Pilot study with 120 mg Andriol treatment for couples with a low fertilization rate during in-vitro fertilization.

Treatment with 120 mg/day of Andriol (testosterone undecanoate; Organon, The Netherlands) was given to 11 men whose semen had either failed to fertilize, or had resulted in a less than 33% fertilization rate in a first in-vitro fertilization (IVF) trial. Repeat IVF at the end of a 3 month treatment period resulted in a highly significant increase in the number of oocytes fertilized from 4/95 (4.2%) before to 23/87 (26.4%, P less than 0.001) after Andriol treatment. One couple attained spontaneous conception during the second month of Andriol intake and three pregnancies occurred among the remaining 10 cases undergoing repeat IVF, for a total ongoing pregnancy rate of 36.4%. Sperm concentration but not motility increased in the native semen after Andriol intake, but there were no significant changes in sperm characteristics after preparation. The improvement in pregnancy rate contrasts favourably with the results obtained by repeat IVF of untreated historical controls. The result obtained in the present pilot study should encourage the performance of a larger, placebo-controlled investigation protocol.     

Evaluation of {beta}-endorphin and interleukin-6 in seminal plasma of patients with certain andrological diseases

Human semen contains large amounts of opioid peptides and cytokines.We have measured the concentrations of interleukin (IL)-6 in140 semen samples and of -endorphinin 77 semen samples. Themedian concentration of endorphinin seminal plasma from normozoospermicmen(n = 23) was 154.7 pg/ml (10th—90th percentiles, 42.0—774.6),and there was no significant difference in the -endorphin concentrationamong normozoospermic, oligozoospermic (n= 28), asthenozoospermic(n= 15), azoospermic(n= 4) and post-vasectomy (n= 7) samples.There was no correlation between -endorphin concentration andsperm characteristics, nor with blood hormones. Endorphinconcentration was lower in cases with immunelogical infertility,as revealed by a positive direct mixedantiglobulin reactiontest (n = 12) ( > 0.01), than inmatched controls. The medianconcentration of IL-6 insamples with normal sperm concentration,motility andmorphology with or without white blood cells (n=39) was 26.1 pg/ml (10th–90th percentiles, 7.3–172.3),and there was no significant difference in the IL-6 concentrationamong normozoospermic, oligozoospermic (n= 46),asthenozoospermic(n= 32), azoospermic (n= 13) and post-vasectomy (n= 10) samples.The IL-6 concentration was significantly higher in cases ofvaricocele (n= 22)without white blood cells in semen (P <0.001) than in matched controls without varicocele (n= 23).In addition, the IL-6 concentration was elevated (P < 0.0001)in cases with accessory sex gland inflammation (n= 40). IL-6concentration was positively correlated with white blood cellsin semen (n= 60, r = 0.59, P < 0.0001), but there was nocorrelation with -endorphin concentration. The IL-6 concentrationchosen to differentiate between cases with and without accessorygland inflammation was 45.3 pg/ml, with a specificity of 80.6%and a sensitivity of 92.5%. It is concluded that -endorphinin seminal plasma playsan immune suppressive role, and thatincreased IL-6 concentration may be related to testicular dysfunctionincases with varicocele. Furthermore, IL-6 is an accurate markerof accessory sex gland inflammation.     

Male contraception: hormonal, mechanical and other

Methods of male contraception that have been developed so farhave mainly focused on the inhibition of spermatogenesis throughsuppression of the hypothalamo- pituitary secretion of gonodotrophins,and simultaneous supplementation with androgens. These methodsinclude the use of combinations of progestogens or luteinizinghormone-releasing hormone antagonists and testosterone derivatives,or high dose testosterone. Though effective contraception canbe obtained, side-effects and/or the high cost of treatmentlimit the widespread use of these approaches. Inhibition ofsperm maturation in the epididymis, or direct interference withspermatogenic cells or the cells of Sertoli by e.g. gossypolhave been abandoned because of toxic side-effects. Voluntarysterilization by vasectomy is the most commonly used methodof male contraception, but its surgical nature, problematicreversibility and suspected link with subsequent prostate cancerrender the method far from ideal. Non-surgical vas occlusionmay overcome some of these problems, but data on long-term side-effectsand reversibility are lacking. New contraceptive developmentsshould focus on interfering with highly specific aspects ofspermatogenesis such as unique enzymatic processes and intercellularcommunication through cytokines, or application of antibodiesagainst antigens of the epididymis or the spermatozoa. Onlythrough better understanding of normal and pathological spermatogenesiswill it be possible to develop an acceptable male contraceptive.     

