Showing papers in "Human Reproduction Update in 1995"
TL;DR: In this review, comparative information on epigenetic regulation of embryo development is discussed, including information on energy substrate and amino acid preferences of embryos and improvements in the design of culture media are discussed, so that higher yields and increased viability of embryos are achieved.
Abstract: Mammalian preimplantation embryos normally develop within the protected environment of the female reproductive tract, which virtually precludes studies on embryogenesis in situ. Information must therefore be derived from experiments on cultured embryos. Consequently, studies on the epigenetic regulation of embryogenesis have long been interwoven with efforts to formulate culture media capable of sustaining normal development. In this review, comparative information on epigenetic regulation of embryo development is discussed, including information on energy substrate and amino acid preferences of embryos. Advantages of simple versus complex culture media, and of substituting serum albumin or synthetic macromolecules for serum, are discussed. Some potential pitfalls of co-culture are described. Culture appears to induce anomalies in embryo metabolism, which may derive from disturbed intracellular pH. Rationales for selecting endpoints to evaluate the outcome of experiments are considered, including incorporation of timing of embryo development into the analysis. Poor experimental design and/or data analysis can detract from or even negate the value of data obtained from embryo culture; examples are examined to help correct this problem. All of these points are discussed with a view to using data on the needs of embryos for making improvements in the design of culture media, so that higher yields and increased viability of embryos are achieved.
868Â citations
TL;DR: The environment provided by the oviduct, in which the embryos of most mammalian species spend their first 3 days, may be considered as facilitatory rather than obligatory for early embryo development, whereas the uterine environment is required to provide a more complex milieu.
Abstract: Metabolic control during preimplantation development may be either intrinsic to the embryo or extrinsic, i.e. mediated via the environment within the female tract. Intrinsic control is exhibited by early preimplantation embryos, which are undifferentiated, largely autonomous and show no growth. The best characterized intrinsic metabolic control mechanism is the switch from pyruvate to glucose as major energy substrate during mouse preimplantation development. A shift to extrinsic control occurs during the later preimplantation stages, when differentiation into trophectoderm and inner cell mass occurs, net growth begins and the embryo prepares for implantation. Thus, the environment provided by the oviduct, in which the embryos of most mammalian species spend their first 3 days, may be considered as facilitatory rather than obligatory for early embryo development, whereas the uterine environment is required to provide a more complex milieu. The 'facilitators' provided by the oviduct include physical factors, such as ciliary and muscular action, and chemical factors, including oxygen, nutrients, ions and macromolecules. Oviduct fluid secretion is under adrenergic influence, defects in which could contribute to impaired mucosal defence and tubal blockage in women. Preimplantation embryos exhibit metabolic adaptation, whereby their metabolism responds to changes in the external environment. Such adaptation explains the ability of early embryos to develop in a variety of culture media, a situation similar to that which they will experience in the female tract. Thus, the provision of a variety of media in vitro is likely to ensure the development of embryos in a physiological manner.
234Â citations
TL;DR: In this article, the authors reviewed the applicability of sperm morphology assessment as a predictor of a man's potential for fertilization in vitro and found that accurate and strict morphology assessment is very useful in evaluating a patient's fertilizing potential.
Abstract: Careful analysis of sperm morphology has always been an important part of a routine semen examination. However, the usefulness of sperm morphology assessment as a predictor of a man's fertilizing potential has often been challenged due to different classification systems, various slide preparation techniques and inconsistency of analyses within and between laboratories. Automated sperm morphology analysis instruments may overcome the subjective nature of visual assessments of sperm morphology, but the technical problems are numerous and the validity of these instruments has still to be proven. Having reviewed the literature, it seems clear that there is general agreement concerning the clinical relevance and predictive value of this single semen parameter in vivo and in vitro. Nevertheless, even in cases of severe teratozoospermia, fertilization may be possible. Studies on the acrosome reaction are very promising for patients with severe sperm morphology abnormalities that do not have major effects on the fertilizing potential. Most promising is the development of intracytoplasmic sperm injection (ICSI) as the treatment of first choice in cases of severe teratozoospermia with failed fertilization in vitro. Normal fertilization and pregnancy rates can be obtained with ICSI in the presence of extreme teratozoospermia, suggesting that sperm morphology may be important in spermatozoa-zona binding, penetration and spermatozoon-oocyte fusion but fails to be of any predictive value once the spermatozoon reaches the cytoplasm of the oocyte. To conclude, accurate and strict sperm morphology assessment is very useful in evaluating a patient's fertilizing potential, with the main advantage that the methods used to examine this parameter are easy to learn on equipment found in most laboratories.
