John MacLeod

Seminal Cytology in the Presence of Varicocele

n The role of varicocele in subfertility was examined in 200 men with poor semen quality and in 87 additional men with fair to good semen quality despite varicocele. Semen quality was evaluated in terms of sperm count, sperm motility, and sperm morphology. Of the 200 men with poor sperm quality, 65% had a sperm count below 20 million/ml and 42% were in the 0-9 million/ml range. In contrast, most sperm counts in the 87 subjects with fair to good semen quality were above 40 million/ml and none was below 20 million. Ligation was not recommended for the latter group. 106 of the 200 men in the 1st group consented to ligation of the left internal spermatic vein, and the semen quality of 77 men was followed at monthly intervals for an average of 10 months. After ligation, the percentage of those with counts below 20 million/ml fell from 63.5 to 29.7, and 40.7% appeared in the above 40 million/ml category (up from 12.5%). Before ligation, 63.3% of the 77 subjects with adequate follow-up reached an acceptable motility level (120) in contrast to 7.8% in this category before operation. More than 50% of excessively subnormal motility indexes improved to a level approaching or surpassing normal, making motility the single most significant aspect of the effects of ligation on semen quality. In terms of morphology, 91% of the 200 subjects with poor semen quality showed moderate to marked stress pathology (e.g., tapering and amorphous cells and the exfoliation of immature cells of the germinal line into the ejaculate. After ligation, the percentage of men with amorphous cells fell from 78 to 44, and the percentage of those with tapering in conjunction with immature forms dropped from 65 to 28.5. The conception rate among the 68 men for whom information was available was 47.6% (32 cases). 81% and 37% of these conceptions occurred at sperm count levels below 60 and 20 million/ml, respectively. However, 29 of the 32 cases showed passable to excellent motility indexes (120-300), suggesting that motility is a more important factor in conception than sperm count. It is hypothesized that varicocele itself may not be the causative factor in disturbed spermatogenesis. Retrograde flow of blood into the left internal spermatic vein, stasis of blood in the renal vein, and the close proximity of the outflow of hormones from the adrenal cortex may create an abnormal environment around the left testis.n

The Male Factor in Fertility and Infertility. II. Spermatozoön Counts in 1000 Men of Known Fertility and in 1000 Cases of Infertile Marriage

Spermatozoon counts in 1000 men of known fertility and in 1000 cases of infertile marriage were studied to determine the lowest semen standar ds compatible with relative ease of conception. The mean volume of ejaculate for fertile men was 3.4 cc and 3.7 cc for infertile men. 5% of fertile men had sperm counts under 20 million/cc while 16% of the infertile fell into this catagory. Peak for the infertile group was less than 20 million/cc while the modal count class for the fertile group was 60-80 million/cc. 50% of the infertile men had counts of 74 million/cc or less while half of the fertile men had counts over 90 million. In studying the infertile group 8% of the group with a previous conception had sperm counts under 20 million/cc while 19% of the nonconception group had this count. At the 95% level of confidence the minimum standard for fertility based only on sperm counts was 20 million/cc. In the 1000 fertile specimens the relationship between ejaculate volume and sperm counts was insignificant. There was a highly significant relationship between volume and count in the infertile group. The essential difference between fertile and infertile lies at a low sperm count level. However above this level fertility and sperm count increase inconsistently.

Further Observations on the Role of Varicocele in Human Male Infertility

n 108 patients with varicocele and severe oligospermia and other disturbances in semen quality were studied as a supplement to an earlier study of 77 patients. All 108 subjects in Group 2 were cases of primary sterility lasting from 1 to several years. In many patients, the presence of varicocele was predicted on the basis of the seminal cytology. The operation performed for ablation of the varicocele was in most cases a high ligation of the internal spermatic vein above the varicocele. Results are based on at least 2 semen examinations before operation and 2-6 done after a minimal time lapse of about 4 months postoperatively. The average sperm count/ml before operation was 19 million, but following ligation 58% of subjects remained under 20 million/ml, compared to 30% in Group 1. 36% of patients in Group 2 but only 6.4% in Group 1 remained under 10 million/ml. The number of subjects with sperm-count levels of 40 million/ml or more increased from 18 to 25 after operation. Only 17 men showed a substantial postoperative increase, while the counts in 11 fell considerably. 97% in Group 2 had fewer than 60% normal oval-form sperm and 64% had fewer than 41%. After ligation, 77% in Group 2 remained in the 60% or under class, compared to 67% in Group 1. In Group 2, 95% of patients showed the stress pattern common in varicocele before ligation; the proportion fell to 39% following ligation, compared to 28% in Group 1. In Group 2 86% of subjects had sperm motility below the normal range before operation. The sperm motility of 80 of the 108 subjects improved within a period of 9 months following the operation. 48 postligation pregnancies in the group had occurred by the time of writing, and only 3 miscarriages had been reported. The mean period of sterility before treatment was 2.76 years. The average time necessary for the 1st pregnancy was 8.3 months. 28 individuals were not seen within the last year and lost to follow-up, so that the pregnancy rate of 44% may be too low. In approximately 35% of pregnancies, the conception apparently occurred at sperm counts of 10 million/ml or less. 3 conclusions are suggested by the work: 1) tests available to assess female fertility appear to be good 2) sperm motility is the most important factor in semen quality, and 3) pregnancies are possible at very low count levels providing the motility of the few cells present is good.n

