[Do folates have an impact on fertility?]. / Les folates: quel impact sur la fertilité?

Folates are group B vitamins involved in the one-carbon metabolism. They are required for purine and pyrimidine, and thus DNA synthesis, as well as for the remethylation of homocysteine into methionine which is further metabolized into S-adenosylmethionine, the universal methyl donor for transmethylation of DNA. By this way, folates play a key role in epigenetic regulation of gene expression. Folate deficiency, either by insufficient nutritional uptake or linked to some single nucleotide polymorphism, will lead to an impaired DNA synthesis and repair, a hypomethylation of DNA and other molecules, and homocysteine accumulation. This situation has been associated with several pathologies, such as cardiovascular and neurodegenerative diseases, and pregnancy complications. However, much less is known until now about the impact of one-carbon metabolism on initial events of human reproduction, from gametogenesis to early embryonic development. The present review will deal with these aspects of folate metabolism with respect to male and female fertility.

[Sophrology: a different tool for infertile couples]. / La sophrologie caycédienne: une autre approche du couple infertile.

Because of the high degree of complexity of assisted reproduction techniques (ART), the human and conscious dimensions of infertility problems are often neglected. Different strategies may help infertile couples coping with infertility and related treatments; among these, Caycedian sophrology relies on the cognitive, emotional, and somatic aspects of consciousness. In the present article, the authors report on their experience with sophrologic support for infertile patients by a midwife qualified in caycedian sophrology. Overall, since 1988, 310 couples have benefied from this kind of support, with an average of 10 sophrologic trainings per patient. Whereas some couples consider sophrology as a short time training to better cope with any particular aspect of their infertility treatment, others want to undertake more profound work on their body scheme. The authors wish to call the attention of ART professionals to this kind of medical support for infertile couples, and also to the particular role of midwives with sophrologic competence in an ART center.

[Cigarette smoking and fertility in women and men]. / Tabac et fertilité chez la femme et l'homme.

Cigarette smoking consequences on female and male reproduction have been evaluated for twenty years only and thus poorly spread in the general population. However, several studies have noticed noxious effects of tobacco before and after conception, in both women and men, from smokers gametes to their offspring. This negative impact occurs in spontaneous as well as in assisted reproduction (ART). For women, pregnancy rate is decreased, early spontaneous abortions are increased and ovarian reserve is altered. For men, standard sperm parameters are modified and spermatozoon nuclear quality is compromised. One of the mechanisms involved in those anomalies could be the oxidative stress produced by some cigarette smoking components. The consequences on smokers offspring are hardly evaluated yet: pathologies of the respiratory system, decrease of fecundity and cancers outcomes. In conclusion, it seems obvious that smokers - men as women - have to quit smoking before having a parental project.

Pathophysiology of impaired ovarian function in galactosaemia.

Classical galactosaemia is an inherited inborn error of the major galactose assimilation pathway, caused by galactose-1-phosphate uridyltransferase (GALT) deficiency. Many GALT mutations have been described, with different clinical consequences. In severe forms, newborns present with a life-threatening, acute toxic syndrome that rapidly regresses under a galactose-restricted diet. However, long-term complications, particularly cognitive and motor abnormalities, as well as hypergonadotrophic hypogonadism in female patients are still unavoidable. The pathogenesis of galactose-induced ovarian toxicity remains unclear but probably involves galactose itself and its metabolites such as galactitol and UDP-galactose. Possible mechanisms of ovarian damage include direct toxicity of galactose and metabolites, deficient galactosylation of glycoproteins and glycolipids, oxidative stress and activation of apoptosis. As there is no aetiological treatment, clinical management of ovarian failure in galactosaemic patients principally relies on hormonal replacement therapy to induce pubertal development and to prevent bone loss and other consequences of estrogen deprivation. Further investigations will be necessary to better understand the metabolic flux of galactose through its biochemical pathways and the mechanisms of these secondary complications. The aim of this article is to present an extensive review on the pathogenesis and clinical management of galactose-induced premature ovarian failure.

[Ovarian autoimmunity and ovarian pathologies: antigenic targets and diagnostic significance]. / Auto-immunité anti-ovarienne et pathologies ovariennes: cibles antigéniques et implications diagnostiques.

The involvement of serum anti-ovarian autoantibodies (AOA) in ovarian pathology still remains controversial. In some cases of clinically patent ovarian failure, there seems to be a causal relationship between AOA and the ovarian disease. In patients with various organ-specific or systemic autoimmune diseases, or with unexplained, repeated reproductive failure, but otherwise normal ovarian function, it is even more difficult to determine the significance of AOA for several reasons: i) AOA recognize many different antigenic targets in the ovary ii) the antiovarian response may be transient or variable with time iii) the presence of AOA does not imply their aetiopathogenic role in the disease. The present paper reviews the clinical significance of AOA based on their ovarian targets as far as they have been identified until now.

Immunolocalization of sex hormone-binding globulin (SHBG) in human ovarian follicles and corpus luteum.