140Â citations
TL;DR: A novel protein, termed SAA-1, that was first detected on human spermatozoa is discussed with respect to its potential role as a regulatory protein closely involved in the initiation of the acrosome reaction.
Abstract: The acrosome reaction is a crucial step during gamete interaction in all species, including man. It allows spermatozoa to penetrate the zona pellucida and fuse with the oocyte membrane. Spermatozoa unable to undergo the acrosome reaction will not fertilize intact oocytes. This article concentrates on the characteristics and regulatory mechanisms of the acrosome reaction in human spermatozoa. During recent years, various entities found in the vicinity of the ovulated oocyte have been identified as stimulators of the acrosome reaction, of which zona protein is considered the prime physiological inducer in vivo. The steroid hormone progesterone has been shown to evoke critical responses in sperm cells leading to the acrosome reaction. Calcium has also been shown to play a central role during the acrosome reaction. Calcium flux is induced specifically by progesterone in capacitated and uncapacitated sperm cells, whereas only capacitated spermatozoa are able to subsequently complete the acrosome reaction. Progesterone as well as zona protein has been shown to evoke crucial responses within human spermatozoa, shedding light on the cascade of intracellular signalling events leading to the completion of the acrosome reaction. Furthermore, chemical agents which bring about the reaction in vitro, such as the ionophores ionomycin or A23187, have been used to shed light on its regulatory mechanisms. A number of molecules have been postulated to regulate the acrosome reaction in mammals, for example a galactosyl-transferase and a sperm protein tyrosine kinase. In addition, a novel protein, termed SAA-1, that was first detected on human spermatozoa is discussed with respect to its potential role as a regulatory protein closely involved in the initiation of the acrosome reaction.
120Â citations
TL;DR: The results demonstrate that sperm nuclear migration to the maternal perinuclear region is rapid and linear, occurs in the absence of a detectable cytoskeletal system and appears to be assisted by an unusual configuration of the sperm tail principal piece which results from either retained intracytoplasmic motility or the process by which the sperm Tail is progressively incorporated into the oocyte.
Abstract: This report describes spatial and temporal aspects of sperm penetration and intracytoplasmic migration, pronuclear evolution and the specificity of presyngamic opposition, stage-specific changes in cytoskeletal organization and the relative contribution of maternal and paternal components to mitotic spindle formation. These studies involved observations of living human oocytes during conventional insemination in vitro and after intracytoplasmic deposition of spermatozoa, analysis of chromatin organization and distribution during pronuclear evolution, and detection of actin and alpha-, beta- and gamma-tubulin by confocal immunofluorescence microscopy. Immature and mature oocytes, penetrated but unfertilized oocytes, fertilized but arrested eggs, and cleavage-stage embryos from normal and dispermic fertilizations were examined. The results demonstrate that sperm nuclear migration to the maternal perinuclear region is rapid and linear, occurs in the absence of a detectable cytoskeletal system and appears to be assisted by an unusual configuration of the sperm tail principal piece which results from either retained intracytoplasmic motility or the process by which the sperm tail is progressively incorporated into the oocyte. Our findings also show a specificity of pronuclear alignment that is associated with a polarized distribution of both maternal and paternal chromatin, and with the position of the sperm centrosome and the presence of microtubules nucleated from this structure. The results also indicate that a maternal microtubule nucleating capacity is present in the immature oocyte but is apparently inactive until spindle formation. The poles of the first mitotic spindle appear to be derived from the sperm centrosome, although some maternal contribution cannot be excluded. The sperm tail and centrosome persist in a single cell through the cleavage stages, and the latter serves as a prominent site of cytoplasmic microtubule nucleation. The results provide a detailed understanding of the cellular and nuclear morphodynamics of the human fertilization process and indicate subtle defects that may be responsible for early developmental failure.
110Â citations
108Â citations
TL;DR: The information on cytokines is complex and often contradictory but it is recognised that they play an important role in the success of pregnancy.
