The Male Factor in Fertility and Infertility

Transcription

1 The Male Factor in Fertility and Infertility III. An Analysis of Motile Activity in the Spermatozoa of 1000 Fertile Men and 1000 Men in Infertile Marriage John Macleod, Ph.D., and Ruth Z. Gold, M.A. IN TWO recent studies,7. 8 we have analyzed ejaculate volume and spermatozoan counts in the semen of 1000 men of known fertility and in that of 1000 men who had been studied because of infertile marriage. As we have outlined in more detail in these prior studies, the purpose of this work is to define more precise standards for human male fertility after thorough analysis of all the variables associated with it. This study eventually will correlate both male and female histories in infertile marriage, the initial aim being to define the role of the male as precisely as statistical analysis will allow. The analysis of ejaculate volume in the fertile and "infertile" population showed that in the "infertile" group it tended to be higher and that the highest volumes were associated with semen specimens of poorest fertility as measured by sperm counts. The analysis of spermatozoan counts brought out two significant points, namely, (1) that the essential difference between the fertile and "infertile" populations lay at the 20 million/ cc. count level, and (2) that above this level there was no appreciable rise in potential fertility with rising count. We are now in the position to present a complete analysis of the "motility factor" in male fertility, but before doing so, it is necessary to define the rather difficult approach to the problem. From the Departments of Anatomy and Obstetrics and Gynecology, Cornell University Medical College, New York.. We are deeply indebted to Cornelius Vanderbilt Whitney for the financial support necessary for the continuance of this research. 187

2 188 MaclEOD & GOLD [Fertility & Sterility Until evidence is produced to the contrary we must believe that for a spermatozoan to reach and to fertilize the ovum, it must possess motile activity. Admitting this premise it follows that a semen specimen of high spermatozoa content will not produce conception unless a percentage of the spermatozoa show motile activity. It is certain that even in the best of semen specimens not all of the spermatozoa show motile activity. It is equally certain that in the semen of men of normal fertility, the quality of motility shown by the active cells may vary considerably in the semen of different individuals. Thus, in assaying motile activity, we have two prime factors to consider, the first being the percentage of active cells in the semen and the second, the quality of motility shown by these cells. A third question which adds to the complexity of these determinations lies in whether all the active cells in any given specimen show the same quality of activity. We can state with certainty that they do not and that almost without exception in any given semen specimen there are always a few cells showing extremely sluggish activity. Can we neglect these cells in our assay of the motility? We believe we can because of the fact that we can present no positive evidence that spermatozoa which show no or extremely sluggish motile activity in the semen examined in vitro may not attain aggressive motility in the secretions of the female genital tract. This question raises a most important point in semen analysis which, of necessity, must be conducted in vitro. Can we transfer our findings of sperm motility in the seminal fluid in vitro to a prediction of their motile behavior in the secretions of the female genital tract? More precisely, is it permissible to estimate the motile activity of the cells in seminal fluid at, say, four, eight, twelve, and twenty-four hours after ejaculation and use their inevitable decline of activity over that time as a criterion of their behavior over the same period in the female genital tract? We do not believe it is permissible to do this for the following reasons. First, when we consider the physiologic process of the transference of the spermatozoa from the male to the female, the spermatozoa do not reach the main bulk of the seminal fluid until the moment of ejaculation. 9 Almost simultaneously the whole ejaculate is deposited at or in the immediate vicinity of the external os. There is good reason to believe that the spermatozoa which eventually reach the tubal environment of the ovum pass immediately, or very quickly, into the cervical mucus (the soundest reason for believing so is that the spermatozoa cannot long survive the acid environment of the vagina). It is extremely unlikely that any appreciable amount of seminal t f

