Very late return of spermatogenesis after chlorambucil therapy: case reports.

Two men were treated for a nephrotic syndrome with high-dose chlorambucil therapy; 6.5 and 14 years later, respectively, both were azoospermic with high plasmatic FSH values. Both patients showed active spermatogenesis, 15 and 19 years after the end of the treatment. This suggests that a return of spermatogenesis can occur even after very high cumulative doses of chlorambucil (between 3,000 and 6,500 mg) and after a very long time.

Semen analysis in subfertile balanced-translocation carriers.

The spermograms of 19 subfertile translocation carriers were analyzed. Most of these men had moderate oligo-/astheno-/teratospermia. The results were widely spread, and some reached normal values, suggesting that autosomal rearrangement of the karyotype does not lead to severe oligospermia or azoospermia as do sex chromosome aberrations. No statistically significant differences in sperm count, motility, or morphology were found when semen analysis results of subfertile balanced-translocation carriers were compared with those of subfertile men with normal karyotypes. Since semen analysis alone is insufficient to allow prediction of an autosomal rearrangement of the karyotype, chromosome analysis should become a part of the routine investigation of subfertile men. The association between translocation heterozygosity and reduced fertility in men cannot be easily explained. The possible reasons underlying impaired spermatogenesis in some translocation carriers are discussed in relation to meiotic findings in animals.

[Fertility after antimitotic treatments]. / Fertilité après traitements cytostatiques.

Antimitotic chemotherapy and radiation therapy can induce temporary or permanent infertility in men, transitory amenorrhea or premature ovarian failure in women, and genetic mutations responsible of foetal deaths or congenital malformations in the progeny. Alkylating agents and radiotherapy can provoke definitive male infertility and ovarian failure, but individual susceptibility seems quite variable. In man, return of spermatogenesis can still be observed more than 10 years after treatment and pregnancies are obtained with very low sperm counts. In women, the progressive depletion of the follicular pool explains the increasing frequency of ovarian failure, with lower doses of treatment. Antimitotic and immunosuppressive therapy can also induce irreversible lesions in children's gonads.

[Toxicology of reproduction: predictive value of experimental models. Round Table No 1 at Giens XIII]. / Toxicologie de la reproduction: valeurs prédictives des modèles expérimentaux. Table Ronde No 1 de Giens XIII.

The carrying out of clinical trials with a view to the marketing of drugs for human use is directly related to results of some animal studies. This workshop was devoted to evaluation of the quality and interest of these experimental models in reproductive toxicology. The predictive ability of preclinical trials to make extrapolations from animals to man decreases from foetotoxic to tetratogenic risks respectively and from the effects on fertility in both sexes to postnatal risks. As a result of this workshop, we propose the following improvements: (1) standardization and generalization of fertility test evaluations, especially the spermogram, in order to improve animal and human correlations; (2) development of knowledge and standardization of the follow up of the oestral cycle; (3) improvement of standardization, harmonization and diffusion of postnatal tests that prove relevant in animals; (4) increase in initiatives aimed at better mutual understanding of all drug partners; (5) creation of registers for new drugs, as soon as possible during clinical trials, to study their effects on the whole reproductive process; (6) recommendations for the creation of guidelines for International Conference on Harmonisation (ICH) to enable classification of observed effects in experimental models. This could lead to specific (potentially for each phase of the reproductive cycle) guidelines, precautions for use and/or contraindications which are listed in the summary of product characteristics.

[Flagellar anomalies in routine spermatozoa cytograms]. / Les anomalies du flagelle dans le spermocytogramme.

In routine semen morphological analysis, flagellar abnormalities are often neglected. Four flagellar anomalies (absent, short, coiled and duplicated) are included in the French usual classification proposed by G. David et al. The present paper describes two new flagellar anomalies (thick and irregular) which are present in about 5% of spermatozoa in subfertile patients. These anomalies should be included in the morphological classification: first, chances of pregnancy are only correlated with precise morphological analysis. Furthermore, some infertile patients have severe asthenospermia due to flagellar anomalies which can be easily detected in routine semen analysis using this flagellar anomaly classification.

["In vitro" glass fiber filtration of sperm (author's transl)]. / La filtration "in vitro" du sperme sur laine de verre.

Filtering sperm through glass fiber has been suggested as a method for improving its fecundity before homologous artificial insemination. Various technical modification of this procedure have enabled good results to be obtained on spermatozoid mobility but at the expense of a marked drop in numbers: sperm counts per ml are diminished by a half. A comparative in vitro study of the penetration of filtered and non-filtered sperm into the cervical mucus showed that glass fiber filtration produced generally no great improvement, and may indeed reduce penetration into the cervical mucus to a marked degree in some cases.