Abstract: The process of implantation in the human involves 'invasion' of the maternal endometrium by the trophoblast surrounding the developing blastocyst, in response to which there is a cellular reaction in the endometrium. The overall situation has some features analogous to invasion by a tumour and some which are more characteristic of an inflammatory response. In addition, and also in common with cancer and inflammation, there is a release of biologically active molecules, including cytokines, at and around the implantation site. It is believed that these cytokines may play an important role in the successful establishment of the pregnancy; the evidence for this belief is examined in this review.
102Â citations
TL;DR: This review proceeds to examine what is known about the cytoskeleton of uterine epithelial cells, and examines how membrane-skeletal elements could contribute to the membrane transformation.
Abstract: During early pregnancy and the period of blastocyst attachment, the plasma membrane of uterine epithelial cells, which is the first site of contact between maternal and fetal cells, undergoes a remarkable change in configuration, with morphological and biochemical alterations occurring apically and basolaterally. These alterations are collectively referred to as 'the plasma membrane transformation' of early pregnancy. It would be remarkable if this transformation did not also involve alterations in cytoskeletal elements and, in particular, the membrane-associated cytoskeleton. This review therefore, after an overview of the morphological and molecular aspects of the membrane transformation as background, proceeds to examine what is known about the cytoskeleton of uterine epithelial cells. Cytoskeletal elements particularly associated with the plasma membrane are then examined and some new approaches to understanding membrane-skeletal dynamics, including detergent-permeabilization techniques for transmission and high-resolution scanning electron microscopy of uterine epithelial cells, are reported, together with recent work on these structures. The review concludes with an examination of how membrane-skeletal elements could contribute to the membrane transformation.
93Â citations
TL;DR: The aim of the present article is to review the current status of development of contraceptive vaccines based on antigens derived from sperm cell, oocyte zona pellucida and HCG, and to discuss their relative merits and future development.
Abstract: Contraceptive research has entered a new phase of development with the advent of hybridoma and DNA recombinant technologies. During the past 5 years, significant advances have been made in this area and now it seems that realistic prospects exist for the development of contraceptive vaccines for use in humans and animals (veterinary, wild and domestic), applicable to both the female and male sexes. Contraceptive vaccines will be valuable supplements to the presently available methods of family planning, and, due to high specificity, the occurrence of limited side-effects if any, low cost and infrequent administration, contraceptive vaccines may have greater acceptability than the currently available methods. Mammalian reproduction starts with the unison of gametes contributed by the male and female partners. Both spermatozoon and oocyte have antigens on the cell surface that are unique, tissue-specific, immunogenic and accessible to antibodies, and binding of the antibodies to these antigens can cause inhibition of gamete function, resulting in a failure of fertilization. Fertilization is followed by embryogenesis, with the early embryo producing several proteins, some of which, e.g. human chorionic gonadotrophin (HCG), have a vital role in the establishment and maintenance of early pregnancy. Again, these proteins are accessible to antibodies, and their immunoneutralization can cause anti-fertility effects with loss of early embryo. Thus, the antigens derived from proteins on spermatozoa, oocyte and early embryo, especially HCG, constitute interesting molecules for the development of contraceptive vaccines. The aim of the present article is to review the current status of development of contraceptive vaccines based on antigens derived from sperm cell, oocyte zona pellucida and HCG, and to discuss their relative merits and future development.
85Â citations
TL;DR: The available data concerning hysteroscopic myomectomy for submucous myomas has been reviewed with the aim of evaluating the safety and efficacy of this technique in infertile women who wish to preserve or to enhance their fertility potential.
Abstract: The available data concerning hysteroscopic myomectomy for submucous myomas has been reviewed with the aim of evaluating the safety and efficacy of this technique in infertile women who wish to preserve or to enhance their fertility potential. A total of 134 infertile patients undergoing hysteroscopic myomectomy by resectoscope or by Nd: YAG laser or by scissors have been collectively recorded. Of these, 79 (58.9%) patients conceived. This clinical outcome is similar to that occurring after laparotomic submucous myomectomy. Moreover, the hysteroscopic approach has several advantages over its abdominal counterpart, such as reduction of length of time of hospitalization, less morbidity and no hysterotomy. The operative risk of hysteroscopic myomectomy is < 3%. Uterine perforation, distension system hazard, infection and haemorrhage are the commonest complications. Hysteroscopic myomectomy is a safe, effective and relatively simple surgical procedure for the restoration of fertility.