3 Vol. 2, No.3, 1951] SPERM MOTILITY 189 fluid passes into the cervical mucus with the cells. Therefore, in the physiologic course of events, the spermatozoa which reach the uterus and Fallopian tubes are in the environment of the seminal fluid for only a very short period of time-which may be measured in minutes if not at times in seconds. It follows that the seminal fluid is not a physiologic environmental medium for the spermatozoa for protracted periods and that their survival in that medium, so far as motility is concerned, is of academic interest and may have no relation to their longevity in the female genital tract. Even if we assume that the seminal fluid is a physiologic medium for the spermatozoa for many hours, can we say that the changing conditions of the fluid in vitro during this time are the same in all semen specimens and therefore, that the spermatozoa of all individuals are affected equally by in vitro changes? For example, many authorities in the field of male infertility use a survival period of twenty-four hours or longer in seminal fluid at room temperature as a criterion of the motile viability of the spermatozoa in question. They do so in face of well-known facts: First, the ph of semen in vitro (unless maintained constantly under a gas pressure of C02) changes rapidly from a physiologic ph of at the time of ejaculation to a very alkaline ph of anywhere between 8 and 9 within three or four hours. These changes will take place at different rates in different seminal fluids depending upon the bicarbonate content of the fluid. Second, the ejaculate is by no means free of bacteria at the time of ejaculation and seminal fluid is an ideal growth medium for bacteria as evidenced by the extremely rapid and logarithmic increase in the bacterial population in this medium. 6 We have good reason to, believe (1) that the original bacterial contamination of semen from different individuals is highly variable; (2) that the type of bacteria found in the semen of different individuals-and therefore, their rate of growthvaries; and (3) that bacterial growth of all kinds has varying degrees of inhibition of the motile activity of human spermatozoa. We therefore cannot believe that the in vitro determination of the motile activity of human spermatozoa in seminal fluid over a period longer than a few hours need have, necessarily, any relationship to their motile behavior in the female genital tract. 0 We would agree that if good motile activity remained at the end of twenty-four hours in seminal fluid the spermatozoa concerned would be likely to have good and sustained motility in the female genital tract.

4 190 MaclEOD & GOLD [Fertility & Sterility We have said that, of necessity, we must use the motile activity of the spermatozoa in seminal fluid as a partial measure of their potential fertility. The methods to be adopted have long posed disturbing problems in this field, the main one being to formulate a procedure: (1) which would allow the determinations to be made in simple and rapid fashion, and (2) allow readings made by one observer to be understood by another. The latter is essential particularly for the estimation of quality of motility. It has been extremely difficult to devise such methods. The technic allocated by Harvey and Jackson and its modification by Farris,2 use the hemocytometer chamber to estimate the percentage active cells and the passage of the motile cells across the ruled squares of the chamber as a measure of their rate of movement. The Farris modification has the advantage of giving the speed of movement in quantitative terms. We have not found either method satisfactory, particularly when, as in our studies, a large number of specimens may have to be examined on certain days. Furthermore, both technics require an elaborateness of procedure which not only introduces errors but, in our opinion, is not appropriate for the necessarily simple routine.required for office examinations. In this study we have followed the Hotchkiss method (1) because it is the procedure we have used for years, and (2) because in our hands it has a reproducibility which we find reliable. We have modified the Hotchkiss method by eliminating the use of the 3/4 blacked out ocular and making a simple estimate of the percentage of active cells in scanning several high power fields. The appraisal of quality of motility is much more subjective inasmuch as arbitrary figures are used to designate quality. For example, the best quality of motility, a rapid and undeviating progression of the cells across the high power field, is designated as quality 4 and slower or more erratic progressions as 3+, 3, etc. down to 1, the latter being one order of motile activity which corresponds to an extremely sluggish, barely progressive movement of the cells. The practiced eyes of a single observer can make these estimates with rapidity and accurate reproducibility. The major defect of this method is that unless every semen analyst in the country is trained in its use, the appraisal of one analyst cannot readily be transmitted to another. On the other hand, we are certain that all experienced workers in this field (and only such individuals should appraise semen quality) agree very closely on what constitutes good or poor motile activity whether arbi-