Sex hormone-binding globulin (SHBG), a hepatic carrier protein for sex steroids is expressed in different steroid-sensitive tissues, including Sertoli cells of the testis. It has been suggested that this protein may be one of the local regulators of spermatogenesis. The expression of SHBG in the ovary is currently unknown. We have previously demonstrated the synthesis of SHBG in granulosa-lutein cells from patients undergoing in vitro fertilization. In this study, the presence of SHBG in human ovarian follicles and corpora lutea is investigated, using immunohistochemistry on adult and fetal ovarian tissue sections. SHBG is localized in the whole granulosa layer at all stages of folliculogenesis, whereas, only isolated theca cells are immunostained. In primordial and primary follicles, the oocyte cytoplasm shows an intense immunostaining, which disappears after the secondary stage. In the microenvironment of the mature oocytes, SHBG is present in the surrounding cumulus cells, the perivitelline space, and nearby the oolemma. In the corpus luteum, SHBG is localized in large luteal cells, whereas, small luteal cells do not show any significant staining. By analogy with the testis, these results raise the question of an involvement of SHBG in the regulation of follicular maturation as well as in luteal function.

[Consequences of cigarette smoking on male fertility]. / Conséquences du tabac sur la fertilité masculine.

The different studies conducted over the last fifteen years on the consequences of cigarette smoking on male fertility have shown a decrease of sperm quality in smokers. In fact, the components of cigarette smoke pass through the blood-testis barrier and thus induce an alteration of sperm parameters and nucleus quality of the spermatozoa. Beyond this decrease of sperm quality, cigarette smoking also appears to have an impact on the smoker's offspring: lower embryo quality, increased risks to develop a childhood cancer. The pathophysiologic mechanisms are not yet clearly understood, but one of the most likely hypotheses is the production of an oxidative stress which is responsible for DNA fragmentation compromising the chances of pregnancy. In addition to the spermogram, further tests available in specialized laboratories can be prescribed to evaluate spermatozoal DNA fragmentation (TUNEL Assay, SCSA...). Antioxidant treatment can be administrated to reduce DNA fragmentation and increase the chances of pregnancy.

[Is there a future for Fallopian tube insemination in women?]. / L'insémination tubaire chez la femme a-t-elle un avenir?

In unselected patients, the pregnancy rate after intrauterine insemination (i.u.i.) seldom goes beyond 10-15% per cycle. An insufficient number of spermatozoa at the fertilization site has been hypothesized for a long time to explain the low efficacy of this technique. Thus, the introduction of a larger number of male gametes into the female tubes has been thought of to give better results since the late eighties. First, a direct tubal catheterisation has been proposed for injection of spermatozoa, either by laparoscopy or transvaginally under ultrasound guidance or by tactile sensation. However, these procedures have been abandoned because of some severe traumatic and infectious complications. Alternatively, a spermatozoa suspension of several millilitres can be injected under pressure into the uterine cavity while sealing the cervical os, by various systems. This technique called Fallopian sperm perfusion (FSP) has yielded some interesting results, particularly in unexplained infertility. Nevertheless, the superiority of FSP over i.u.i. still remains controversial. This review describes the current knowledge about intratubal insemination and its potential role in the management of human infertility.

[Negative impact of cigarette smoking on male fertility: from spermatozoa to the offspring]. / Impact négatif du tabac sur la fertilité masculine: des spermatozoïdes à la descendance.

Cigarette smoking has negative effects on male fertility. Recent studies showed an active transfer of several components of cigarettes through the blood-testis barrier. The presence of these components in the seminal plasma may induce a degradation of sperm parameters and nuclear quality of spermatozoa, and compromise the chances of pregnancy. Moreover, smoking may have a negative impact on the smokers'offspring: poor quality embryos, development of childhood cancers. Oxidative stress-induced DNA damage seems to be one of the major causes of sperm quality alteration. Several methods are now available to analyze the degree of DNA fragmentation. In order to optimize the success rate of assisted reproduction technologies, the deleterious effects of smoking on male fertility and the necessity of cessation have to be explained in detail to these patients.

Expression of sex hormone-binding globulin (SHBG) in human granulosa-lutein cells.

Sex hormone-binding globulin (SHBG) was classically thought to be a plasma steroid-carrying protein of hepatic origin, but recently, locally produced, membrane-bound SHBG has been shown to influence cell functions in several steroid-responsive tissues. In the ovary, SHBG is known to be present in the follicular fluid, but information about a possible intracellular presence of SHBG in this organ is still very scarce. In this study the presence of SHBG was assessed by immunohistochemistry in human granulosa-lutein cells (GLC) collected by follicle puncture for in vitro fertilization. SHBG was detected in the cytoplasm of GLC before and after in vitro culture for up to 96 h. The presence of full-length SHBG messenger RNA was demonstrated in GLC by reverse transcription-polymerase chain reaction (RT-PCR) in both cultured and uncultured cells. These results demonstrate a local synthesis of SHBG in GLC and raise the question of the physiological significance of these findings in follicular physiology.