83Â citations
TL;DR: R-FSH has recently been used successfully in association with recombinant human LH for inducing ovulation and pregnancy in WHO group I anovulatory patients and is likely to replace all urinary-derived FSH preparations for stimulating ovarian follicular development.
Abstract: Human follicle-stimulating hormone (FSH) is now produced in vitro by recombinant DNA technology. FSH being a complex heterodimeric protein, a eukaryotic cell line has been selected for expression work (Chinese hamster ovary cells). The pharmaceutical preparation of recombinant human FSH (r-FSH) differs from that of human menopausal gonadotrophin (HMG) and the first generation of urinary human FSH (u-FSH) in terms of (i) source of bulk materials, (ii) purity and specific activity, (iii) batch to batch consistency, and (iv) complete absence of luteinizing hormone (LH) activity. Pharmacokinetic characterization of r-FSH has shown an absolute bioavailability of approximately 75% after both s.c. and i.m. administration and an apparent terminal half-life of 37 +/- 25 h. These characteristics are very similar to those of u-FSH. Clinical efficacy and safety are currently demonstrated through several randomized, well controlled studies, comparing r-FSH administered s.c. with u-FSH administered i.m. for stimulating follicular development prior to assisted reproduction treatment and in World Health Organization (WHO) group II anovulation. To date, approximately 1000 patients have been treated with r-FSH. Moreover, r-FSH has recently been used successfully in association with recombinant human LH for inducing ovulation and pregnancy in WHO group I anovulatory patients. At this stage of r-FSH preparation assessment, it is likely that r-FSH will replace all urinary-derived FSH preparations for stimulating ovarian follicular development. For clinicians, current experience with r-FSH indicates that it should be used with the regimes and doses applied to u-FSH.
TL;DR: It has been found that the local testicular immunoregulatory environment partially impedes autoimmune responses to ontogenic testis antigens and regulatory T cells usually control pathogenic T cells that are found in the normal peripheral immune system.
Abstract: This article reviews recent research on autoimmune diseases of the testis and ovary based on two experimental approaches for induction of autoimmune diseases of the gonads (immunization with testis or ovary antigen, usually with adjuvant, and deliberate alteration of the immune system in normal animals, without injecting antigen or adjuvant) It has been found that the local testicular immunoregulatory environment partially impedes autoimmune responses to ontogenic testis antigens and regulatory T cells usually control pathogenic T cells that are found in the normal peripheral immune system If the clonal balance of these CD4+ T cell subsets is tipped in favour of pathogenic T cells, autoimmune diseases of the gonads could ensue Loss of regulatory T cells may occur through aberrant T cell development, or oophoritogenic T cells can be activated by non-ovarian peptides that crossreact with self peptides at the level of the T cell receptor The inflammatory CD4 (Th1) T cell mechanism has been established to be a critical pathway for autoimmune orchitis and autoimmune oophoritis; tumour necrosis factor has been shown to be required for amplification of the pathogenic T cell response Histopathology has suggested tissue locations wherein pathogenic T cells encounter testicular and ovarian target antigens Antibodies bind to both testicular and ovarian target antigens during the development of autoimmune orchitis and autoimmune oophoritis, but the precise role of the antibodies has not been determined Resolution of this role may influence the clarification of the mechanism whereby autoantibody may access ejaculated human spermatozoa to cause infertility and the future of contraceptive vaccine development based on ovarian antigens A novel mechanism of autoantibody induction and an immunogenetic approach to autoimmune oophoritis and orchitis, based on molecular linkage analysis of inbred mice, are also reviewed
TL;DR: It is postulated that embryo fragmentation is a consequence of activated programmed cell death (PCD) and subsequent apoptosis and evidence of morphological, histological and biochemical features compatible with the occurrence of PCD in preimplantation embryos is discussed.
Abstract: Fragmentation is frequently observed in animal and human embryos obtained via in-vitro fertilization (IVF), and is known to be associated with decreased pregnancy rates and poor survival following cryopreservation. We postulate that embryo fragmentation is a consequence of activated programmed cell death (PCD) and subsequent apoptosis and discuss evidence of morphological, histological and biochemical features compatible with the occurrence of PCD in preimplantation embryos. If PCD is an underlying cause of the high incidence of the fragmentation seen in human pre-embryos, it remains to be determined whether this is reflective of the natural incidence of lethal chromosomes in the human population or due to the IVF procedure and culture conditions.
