Ulrich A. Knuth

Computerized semen analysis: objective measurement of semen characteristics is biased by subjective parameter setting

To test the influence of parameter settings on results of automated semen analysis, microscopic images of 43 semen samples were videotaped. Tapes were analyzed by the CellSoft system (CRYO Resources Ltd., New York, NY) at 12 different parameter combinations for gray scale, number of frames analyzed, and minimum number of frames analyzed for velocity measurements. The data indicate that values obtained for concentration, percentage of motile sperm, velocity, and linearity depend, to varying degrees, on the settings of the computer. It is concluded that results of automated semen analysis may not be comparable among different laboratories unless identical parameter settings are used. The need for general agreement of these details among different users is stressed.

Anabolic steroids and semen parameters in bodybuilders

The influence of high-dose anabolic steroid administration on endocrine and semen parameters of 41 bodybuilders (age, 26.7 +/- 0.7 years [mean +/- SEM]; height, 182 +/- 1 cm; weight, 97.5 +/- 2.0 kg) was investigated. History of anabolic steroid administration was recorded retrospectively, and results of semen analysis were compared with data from 41 consecutively recruited normal volunteers not using any steroids or other drugs. Doses of anabolic steroids taken by bodybuilders exceeded those generally applied for clinical purposes by up to 40-fold. Although only 5 of the normal volunteers had sperm counts below the lower normal limit of 20 x 10(6) sperm/mL, 24 of the bodybuilders showed subnormal values. Depending on the duration of anabolic steroid use and the period since last drug intake before the investigation, percentages of motile and normally formed sperm were significantly reduced in bodybuilders compared with normal volunteers. In those bodybuilders who had stopped consumption of anabolic steroids greater than 4 months previously, sperm numbers were in the normal range. Results suggest that even after prolonged use of extremely high doses of anabolic steroids, sperm production may return to normal.

Comparison of computerized semen analysis with the conventional procedure in 322 patients

To compare the results of computerized image analysis for semen evaluation with classical semen analysis, semen samples from 322 consecutive patients attending our infertility clinic were studied. In men with sperm concentrations less than 20 X 10(6)/ml, major discrepancies existed between both methods for sperm concentration. In many instances, debris could not be distinguished from normal sperm by the computerized system. This caused an overestimation of sperm concentration and led to a reduction of motility estimates. As a consequence, frequency distribution of motility, expressed as the percentage of motile sperm, differed to a major extent in both systems.

Combination of 19-nortestosterone-hexyloxyphenylpropionate (Anadur) * and depot-medroxyprogesterone-acetate (Clinovir) † for male contraception

Because monotherapy with 19-nortestosterone hexyloxyphenylpropionate (Anadur, Pharmacia Arzneimittel, Ratingen, Federal Republic of Germany) suggested improved results for male contraception compared with available testosterone esters, it was tested for induction of complete azoospermia when combined with depot-medroxyprogesterone acetate (DMPA, Clinovir, Upjohn GmbH, Heppenheim, Federal Republic of Germany). Twelve men were treated for 7 weeks with weekly intramuscular (IM) injections of 200 mg Anadur followed by 3-weekly IM injections of Anadur up to week 15. Clinovir (250 mg) IM was administered at the start of treatment and during weeks 6 and 12. Anadur and Clinovir suppressed serum gonadotropins. Although serum testosterone declined steeply, in general, libido and potency were not impaired. Sperm concentrations were reduced significantly after 3 weeks of treatment. Lowest sperm counts were seen during week 8 of follow-up, when only 2 volunteers showed measurable sperm counts of 2.1 and 3.0 X 10(6)/ml, with a declining tendency. After 43 weeks, sperm concentrations were still below pretreatment range in 2 men, but later returned to pretreatment values. Computerized sperm motion analysis revealed that motility parameters in the residual sperm were reduced. In vitro analysis excluded a direct effect of medroxyprogesterone acetate in seminal plasma on sperm motion. The data indicate that the combination of Anadur with Clinovir increases the rate of azoospermia in normal volunteers seen under Anadur monotherapy, although the goal of azoospermia in all participants was not quite achieved.