5 Vol. 2, No.3, 1951] SPERM MOTI LlTY 191 trary or semiquantitative methods are used. No matter what method is followed, it is essential in any statistical analysis, that the same method be used throughout the study by the same observer. \Ve have followed this policy consistently inasmuch as every motility determination in this study was made by the senior author. In most cases, enough semen specimens were obtained from the fertile and "infertile" men on any given day to allow the motility examinations to be made with no knowledge on the part of the observer as to whether the semen was from a fertile or "infertile" individual. In this sense, complete objectivity was maintained. The complete procedure is given in summary: 1. The semen specimens were obtained either manually or by withdrawal at intercourse. 2. The patients were instructed not to have intercourse for at least three days prior to obtaining the specimen. 3. The specimens were submitted to the laboratory preferably within one hour after ejaculation but many were not received until six or seven hours later. 4. Motility examinations were made between slide and coverglass immediately upon receipt of the semen but were not repeated at four-hour intervals for the reasons given above. Observations were made up to the sixth hour after ejaculation and all the observations reported below are based on motility examinations made at five and one-half hours after ejaculation. We have been forced to use this five and one-half hour point because of circumstances which may have a most important bearing on the motility aspect of the semen problem. We have pointed out previously7 that our fertile and "infertile" populations differ in one respect: the fertile group are not forced to bring semen specimens whereas the "infertile" group have a keen motivation in submitting specimens and will do so at the time requested. We have found that only a small percentage (4) of our fertile population submitted their specimens within two hours after ejaculation whereas 25 per cent of the infertile group were able to do so. Upon analysis we have found that taking "percentage active" cells, there is a sharp drop in this classification in both groups after six hours but, in addition, in the "infertile" group between two and four hours after ejaculation there is a significant drop in the "percentage active" cells, there being no significant change between four and six hours. Unfortunately, because of the small number submitted under two hours in the fertile group, we are not able to say at this time that the same changes take place in the fertile group. This must await further study on our part. For these reasons, we should make clear at this time that our analysis of motile activity is based entirely on observations made at five and one-half hours or less after ejaculation.

6 [Fertility & Sterility MacLEOD & GOLD 192 RESULTS Percentage Active Spermatozoa Figure 1 shows the relative frequency distributions (RFD) for the percentage of active cells in the semen specimens of 732 men in the fertile group and 869 in the "infertility" group, all observations being made at five and one-half hours or less after ejaculation. In each group, a considerable num- Cumulative Frequenty (%) Fertil. 80 Infertile (869 Cases) (732 Cases) SO ~= "11: 9 30 PL % Active Cells (at Sy, hours or less) FIGURE 1. Relative frequency distributions of percentage active cells of 732 fertile men and 869 men in infertile marriage. bel' of observations on the semen of individuals has been omitted because their specimens were not examined until six hours or later after ejaculation. The median percentage of active cells in the fertile group is 61 and 54 in the "infertile" group. This difference is significant but the difference between the RFD's as a whole in both groups is highly significant. For example, whereas the specimens of 25 per cent of the fertile group have under 51 per cent active spermatozoa, 25 per cent of those of the "infertile group" are under 41 per cent. The arithmetic mean for the fertile group is 58 per cent with a standard deviation (SD) of 16 per cent and for the "infertile group" 51 per cent, with a standard deviation of 19 per cent.

7 Vol. 2, No.3, 1951] SPERM MOTILITY 193 Table 1 presents the same data in more convenient form for arriving at standards which we can accept as being normal or subnormal. If we combine the fertile and "infertile" groups we have a total of 1601 individuals to which the fertile group contributes 732 cases (45.7 per cent). We now divide the 1601 cases according to "percentage active" starting with "less than 10 per cent" and progressing in groups of 10 per cent to "80 per cent and over" (Column 1). If fertility were not related to "percentage active" cells then we may expect the same proportion (45.7 per cent) to be contributed by the fertile group at each "percentage active" level. That this is not so can be TABLE 1. Proportion Fertile by Percentage Active Cells Per cent active No. at cases Percentage of cases Difference from cells in class fertile in class 45.7 per cent All Cases Less than 10% Signif Mod. Signif Signif Signif Not Signif Not Signif Signif Signif. 80 and Over Mod. Signif. seen in the percentages given in Column 3, Table 1. For example, only 17 per cent of the cases with less than 10 per cent active cells come from the fertile group, compared with 57 per cent in the 80 per cent active or over group. In fact, the proportion contributed by the fertile group rises with one exception in each "percentage active" classification. This implies that the chances of being fertile rise with increased percentage of active spermatozoa in the semen specimen. The figures in Table 1 indicate further that the critical level below which fertility may be considered subnormal is 40 per cent active. At this level (40-45 per cent active) and up to 55 per cent active, the proportion contributed by the fertile group is not significantly different from the expected proportion. But with 60 per cent or more active cells, the chances of fertility rise again and are considerably better than normal. We shall discuss this relationship further when we relate motile activity to sperm count.