TL;DR: The purpose of this review is to highlight some of the signals and molecular events which are associated with and that may participate in apoptosis, and a review of the current literature regarding apoptosis in human endometrium.
Abstract: Apoptosis is a selective process for deletion of cells in various biological systems. This event, similar to proliferation, is tightly regulated, with both processes playing essential roles in the homeostasis of renewable tissues. In human endometrium, proliferation and apoptosis occur at opposing poles of the menstrual cycle. The proliferative phase is marked by rapid growth of the endometrial epithelial lining, whereas progressive increase in apoptosis in this tissue is the hallmark of the secretory and menstrual phases. The purpose of this review is to highlight some of the signals and molecular events which are associated with and that may participate in apoptosis. This is followed by a review of the current literature regarding apoptosis in human endometrium.
TL;DR: New generation-oral contraceptives containing desogestrel or gestodene, and possibly also norgestimate, are more or less similar with respect to contraceptive efficacy, cycle control and acceptability, and show a more favourable metabolic profile in comparison with older preparations.
Abstract: New generation-oral contraceptives containing desogestrel or gestodene, and possibly also norgestimate, are more or less similar with respect to contraceptive efficacy, cycle control and acceptability. They also show a more favourable metabolic profile in comparison with older preparations. The desogestrel-containing preparations Gracial and Marvelon, and possibly also the gestodene-containing preparation Gynera, have demonstrated a good efficacy in well-controlled studies in the treatment of mild to moderate acne and/or hirsutism. There may be differences between new generation oral contraceptives with respect to their effects on metabolic variables like high-density lipoprotein cholesterol and sex hormone-binding globulin. These differences are most probably modulated by variations in both the pharmacokinetics and selectivity of the progestogenic components. Of particular relevance here may be the recent finding that approximately 20% of administered norgestimate is metabolized into levonorgestrel. For use in clinical practice, it is of considerable help to have different preparations containing a range of oestrogen doses with the same progestogen. They allow the clinician to 'tailor make' the choice of oral contraceptives for those starting pill use or those switching to another combination due to symptomatology or changed circumstances, e.g. advancing age, smoking, etc. In this respect, desogestrel-containing oral contraceptives allow the most flexible approach.
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TL;DR: Conventional methods of semen analysis, the resazurin test and home fertility scoring, and advanced methods for the objective assessment of conventional sperm characteristics and motility parameters are covered.
Abstract: Rapid developments have occurred in the management of couple infertility due to a male factor. These have stimulated renewed interest in semen analysis, which has become more correct, more reliable and more informative. The so-called basic semen analysis, which includes subjective estimation of sperm concentration, motility and morphology, has largely become obsolete. It has been replaced by several alternative techniques such as the home testing of semen by the man himself, the elaboration of methods and equipments for the exact assessment of conventional sperm characteristics, and the measurement of new parameters evaluating the functional state and capacity of spermatozoa, accessory sex glands and seminiferous epithelium. The present paper covers the following items: (i) conventional methods of semen analysis, (ii) the resazurin test and home fertility scoring, (iii) advanced methods for the objective assessment of conventional sperm characteristics and motility parameters.
TL;DR: Serum CA125 is not a good marker for endometriosis but it is a helpful additional parameter to diagnose endometRIotic disease in patients with chronic pelvic pain, and its clinical value has been questionable.
Abstract: This review covers the literature on CA125 and endometriosis; data on CA125 and oncology are not discussed. In normal women, plasma concentrations of CA125 are increased slightly at ovulation and significantly during menstruation. Marked increases are observed during pregnancy and following peritoneal irritation by infection or surgery. These data are consistent with the concept that CA125 in normal women is mainly derived from the endometrium and the irritated peritoneum. Plasma concentrations of CA125 are markedly elevated in women with cystic ovarian endometriosis and/or deeply infiltrating endometriosis, but not, or only slightly, in the luteal phase of women with minimal or mild endometriosis. This is consistent with the recent concept which considers minimal endometriosis as a normal condition occurring intermittently in many women, in contrast with deep endometriosis and cystic ovarian endometriosis which are called 'endometriotic disease'. Serum CA125 is not a good marker for endometriosis but it is a helpful additional parameter to diagnose endometriotic disease in patients with chronic pelvic pain. Following treatment of endometriosis, elevated plasma concentrations of CA125 could be used as an argument that treatment has been incomplete, or that the condition has recurred. Assaying CA125 in peritoneal fluid requires high sample dilutions or a modified immunoradiometric assay, and until now, its clinical value has been questionable.
