6 months. Patient age, duration of sterility, testicular volume, sperm motility, morphology, semen volume, serum LH, testosterone, prolactin, and estradiol showed little difference between responders and non-responders. A small left testis, or a grade III varicocele decreased the likelihood of improvement. Patients with a sperm count of 10-20 x 10(6)/ml were significantly more likely to respond to varicocelectomy than those with sperm counts <5 x 10(6)/ml. Patients with elevated FSH were less likely to respond, as were those with a Johnsen score below 6. Varicocelectomy alone is unlikely to improve sperm counts of patients with a sperm count below 5 x 10(6)/ml, high FSH, small left testes, or Johnsen scores below 6. In conclusion, for couples in this situation, assisted reproductive technology coupled with varicocelectomy should be proposed.

Adolescent↗

Inhibition of spermatogenesis in men using various combinations of oral progestagens and percutaneous or oral androgens.

Eight men (experiment 1) requesting male contraception received a daily oral dose of 20 mg medroxyprogesterone acetate (MPA) combined with 125 mg percutaneous dihydrotestosterone (DHT). Three months later the mean sperm count was only diminished slightly; the replacement of DHT for four men by percutaneous testosterone at the same concentration led to a dramatic fall in sperm count. For 6-18 months all men were treated with MPA plus percutaneous testosterone (250 mg daily). The latter dose restored physiological levels of plasma testosterone. Follicle-stimulating hormone levels were inhibited more severely than in the DHT-treated group, whereas LH levels were variable. Azoospermia was achieved and maintained in six cases; two men were oligozoospermic and in one case a moderate secondary rise in the sperm count was observed. Twelve volunteers (experiment 2) received a daily oral dose of either 5 or 10 mg norethisterone acetate plus percutaneous testosterone (250 mg daily). All of them achieved azoospermia within 2 months, but two subjects later exhibited a partial restoration in sperm count. Follicle-stimulating hormone and LH levels were inhibited more severely than in the first experiment. The sperm count and gonadotrophin levels returned to initial values within 6 months after cessation of the treatment in both experiments. No side-effects were noted concerning blood parameters, libido or body weight. However, several female partners had elevated levels of plasma testosterone. In experiment 3 (13 volunteers), percutaneous testosterone was replaced by oral testosterone undecanoate (160 mg daily). Only seven men were azoospermic and most of them had lowered levels of plasma testosterone. Thus, the combination of percutaneous testosterone and oral progestagens appears to be the most convenient for male hormonal contraception.

Administration, Cutaneous↗

Role of environmental estrogens in the deterioration of male factor fertility.

OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.

Adult↗

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 role of testicular biopsy in the investigation of male infertility.

Sixty-five testicular biopsies from infertile men were assessed retrospectively. In 21 patients infertility was attributed to varicoceles. In the remaining cases the testicular histology was classified into 3 major groups. Normal, hypospermatogenesis and germ cell aplasia. These histological categories were correlated with serum gonadotrophic hormone levels and sperm counts. All cases of germ cell aplasia showed azoospermia or severe oligospermia, but sperm counts alone were not reliable indicators of spermatogenesis. Patients with very low sperm counts and raised levels of serum FSH invariably had germ cell aplasia. These patients made up a group in whom testicular biopsies were of limited value in assessment. In all other instances the testicular biopsy was still an important tool in the assessment and prognostication for fertility in the subfertile male.

Biopsy↗

Steroid treatment of male subfertility caused by antisperm antibodies.

47 subfertile men with significant titres of antisperm antibodies were treated with one of two steroid regimens. The results were assessed by changes in sperm-counts and in serum antibody titres and by subsequent pregnancies. 15 oligozoospermic men were treated with prednisone 5 mg three times a day for 3--12 months. Sperm-counts became normal in 10 men and 4 of their wives became pregnant. 14 men with normal sperm-counts received the same treatment: antibody titres fell slightly and 3 of their wives became pregnant. 18 other men with normal sperm-counts were given one or more courses of methylprednisolone 96 mg/day for 7 days. There was a more pronounced fall in antibody titres in these men, and 7 of their wives became pregnant. Testicular biopsies in 3 men with high titres of antibodies and very low sperm-counts which became normal with prednisone showed adequate spermatogenesis; however, focal round-cell infiltration of seminiferous tubules was observed in 1 case. It is suggested that a steroid-responsive immune orchitis can occur spontaneously in man, and may contribute to the infertility of men with antisperm antibodies.

Autoantibodies↗

The effects of carbon disulfide on the reproductive system of the male rat.