Clinical trial of 19-nortestosterone-hexoxyphenylpropionate (Anadur) for male fertility regulation

To test the effectiveness of 19-nortestosterone (19NT) as an antifertility agent, 12 normal men (age, 24.0 +/- 2.2 years) received 19NT-hexoxyphenylpropionate (19NT-HPP), 200 mg/week intramuscularly for 7 weeks. After this initial phase, two groups were formed that received injections at different intervals. Except for the 19NT serum levels, there was no difference in treatment effects between both groups. 19NT-HPP administration in general suppressed gonadotropins below detection limits, accompanied by testosterone levels well in the castrate range. At the end of the treatment phase, azoospermia or severe oligozoospermia (total sperm count less than 5 X 10(6)) was present in ten volunteers. No loss of libido or potency was reported. Administration of 19NT-HPP did not affect liver enzymes, creatinine, uric acid, serum electrolytes, or serum lipids. The presented data demonstrate that 19NT-HPP as a single entity given every 3 weeks can suppress sperm output in a high proportion of men and simultaneously maintain virility.

PULSATILE GnRH‐THERAPY IN OLIGOZOOSPERMIC MEN DOES NOT IMPROVE SEMINAL PARAMETERS DESPITE DECREASED FSH LEVELS

In order to evaluate GnRH administration for the treatment of infertile men with elevated serum FSH levels we administered GnRH in pulses via portable electronic infusion pumps initially to seven patients with low sperm counts and high FSH values over 12 weeks and later to nine further patients over 24 weeks who also underwent testicular biopsies. Fifty microlitres containing 5 pg GnRH were infused subcutaneously for 1 min every 120 min in the short‐term study and every 90 min in the long‐term study. Although FSH levels could be lowered in both groups of patients, none showed any improvement in sperm count or other seminal parameters. Therefore, pulsatile GnRH treatment cannot be recommended for therapy of severe oligozoospermia with elevated FSH levels.

6Endocrine approaches to male fertility control

Summary As in the female, gametogenesis in the male is under the control of luteinizinghormone (LH) and follicle stimulating hormone (FSH). Their suppression should inhibit spermatogenesis. If a non-androgenic substance is used to suppress gonadotrophins, androgens must be supplemented to maintain virility, potency and metabolic processes. To avoid administration of several substances, testosterone and its esters were used to develop a male antifertility agent. Although azoospermia can be induced in a high proportion of men with administration of testosterone esters alone, this effect is not uniform. Even frequent injections with testosterone enanthate at weekly intervals fail to inhibit spermatogenesis in all participants. Combinations of gestagenic compounds with testosterone esters show a somewhat better effect, but again azoospermia is only achieved in around 50% of participants. LHRH analogues, although considered by many to offer a realistic potential for male fertility regulation, have not been proven to be successful for this purpose so far. Animal studies in monkeys and preliminary clinical trials demonstrate that agonistic analogues of LHRH have to be given continuously by pump or implant to achieve a pronounced effect on spermatogenesis. But even under these provisions, results in clinical trials have been worse than effects achieved with testosterone/gestagen combinations. Whether new antagonistic compounds offer a better potential awaits clinical trials. Studies in non-human primates demonstrate that testosterone by itself can maintain and initiate spermatogenesis. Based on these findings one could postulate an attenuating effect of high serum androgen levels after supplementation with available testosterone esters. Trials of alternative androgenic substances with slow-release characteristics and without high serum levels after single injections, like 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), tend to support this theory. With slow-release testosterone preparations under development by the WHO and more advanced delivery systems for LHRH analogues it is not unreasonable to speculate that an effective endocrine antifertility agent for the male will become available.

Selective reduction of elevated FSH levels in infertile men by pulsatile LHRH treatment.

In order to investigate whether isolated elevated FSH levels in men with idiopathic oligospermia can be lowered by pulsatile LHRH therapy, six patients were treated for 6 weeks with 5 μg LHRH pulses every 2 h. The pulses were delivered from a portable minipump (Zyklomat) through a subcutaneously inserted needle. At the end of treatment prepulse serum LH levels were no different from the levels before treatment while serum FSH was significantly reduced in all patients (16·9±2·5 U/1 vs 11·3±1·9 U/1, mean±SEM; P < 0·01). The normal FSH range was reached in one of the six patients. The areas under the LH curves following the first and the last (i.e. 504th) pulse were no different, while the areas under the FSH curves were significantly smaller (2870±434 vs 1776 ± 237 U/l×min; P < 0·01). Serum testosterone and oestradiol were significantly higher at the end of treatment (11·0±1·2 vs 15·2±1·9 nmol/1 146±18 vs 214 ± 25 pmol, respectively). Thus increased FSH levels in men with idiopathic oligospermia can be selectively reduced by pulsatile LHRH treatment. If the increased FSH levels are not the result but rather a factor contributing to the pathogenesis of certain types of oligospermia these findings may have implications for the treatment of this condition.