Subfertile Men Research Articles

Role of semen analysis in subfertile couples

To evaluate the associations between the results of the male partner's semen analysis (classified according to the World Health Organization [WHO] criteria) and fathering a child without any treatment. Prospective multicenter cohort study. Twenty subfertility centers in The Netherlands. A total of 3,345 consecutive couples presenting for subfertility. None. Associations between the results of the male partner's semen analysis, classified according to the WHO criteria, and fathering a child without any treatment within a time horizon of 1 year. Subsequently, we redefined semen quality criteria and reevaluated the associations. Follow-up data of 3,129 couples (94%) were available, of which 517 (17%) had a healthy pregnancy without treatment. The 1-year pregnancy rate in men with WHO normozoospermia did not differ significantly from that in men with WHO impaired semen (24% vs. 23%). In contrast, we observed lower chances of fathering a child for sperm concentrations <40 × 10(6)/mL, total sperm count <200 × 10(6), and sperm morphology <20% normal forms. With a multivariable regression model based on the redefined male semen subfertility criteria we were able to make a finer differentiation between subfertile men, with probabilities of fathering a child ranging from 7% to 41%. The current WHO criteria for semen quality do not discriminate between fertile and subfertile men. Our redefined and graded semen criteria have strong predictive value. If interpreted correctly, the fast and inexpensive semen analysis remains the gold standard for defining a man's role in subfertility.

The significance of Y chromosome microdeletion analysis in subfertile men with clinical variocele.

IntroductionThe aim of study is determining the cost-effectiveness of detection analysis in the presence of exceptional patients who have mild semen disorders, and beware of unnecessary varicocele repairs; and to ascertain whether patients with clinical varicocele should undergo Y chromosome (Yq) microdeletion analysis as a routine procedure.Material and methodsVaricocele with reflux was diagnosed in 51 male patients with subfertility symptoms upon physical examination (PE), confirmed by scrotal colour-Doppler ultrasound (CDU). After cytogenetic examination, Yq microdeletion analysis was performed on the peripheral blood samples using Promega Y Chromosome Deletion Detection System Version 2. Varicocele repair was performed under general anaesthesia with optical magnification (3-fold) through a subinguinal approach.ResultsThe mean age of the patients was 27.9. Values of semen concentration ranged from 0 to 72 million/ml, motility from 0 to 65% (A + B) and Kruger from 0% to 18%. The PE revealed normal size and consistency in the bilateral testicles. All patients were cytogenetically normal. However, Yq microdeletion was detected in 2 patients, 1 with mild oligoteratozoospermia and partial AZFb deletion (sY121) and the second patient with severe oligozoospermia and partial AZFc deletion (sY254 and sY255), and they were not subjected to varicocelectomy.ConclusionsThe routine performance of pre-operative Yq microdeletion analysis in patients with clinical varicocele does not seem to be cost-effective but the omission of patients with mild oligozoospermia would have subjected them to an unnecessary varicocelectomy and/or further ICSI applications and also would have caused the failure of referral for genetic counselling.

Normal reference ranges for semen quality and their relations to fecundity

Several recent studies have shown that the fecundity of a man decreases progressively with sperm concentrations below 40 million spermatozoa per mL. Therefore, it is unfortunate that the new World Health Organization guidelines for semen analysis recommend lowering the lower cutoff value for normal sperm concentration from 20 to 15 million spermatozoa per mL. As a result large groups of subfertile men across the world may not receive appropriate andrological help in the future.

Objective assessment of outcome of transinguinal varicocele ligation in oligozoospermic subfertile men

Ceylon Medical Journal (CMJ) is a peer-reviewed, open access journal published quarterly by the Sri Lanka Medical Association in the last week of March, June, September and December each year. The mission of the CMJ is to promote the science and art of medicine and betterment of public health. The Journal publishes original papers and commentaries which have relevance to medicine and allied sciences. The CMJ is committed to maintaining and conforming to the editorial and ethical standards recommended by the International Committee of Medical Journal Editors.