TL;DR: This review is provided to update the reader with available information on the topic as it relates to FSH and to point out issues that require re-evaluation in this area.
Abstract: The existence of a heterogeneous population of follicle stimulating hormone (FSH) was described many years ago. Other pituitary glycoproteins, such as thyroid stimulating hormone (TSH) and luteinizing hormone (LH) as well as placental human chorionic gonadotrophin (HCG) also exhibit heterogeneity. Because FSH plays a significant role in a variety of ovarian activities such as follicular maturation, selection of the dominant follicle and ovulation, the possible role of subpopulations of FSH with distinct physicochemical characteristics is of great interest. After a great deal of investigation, the physiological significance of this biochemical phenomenon has yet to be fully understood. Investigators have employed immunoassays, in-vitro bioassays and radioreceptor assays to study the biological activity of the individual isoforms of FSH. As more information has accumulated, it has become clear that some of the initial assumptions used to interpret data may be incorrect. This review is provided to update the reader with available information on the topic as it relates to FSH and to point out issues that require re-evaluation in this area.
TL;DR: The results of this study suggest that anaerobic bacteria are often not detected when routine methods for microbial evaluation are used, and should be considered during assisted reproduction and in patients with symptoms of genital tract infection.
Abstract: The clinical significance of micro-organisms in semen samples of asymptomatic subfertile patients is a matter of constant debate. Usually little attention is paid to anaerobic bacteria as they are sensitive to transportation and culturing, and differentiation is difficult, costly and time-consuming. In the present study, special screening was carried out for anaerobes in ejaculates in addition to the routine microbial cultures of genital secretions of both partners. In addition to standard semen analysis and evaluation of sperm ability to penetrate cervical mucus (CM) in vivo (post-coital testing) and in vitro using a standardized test system, semen samples from 126 randomly chosen males of couples with a median duration of infertility of 4 years were examined for colonization with anaerobic bacteria. All couples were without clinical signs or symptoms of genital tract infection. The special care taken for anaerobic growth in semen samples gave a high rate of positive cultures and showed that nearly all ejaculates (99%) were colonized with anaerobic micro-organisms, and potentially pathogenic species were found in 71% of men. This rate was more than four times higher than that obtained with routine cultures and standard transportation (16%). Anaerobic bacterial growth of > or = 10(6) colony forming units (CFU)/ml was seen in 42% (total range 10(3)-10(8) CFU/ ml). In addition, aerobic growth was found in 96% (> or = 10(6) CFU/ml in 21%), potentially pathogenic species in 61% of semen specimens. There were no marked differences in the prevalence of anaerobic micro-organisms in patients with reduced or normal sperm count, motility or morphology. Nor was there any significant difference in anaerobic colonization between samples with impaired or good ability to penetrate CM of female partners (in vivo or in vitro), or the CM of fertile donors in the in-vitro sperm-cervical mucus penetration test (SCMPT) in this asymptomatic group of patients. There was no clear association between microbial colonization and subsequent fertility in vivo within an observation period of 6 months. The results of this study suggest that anaerobic bacteria are often not detected when routine methods for microbial evaluation are used. This should be considered during assisted reproduction and in patients with symptoms of genital tract infection and should lead to further studies in infertile patients where subclinical infection or inflammation is indicated by specific markers in semen samples.
TL;DR: Early results from MR imaging suggest that in patients treated with standard regimen of GnRHa, followed by human gonadotrophin (HMG), neither the endometrial thickness nor the volume is related to outcome, however, the relative signal intensity of the uterine layers provides good discrimination prior to embryo transfer, between pregnant and non-pregnant groups.