Accuracy of sperm characteristics in predicting the in vitro fertilizing capacity of semen

Based on the results of in vitro fertilization (IVF) in 56 couples, the power was assessed of traditional sperm characteristics of native semen to discriminate between in vitro fertile and in vitro infertile semen. The number per ejaculate of spermatozoa with regular oval heads was the best discriminant, followed by the concentration of progressively motile spermatozoa. This contrasts with the in vivo fertilizing capacity, which depends mostly on the proportion and concentration of spermatozoa with rapid linear progression. The lower limit of sperm characteristics was assessed as the fifth percentile of in vitro fertile semen and was compared with the lower limit of semen of fertile men and of subfertile men who achieved spontaneous or treatment-related conception in vivo. It appeared that the semen quality needed for in vitro fertilization is inferior to that of fertile men but not remarkably different from that of subfertile men who achieved spontaneous conception during 1-year follow-up after consultation. If conventional methods for semen preparation are used, there seems to be no major advantage in favor of IVF for the treatment of male infertility due to sperm deficiency. An increased success rate may, however, be attained, thanks to improved techniques of semen collection, semen preparation, and oocyte insemination.     

Comparison between thermography and venous scintigraphy of the scrotum in the diagnosis of varicocele

Fifty-one consecutive infertile men were examined for the presence of (sub)clinical varicocele with both scrotal thermography and venous radionuclide scintigraphy. Venous scintigraphy with 99^mTC yielded false negative results in about half of the patients suspected of varicocele because of clinical findings and/or abnormal scrotal thermography. Venous scintigraphy cannot serve as an alternative for scrotal thermography for the detection of spermatic venous reflux in varicocele.     

Effect of high dose oral Kallikrein treatment in men with idiopathic subfertility: evaluation by means of in vitro penetration test of zona free hamster ova

High dose oral Kallikrein treatment (600 U Padutine per day) was given to 10 infertile men with poor semen quality. After 3 months of this treatment no pregnancies occurred, and no significant changes in routine semen characteristics were observed. Moreover, the capacity of the spermatozoa to migrate in vitro and to penetrate zona free hamster ova remained unchanged after Kallikrein ingestion. It is concluded that Kallikrein treatment was ineffective in these men.     

Pregnancy After in vitro Fertilization and Embryo Transfer in Severe Immune Male Infertility/Schwangerschaft nach in-vitro-Fertilisation und Embryo-Transfer bei schwerer immunologisch bedingter Infertilität des Mannes

The male partner of an infertile couple was found to have anti-spermatozoal antibodies (ASA) of the IgG and IgA class in his semen as well as agglutinating and cytotoxic antibodies in serum. His wife conceived twice after IVF-ET with ongoing pregnancies.     

Genetic regulation of gametogensis: The receptor encoded by the human C-MET oncogene is expressed in testicular tissue and on human spermatozoa

Because of its distinctive ability to act as a mitogen, a mitogenand a morphogen, hepatocyte growth factor/ scatter factor (HGF/SF)has all the characteristics of a molecule able to function inregulatory networks of motility, such as the spermatogenic epithelium,and this through binding of its receptor p190^MET (C-MET). Inthis study we report the expression of C-MET in the human seminiferousepithelium and on spermatozoa from men being treated for infertilityand sperm donors. The presence of C-MET was demonstrated byimmunochemistry on the cell membrane of spermatogonia, spermatocytes,spermatids and on spermatozoa, whereas Sertoli cells and Leydigcells did not show expression. Comparison of C-MET expressionon spermatozoa of the 90% Percoll layer of subfertile patientsand donors revealed clearly two distinct groups (unpaired t-test,P < 0.001), whereas comparison of C-MET expression on spermatozoain the 47% Percoll layer was not significantly different betweenpatients and donors. In addition, there was a significant inversecorrelation between sperm concentration and the C-MET expressionof spermatozoa in the 90% Percoll layer (r = –0.80, 95%confidence interval, –0.92 to –0.55; P < 0.0001),but not with the C-MET expression of spermatozoa in the 47%Percoll layer. In conclusion, the presence of C-MET was demonstratedin the seminiferous epithelium and on mature and immature spermatozoa,indicating a role for this growth factor receptor in the differentiationand/or migration that occurs during human spermatogenesis. C-MET/male infertility/spermatozoa/testis