Relationship between seminal plasma zinc concentration and spermatozoa–zona pellucida binding and the ZP-induced acrosome reaction in subfertile men

The aim of this study was to determine the relationship between seminal zinc concentration and spermatozoa-zona pellucida (ZP) binding and the ZP-induced acrosome reaction (ZPIAR) in subfertile men. Semen analyses and seminal zinc concentration assessments were carried out according to the World Health Organization manual for 458 subfertile men. A spermatozoa-ZP interaction test was carried out by incubating 2 x 10(6) motile spermatozoa with a group of four unfertilized oocytes obtained from a clinical in vitro fertilization programme. After 2 h of incubation, the number of spermatozoa bound per ZP and the ZPIAR of ZP-bound spermatozoa were examined. The effect of adding 0.5 mmol L(-1) zinc to the media on the ZPIAR of spermatozoa from normozoospermic men was also tested in vitro. Seminal zinc concentration positively correlated with sperm count and duration of abstinence, but negatively correlated with semen volume. On analysis of data from all participants, both spermatozoa-ZP binding and the ZPIAR were significantly correlated with sperm motility and normal morphology, but not with seminal zinc concentration. However, in men with normozoospermic semen, the seminal zinc concentration was significantly higher in men with defective ZPIAR (< 16%) than in those with normal ZPIAR (>or= 16%) (P < 0.01). The addition of 0.5 mmol L(-1) zinc to the culture media had no effect on spermatozoa-ZP binding, but significantly reduced the ZPIAR in vitro (P < 0.001). In conclusion, seminal zinc concentration is correlated with sperm count and the duration of abstinence in subfertile men. In men with normozoospermic semen, high seminal zinc concentration may have an adverse effect on the ZPIAR.

Andrologische Fertilitätsstörungen

Because of both external and individual factors, nowadays more men seek clarification and consultation about their fertility. This article reviews the current diagnostic work-up of subfertile men and the evidence based treatment options. Also testicular biopsy and cryopreservation of sperm or testicular tissue are addressed. Finally, the issues of vasectomy reversal and aplasia of the vas deferens are discussed. The paper emphasizes practical issues and practicability in office urology.

Assisted reproductive technologies may obviate apparent immunologic infertility*

Spermatozoal autoantibodies have been associated with reduced fertilization by natural coital methods. Nine subfertile men were evaluated who repeatedly tested positive for spermatozoal autoantibodies as characterized by direct immunobead test. Using the hemizona assay, we determined whether tight binding of spermatozoa to the zona pellucida was reduced in these test males as compared to a fertile male whose semen had been cryopreserved and thawed immediately prior to testing. The average number of spermatozoa tightly bound to the zona pellucida from the subfertile male was significantly reduced compared to the fertile male (mean +/- SD, P less than or equal to 0.01) 19.5 +/- 8 versus 77.1 +/- 49. Seven of the nine couples eventually had successful fertilization using intrauterine insemination or gamete intrafallopian tube transfer and one couple conceived with natural coital insemination. Our findings, albeit limited, suggest that greater caution should be used in implicating associations of spermatozoal autoantibodies with absolute infertility, because novel assisted reproductive technologies often may obviate conventional encumbrances on opportunities for pregnancy.

Isolation and storage of progressively motile human sperm.

Human sperm progressively motile and free of seminal debris can routinely be isolated, during a 1.5 hour process, from semen of normal and subfertile men. Serum albumin, in a vertical column, acts to filter sperm based on their swimming abilities of forward progression. The isolated sperm constitute a population that can be inseminated as an aid to male subfertility or, to enhance the chances of sperm survival upon deep-freeze preservation. The latter use resulted in twice the survival rate, based on sperm motility, or random populations of control sperm.

The effect of tamoxifen on spermatogenesis in subfertile men.

Forty three subfertile male patients exhibiting a wide range of sperm counts received Tamoxifen (Nolvadex, I.C.I.) 20 mg daily for six months continuously; nine pregnancies resulted, a rate of 21 per cent. Although a significant improvement in sperm output occurred in three patients with initial sperm counts of less than 20 x 10(6)/ml the response was most marked in those with an initial count of less than 5 x 10(6)/ml and four pregnancies occurred in this latter group. Patients whose initial count was greater than 20 million per ml showed no significant response and four exhibited a steady fall in sperm output. No correlation was found between the response to treatment and basal serum levels of FSH, LH, testosterone and prolactin. Four markedly oligozoospermic patients with a significantly elevated FSH, normally associated with severe tubular dysfunction, showed a pronounced increase in sperm count. Seven patients (16 per cent) experienced minor side effects.