Abstract: This article aims to review in detail the current literature concerning the efficacy of, and problems associated with, the use of ultra-sonography and magnetic resonance imaging in predicting uterine receptivity and hence the outcome of assisted conception. Although the quality of the embryo and transportation to the uterine cavity are obvious requirements for in-vitro fertilization/embryo transfer treatment, attention has recently centred on the receptivity of the endometrium to the growing blastula. High resolution ultrasonography is currently the imaging modality of choice, but measurement of endometrial thickness is only associated with successful treatment outcome if ovarian stimulation includes clomiphene citrate. However, the ultrasonographic texture of the endometrium may have a greater prognostic value for implantation. The current literature is relatively unanimous that a 'triple' layered appearance of the uterus is associated with a 23-42% pregnancy rate and that endometrium is unreceptive when iso- or hyperechoic compared with myometrium. In an attempt to improve prediction rates, new techniques including magnetic resonance (MR) imaging are being used to determine uterine receptivity. Early results from MR imaging suggest that in patients treated with standard regimen of GnRHa, followed by human gonadotrophin (HMG), neither the endometrial thickness nor the volume is related to outcome. However, the relative signal intensity of the uterine layers provides good discrimination prior to embryo transfer, between pregnant and non-pregnant groups.
TL;DR: Mifepristone alone, without adjuvant prostaglandin, has yielded promising results as an anti-implantation agent and in emergency contraception, and other potential uses include once-a-week contraception, ovulation inhibition (in a sequential regimen with a progestogen), and as a daily mini-pill.
Abstract: Antiprogestogens, which block the action of progesterone at the cellular level through binding to the progesterone receptor, are proving to be one of the most significant developments in endocrinology in recent years. Several hundreds of such compounds have been synthesized, but only a few of them have been evaluated to any significant extent in biological screening models and, to our knowledge, only three compounds, namely mifepristone, lilopristone (ZK 98.734) and onapristone (ZK 98.299) have been given to humans. Most of the clinical research to date has focused on the use of mifepristone given in combination with prostaglandin for termination of early pregnancy, an indication for which the compound is being used routinely in four countries so far, i.e. China, France, the UK and Sweden. The gynaecological and obstetrical applications in which antiprogestogens have been shown to be of value to date include ripening of the pregnant cervix prior to pregnancy termination, sensitization of the uterus to prostaglandins in second-trimester abortion, and induction of labour. Available data suggest that antiprogestogens have no place in the conservative treatment of ectopic pregnancy or in the treatment of premenstrual tension. In fertility regulation, the sequential combination regimen of mifepristone plus prostaglandin as used for inducing abortion has proved to be effective also for menses induction and can be expected to be an efficacious once-a-month contraceptive. Mifepristone alone, without adjuvant prostaglandin, has yielded promising results as an anti-implantation agent and in emergency contraception. Other potential uses include once-a-week contraception, ovulation inhibition (in a sequential regimen with a progestogen), and as a daily mini-pill. Mifepristone, and other antiprogestogens for which biological data have been reported also bind to the cellular receptors for glucocorticoid hormones and, consequently, possess antiglucocorticoid in addition to their antiprogestational activity. Because of this antiglucocorticoid effect, mifepristone has been employed successfully in the palliative treatment of hypercortisolism due to Cushing's syndrome, and its use has been proposed for treating certain forms of depression and of glaucoma, and in wound healing. However, for scientific and practical reasons, it would be preferable if molecules were developed that have only the antiprogestational or the antiglucocorticoid activity rather than both.
TL;DR: A critical review of clinical trials exploring the use of GH as an adjuvant for ovarian stimulation with human menopausal gonadotrophin pinpoints a select group of infertile patients who may benefit from this co-treatment, particularly those who have a surgical, pathological or medically induced dysfunction of GH kinetics.
Abstract: The realization of the existence of an intra-ovarian regulating mechanism involving insulin-like growth factor-I (IGF-I), a mediator of growth hormone (GH) action that augments the ovarian response to gonadotrophins, has prompted a number of clinical trials exploring the use of GH as an adjuvant for ovarian stimulation with human menopausal gonadotrophin. A critical review of these studies pinpoints a select group of infertile patients who may benefit from this co-treatment, particularly those who have a surgical, pathological or medically induced dysfunction of GH kinetics. The mechanism of this action, the effective dose needed and the implications regarding the interface of GH, IGF-I and ovarian physiology and pathology are now becoming clearer. A greater understanding of GH action on the ovary may in future benefit patients afflicted by anovulatory infertility and those requiring ovulation induction for in-vitro fertilization.