8 [Fertility & Sterility MacLEOD & GOLD 194 Quality of Motility Figure 2 gives the RFD's for quality of motility in both groups. There are two important features in these distributions. The first is that whereas only 3 per cent of the fertile group fall in the under 2 (definitely poor) quality classification, 10 per cent of the "infertile" group are found there. In contrast, 19 per cent of the fertile group are found in the high motility quality (over 3+) as compared to only 12 per cent in the "infertile" group. These Cumulative Frequency (%) ~o\\..e 100 <,~~,,<,,\ / 90 Fertile 80 Infertile (869 Cases) (732 Cases) \,,~ x': n: 9 40 Pl = 00 I QUALITY OF MOTION (at 5' 1: hours or less) FIGURE 2. Relative frequency distributions of quality of motion of 732 fertile men and 869 men in infertile marriage. differences acquire further significance when the figures in Table 2 are examined. These have been compiled in similar fashion to those in Table 1. If there is no relationship between quality of motility and fertility we would expect the fertile group to contribute equal proportions (45.7 per cent) at all quality levels. That there is such a relationship is seen by the rising percentage contributed at each quality level until the level of quality 2 is reached at which point the proportion contributed is not Significantly less than the one predicted. This contribution by the fertile group remains constant through the quality levels up to 3-, rises through the qualities of 3 and 3+ and then at the 3+ quality level takes another sharp rise. We

9 Vol. 2, No.3, 1951] SPERM MOTILITY 195 TABLE 2. Proportion Fertile by Quality of Motion Quality at No. of cases Percentage fertile Difference from motion in class in class 45.7 per cent All Cases and Under Signif. 1+ to Signif Not Signif Not Signif Not Signif Not Signif Not Signif. Over Signif. interpret these figures to mean that below the quality level of 2, the chances of conception diminish. From qualities 2 on the chances rise but not significantly until the quality of 3+ is reached. Motile Activity in Conception and. No Conception" Groups In the study of sperm counts 8 valuable information was gained by taking the «infertile" group and dividing it so that conception was taken as the end-point for fertility. In other words, not all of the' men in the «infertile" group can be classified as infertile inasmuch as they may have in the marriage produced a conception which resulted in a successful pregnancy «onechild" sterility or in a conception or conceptions which resulted in miscarriage or still-birth. If we now divide the «infertile" group in similar fashion and relate any type of conception to motile activity we have 208 men who have produced a conception in the marriage and 580 who never have produced conception. Figure 3 shows the relative frequency distributions for "percentag~ of active cells" and for "quality of motility" in both groups. The differences between the two groups are moderately significant, the main differences being concentrated at the poor motility levels. In contrast to the differences between the fertile and "infertile groups" (Figs. 1 and 2) at the higher levels of motile activity (both in "percentage active" and quality) the two groups are about the same. More specifically, the only levels at which the two groups differ significantly are at less than 40 per cent active and at quality less than 2. We should point out that these are the same low levels at which large differences occurred between the fertile and "infertile" groups. However, the latter groups showed another level of high Significance

10 MaclEOD & GOLD 196 Conceplions (208 Cases) [Fertility & Sterility No Conceplions (580 Cases) PERCENT OF AalYE CELLS X,': 808 <40 c=j ~ ~ 7C1f''' p" All' 3.05 QUALITY OF MOTION <2 CJ 2.3-~ 3.3~ X' At, WEll 3 3'" p" Relative frequency distributions of percentage active cells and of quality of motion of 208 men in infertile marriage with a history of one or more conceptions and of 580 cases with no conceptions prior to the semen examination. FIGURE at above 60 per cent active and better than 3+; no such difference is seen at these levels in the conception and "no conception" classes when the "infertile" group is divided in this manner. Relationship Between Quality of Motility and Percentage Active Cells Figure 4 shows the average "percentage active" cells for various qualities of activity (A) for the fertile and "infertile" groups. In both groups there is

