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In this last century, an increase of men infertility has been registered. It has been suggested that environmental factors could a negative impact over sperm quality. Among these factors, impact of environmental toxicant has been spread by media. In this review of scientific literature, we identify several environmental factors that could impact men fertility in a negative way. These factors are tobacco, marijuana, weight, body mass index, heat, nutritional state, electromagnetic waves and altitude. For each of these factors, the impact over men fertility, their mechanism, as well their influence over the use of Assisted Reproductive Technics are reported., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

In France, there does exist any age limit for infertile men management neither in the law nor for the coverage by the "French Assurance Maladie". French law specifies only that both partners of the couple have to be "of childbearing age", but there is no definition for men of childbearing age. Does legislation have to determine a limit on man management in function of his age? Could ART practitioners decide (themselves) whether they take care of infertile men or not? Should male age be a criteria to decide this management? Would ART practitioners "need" a legislation to help them to decide? In 2016, the "French Assurance Maladie" covers all costs for infertile couple if woman is less than 43 years old, whatever male age. If an age-threshold should be establish for the coverage of infertile men management by the "French Assurance Maladie", then what should be this threshold? In order to try to answer these questions, we asked them to French ART practitioners (gynecologists and embryologists) and gynecologists. The first questionnaire included 13 questions and was filled by 244 ART specialists; the second was filled by 138 gynecologists. Most of them agree to limit the male management and the coverage by the "French Assurance Maladie" at 60 for men in ART. Gynecologists who does not practice ART wish a limit for insurance (80% of them but are only 57% to wish a legal limit)., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The presence of bacteria in semen could induce impairment of sperm morphology, alteration of sperm function and mechanical or functional obstruction of the seminal tract. The term of bacteriospermia does not signify infection. Bacteriospermia and male accessory gland infection (MAGI) have indeed to be distinguished. They may lead both to male infertility but their diagnosis and treatment options differ. This review summarizes effects of bacteria and leucocytospermia on sperm parameters and functions. Then, indications, benefits and risks of treatment of bacteriospermia and MAGI, in assisted reproductive techniques (ART) will be discussed. For bacteria commonly observed in semen, this review aims at defining some thresholds above which a treatment is required. These thresholds were established according to literature, according to French microbiology society and in function of our usual practice. This review should help practitioners of reproductive medicine to take care of bacteriospermia in semen., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The development of FISH and ART identified aneuploidy in polar body. The presence of these oocyte abnormalities conducts to implantation failure. The aim of the new technique is to select the best oocyte by complete chromosome analysis, and study of second polar body., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

When one thinks of the failures of ART one naturally thinks of the suffering that they generate; but behind this pain, there is the suffering of infertility and, behind this latter, other distress we showed at the time of a recent research that they could play a part in infertility itself. The psychotherapy will help assume the failures, so that the traumatisms do not come to solidify in an impossible mourning, covering non elaborate former grieves. A sublimation of the desire of reproduction can make it possible for the unfertile man to peacefully consider other forms of paternity. For it to be possible, it is necessary that the subject should not be in the refusal of the psychic effraction, which the announcement of its infertility produces. When it is the case, to put on the couple on psychological assistance may help to restore a share of the narcissistic wounds; more particularly the one related to the suffering of the couple that often comes to be added to the wound of infertility.

Numerous recent studies involve DNA damages associated with poor fertilization rates, early embryo development defect, and poor quality of conceptus following Assisted Reproductive Technologies (ART). The authors denounce a particularly high rate of miscarriages and childhood cancer or dominant genetic mutations such as achondroplasia, Apert syndrome or aberrant gene imprinting such as Angelman and Beckwith Wiedeman syndromes. Gametes DNA defects have numerous origins which are difficult to determine; they are known to involve hypomethylation, oxydative stress and environmental factors.(adducts formation). DNA defect is also linked to a more or less delayed apoptotic phenomenon. Exposure to radiations or radiofrequency electromagnetic emissions can also induce DNA alterations into the spermatozoa of infertile men. Although the underlying mechanisms are unclear, these DNA defects have obvious consequences on reproduction of mammalian species. Detection of such anomalies before ART, are an important step toward developing strategies for clinical management according to the aetiology.

