Daniel Schwartz

Explanatory and Pragmatic Attitudes in Therapeutical Trials

It is the thesis of this paper that most therapeutic trials are inadequately formulated, and this from the earliest stages of their conception. Their inadequacy is basic, in that the trials may be aimed at the solution of one or other of two radically different kinds of problem; the resulting ambiguity affects the definition of the treatments, the assessment of the results, the choice of subjects and the way in which the treatments are compared. It often occurs that one type of approach is ethically less defensible than the other, or may even be ruled out altogether on ethical grounds. We postpone consideration of this aspect of the question until a later section.

Semen characteristics as a function of age in 833 fertile men.

The relationship between age and semen characteristics has been studied; any effect due to the influence of the length of abstinence preceding ejaculation was eliminated. There is an improvement in semen characteristics up to 25 years of age, followed by a leveling off and a subsequent decrease. This variation is not significant as far as the sperm count, semen volume, and the total number of spermatozoa are concerned. The variation, although small, is highly significant for the morphologic characteristics and prefreeze and postthaw motility. The values for the older subjects were significantly lower for postthaw motility in the group 36 to 40 years of age, in the group 41 to 45 years of age for morphologic normality, and in the group 46 to 50 years of age for prefreeze motility. The lower values in the group 21 to 25 years of age are particularly noticeable with regard to morphologic characteristics. The same curve is encountered in the variation with age of each abnormal form, but the most marked variation is found in the increased percentage of coiled tails, which first appears in the group 36 to 40 years of age.

Smoking during pregnancy and placental weight.A multivariate analysis on 3759 cases

The analysis of a survey of 3759 births shows that the difference in placental weight between smokers and nonsmokers is, if not nil, at least minimal, and that is definitely less than might be expected taking birth weight and other factors into consideration in a multivariate analysis (Tab. II). The distortion between the fetal and placental weights, which are very closely correlated, assigns to smoking a peculiar place among the factors influencing these two weights, a result which may lead to various interpretations.

Conception Rate According to Semen Characteristics in a Series of 15 364 Insemination Cycles: Results of a Multivariate Analysis

Summary:  The study was undertaken on 1438 ejaculates from 342 donors. The sperm count, volume, prefreeze and postthaw motility were evaluated for each ejaculate and the morphology for the first ejaculate of each donor. The success rate was found to increase steadily with the sperm count, prefreeze and postthaw motility. For the volume and percentage of all abnormal forms, the success rates are stable up to 5,5 ml and 40% respectively and then decrease. Among all the abnormal forms considered, only the microcephalics and irregular heads were found to be linked to the success rate. As most of the studied characteristics are correlated, a multiple stepwise regression was completed in order to determine the proper role of each variable. The most predictive variable is the postthaw motility. The second variable is the percentage of microcephalics. The other variables bring no further information. In particular, at a given postthaw motility, the prefreeze motility and consequently, the loss in motility have no influence on the success rate.

Study of Sperm Morphologic Characteristics in a Group of 833 Fertile Men

Summary:  For the 13 abnormalities under consideration, the mean percentages were found to be the following: irregular head (15.2), microcephalic (9.8), elongated head (5.9), coiled tail (5.8), bent tail (4.7), thin head (4.6), cytoplasmic remains (3.2), macro‐cephalic (1.6), short tail (1.1), no tail (0.6), duplicate tail (0.5), duplicate head (0.4), lysis (0.4). In so far as the group studied is representative, the results obtained may be considered as “norms” with the 90th percentiles showing the upper limit of the “normal”. The same mean percentages were found by MacLeod and Gold (1951) for the five abnormalities they had identified. The length of abstinence preceding the collection of the ejaculate was found to have no influence on the percentage of abnormal forms.

Between and within Subject Correlations and Variances for Certain Semen Characteristics in Fertile Men

Between subject and within subject variances and correlations for different semen characteristics have been determined for a population of 315 fertile men who provided one or more ejaculates within an abstinence period of 1 to 5 days. The semen characteristics measured were sperm count, semen volume, pre‐freeze motility and post‐thaw motility. An approach via a decomposition of the variance or via a decomposition of correlation leads essentially to the same conclusions i.e. the within subject factors are not negligible but are less important than the between subject ones. Thus there is broad evidence for overall differences in the quality of the ejaculate from one subject to the other but not for different ejaculates of the same subject.