11 Vol. 2, No.3, 1951] SPERM MOTI LlTY 197 a significant relationship. The "percentage active" cells increases consistently with increasing quality. As might be expected, the proportion of cases with a subnormal percentage of active cells (B in Fig. 4) decreases as the quality of motility improves. For any quality of motility, however, the "average percentage active cells" is higher and the proportion of cases with under ~..., ffi a.. 80 \,~ I,! \~ 70,to so 40 \ -' '!\ ~\ A Average % Active Cells 8 Proportion of Cases with less than 40% Active Cells t G~c... 3i' FIGURE 4. QUALITY OF MOTION Relationship between percentage active cells and quality of motion in the fertile and infertile marriage groups. 40 per cent active cells fewer in the fertile group than in the "infertile" group. Some other interesting comparisons under this heading in the two groups not shown by Fig. 4 are: 1. Of the cases with under 40 per cent active cells, in the fertile group, 24 per cent also had subnormal quality (under 2) as compared with 40 per cent in the "infertile" group.

12 198 MacLEOD & GOLD [Fertility & Sterility 2. Only 2 per cent of the fertile group had both subnormal quality and "percentage active" compared with 8 per cent in the "infertile" group. 3. Eleven per cent of the fertile group had either subnormal quality or "percentage active" cells as compared to 23 per cent of the "infertile" group. These facts suggest that the fertile group is compensated for one deficiency in quality by some other superior character, the latter not being present in the "infertile" group to the same extent. Relationship of Motility to Volume Throughout this study, as each characteristic of semen quality is analyzed, we propose to investigate the relationship of each quality to the other if TABLE 3. Proportion of Cases with Low and High Volumes by Motility Percentage of Cases with given Ejaculate Volume Category Volume-Under 2 cc. Volume-5 cc. and over Fertile Infertile Fertile Infertile All cases Cases with under 40% active cells Cases with 60% and over active cells Cases with quality of motion of under Cases with quality of motion of over any such relationship exists. We have completed the analysis of ejaculate volume and of sperm counts and the relationship between these. Now that we have presented the data on motile activity we can determine the relationship, if any, of motility to volume and to sperm counts. We propose to summarize these findings briefly though they are compiled from a rather prodigious analysis of the data. 1. There is no relationship between volume and motile activity in the "infertile" group. Poor (or good) motility in this group is evenly distributed throughout the various volume levels (Table 3). 2. However, in the fertile group there is a relationship between motility and ejaculate volume in that poor motile activity is associated with low volume. Furthermore, the best quality of motility is observed less frequently

13 Vol. 2, No.3, 1951] SPERM MOTILITY 199 with high volumes (above 5.0 cc.). The best motility is found in the moderate volume range (2-5.0 cc.) (Table 3). Relationship of "Percentage Active" Cells to Spermatozoon Count Figure 5 shows the average "percentage active" cells for various sperm count levels in the fertile and "infertile" groups and also the proportion of cases with under 40 per cent active cells at each sperm count level. In both groups, fertile and "infertile," above a count of 40 million/ cc. the distribu ~... Do. 60 so /, / Y /\ / \ \./ ;' \ \, Fertile, ~ ;' - '"!n!!r!l!~_ A Average % Active Cells B Proportion of Cases with less than 40% Active Cells \ ".-..!.."!!!tile \ / --- \ // '\ ,.---- / B Fertile... ".",.. 0L ~60~--8~0~~17.00~~12~0~-,14A.0--~16~0--~180 FIGURE 5. Count per CC in Millions Relationship between percentage active cells,and sperm count per cubic centimeter in the fertile and infertile marriage groups. tions of the "percentage active cells" do not vary significantly with increasing sperm counts. Three levels of motility are seen in relation to sperm counts: 1. For counts under 20 million/ cc., the "percentage active" cells is lowest. 2. From million/ cc. the "percentage active" cells is significantly better than for less than 20 million/ cc. but significantly poorer than for counts of 40 million/ cc. or over. 3. At a count level of 40 million/ cc. or over, the "percentage active" cells does not change significantly through the upper count range.

