A. Demoulin

Clinical Use of LH-RH Test as a Diagnostic Tool

The response to LH-RH is never characteristic of a given disorder of the hypothalamo-hypophysial-gonadal axis except in the cases of severe gonadal disturbances, but reflects the functional states which can be observed under various circumstances. The same functional state may be found in different diseases and, in contrast, one disease can evolve through different functional states with time.

Organ Culture of Mammalian Testis

Mouse testes were cultured for 19–20 days at either 31 or 37 °C with a change of medium every 4 days. After treatment with charcoal and dextran T, the recovered testis media were incubated with rat an

Is Ultrasound Monitoring of Follicular Growth Harmless

Monitoring of the growth of ovarian follicles by ultrasound (US) is now frequently utilized in such procedures as hMG stimulation, artificial insemination, and in vitro fertilization. While experimental studies have demonstrated that ultrasound, when used at diagnostic intensities, is not toxic for cells or tissues,1 until now there has been no study concerning the effect of ultrasound waves on preovulatory follicles. Using ultrasound to determine the appropriate time for artificial insemination with donor semen (AID) in 1980, we have compared the pregnancy rates in two populations of AID patients (with US versus without US). The success rate is reduced in the US‐monitored group. Animal experiments confirm these results.

Inhibin and related peptides: Mechanisms of action and regulation of secretion☆

The structure of inhibin is known; it consists of a heterodimer composed of one alpha and one beta subunit. The homodimer of beta A (beta A-beta A) and the heterodimer beta A-beta B, called activin A and B, respectively, stimulate the release and synthesis of FSH by gonadotrophs. Inhibin exerts effects at the hypophyseal, hypothalamic, and gonadal levels. Produced by granulosa cells in the female and by Sertoli cells in the male, inhibin synthesis is stimulated by FSH and reduced by hypophysectomy and progesterone. At present, there is no evidence for a signal from germinal cells to modify inhibin production. Inhibin secretion evolves in parallel with follicular maturation and aromatase activity, whereas luteinization arrests its production. Nevertheless, important differences in the regulation of inhibin secretion seem to exist from one species to another. Sperm inhibin levels can be correlated with spermatozoa number. Administration of inhibin to sheep induces either anovulation or an increase in the rate of ovulation depending on the scheme of treatment.

Relationship between gonadotrophins, spermatogenesis and seminal plasma

Abstract The correlations between basal FSH and LH levels, FSH and LH response to LH RH injection, sperm count, stage of spermatogenesis and prolactin levels have been investigated in patients with oligospermia and azoospermia. There was no correlation between serum FSH and LH levels. Basal FSH levels and FSH response to LH-RH are always abnormally high when spermatids are not yet formed in the biopsy specimen. There is no correlation evident between LH levels and LH response to LH-RH on the one hand and the stage of spermatogenesis on the other. Prolactin secretion seems to be normal in these patients. In normal seminal plasma a protein substance was found lowering basal FSH levels without altering those of LH and preferentially decreasing the FSH response to the injection of LH-RH in the castrate and normal rat. The substance may be involved in the regulatory mechanism of FSH secretion.

Variations of luteinizing hormone serum concentrations after exogenous human chorionic gonadotropin administration during ovarian hyperstimulation

Changes in luteinizing hormone (LH), estradiol, and progesterone (P) serum levels before and after preovulatory administration of human chorionic gonadotropin (hCG) were assayed in 30 patients stimulated with clomiphene citrate (CC) and human menopausal gonadotropin (hMG) and compared with LH variations in 43 patients submitted to pharmacological hypophysectomy with a gonadotropm-releasing hormone agonist (GnRH-a) and stimulation with hMG. In CC+hMG-treated patients, an endogenous LH surge occurred systematically 4.25±2.75 hours after hCG injection. Multiparametric analysis indicated an inverse correlation between the delay in the initial rise of the LH surge and the increase in P levels during the 6 hours after hCG administration. Gonadotropin-releasing hormone agonist+hMG treatment did not lead to an LH surge after hCG but to a significant fall in LH levels. Thus, exogenous hCG, administered before ovulation, induces an endogenous LH surge if pituitary function is not blocked by a GnRH-a, probably through an increase in P secretion.