The Immediate Postcoital Test

A series of 47 immediate postcoital tests were performed at the fertile period on ovulatory women with normal cervices to determine the time and process of penetration of the cervical mucus by the spermatozoa. Virtually immediate penetration of the spermatozoa into the cervical canal was observed. The conclusions of the tests would indicate that 2 hypotheses for explaining the rapid penetration into the cervical mucus are untenable: 1) direct insemination into the cervical canal and 2) sucking in of semen of the cervix. It is believed that the penetration of the spermatozoa into the cervical mucus and canal is a phenomenon for which only the motion of the sperm is responsible. The movement of the cervical mucus during intercourse ejaculation and for a brief period after ejaculation may facilitate contact between sperm and mucus and account for the rapidity (90 seconds to 3 minutes) of sperm penetration.

The Significance of Deviations in Human Sperm Morphology

If the premise is accepted that the spermatozoa released from the germinal epithelium do not, in the light microscope at least, undergo marked changes in head-structure in their subsequent passage through the duct system to the ejaculate; and if it is further assumed that, under physiological conditions, the germ cells are not absorbed in numbers by the ductal epithelium, then the cellular components of the ejaculate can be accepted, qualitatively and quantitatively, as truly representing the output of the germinal epithelium. It is certain that the spermatozoa in all species studied do undergo further maturation in the epididymis and possibly in the ductus deferens. The size, shape and internal structure of the acrosome are modified (1,2) as is the organization of the mitochon dria of the middle piece (3). In confirming earlier work that the capacity for motility increases as the spermatozoa pass through the epididymis, Blandau (4) and Gaddum (5) have shown in the rabbit that this potentiation of motility is produced partly by an alteration in the head-tail relationship of the cell. Undoubtedly chemical changes in the cells occur in the epididymal transit which, in turn, may induce changes in their metabolic properties and an increasing capacity for the ultimate utilization of substrates.

A Possible Factor in the Etiology of Human Male Infertility: Preliminary Report

NN1-bis(dichloroacetyl)18-octanediamine Cl2CHCONH(CH2)8NHCOCHCl2 was tested. Cytologically the semen of some infertile males show low sperm count poor motility abnormal sperm morphology with a high percentage of tapering forms and the presence of many immature cells of the germinal line. Since this seminal picture can be produced experimentally by the antispermatogenic compounds tested in these experiments and may be induced temporarily by illness the author reasons that the apparently spontaneous appearance of the combination of exfoliated cells and tapering form in individuals lacking overt clinical symptoms may be due to a disturbance in hormone distribution or to an abnormal metabolite. Evidence was sought of excessive or abnormal steroid excretion in 6 individuals presenting the required seminal picture. The data though scant point in the expected direction.

Semen analysis in 1,500 cases of sterile marriage

Abstract 1. 1. Examination of semen specimens in 1,500 cases of sterile marriage showed that about 50 per cent had deficiencies either in spermatozoa count, motility, or morphology. 2. 2. As the spermatozoa count falls below 60 million per c.c., other defects, such as motility and abnormal morphology, become more apparent until, in the very low count range, all three deficiencies together are likely to be found. 3. 3. Where successful pregnancies eventually occurred in this large group, the greatest number were found where no obvious fault was apparent in either partner and where the spermatozoa count was consistently in the higher brackets. 4. 4. It is suggested that the 60 million per c.c. spermatozoa count level is a reasonable dividing line between good and impaired fertility.

Lactic dehydrogenase activity in human semen.

Summary 1. Lactic dehydrogenase is present in high concentration in normal human semen and in seminal fluid of azoospermic individuals. 2. As compared to normal human blood plasma, LD activity of seminal fluid is high and is comparable to values obtained from tissue fluids which contain or bathe growing malignant cells. 3. There appears to be a semi-qualitative relationship between LD activity of semen and its content of spermatozoa but a considerable portion of LD activity is present in sperm-free seminal fluid. The latter activity seems to be derived principally from the prostatic secretions.

The Metabolism of Human Spermatozoa.

Summary The metabolism of human spermatozoa in Ringer-glucose is almost exclusively glycolytic and not respiratory. Aerobic lactic acid production is 80% of the anaerobic and falls off with time whereas anaerobic glycolysis is linear over a period of many hours. Maximal motility is maintained for many hours under anaerobic conditions but shows a marked tendency to decrease in air or in pure O2. This suggests that the presence of O2 has an inhibiting effect on the normal function of human spermatozoa.

A Testicular Response During and Following a Severe Allergic Reaction

A complete and reversible depression of spermatogenesis is described which took place during the course of and following a severe allergic reaction. Semen specimens from inmates of a penitentiary who underwent severe allergic reactions were sent from the penitentiary to New York for examination. A technician at the penitentiary made all motility determinations. The changes that took place in the testes and in the ejaculate were attributed to the reactions induced by the antigen-antibody complex. It was shown that the cytologic response of the testes to the toxic phenomena involved is nonspecific in that the germinal epithelium responds in similar fashion to other forms of trauma. The severe depression of spermatogenesis which occurred during the allergic reaction was accompained by complete inhibition of sperm motility and the exfoliation of large numbers of immature germinal cells into the ejaculate.