Pattern of menstrual cycles and incidence of congenital malformations

An analysis has been made of the general reproductive characteristics of mothers, including the temperature curves of preconception and conception cycles, in a prospective study which ended in the birth of 22 malformed infants and 894 normal infants. The differences observed have shown that the mothers of malformed infants had their first menstrual period at a later age (13.4 vs 12.8 years), their menstrual cycles were more often irregular (77% vs 40%) and lasted longer (32.9 vs 30.1 days). Moreover, they had a longer hypothermic phase during both their preconception cycle (21.7 vs 17.6 days) and during their conception cycle (24.0 vs 18.1 days), as well as a longer temperature rise during their conception cycle (3.7 vs 3.0 days). By taking into account the relation between these variables, we have been able to show that increased risk of malformation is associated with increase in the length of the hypothermic phase and the temperature rise of the conception cycle.

ARTIFICIAL INSEMINATION WITH FROZEN SPERM: PROTOCOL, METHOD OF ANALYSIS AND RESULTS FOR 1188 WOMEN

The experience of a sperm bank during a five year period is reported. Artificial insemination by donor (AID) was carried out on 1188 women using frozen sperm prepared in doses of 0.25 ml. A single insemination was called for during each of the first two cycles. The patients were classified in 4 categories: lost to follow‐up, successes, dropouts and open cases. The success rate per cycle was about 10 per cent and was very stable for each of the first 12 cycles. The cumulative success rate was calculated by the life table technique adapted for AID analysis. A theoretical success rate (without dropouts) and an effective success rate (with dropouts) were calculated. These two rates were 68 and 55 per cent respectively after 12 cycles. The median delay to conception was 7 and 9 cycles, respectively, under theoretical and effective conditions. The spontaneous abortion rate (17 per cent) and sex‐ratio (106 males for 100 females) resemble those for natural reproduction but the success rate per cycle was markedly lower even after adjusting for age.

Fertility of couples following cessation of contraception.

A retrospective study of the delay in conception after stopping different methods of contraception is undertaken among 5108 pregnant women residing in a departement in the Paris region. Particular attention is paid to the delay that sometimes separates the cessation of contraception and the beginning of intercourse without precautions. The counfounding factors considered are: the observation of a waiting period following cessation of contraception; the existence of a strategy, i.e., a coital pattern adopted by certain couples who have intercourse more often during the middle of the cycle, hoping to conceive more rapidly; the regularity of the menstrual cycle and the womans age at the beginning of unprotected intercourse. The statistical techniques include chi-square analysis, analysis of variance correlation, partial multiple regression and actuarial rates of infecundity. The mean age of women at their last period was 26.3 years; 37.6% were primagravida; 87.3% worked outside the home and 36.6% were smokers. 72% of the women used oral contraceptives; 14% the IUD, and 14% other methods. Among all factors studied, 4 are strongly related both to fertility and to mode of contraception: the waiting period, coital strategy, regularity of the menstrual cycle and the womans age. Shorter average time required to conceive (TRC) and greater fecundability are associated with the observation of a waiting period, no coital strategy, and regular cycles. The womans age at the time of unprotected intercourse shows no correlation with TRC; it does, however, show a correlation with fecundability, which increases with age to reach a maximum in the age group 25-29 and then decreases progressively. These 4 factors are also related to the mode of contraception. Those using hormonal contraception were more likely to observe a waiting period. However, they report a coital strategy less frequently, their usual cycle is more often irregular and they are younger than IUD or other method users. Results demonstrate a decreased fertility for couples after the pill and, to a lesser degree, after IUD use, but only among those who did not take other precautions (waiting period). For couples observing a waiting period, there is no decrease of fertility following the initial exposure to the risk of conception. This comparison of return of fertility following cessation of different contraceptive methods shows that raw data must be interpreted with caution. It is essential to take into account the possibility of delay in becoming exposed to the risk of conception while various confounding factors must also be considerd.

Abortion Rate in A.I.D. and Semen Characteristics: A Study of 1345 Pregnancies

Summary:  A study undertaken on 1345 pregnancies resulting from artificial insemination with donor showed an 18% risk of abortion. This figure is the same as that admitted for natural reproduction. It does not depend on any of the classically studied semen characteristics and in particular remains invariant whatever the postthaw motility, the factor most strongly linked to conception rate. Two results, well known from the literature, i.e. the increased abortion rate mentioned in natural reproduction when the sperm is of poor quality and the high incidence of repeated abortions when sperm quality is particularly good are discussed. The first of these results cannot be considered as being established in a statistically significant way. The second may result from different sources of bias, some of which are identified. In essence a high frequency of abortions signifies simply a high frequency of pregnancies, it is therefore not surprising that the semen is in this case particularly good.