Several epidemiologic studies have demonstrated during the last 50 years an increased incidence in testis cancer, male genital tract malformations (cryptorchidism and hypospadias) and a decrease in sperm quality in men. These three pathologies seem to be linked and to belong to the testicular dysgenesis syndrome (TDS). It was suggested that TDS is a consequence of intra-uterine exposure to environmental compounds that disrupt the metabolism of native hormones. Such substances are so called endocrine disruptors (EDs). EDs are present in our daily environment such as food and water (through the use of pesticides), cosmetics, house-care products etc. Experimental models have been carried out to (i) establish a link between EDs exposure and SDT and (ii) identify the mechanisms that are involved in. After a brief definition of EDs and having underlined the importance of the window of exposure to EDs, several mechanisms will be described such as (i) intergenerational transmission (epigenetic), (ii) programmed cell death of testicular cells, (iii) modification of the androgenic signal and (iv) role of the germ cells-nourishing cells. To conclude, we will try to propose some biomarkers that would be useful to identify the potential link between fetal exposure to anti-androgenic EDs and male testicular pathology.

The effect of maternal age on the risk of meiotic abnormality is well documented. In contrast little is known about the effect of the paternal age. The question of the risk related to paternal age is raised because of the increased demand of Assisted Reproduction Techniques for older men. This review focuses on the alterations of male semen parameters, testis histology and genetic risks related to age. The motility, vitality and morphology of spermatozoa and semen volume are found decreasing with age. Histomorphometric studies reveal various alterations including a thickening of the basal membrane when spermatogenesis is arrested. The number of germinal and Sertoli cells decreases with increased age. Up to 95 years old, we could find subjects with complete spermatogenesis. Chromosomal analyses in different studies have provided controversial results. Our investigation on subjects aged from 29 to 102 showed that the rate of aneuploidy in the group of aged subjects with preserved spermatogenesis was not statistically different from the young control group. However the incidence of postmeiotic aneuploidy was increased when spermiogenesis had stopped. On the other hand from epidemiological studies, autosomal dominant diseases are known to be associated with paternal age. However, in the case of achondroplasia and Apert syndrome, direct DNA sperm analysis did not reveal significant increase in the mutation frequency with paternal age.

In our species, reproduction failure rate is high. Clinical evidence is miscarriage where chromosomal origin was largely involved (66% of cases). The development of assisted reproduction techniques made possible to analyse unfertilized oocytes and preimplantation embryos. The results have shown a high rate of chromosome abnormalities before implantation (50%). Two mechanisms were identified which could generate aneuploidy, the meiosis non-disjunction and the premature separation of sister chromatids (PSSC). A FISH analysis of the first polar body, a cell complementary to the oocyte after meiosis, can be performed before intracytoplasmic sperm injection. We studied 2 distinct populations (patients over 38 years old and patients with recurrent implantation failure) and we confirmed that PSSC is the major mechanism linked to advanced maternal age in human.

Objective: The increase of frequency of Assisted Reproductive Techniques (ART) for elder men raises the question of the genetic risk for the offspring. Our aim was to evaluate the influence of ageing on the testicular histology, the aneuploidy rate in testis postmeiotic cells and the DNA fragmentation in sperm., Patients and Methods: We performed a histomorphometric study of 36 men aged from 61 to 102 years and 10 young men from 29 to 40 years. The aneuploidy rate was evaluated by fluorescent in situ hybridation (FISH X, Y, 18) and DNA fragmentation in spermatozoa was evaluated by TUNEL., Results: Histomorphometry showed various alterations of testicular histology with age including thickening of the basal membrane when spermatogenesis was arrested. The number of germinal cells and Sertoli cells decreased with age with important individual variations. Nevertheless spermatogenesis could be possible until 95 years. The rate of aneuploidy was not influenced by age when spermatogenesis was complete. However, we observed an increased aneuploidy rate in postmeiotic cells when spermiogenesis was arrested. On the other hand apoptosis was not increased with age., Discussion and Conclusion: Our study confirms that spermatogenesis is possible until a very advanced age (95 years) without any specific chromosome risk. The question of mutagenesis remains to be solved.