14 [Fertility & Sterility MaclEOD & GOLD 200 It should be noted from Fig. 5 that at every sperm count level the motility of the fertile group as measured by "percentage active" cells is superior to that of the "infertile" group. Other interesting observations not shown in Fig. 5 are: 1. Of the semen specimens in the fertile group with less than 40 per cent active cells, 16 per cent of them also had counts less than 20 million/ cc., compared with 33 per cent in the "infertile" group. 2. Only 1.5 per cent of the fertile group had both subnormal "percentage c.tpercc <20M c..., per CC c..t per CC 20-39M 40 Mof 1% quality 4!20 U.3-5!ll!tt3 FIGURE 6. 3f_ Relationship between quality of motion and sperm count per cubic centimeter in the fertile and infertile marriage groups. active cells" (less than 40 per cent active) and low counts/cc. (under 20 million) as compared with 7 per cent in the "infertile" group. 3. Twelve per cent of the fertile group compared with 28 per cent of the "infertile" group had either subnormal counts/ cc. or subnormal per cent of active cells. Relationship of Quality of Motility to Spermatozoon Counts/ cc This relationship is similar to that between sperm count/ cc. and "percentage active cells" (Fig. 6). There are minor differences. There is a tendency for quality of motion to improve with increasing count/cc. up to a level between 80 and 100 million/ cc. The greatest differences in quality of

15 Vol. 2, No.3, 1951] SPERM MOTILITY 201 motility, however, are evident again at count levels under 20 million/ cc., million/ cc., and 40 million/ cc. and over (Fig. 6). At every count level, the quality of motile activity of the fertile group is superior to that of the "infertile" group. Other comparisons of note not shown in Fig. 6 are: l. In the fertile group, 37 per cent of the cases w~th subnormal quality of motility (less than 2) also had subnormal counts/ cc. (less than 20 million) as compared with 58 per cent of the "infertile" cases with subnormal quality. 2. One per cent of the fertile group and 6 per cent of the "infertile" group had both subnormal quality of motility and count/ cc. 3. Six per cent of t1te fertile group as compared to 18 per cent of the "infertile" group had either subnormal quality or count. 4. Less than 1 per cent of the fertile group showed subnormal values for sperm count, "percentage active" cells and quality of motility, while 5 per cent of the "infertile" group had all three characteristics at subnormal levels. DISCUSSION In this study of large populations it is clear that the percentage of active cells, even in semen specimens of high quality, does not by any means approach 100. This is not a new observation but we believe it is essential to emphasize that a good "percentage active" figure would be 75 and that one between 50 and 60 would be average. By our methods of analysis, the critical level at which the sharp difference between the fertile and "infertile" men becomes apparent is less than 40 per cent active (Table 1). This figure was not obtained simply by analyzing the two main fertile and "infertile" populations (though it is true in this comparison) but also emerged as the critical level of demarcation when the "infertile" group was studied apart in terms of whether a conception ever was attained in the "infertile" marriage. We can state further that in a preliminary analysis, there is an inverse relationship between time taken to produce conception in the fertile group and "percentage active" cells inasmuch as the time taken to produce conception decreases with increasing "percentage active" cells (this data will be presented in extenso in a later study). The Significant fact arising from this analysis is the strong relationship between motile activity and fertility (Table 1). This is true not only for "percentage active" cells but also for the quality of motility shown by these cells: We already have shown 8 that in considering a similar analysis of sperm