Macrophages Lysing Seminoma Cells in Patients with Carcinoma-In-Situ (CIS) of the Testis/Makrophagen, die Seminomzellen lysieren, bei Patienten mit Carcinoma-In-Situ (CIS) des Hodens

Testicles of 15 subfertile men who underwent orchidectomy because of intratubular seminoma cells resp. carcinoma-in-situ (CSI) pattern in testicular biopsy were examined by semithin sections as well as by ultrathin sections. With one exception the volume of the testicles was reduced (means = 16 ml). 6 cases (= 40%) had exclusively intratubular seminoma cells, 4 cases (= 26.6%) intratubular and interstitial seminoma cells and 5 cases (= 33.3%) a solid seminoma near the rete testis. In all patients an interstitial inflammatory infiltration as well as tubular shadows of various degree could be observed. Some tubular shadows contained macrophages in the center heavily loaded with lipid droplets. Furthermore, in two cases many seminiferous tubules could be detected which contained activated macrophages in the lumen lysing tumor cells. One of the patients had only intratubular tumor cells, whereas the other patient had a solid seminoma near the rete testis. Our data suggest that activated macrophages killing intratubular tumor cells in patients with CIS pattern of the testis resp. with an early stage of a seminoma represent a physiological immunological reaction of the host in preventing further invasive tumor growth. Tubular shadows represent the final process of macrophage activity and may explain the reduced testicular volume in patients with CIS. However, the density of the inflammatory reaction and the extent of intratubular macrophages lysing tumor cells does not correlate with a low or high risk of tumor growth.

Changes in Seminal Quality Following Oral Zinc Therapy

33 subfertile men with idiopathic asthenozoospermia and/or oligozoospermia were treated with oral zinc sulphate. After treatment a significant improvement in the percentage progressive and total sperm motility was noted accompanied by a significant increase in seminal fluid zinc levels.

The arsenic content of human semen.

Arsenic concentration was measured by atomic absorption spectrometer in ejaculates of 13 subfertile men, 6 control individuals and pool-ejaculate of 24 further andrological patients. While the detection limit was 1 microgram/l, arsenic concentration amounted to 2 micrograms AS/l in ejaculates. In the cellular fractions of seminal fluid, concentration of arsenic was under the detection limit. Arsenic concentration of smokers and non-smokers did not differ.

Gonadotropins, prolactin, testosterone and estradiol in seminal plasma: effect of clomiphene treatment.

To elucidate the mechanism of clomiphene action in the treatment of male infertility, we studied the effect of three-month clomiphene treatment (50 mg daily) on the radioimmunoassayable concentrations of gonadotropins (FSH, LH), prolactin (PRL), estradiol (E2), and testosterone (T) in seminal plasma and peripheral serum in eleven normogonadotropic subfertile men. Clomiphene therapy increased (p less than 0.01) the levels of FSH and LH in seminal plasma, but to a lesser extent (p less than 0.01) than in peripheral serum. PRL did not change is seminal plasma or peripheral serum. The seminal plasma and peripheral serum T concentrations doubled following clomiphene intake without any demonstrable correlation with the sperm count. The concentrations of E2 increased about ten times (p less than 0.005) in seminal plasma, a significantly greater (p less than 0.05) increase than that in the serum. There was a significant correlation (r = 0.804, p less than 0.01) between the sperm counts and seminal plasma E2 levels following clomiphene treatment. These results suggest that Sertoli cell activation may be a key event in clomiphene action in the treatment of male infertility.

Effects of long-term treatment with human pure follicle-stimulating hormone on semen parameters and sperm-cell ultrastructure in idiopathic oligoteratoasthenozoospermia

Summary. Ten subfertile men affected by idiopathic oligoteratoasthenozoospermia and exhibiting normal serum hormone levels received a long-term treatment with human pure follicle-stimulating hormone (hp-FSH) (150 IU, intramuscularly, three times per week for 6 months). Semen parameters and ultrastructural features of spermatozoa were evaluated before and after therapy. The results showed an increase in sperm cell concentration and, more interestingly, motility. Electron microscopic examination revealed an improved fine architectural pattern, mainly involving acrosome, head and chromatin and middle-piece, in accordance with the positive changes of functional data. No significant changes of hp-FSH treatment on serum hormone levels were observed, since the latter were found to be substantially unchanged after 6 months of therapy. The present data suggest: (i) the benefit of hp-FSH administration in idiopathic oligoteratoasthenozoospermia, when hormone parameters support a substantial integrity of spermatogenetic micro-environment and (ii) an optimal effect after long-term (6 months) therapy.

Seminal Plasma β-Human Chorionic Gonadotropin (β-HCG): Relationships with Seminal Characteristics and Spermatozoal Fertilizing Capacity

Seminal plasma beta-human chorionic gonadotropin (beta-HCG) levels were determined in 254 semen samples collected from fertile and suspected subfertile men, and their relationships with seminal characteristics and spermatozoal fertilizing capacity were evaluated. Radioimmunoassayable beta-HCG, as defined by greater than 5 mIU/ml concentration, was demonstrated in only 44.5% of all the samples studied. beta-HCG concentrations were similar in normospermic, oligospermic and azoospermic samples. There were no significant differences in beta-HCG concentration between high-motility and low-motility samples, between normal-morphology and abnormal-morphology samples, and between high-fertilizing capacity and low-fertilizing capacity samples. No significant correlations between the concentrations of beta-HCG and individual parameters of semen analysis and spermatozoal fertilizing capacity among the various groups of samples were observed. The physiological role of seminal plasma beta-HCG is presently uncertain and the relationship of its determination to male fertility requires further investigation.