Gonadotrophin Levels in Infertile Patients

Publisher Summary This chapter discusses gonadotropin levels in infertile patients. The assays of follicle stimulating hormone (FSH) and luteinizing hormone (LH) are of interest in the investigation of infertile patients for two reasons. First, the FSH and the LH concentrations provide an etiological diagnosis of the infertility, especially when the latter is one symptom of hypogonadism. Second, the FSH and the LH levels may be correlated with the endocrine function of the testis and with the degree of maturation of the germ cell in such patients. In hypogonadism, because of testicular lesions, there is often an extensive or complete loss of germ cell production. In the cases of azoospermia, because of abnormal spermatogenesis, the FSH levels are often greater than normal, indicating that the primary lesion is at the germinal epithelial level and that the pituitary responds to this deficiency by increasing its FSH secretion. In hypogonadism, because of the gonadal lesions, when there is an extensive or complete loss of germ cell production, the FSH levels are invariably elevated and the LH levels may be either normal or high depending on the degree to which sex steroid production is involved. By contrast, in patients with organic pituitary lesions, the FSH and the LH are sometimes below the limits of sensitivity of the assays usually employed but may be detectable, in which case they are generally low but occasionally normal.

Traitements de l’infertilite masculine par les techniques de micromanipulations ovocytaires: Revue de la litterature

During the last few years assisted reproductive technology has seen the introduction of oocyte micromanipulation and sperm microinjection as therapeutic approaches for severe male factor infertility. However, a review of the international literature has revealed that less than 100 pregnancies have been obtained using such techniques. Fertilization rates are extremely variable and influenced by the strictness of the various authors’ criteria for selecting cases. It is concluded that partial zona dissection and zona drilling are less useful than subzonal insemination and intracytoplasmic insemination.ResumeDepuis quelques années, on assiste, dans le domaine des technologies médicalement assistées, à un engouement pour l’utilisation des micromanipulations comme thérapeutique de l’infertilité masculine. Une revue de la littérature nous a permis de constater qu’à ce jour moins de 100 grossesses ont été obtenues et que les taux de fécondation sont trés variables en fonction de la rigueur de la sélection des cas. Alors que la dissection partielle de la zone pellucide ne semble pas être un technique prometteuse, l’injection de spermatozoides dans l’espace périvitellin ou dans le cytoplasme de l’ovocyte pourrait être promise à un bel avenir.

L’échec de fécondation en F.I.V.: intérêt d’un taux de récolte ovocytaire élevé et étude du taux de récidive

ResumeL’analyse de 1132 tentatives de FIV montre comment le taux de récolte détermine la fiabilité de l’estimation de l’échec de fécondation. L’étude de 64 couples ayant réalisé plusieurs tentatives dont une au moins s’est soldée par un échec de fécondation montre que 68,7% d’entre eux obtiennent des embryons lors d’une autre tentative. Les embryons replacés ont les mêmes aptitudes d’implantation et de développement que ceux obtenus par 130 couples ayant subi un premier échec d’implantation. Ces résultats sont mis en relation avec ceux obtenus par insémination subzonale après deux échecs de FIV.SummaryIn case of male indication, IVF is used as the most efficient laboratory test for assessing gamete function. We evaluate how the number of collected oocytes is still a determinant parameter in the establishment of fertilization failure. At least 10 oocytes should be inseminated to conclude to fertilization failure (with a false-negative rate of 10%). We retrospectively analyse all IVF couples (n=64) in our practice who had, besides others, at least one attempt with no fertilization. 68.7% of these couples reached fertilization during another attempt. This value varies from 60 to 90% according to the concentration of motile spermatozoa in the ejaculate. The implantation and development abilities of the replaced embryos are similar to those observed in a reference group consulting for prior implantation failure. These results are discussed in relation to those obtained after subzonal insemination (SUZI) in a group of patients consulting after 2 IVF fertilization failures.

