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At least 307 records · Page 17Linked to original sources
PubMed2003

Biomarkers of endometrial receptivity--a review.

Implantation is a phenomenon that involves an interaction between the embryo and maternal endometrium. There is, in the menstrual cycle, a short and precise period of time in which the maternal-embryonic interaction is optimal and culminates with adhesion and invasion of the blastocyst into the progesterone-induced secretory endometrium. This period is called nidation or implantation window. In the implantation window changes occur in endometrial epithelial morphology, characterized by the appearance of membrane projections called pinopodes. Pinopodes are progesterone-dependent organelles, that look like apical cellular protrusions appearing between days 20 and 21 of the natural menstrual cycle. There are many factors that regulate the changes typical of the implantation window and the appearance of the pinopodes. The embryonic and maternal expression of growth factors and cytokines, calcitonin, HOX genes and cell adhesion molecules might all play a major role in the phenomenon of implantation. The cytokines function as chemical messengers and can serve as biomarkers of uterine receptivity. Understanding the function of these biomarkers and their role in determining the implantation window in women, will help us to diagnose and treat infertile couples more efficiently.

Biomarkers↗
PubMedDate not supplied

A study of placental villi in extrauterine gestation: a guide to the frequency of blighted ova.

Material from 329 tubal pregnancies has been examined histologically. In addition, the villous content of glucosaminoglycans was studied. Depending on the degree of the morphological changes three groups can be differentiated: "abortion in association with normal placental findings", "suspicion of blighted ova", and "blighted ova". In the first group (35 cases, 10.64 per cent) there were distinct differences in the morphological picture in contrast to the normal abortion of intrauterine origin; that is, differing size of chorionic villi, the presence of isolated molar villi and proliferative changes in the epithelium. A normal morphological villous pattern was extremely rare. The second group (146 cases, 44.41 per cent) showed all the morphological signs of transition to blighted ova. Most villi were well-vascularized but there were more molar villi, and proliferative and degenerative changes were seen in the epithelium. Group three (132 cases, 40.19 per cent) showed the full picture of a blighted ova. The morphological pattern of the extrauterine blighted ova was similar to that seen in the blighted ova of intrauterine origin, the only difference being that the vascularization of the villi was more pronounced in blighted ova of tubal pregnancies. Glucosaminoglycans were non-uniformly distributed over the villous stroma in the case of blighted ova, and they were present in greater concentration than in the case of abortions with normal placental findings: this is a useful method for differentiating abortions from blighted ova. It is apparent from the results of this investigation that the proportion of blighted ova is substantially greater in extrauterine than in intrauterine pregnancies. This suggests that unfavourable conditions of nidation within the tube have a decisive influence upon the genesis of blighted ova. Furthermore, the unfavourable environment appears adversely to influence trophoblastic development.

Chorionic Villi↗
PubMed1985

Erythropoietic recovery in human after extended field radiotherapy. Ferrokinetic studies of patients treated by radiotherapy followed by autologous bone marrow transplantation and of patients treated by moderate doses (20 Gy) of radiotherapy.

The ability of human irradiated bone marrow to provide suitable environment for migrating stem cells has been studied in four patients. These had received chemotherapy plus doses of 40 Gy to thoracic vertebrae and sternum, followed by autologous bone marrow transplantation. The erythropoietic activity in the non-irradiated areas was increased but it was low in irradiated areas at 3.5 weeks and undetectable at 6 months after autotransplantation. This shows that no nidation of migrating stem cells actively contributed to bone marrow regeneration after 40 Gy and suggests the existence of environmental lesions. No extramedullary erythropoiesis and no bone marrow extension were found in these patients. Four patients who had received doses of 20 Gy to extended bone marrow volume were submitted to ferrokinetic studies from one to 18 years after radiotherapy. In non-irradiated areas the erythropoietic activity was within the normal range. In irradiated areas, it was significantly lower than in the non-irradiated areas and was intermediate between the erythropoietic activity in the sacrum of six healthy control subjects and in the irradiated areas of the four autografted patients. Bone marrow extension was found in these patients. This study suggests that bone marrow recovery after irradiation might not be an all-or-none phenomenon. It would be of interest to better document the dose-effect relationship.

Adult↗
PubMed2002

Pinopode expression during human implantation.

Implantation failure is considered the major impediment to successful in vitro fertilization pregnancy rate. Despite recent advances in reproductive medicine, the role played by uterine receptivity in contributing to human infertility remains unclear. Several clinical studies suggest the importance of blastocyst implantation in a narrow window of uterine receptivity, between 6 and 8 days after ovulation. This brief and precise period, called "implantation or nidation window", lasts less than 48 h and coincides with the formation of large and smooth projections, called "pinopodes", on the apical membranes of the endometrial epithelial cells. Pinopode expression appears to advance or retard depending on the hormonal treatments and an individual's particular response. This displacement can be followed through endometrial biopsy and scanning electron microscopy (SEM). Therefore, pinopode expression could be considered a useful biological marker to assess endometrial receptivity and to locate the implantation window.

Embryo Implantation↗
PubMed2006

[Angular pregnancy at eleven weeks gestation on a fibromyomatous uterus].