[Toxoplasmosis and pregnancy. Evaluation of 2 years of prevention of congenital toxoplasmosis in the maternity ward of Hôpital Saint-Antoine (1973-1974)]. / Toxoplasmose et grossesse. Bilan de deux ans de prophylaxie de la toxoplasmose congénitale à la maternité de l'hôpital Saint-Antoine (1) (1973-1974)

The authors report the results of prophylaxis of congenital toxoplasmosis in a maternity hospital in Paris for a two years period (1973-1974). 6269 pregnant women were surveyed. 18 toxoplasmosis were detected in evolution at the first prenatal examination, 10 seroconversions were identified among the first examination antibody negative women, when re-examined during the pregnancy. 25 of these 28 women were treated regularly. The seroconversions of the 3 other women were detected only at delivery. In addition 25 women were treated because of high antibody titers (Dye-Test greater than or equal to 300. U.I/ml). 6 congenital toxoplasmosis, 2 of them were manifest, were observed among the children whose mothers were treated for confirmed toxoplasmosis. The extremely low level of seroconversions may be in relation to hygienic and dietetic prescriptions. The difficulties of this prophylaxis are analysed: they are due to studied population and to problems of interpretation or serologic examinations.

[Balanced translocations with abnormal phenotype (author's transl)]. / Translocations apparemment équilibrées à phénotype anormal.

Four cases of balanced translocations with phenotype abnormalities are reported. Three of them are reciprocal translocation, one is a Robertsonnian translocation. The consequences of the phenomene on genetic counselling and prenatal diagnosis are discussed.

[The correlation between the results of caryotype studies and sperm counts. 119 cases (author's transl)]. / Corrélation entre les résultats du caryotype et ceux du spermogramme. 119 cas.

119 patients had sperm counts and caryotyping performed. Seven out of 33 azoospermic patients had a major caryotype abnormality of the gonosomes. Five out of 86 subjects who were not azoospermic had a persistent translocation and other moderate abnormalities in the sperm picture.

[Is today's man really less fertile?]. / L'homme d'aujourd'hui est-il vraiment moins fertile?

In 1992, a statistical analysis of data from 61 studies of semen quality among normal men led to the conclusion that human sperm count fell of 40% from 1940 to 1990. This meta-analysis has since been invalidated for methodological reasons as well as for statistical reasons, but it caused enormous concern to both the scientific community and to the international media. A decline of human fertility was speculated. To date, the most popular hypothesis offered to explain this alleged decline has been increasing exposure to environmental estrogen mimicking chemicals. However, there is no evidence that male or mammal fertility is declining. Moreover, the sperm count of breeding mammals did not declined in the meanwhile. Since 1992, numerous papers reported on men investigated during the last 20 years have shown conflicting results, from sperm count improvement to sperm count decline. However, several publications included methodological and analytical biases. In fact, the techniques used for semen analysis have to be questioned. It is a subjective exam, lacking laboratory standards and quality control procedures. This induces very important variations between laboratories and between biologists. For the sperm count itself, numerous errors can occur, provoked by the technique, the equipment and the reader: for the same sperm, the coefficient of variation can exceed 40% between two technicians. Therefore, the current techniques of semen analysis cannot warrant epidemiological studies. It is indispensable to admit the limits of the semen analysis in order to improve as much as possible its quality and its reliability.

Acute respiratory distress syndrome due to pulmonary involvement by neoplastic plasma cells in multiple myeloma.

Pulmonary involvement with multiple myeloma occurs infrequently and may be difficult to distinguish from more common primary lung tumours, metastatic disease, or other pleural and parenchymal abnormalities. A patient who developed acute respiratory distress syndrome (ARDS) was subsequently found to have multiple myeloma with involvement of lung parenchyma by neoplastic plasma cells. Only one other report of ARDS in association with multiple myeloma was found, and there are no previous reports where the appearance of ARDS antedated a diagnosis of multiple myeloma. In patients with ARDS, parenchymal involvement from multiple myeloma should be included in the differential diagnosis.

[Fertility in women after cancer therapy]. / Fertilité féminine après traitement anticancéreux.

In children and young women, antimitotic chemotherapy and radiotherapy can provoke premature ovarian failure, as well as chromosomal or genic mutations potentially responsible of pregnancy wastage, congenital malformations or genetic diseases in the progeny. After an abdominal radiotherapy, the long term sequelae of uterine irradiation can induce pregnancy wastage, prematurity or low birth-weight. Irreversible ovarian damages are mainly due to alkylating agents and abdominal radiotherapy. The gradual depletion of the follicular pool accounts for the apparent increasing ovarian sensitivity: in women over 40, almost any therapy can be responsible of an immediate menopause, while in younger patients retaining a normal ovarian function at the end of a treatment including alkylating agents or an abdominal radiotherapy, a premature ovarian failure will occur several years later.

[Fertility after cytostatic treatments]. / Fertilité après traitements cytostatiques.