Les traitements médicaux de l’oligoasthénozoospermie idiopathique

ResumeDans un nombre élevé de cas, l’infertilité d’un couple résulte d’une oligoasthénozoospermie dont aucune étiologie ne peut être reconnue. Différentes thérapeutiques médicales ont été proposées dans la littérature pour accroître la numération et la mobilité des spermatozoïdes. Nombre d’études observent une amélioration des paramètres spermiologiques sans prendre en compte les variations physiologiques et sans les comparer à des patients traités par un placebo. Pour d’autres, le but final du traitement n’est pas précisé c’est-à-dire l’obtention d’un enfant par le couple.Dans cette revue de la littérature, seules les études randomisées précisant les taux de grossesses ont été prises en compte. Différentes hormones de l’axe hypothalamo-hypophyso-testiculaire ont été utilisées, le GnRH et ses analogues, les gonadotrophines et leurs formes purifiées, les anti-estrogènes, les androgènes et les inhibiteurs de l’aromatisation. Parmi ces molécules, des effets positifs ont été sporadiquement observés. Ainsi, la mestérolone stimulerait la spermatogenèse dans une étude sur cinq. L’undécanoate de testostérone et la FSH auraient des effets bénéfiques sur le pouvoir fécondantin vitro. Deux anti-estrogènes ont été testés, le clomifène et le tamoxifène avec des taux de grossesse significativement augmentés mais cependant des effets paradoxaux ont été observés. D’autres molécules, non hormonales, ont également fait l’objet de travaux. La plus étudiée est la kallicréine, une glycoprotéine impliquée dans la libération des kinines à partir du kininogène. Des résultats contradictoires ont été obtenus avec cette thérapie. La pentoxifylline, un inhibiteur de la phosphodiestérase est activein vitro mais n’a pas encore fait ses preuvesin vivo. D’autres substances comme l’arginine, la carnitine, les α bloqueurs, les bloqueurs des mastocytes, l’acide folinique, les vitamines, etc, font l’objet de publications sporadiques et aucune conclusion ne peut être tirée.En conclusion, l’oligoasthénozoospermie idiopathique semble toujours rebelle à la plupart des traitements dont nous disposons à ce jour. Dans ce cas, le choix d’une thérapie est empirique et devrait en cas d’échec être rapidement abandonné afin d’orienter le couple vers la procréation médicalement assistée.AbstractIn number cases, couple infertility results of an oligoasthenozoospermia without any recognized etiology. Various medical therapies have been proposed in the literature to increase sperm count and their mobility. Some studies demonstrate an improvement of spermatic parameters without taking physiological variations into consideration and without comparing the results with those obtained in patients treated with a placebo. For others, the final aim of the treatment is not specified, that means to get a pregnancy by the couples.In this review of literature, only randomized studies giving the pregnancy rate, were taken into account. Various hormones of the hypothalamo-hypophyso-testicular axe have been used. GnRH and its analogs, gonadothropins and their purified forms, antiestrogens, androgens and aromataze inhibitors. Among these molecules, positive effects have been sporadically observed. Mesterolone stimulated spermatogenesis in one on five studies. Testosterone undecanoate and FSH have a benefic effect onin vitro fertilization. Two antiestrogens have been tested for a couple of years. Clomiphene and tamoxifen induce a sifnificant increase in the pregnancy rates with however, some paradoxical effects. Other non hormonal molecules have also been studied. The oldest studied medication is kallicrein, a glycoprotein implicated in the release of kinins from kininogens. Contradictory results have been obtained with this therapy. Pentoxifyllin, a phosphodiesterase inhibitor is active on spermatozoa mobilityin vitro, but its activityin vivo is not demostrated.Other medicators as arginin, carnitin, mast cell blockers, α-blockers, vitamins etc have also been tested. Publications are sporadic and any conclusion can be drawn.In conclusion, idiopathic oligoasthenozoospermia seems still unamenable to treat. Choice of a therapy is empirical and must be leaved for trying a medically assisted treatment