Knowledge of the human genome has opened the genomic era. The genome instability, its causes and the possible consequences especially about fertility start to be understood. This instability can be observed on chromosome structure but also on genes. Different chromosomes rearrangements involved in infertility including translocations and Y chromosome deletions are described. The Y chromosome is a model of instability, and this instability is the source of its evolution. All those rearrangements are the results of illegitimate recombinations between homologous sequences. On genes we find punctual and dynamic mutations, polymorphisms and epigenetic abnormalities. They all are the results of ADN replication mistakes not corrected by the cellular machine. This machinery is the guardian of the genome integrity and in case of abnormality the programmed cellular death is induced. The knowledge of all these instability mechanisms is essential to appreciate the risk for the offspring after intracytoplasmic sperm injection. Indeed we go round physiological barriers without a complete understanding of the mechanisms involved. Thus, this is an important challenge for research teams but also for all assisted reproduction centers, dealing with ART. Genome is unstable - the very basis of its evolution. But this is also the cause of mistakes with pathological consequences like infertility and mental retardation.

Objectives: This prospective study aimed to evaluate the impact of oocyte dysmorphy on the fertilization rate and embryonic development rate in an ICSI programme., Patients and Methods: Three hundred and two couples have been included during 302 ICSI cycles, and 1970 oocytes have been studied in 4 ART centres. After decoronisation, 18 morphological criteria, including the size and shape of the oocyte, the thickness of the zona pellucida, the presence or not of debris in the perivitelline space, as well as the appearance of the cytoplasm and polar body have been noted., Results: In total 61.3% of the oocytes presented a dysmorphy, involving, almost equally, the different oocyte compartments. Among the dysmorphic oocytes, half presented more than one anomaly. On average, 9.2% of the oocytes were lysed the day after the micro-injection. The oocytes presenting an enlarged perivitelline space, or multiple vacuoles had a significantly raised lyse rate, 16.3% and 27.8%, respectively. The day after micro-injection, 61.3% of the intact oocytes were fertilized. The rate of fertilization was correlated to the number of abnormalities per oocyte: 1 anomaly: 64.6%, > or = 3 anomalies: 54.6%. The oocytes presenting a large perivitelline space had a slightly lowered fertilization rate (53.4%). On the other hand, those showing a cytoplasm containing refractile bodies had a slightly raised fertilization rate (68.6%). We did not see any statistically significant difference between the different types of oocytes concerning embryonic development at d2., Conclusion: These results confirm and contribute new elements with respect to previously published data, showing that (i) oocyte morphology little affects fertilization and the first stages of embryonic development; (ii) certain dysmorphies, (enlargement of the perivitelline space) are specifically deleterious at certain stages in the process (lowering the fertilization rate); (iii) certain morphological differences (the presence of refringent bodies) are not anomalies, but can reflect physiological cellular changes.

Management of male infertility has been totally changed with the development of intracytoplasmic sperm injection (ICSI). This technique, used for in vitro fertilization, consists in injecting a single spermatozoa into the ovum. Intracytoplasmic sperm injection can be proposed in case of severe male sterility (oligoasthenospermia) or after repeated failure of in vitro fertilization. Satisfactory rates of fecondation and pregnancy have been obtained. Results have also been obtained with sperm taken from the epididymis or testis. The risks involved concern the transmission of poorly understood genetic defects leading to the infertility. The rates of reported malformations and chromosome anomalies are quite low. Intracytoplasmic sperm injection can be useful in managing most cases of male infertility which to date have had to rely on donor sperm. Long-term results have not yet been obtained.

After standard in vitro fertilization (IVF) chromosome analysis of uncleaved oocytes has shown that in about 80% of the cases, there was no fertilization at all while in 10% of the cases there was a premature chromosome condensation and a development arrest. After micro-injection our results suggest that both the technique itself and the pathologies which require micro-injection can influence the results. On the other hand about 20-30% of the metaphase II oocytes are cytogenetically abnormal after IVF attempt while ICSI might increase chromosome breakage. Our results suggest that both the technique used and the gamete pathologies can influence the different steps of development arrest.