TL;DR: The available data from epidemiological studies and case reports do not support a direct causal relationship between ovarian stimulation and ovarian cancer, however, it is possible that ovarian stimulants may have an augmenting role for special categories of tumours, e.g. sex-cord stromal tumours.
Abstract: Increased interest has arisen recently about the possible association between ovarian stimulation and ovarian tumours. In this article, the current knowledge on the epidemiology, pathogenesis and aetiology of ovarian tumours is extensively reviewed in relation to the existing literature on the relationship between ovulation induction and ovarian neoplasia. The available data from epidemiological studies and case reports do not support a direct causal relationship between ovarian stimulation and ovarian cancer. However, it is possible that ovarian stimulants may have an augmenting role for special categories of tumours, e.g. sex-cord stromal tumours. A definite answer to this important issue may be reached through large prospective epidemiological studies or large retrospective well-designed case-control studies.
TL;DR: Analysis of cytogenetic studies on human zygotes and preimplantation embryos suggests that some parameters of IVF procedures might be responsible for the occurrence of some abnormalities.
Abstract: A review of cytogenetic studies on human zygotes and preimplantation embryos is presented. This survey documents the high incidence of chromosomal abnormalities in embryos in vitro. Up to date, 914 zygotes and embryos have been karyotyped. The rate of abnormalities is significantly higher in morphologically poor-quality embryos than in good-quality embryos (86.6 and 36.6% respectively). In both groups, aneuploidy is the most frequently observed abnormality. In addition, various types of aberrations such as polyploidy, haploidy, mosaicism or fragmentation are also found. Among tripronucleated zygotes, 81.9% display chromosomal abnormalities. Data suggest that some parameters of IVF procedures might be responsible for the occurrence of some abnormalities.
TL;DR: The history of infertility and the treatments applied but also the repercussions for infertile women socially are examined, finding that the attitudes of physicians have often reflected the role of the woman and her image in society.
Abstract: Infertility has always been a constant preoccupation. The problems it raises today on medical, social, ethical, political and religious levels bear witness to this emphasis, but also to how complicated infertility is to deal with and understand. This study not only examines the history of infertility and the treatments applied but also the repercussions for infertile women socially. As we look through history, we find that the attitudes of physicians have often reflected the role of the woman and her image in society.
TL;DR: The growing awareness of the importance of plants has coincided with the development of plant molecular biology, which makes them ideally suited for gene engineering and genetic studies in general.
Abstract: Until now most research, and its funding, has been focused on animal and human health care as well as simple microbiological model systems such as Escherichia coli and yeast. Molecular plant studies have generally lagged behind, often simply adapting discoveries from the animal field to plants. Clearly, good health and the efficient tackling of diseases is crucial for the well-being of humans, and good remedies have a high economic value for the pharmaceutical industry. However, one should not forget that plants are an essential component of the large ecosystem that is our planet. They are not only the basic food producers but they are also necessary for a balanced atmosphere (oxygen production) and stable and viable climates. Especially in this period of demographic explosion and growing environmental deterioration, there is a need to rebuild our agricultural systems. Plants also have a wide variety of 'non-food' uses, for instance as energy sources, construction materials, or cosmetics. Last, but not least, they produce a lot of chemicals that can be used as pharmaceuticals. The growing awareness of the importance of plants has coincided with the development of plant molecular biology. Specific features make them ideally suited for gene engineering and genetic studies in general.
TL;DR: Media prepared with egg yolk and two buffers, TES and Tris, called TEST-yolk have been shown to have beneficial effects on the survivability, fertilizing capacity and storage potential of human spermatozoa.
Abstract: Media prepared with egg yolk and two buffers, TES and Tris, called TEST-yolk have been shown to have beneficial effects on the survivability, fertilizing capacity and storage potential of human spermatozoa. Egg yolk lipoproteins are the critical compounds for the beneficial effects, with a synergistic effect due to the TES-Tris buffer component. TEST-yolk media have been used in the sperm penetration assay, the hemizona assay, sperm preparation for clinical in-vitro fertilization, artificial insemination with homologous spermatozoa, cryopreservation, sperm samples with a positive antisperm antibody test, and preparation for techniques requiring capacitated spermatozoa. Few harmful consequences of TEST-yolk have been reported, although controlled trials are required to evaluate therapeutic effects in the treatment of male infertility.