Two experimental protocols were employed to determine the effects of carbon disulfide (CS2) on the reproductive system of the male rat. In the first experiment, adult Long Evans hooded rats were exposed to 0, 350 or 600 ppm CS2 vapor for 10 weeks (5 h/day, 5 days/week). CS2 exposure caused no change in reproductive organ weights nor in plasma gonadotropin levels. However, animals exposed to 600 ppm CS2 had slightly lower epididymal sperm counts and significantly reduced plasma testosterone levels. In order to determine if monitoring hormone levels and sperm status in the same male over time might increase the sensitivity of detecting a toxic reaction, the second protocol was employed. Male rats were exposed to 0 or 600 ppm CS2. After 0, 1, 4, 7 and 10 weeks of exposure, males were observed for mating behavior, and ejaculated sperm count and plasma hormone levels were determined. Animals exposed to 600 ppm CS2 had significantly shorter times to mount and to ejaculate and decreased ejaculated sperm counts. Plasma gonadotropin levels were similar in both groups while plasma testosterone levels were marginally depressed in CS2-exposed animals in the early weeks. These data indicate that CS2 is a toxin of the male reproductive system resulting in abnormal coital behavior and decreased sperm counts. The second experimental protocol proves to be a sensitive method for assessing adverse effects in the male reproductive system.

Animals↗

Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido.

GnRH antagonists suppress pituitary and gonadal function by competing with endogenous GnRH for binding to receptors on pituitary gonadotrophs. We studied the effects of GnRH antagonist administration to men in a protocol simulating a likely male contraceptive regimen combined with a low dose of testosterone. The GnRH antagonist Nal-Glu was given daily (10 mg, sc) for 20 weeks to eight normal men, and a low dose of testosterone enanthate (25 mg, sc) was given every week. Sperm counts started declining during week 4, and complete azoospermia was reached within 6-12 weeks in six of the eight subjects. Subjects 7 and 8, whose sperm counts and serum gonadotropin levels were not suppressed after 10 weeks, were given 20 mg Nal-Glu starting at week 10. One became azoospermic at week 16, while the other's total sperm counts continued declining and reached a nadir of 1.4 million by week 20. Sperm motility and viability in this subject were completely suppressed after week 14. Sperm counts returned to baseline levels 12-14 weeks after the end of Nal-Glu administration. The mean serum LH level of the first six subjects decreased from 3 +/- 03. U/L at baseline to less than 0.1 U/L until week 20, and then levels returned to baseline. FSH levels similarly decreased from a combined mean of 3.6 +/- 0.9 U/L at baseline to below 0.3 U/L after 4 weeks of Nal-Glu administration. Serum mean testosterone levels between weekly injections of testosterone enanthate ranged from 27.4 +/- 5.9 to 4.8 +/- 1.4 nmol/L, but remained in the hypogonadal range (less than 10 nmol/L) for 4 of the 7 days. None of the subjects, however, complained of decreased libido or potency, as assessed by a questionnaire. No systemic or significant local side-effects were observed, other than a minimal reaction at the injection site. These data suggest that complete sustained azoospermia can be achieved in man, without loss of libido, by chronic administration of a GnRH antagonist plus testosterone.

Adult↗

Clinical, physical, sperm and hormonal data in 251 adults operated on for cryptorchidism in childhood.

OBJECTIVE: To determine the clinical, physical, sperm and hormonal status during adulthood in cryptorchid patients operated on during childhood, and to assess these variables according to the age at surgery and preoperative testicular position. PATIENTS AND METHODS: A letter was sent to all 890 patients > 18 years old who underwent surgery for cryptorchidism during childhood; 274 responded and were assessed using a sexual history, physical examination, pituitary axis study and sperm analysis. Data were complete for 251 patients (mean age 21 years, range 18-30); 196 had unilateral (25 anorchic) and 55 had bilateral cryptorchidism. Clinical, surgical and anatomopathological records at surgery during childhood were also reviewed. RESULTS: The mean (SD) age at orchidopexy was 6.4 (3.3) years and the mean age at assessment 21.1 (2.7) years. Semen samples generally showed abnormalities; 10 patients (4%) with bilateral and 57 (23%) with unilateral cryptorchidism had semen values within the normal range. There was no correlation between the sperm count and age at surgery for unilateral or bilateral cases (Spearman test). There was a significant correlation (r = - 0.41) between the sperm count and level of follicle-stimulating hormone (FSH). There were no significant differences in the sperm count for patients with different testicular locations (ANOVA) or in those treated or untreated with human chorionic gonadotrophin (Student's t-test). The only significant relationship (P < 0.001) was between the sperm count and unilateral or bilateral cryptorchidism. CONCLUSIONS: The sperm quality of adults operated on for cryptorchidism during childhood is independent of the age at surgery or testicular location, but is influenced by whether the cryptorchidism was unilateral or bilateral. FSH levels were negatively correlated with sperm density.