Effect of tamoxifen and kallikrein on sperm parameters including hypoosmotic swelling test in subfertile males. A retrospective analysis: Der Einfluß von Tamoxifen und Kallikrein auf das Spermiogramm inklusive Schwelltest subfertiler Männer. Retrospektive

151 subfertile men presenting OAT-syndrome were investigated in respect of an improvement of sperm parameters under therapy with tamoxifen, kallikrein and combined treatment of both drugs. After therapy with 30 mg tamoxifen per day (75 patients), a significant elevation of density and swelling test was seen. Medication with 600 IE kallikrein per day (36 patients) revealed only a slight improvement of motility. Also combined treatment of 30 mg tamoxifen with 600 IE kallikrein per day produced only an elevation of motility without any significant change of other sperm parameters.

Tamoxifen treatment of oligozoospermia.

33 subfertile men with idiopathic normogonadotropic oligozoospermia were treated with the non-steroidal antiestrogen tamoxifen. A significant improvement of sperm count, total sperm output and sperm motility was observed.

Paraoxonase‐1 Activity in Subfertile Men and Relationship to Sperm Parameters

Oxidative stress has been implicated in the pathogenesis of male infertility. Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated antioxidant enzyme that prevents oxidative modification of low-density lipoprotein. Our aims in the study were to investigate 1) seminal PON-1 activity in subfertile men and 2) whether seminal PON-1 activity had any relationship to semen parameters. The study included 28 men with idiopathic subfertility, 32 subfertile men with abnormal semen parameters, and 30 fertile male volunteers. Seminal PON-1 activity was measured spectrophotometrically. Seminal total antioxidant status (TAS) and total oxidant status (TOS) were determined by using colorimetric methods. Oxidative stress index (OSI) was calculated as ([TOS/TAS] x 100). TOS and OSI were significantly higher and PON-1 activity and TAS were significantly lower in subfertile men with abnormal semen parameters than in men with idiopathic subfertility and fertile donors. PON-1 activity was also strongly correlated with sperm concentration (r = .68, P < .0001), motility (r = .58, P < .0001), and morphology (r = .62, P < .0001) in the overall group. The receiver operating characteristic curve analysis revealed a high diagnostic value for PON-1 activity with respect to male-factor subfertility, with an area under curve of .95 (95% confidence interval = 0.89-1.01), sensitivity = 97%, and specificity = 88%. Men with abnormal semen parameters have decreased levels of PON-1 activity in their seminal plasma. This may play an important role in the pathogenesis of male-factor subfertility.

Spermatogenesis in a Man with Complete Deletion ofUSP9Y

Deletions in the azoospermia factor region AZFa on the human Y chromosome and, more specifically, in the region that encompasses the ubiquitin-specific peptidase 9, Y-linked gene USP9Y have been implicated in infertility associated with oligospermia and azoospermia. We have characterized in detail a deletion in AZFa that results in an absence of USP9Y in a normospermic man and his brother and father. The association of this large deletion with normal fertility shows that USP9Y, hitherto considered a candidate gene for infertility and azoospermia, does not have a key role in male reproduction. These results suggest that it may not be necessary to consider USP9Y when screening the Y chromosome of infertile or subfertile men for microdeletions.

Correlation of sperm DNA damage with protamine deficiency in Iranian subfertile men

To compare the extent of sperm DNA damage with the degree of protamine deficiency in spermatozoa of normal and subfertile individuals, 30 semen samples from three groups of subfertile individuals (oligozoospermic, asthenozoospermic and oligoasthenozoospermic) and 14 samples from normal individuals were collected from men referred to the Fertility and Infertility Centre of Shariati Hospital, Tehran. DNA damage was measured using the alkaline Comet assay, and protamine deficiency was measured using chromomycin A3 (CMA3) staining. Results indicated a significant difference in the extent of DNA damage in spermatozoa of subfertile patients compared with normal patients (P < 0.01). Spermatozoa from oligoasthenozoospermic patients showed a higher level of DNA damage compared with the other two study groups of subfertile men. The percentage of CMA3-positive spermatozoa was also higher in subfertile individuals compared with normal patients (P < 0.01), with the highest level occurring in oligoasthenozoospermic patients. A direct correlation between protamine deficiency and sperm DNA damage was found for all subfertile patients studied.