Autoimmunity and antigenic targets in ovarian pathology.

The involvement of autoimmune mechanisms in premature ovarian failure has been put forward by numerous investigators. In various other ovarian pathologies, such as idiopathic infertility, polycystic ovary syndrome, or endometriosis, similar mechanisms have been suggested. However, the exact role of autoimmunity in the pathophysiology of these diseases still remains controversial. The diagnosis of autoimmune ovarian disease relies on several clinical, biological and histological findings, but special interest has been focused on antiovarian autoantibodies. The search for these antibodies has been undertaken by several authors and yielded somewhat conflicting results which might be conditioned by methodological differences and by the multiplicity of potential immune targets. These targets, which comprise various steroidogenic enzymes, gonadotrophins and their receptors, the corpus luteum, zona pellucida and oocyte, are reviewed. Further investigation of these targets is required to improve the diagnostic tools that will lead to a precocious and reliable diagnosis of autoimmune ovarian disease, an appropriate clinical surveillance as well as the selection of patients who may benefit from immune-modulating therapy and possibly recover ovarian function and fertility.

[What are the antigenic targets in the ovary?]. / Quelles cibles antigéniques dans l'ovaire?

The ovary can be the target of an autoimmune disease involving many different autoantigens. The clinical feature of this disease often results in premature ovarian failure or infertility and may be either isolated or associated with other autoimmune pathologies, especially with adrenal autoimmunity. The diagnosis of an autoimmune mechanism relies on the presence of anti-ovarian antibodies, whose prevalence is quite variable according to the different methods used to detect them, and to the different stages of the disease. In addition, their clinical significance is not always clear, as to their pathologic or epiphenomenal nature. However, the study of these autoantibodies has led to the identification of some of their antigenic targets which have to be known for a better understanding of the pathologic mechanisms involved. This paper reviews anti-steroid producing cells, anti-gonadotrophin receptor, anti-gonadotrophin, anti-corpus luteum, anti-zona pellucida and anti-oocyte antibodies.

[Premature ovarian failure in galactosaemia: pathophysiology and clinical management]. / L'insuffisance ovarienne prématurée dans la galactosémie congénitale: physiopathologie et prise en charge.

Classic galactosaemia is a rare aetiology of premature ovarian failure. It is caused by galactose-1-phosphate uridyltransferase deficiency and leads to a severe disease in the newborn. This acute toxic syndrome will completely regress under a galactose-free diet, but some long-term complications, particularly hypergonadotropic hypogonadism in female patients, are frequently observed. Ovarian toxicity could be due to intracellular accumulation of galactose metabolites or to deficient glycosylation reactions. Moreover, the tremendous follicular decrease in the galactosaemic ovary could also involve programmed cell death (apoptosis). As the exact mechanisms of this ovarian injury are still unknown, there is no prevention of follicular loss, thus clinical management especially includes hormonal replacement therapy in order to prevent bone loss and cardiovascular risks and sometimes to allow patients to become pregnant.

[The genetic basis of premature ovarian failure]. / Les bases génétiques de la défaillance ovarienne prématurée.

Premature ovarian failure is defined by the association of amenorrhea, elevated levels of serum gonadotropins and hypoestrogenism occuring before the age of forty. In a growing number of these cases, genetic disorders have been shown to be involved. Cytogenetic abnormalities predominantly concern the X chromosome, including Turner syndrome, but also rearrangements such as deletions and X-autosome translocations. Molecular investigation of these abnormalities has led to the identification of a number of candidate genes most of them still having unknown functions. Testing for premutation of the FMR1 gene, whose full mutation determines the fragile X syndrome, is particularly worthwhile in these patients because of its high frequency, not only among the patients with ovarian failure but also in the general population. Other, much less frequent mutations have been located for example in the gonadotropin and gonadotropin receptor genes and their study contributes to the understanding of ovarian physiology. Here we review most of the etiologies which have to be taken in account in the genetic screening of premature ovarian failure patients.

A case of total peripheral aneosinophilia associated with complete deficiency of myeloperoxidase.

Complete and permanent absence of peripheral eosinophilic granulocytes was observed in a patient also presenting with total myeloperoxidase deficiency. The anomaly was suspected because of complete absence of the eosinophilic cluster in the display of a H*3 Technicon hematological automate and was confirmed by traditional staining of more than 100,000 leukocytes. A severe infectious problem during adolescence could be related to MPO deficiency in this patient. No specific disorder attributable to aneosinophilia was however observed subsequently.

A case of eosinophil peroxidase deficiency.

A case of eosinophil peroxidase deficiency is described after fortuitous detection by the H*3 Technicon hematological analyzer. From the cytochemical aspect total deficiency is admitted. The abnormality is thought to be extremely rare in a well-mixed population as exists in the Grand-Duchy of Luxembourg.