Antimitotic chemotherapy and radiation therapy can induce temporary or permanent infertility in men, transitory amenorrhea or premature ovarian failure in women, and genetic mutations responsible of fetal deaths or congenital malformations in the progeny. Alkylating agents and radiotherapy can provoke definitive male infertility and ovarian failure, but individual susceptibility seems quite variable. In man, return of spermatogenesis can still be observed more than 10 years after treatment and pregnancies are obtained with very low sperm counts. In women, the progressive depletion of the follicular pool explains the increasing frequency of ovarian failure, with lower doses of treatment. Antimitotic and immunosuppressive therapy can also induce irreversible lesions in children's gonads.

Male reproductive potential after MOPP therapy for Hodgkin's disease: a long-term survey.

The testicular function of 47 men who had been treated by MOPP chemotherapy for a Hodgkin's disease was studied in a long-term survey. Azoospermia was constant during at least 14 months after completion of the treatment. After a follow-up period of 89.4 +/- 54.7 months, 26 men were still azoospermic. No correlation could be found between the therapeutic regimen and the results of semen analysis. For the same treatment, some men recovered spermatogenesis within 5 years, others after more than 10 years while some were still azoospermic after 20 years. However, the association of infra-diaphragmatic irradiation to high dose MOPP therapy had a profound detrimental effect on spermatogenesis: only 3/13 men recovered. Sperm recovery was often incomplete: 17/21 men had a sperm count below 20 million ml-1. Yet, spontaneous pregnancies were obtained with severe oligozoospermia: only 1/11 sperm counts performed close to fertilization exceeded 20 million ml-1, and 8 were below 5 millions ml-1. FSH failed to be either a sensitive or a specific marker of sperm recovery, a discrepancy between FSH level and spermiogram being noticed in 18.2% of cases.

[Spermatology, a whole separate discipline]. / La spermiologie, une discipline à part entière.

The diagnosis of semen anomalies is mainly subjective and requires therefore extensive training. Presently, no automated technology, no recent exam has proven to be superior to the spermogram and the analysis of sperm penetration into cervical mucus for the diagnosis and prognosis of male infertility. Furthermore, the preparation of an abnormal semen for insemination or IVF requires a good experience of the different techniques and a lot of time. Even when the number of motile spermatozoa recovered reaches normal values, the pregnancy rate is always low when compared with the results obtained with a normal sperm.

Male infertility due to asthenozoospermia and flagellar anomaly: detection in routine semen analysis.

Major monomorphous teratozoospermia, due to sperm tail structural anomalies, were detected in 42 out of 4231 infertile patients during routine semen analysis. The flagella were very short or absent in 16 cases, shortened with thickness irregularity in 18 cases, and of normal length with diameter anomalies in eight cases. These syndromes were always associated with poor forward motility, while mobility and penetration into human cervical mucus were sometimes impaired only partially. With good sperm smears and an experienced observer, the diagnosis could be made without the need for electron microscopic analysis. All the affected patients were sterile and several syndromes could have been transmitted genetically.

Semen analysis in Hodgkin's disease before the onset of treatment.

A spermogram was performed before treatment in 57 young patients with Hodgkin's disease. The mean results were normal, and similar to those reported in fertile populations. Nineteen patients had an abnormal spermogram; 12 of these men had had fever recently or were febrile at the time of the exam. When the temperature was below 38.5 degrees C, there was only asthenospermia. With a higher temperature, semen anomalies were more severe, with oligoasthenospermia or even azoospermia. Only five febrile men had a normal spermogram, and all had slight fevers. Therefore, semen anomalies noted in about one third of patients with Hodgkin's disease are probably not due to a disease specific gonadal alteration, but can be attributed to fever which gonadal effects have been recognized for a long time and are well-documented.

WAIS-III and WMS-III profiles of mildly to severely brain-injured patients.

Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-III (WMS-III; The Psychological Corporation, 1997) scores of patients with mild traumatic brain injury (MTBI, n = 23) to moderate-severe traumatic brain injury (M-S TBI, n = 22) were compared to those of 45 matched normal control patients. WAIS-III results revealed that IQ and index scores of MTBI patients did not significantly differ from those of controls, whereas M-S TBI patients received significantly lower mean scores on all measures. All M-S TBI patients' WMS-III index scores also revealed significantly lower scores in comparison to those of control participants, with the exception of Delayed Auditory Recognition. MTBI patients showed significantly lower mean index scores compared to normal controls on measures of immediate and delayed auditory memory, immediate memory, visual delayed memory, and general memory. Eta-squared analyses revealed that WMS-III visual indexes and WAIS-III processing speed showed particularly large effect sizes. These results suggest that symptomatic MTBI patients obtain some low WMS-III test scores comparable to those of more severely injured patients.