Adolescent↗

[Clinical efficacy of mecobalamin in the treatment of oligozoospermia--results of double-blind comparative clinical study].

The clinical efficacy of mecobalamin in the treatment of male infertility was investigated by means of a multicenter collaborative study with 25 participating institutions. The study was carried out as a double-blind, comparative trial using three administration groups: 6,000 micrograms of mecobalamin per day, 1,500 micrograms of mecobalamin per day and a placebo group for 12 wk. The following results were obtained. 1. The total number of evaluated subjects was 375, consisting of 125 in the 6,000 micrograms/day mecobalamin group, 124 in the 1,500 micrograms/day mecobalamin group and 126 in the placebo group. There were no significant differences among the three administration groups in terms of the patient's background factors. 2. When all of the patients were analyzed, there were no statistically significant differences among the three administration groups in terms of the efficacy in relation to the sperm count or the motility rate. 3. However, it was decided to perform a more detailed analysis of the therapeutic efficacy in patients whose pretreatment sperm counts were 20 x 10(6)/ml or less. The reasons for this decision were two-fold: 1) There was a large degree of fluctuation in patients whose pretreatment sperm counts showed a mean value of more than 20 x 10(6)/ml for two or more determinations, and it was surmised that this fluctuation might have masked any therapeutic effect in those cases. 2) The WHO definition of oligozoospermia was recently decided as a sperm count of 20 x 10(6)/ml or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of acute postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl on sperm function and hormone levels in adult rats.

Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'-tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.

Analysis of Variance↗

Serum prolactin in male infertility.

Hyperprolactinemia was found only in two out of 71 patients with male infertility and in none of 53 patients with impotentia coeundi indicating that hyperprolactinemia is of minor significance in these patients. There was only a weak negative correlation between hPRL and testosterone in oligozoospermic men. No correlation was found between hPRL and hLH, hFSH, sperm count and sperm motility. Nevertheless measurement of hPRL should be performed in all cases with hypogonadotropic hypogonadism, loss of libido or impotence since these symptoms may be signs of a prolactin-producing pituitary adenoma.

Cell Count↗

Testicular size in infertile men: relationship to semen characteristics and hormonal blood levels.

Testicular volume was assessed in 1029 infertile men and found to be normal in 704; 71 patients had unilateral and 213 had bilateral testicular hypotrophy; 4 had unilateral and 37 had bilateral atrophy. Sperm count and motility decreased in accordance with testicular volume. The lowest mean sperm counts and lowest mean motility percentages were found in patients with bilateral testicular atrophy. An increase in mean FSH and LH was also significantly linked to decreasing testicular volume; the increase in the former was not related to a drop in sperm count. A significant correlation was found between testicular volume and spermatogenesis and testicular volume is considered to be a reliable indicator of testicular function.

Follicle Stimulating Hormone↗

Combined mesterolon-clomiphene citrate therapy for treatment of oligospermia.

42 subfertile patients with normal levels of plasma testerone (26 subnormal, suffering from oligospermia) have been treated with a combination of clomiphene citrate (50 mg Clomid daily) and mesterolon (50 mg Proviron daily) over a period of at least 3-6 months. The treatment resulted in pregnancy in 6 cases and in a significant improvement of the sperm count in 16. In 7, however, whilst the sperm count improved the qualitative results were unsatisfactory as many sperms were immature. Restricted spermatogenesis and a sperm count below 5 million/ml must be considered unfavourable but does not constitute a counter-indication to the combined therapy. No hazardous complications were observed.

Cell Count↗

[Evaluating the effect of smoking tobacco on some semen parameters in men of reproductive age].

Seminal fluid indexes (sperm count, motility, pH, morphology) were examined in 40 smokers and 30 nonsmokers. The sperm count and motility were lower in smokers. Smokers have also higher incidence of oligospermia compared to nonsmokers. There was no difference between pH and sperm morphology in smokers and nonsmokers. Additionally, smokers have higher levels of endogenous 17 beta-estradiol and sperm count below normal in nonsmokers. These results suggest that inveterate smoking can diminish fertility in men.

Adult↗