16 202 MacLEOD & GOLD [Fertility & Sterility counts, there is no relationship between sperm count and fertility above the level of 20 million cells/ cc. The latter fact increases the significance of the relationship between motile activity and fertility and, conversely, removes a considerable amount of emphasis which, hitherto, has been placed on sperm count. Considering this point further, there is a relationship between sperm count and motile activity in both fertile and "infertile" groups. Is it then enough to consider sperm count or motility alone as an index of fertility? The answer is "No" for two reasons: First, at the low sperm count levels, the motility of the fertile group is always better than the "infertility" group at the same count level (Figs. 5 and 6) and, conversely, at the low motility level, the fertile group always has better counts than the "infertile" group. The second reason is that even at the higher count levels the motility of the fertile group is consistently better than that of the "infertile" group. But the real importance of motile activity as a compensatory feature obviously would be at the lower count levels and, as we have shown, this compensation is found in the fertile group. Another important question is whether the quality of motility is more important than "percentage active" cells. We have shown that the chances of conception rise with increase in the "goodness" of both aspects of motility. Is one more important than the other? We cannot say so with any conviction at present because we have far too few cases in the fertile group with low sperm counts and with poor quality of motility. What we can say with conviction is that there is a close relationship between "percentage active" cells and quality of motility irrespective of the sperm count and this is true of both fertile and "infertile" groups. But the relationship between quality and "percentage active" in both groups is not the same. For any given quality, the fertile group has a better "percentage active" than the "infertile" group and, conversely, for any given "percentage active" the fertile group has better quality. In other words, in the fertile group, one aspect of motility compensates for a deficiency in the other. With the completion of our analysis of spermatozoon counts and motile activity in these two populations we are in position to estimate the lower levels of normal male fertility for these aspects of semen quality. We already have stated that the minimal level of normal fertility for the spermatozoon count is 20 million/cc. (a total sperm count of 50 million). We have shown now that the minimal level for "percentage active" is 40 per cent. This would mean that a total active sperm count in the ejaculate of 20 million

17 Vol. 2, No.3, 1951] SPERM MOTILITY 203 is the lower level of normal fertility. Farris in a study of 49 fertile men concludes that "no man with a total active sperm count of less than 83 million had been able to have children." In view of our data, we cannot agree with such a statement. Lastly, the 20 million active cells which we consider necessary as the lower level of normal fertility should have a motility quality (speed of movement) of at least 2, a quality which by our methods of observation, is not impressive. To return to our discussion as to whether it is permissible to carryover in vitro observations of motile activity in seminal fluid to the probable motile behavior of the spermatozoa in the female reproductive tract, we believe that the data show that, up to five and one-half hours at least, such observations are a reliable index of the probable behavior of the cells beyond the environment of the vagina. As expected, we have found it most difficult to compare our findings on motile activity with those of other observers. Falk and Kaufman, in their series of 100 fertile men, record an average of 61 per cent active cells active up to four and one-half hours after ejaculation, a figure which corresponds with our average of 58 per cent. We have not found a significant difference between the "percentage active" at four and one-half or five and one-half hours so that their data and ours are comparable. We should state at this time that we are fully aware of the excellent studies of Harvey and Jackson and of their attempt to standardize methods of semen analysis. At this time, unfortunately, our data have not reached a stage of analysis at which proper comparison can be made with theirs. SUMMARY 1. The motile activity of human spermatozoa in fertile and "infertile" populations is analyzed in terms of ability to produce conception. 2. By the use of several methods of analysis it is shown that the motile activity of the fertile group consistently is better than that of the "infertile" group. 3. The chances of fertility increase with rising quality of motility. 4. There is a definite relationship between sperm counts and motile activity in both the fertile and "infertile" groups. 5. The fertile group demonstrates the ability to compensate for one de-

18 204 MaclEOD & GOLD [Fertility & Sterility ficiency in semen quality by relative excellence in another to a greater degree than the "infertile" group. 6. Motility standards for the lower level of normal fertility are given. REFERENCES 1. Falk, C., and Kaufman, S. A.: Fertility & Sterility. 1:489, Farris, E. J.: J. Urol. 58:85, Farris, E. J.: J. Urol. 61:1099, Harvey, C., and Jackson, M. H.: Lancet 2:99, Hotchkiss, R. S.: Fertility in Men. Philadelphia, J. B. Lippincott & Co., MacLeod, J.: Am. J. Physiol. 132:193, MacLeod, J.: Fertility & Sterility. 1:347, MacLeod, J., and Gold, R. Z.: J. Urol., in press. 9. MacLeod, J., and Hotchkiss, R. S.: J. Urol. 48:225,1942.