Prenatal diagnosis based on sampling of fetal tissues, amniotic fluid or chorionic villi is associated with the risk of miscarriage and fetal damage. These risks would be avoided if diagnosis could be performed in desquamated trophoblast cells recovered non-invasively from the maternal cervix. We report on our experience of fetal karyotyping on endocervical lavage using in situ hybridization (FISH) and DNA amplification (PCR) fetal sex was correctly predicted in 8/10 cases by FISH and in 6/10 by PCR. FISH appeared to be a reliable technique for karyotyping when trophoblast can be recovered from the maternal endocervix (8/10).

In spite of the progress in in vitro fertilization (IVF), implantation rate of IVF embryos remains low. Many factors seem to be involved in these results. Among them, impairment of the hatching process was incriminated by some authors. Assisted hatching seems to be an interesting method for repeated failures of IVF.

From a collaborative study of the French "Federation des CECOS" who collected the follow up of 11,535 pregnancies, the effect of parental age on the offspring is studied. A significant influence of the donor's age is demonstrated for the occurrence of trisomy 21 (37.4 +/- 7.8 vs 34.5 +/- 6.0; p < 0.05).

The level of circulating myeloid progenitor cells (CFU-G), considered to be a good index of the quantity of circulating hemopoietic stem cells, was measured in the peripheral blood of 5 patients with acute leukemia as they entered first remission. High levels of circulating CFU-G were found in 4 of these 5 patients, depending on the intensity and the number of courses of induction chemotherapy. Repeated cytaphereses were done on 3 of these patients in order to collect and to cryopreserve circulating stem cells, to be used later for autologous transplantation. We propose a model which calculates the number of cytaphereses sufficient to obtain a level of 10(5) CFU-G/kg of weight, considered necessary to achieve a good hemopoietic reconstitution after transplantation.

A case of congenital dysmyelinating neuropathy is reported, in which computerised morphological analysis showed a prominent loss of fibers with large axons, in addition to overall thinness of myelin sheath. Ultrastructural examination showed aberrant formation of basal lamina and abnormal ensheathment by Schwann cells of both myelinated and unmyelinated fibers. Hypomyelination appears to be only one aspect of this neuropathy, in which axonal pathology plays a major role.

An investigation of Cad phenotypes in the French population had been carried out in 1973, in four Blood Transfusion Centers (Mulhouse, Nancy, Paris, Versailles), B and O red cells were tested with the Dolichos Biflorus lectin. Out of 78.528 donors, 56 were found to have the Cad antigen on their red cells. The mean frequency was 0,07%. Nevertheless, this frequency varied among the four above mentioned Blood Transfusion Centers: the observed differences were probably due to the preparation procedure of the Dolichos biflorus extract. The family investigation permitted the analysis of four families with at least three Cad individuals. The independence of the Cad system and of Auberger, Gc, Hp, C'3, PGM, Pac and ADA was demonstrated. A quantitative agglutination study on these Cad samples using the Dolichos biflorus lectin,and a selected AB serum showed a high variability of the erythrocyte Cad Strength, even within one family. Most Cad samples were found polyagglutinable when a sensitive technique and selected AB sera were used. All adult sera contained an anti-Cad1 antibody, except Cad1 individuals. Although strong Sda reactivity was always found in Cad red cells, the anti-Cad and anti Sda specificities were not identical: this was demonstrated by the absorption and inhibition tests of anti-Cad and anti-Sda reagents absorption and inhibition tests of anti-Cad and anti-Sda reagents with Sda material. From thf Cad red cells, there was no evidence of the existence of separable anti-A1 and anti-Cad agglutinins in the Dolichos biflorus lectin.

Artificial insemination with donors has genetic repercussions which increase with its impact on demography. Genetic control of semen donors offers a possibility of preventing the main genetic handicaps. The French Federation of Human Semen Study and Preservation Centres (CECOS) is currently organizing such a control system. The reasons for this and the modalities of the system are given in this article.