Reported cases of angular pregnancy, which by definition corresponds to pregnancy developing in a uterine horn, are rare. Etiologies as well as the diagnostic and therapeutic strategies are discussed. The anatomic modifications resulting from uterine fibromyoma and affecting embryo nidation in the uterine cavity of the uterus are the leading cause of angular pregnancy. The course of pregnancy depends on the evolution of the fibromyoma. Treatment therefore depends on the clinical course. Early diagnosis is essential for conservative treatment. In the case presented here, angular pregnancy was diagnosis following development of aseptic necrobiosis, the most common complication of fibromyosma.

Adult↗
PubMed2001

Uterine and fetal findings at hysteroscopic evaluation of spontaneous abortions before D&C.

STUDY OBJECTIVE: To evaluate the diagnostic benefit of fluid hysteroscopy before dilatation and curettage (D&C) in women with missed abortion, with respect to frequency of congenital and acquired uterine anomalies and geographic relationship of uterine anomalies to nidation site. DESIGN: Prospective case study (Canadian Task Force classification II-2). SETTING: Obstetric-gynecologic clinic of an academic teaching hospital. PATIENTS: One hundred five women with one or more recurrent missed abortions. INTERVENTION: Hysteroscopy before D&C. Inspection of the fetus was attempted in 62 patients. Control hysteroscopy of the nonpregnant uterus was performed in 20 patients. MEASUREMENTS AND MAIN RESULTS: The uterine cavity was visualized in 87 patients (83%). These women had an obstetric history significant for 143 spontaneous abortions in 208 pregnancies. Except for three small, finger-shaped polyps in the tubal ostia, no uterine anomalies were detected. In 20 women control hysteroscopy of the nonpregnant uterus confirmed initial findings. The fetus was successfully visualized in 30 cases (48%). We observed one case of umbilical cord torsion at 12 weeks' gestation. CONCLUSION: Absence of uterine anomalies in patients with single as well as recurrent spontaneous abortions was unexpected since it contradicts the existing literature. However, all previous data were gathered from hysteroscopies of nonpregnant uteri. Larger comparative studies are required.

Abortion, Spontaneous↗
PubMed2005

Implantation markers and endometriosis.

The receptive phase of the endometrium seems to occur in close association with the appearance of pinopodes and endometrial integrins that may be activated by the interleukin-1 system (IL-1). Embryo attachment is the result of adhesion protein expression, and the invasion of the embryo is governed by proteolytic enzymes. Leukaemia inhibitory factor (LIF) is produced by natural killer lymphocytes that interact with the invading trophoblast. This may activate urokinase plasminogen activator (uPA) and gelatinase enzymes, which play a crucial role in trophoblast invasion. Oestrogen stimulates, while progesterone inhibits, LIF. The role of endometrial contractility in displacing human embryos from the Fallopian tube to the lumen cavity of the uterus or vagina in terms of pregnancy or wastage is still a matter of discussion. Endometriosis and its associated abnormal uterine contractions may be also linked to implantation failure. Unless new evidence emerges to indicate otherwise, it can be assumed that progesterone is, either in a direct (non-genomic: contractility) or indirect (genomic: decidualization) manner, the only determinant of endometrial priming necessary for embryo nidation.

Biomarkers↗
PubMed2003

Embryonic production of nitric oxide and its role in implantation: a pilot study.

PURPOSE: To investigate the ability of human embryos to produce nitric oxide (NO) and correlate its production with embryo quality and pregnancy rate. METHODS: Twenty-three women participated in the study and were submitted to controlled ovarian stimulation and intracytoplasmic sperm injection. Embryos were singularly cultured in medium microdrops of 50 microL and were replaced, by transcervical transfer, at the 2- to 6-cell stage. In the culture media of each embryo the NO production was assessed by monitoring the levels of its stable oxidation products (nitrites/nitrates). RESULTS: All the 23 patients underwent embryo transfer. After microinjection 64 embryos were obtained. The mean number of transferred embryos was 2.61 +/- 0.46 and the pregnancy rate was 26%. The mean nitrite/nitrate concentrations of culture medium of each embryo was significantly higher (5.88 +/- 2.34 micromol/L) than in pure P-1 medium (0.81 +/- 0.21 micromol/L; p < 0.001) demonstrating an embryonic secretion of NO. Comparing pregnant (7.34 +/- 2.72 micromol/L) versus nonpregnant patients (5.53 +/- 1.49 micromol/L; p = 0.022), the mean nitrite/nitrate concentrations were significantly higher. Furthermore, the best quality embryos of pregnant women produced significantly higher nitrite/nitrate concentrations than those of not pregnant patients. CONCLUSIONS: It seems that NO production in nidating embryos is increased and that it may be primarily associated with a better morphology and a better growth potential of developing embryos.

Adult↗
PubMed2000

Structure-function relations in the human placenta.

The human haemochorial placenta is a complex and dynamic interface between embryonic and maternal tissues. A myriad array of compounds has been identified at this interface, some of which exert local effects which might be important in maintaining the integrity of the organ. These compounds are diverse in nature and function; they include enzymes, hormones and bioactive peptides. Successful nidation requires the synchronization of endometrial maturation and embryonic development. The complex nature of this interface requires the application of sound sampling strategies. The new stereological methods have thrown fresh light on the growth and development of the human placenta. These methods permit the objective, quantitative description of morphology by efficient design-based methods. This approach has permitted a better definition of the functional morphology of the placenta. Applications of these methodologies are providing a spatial and temporal framework on which to lay the new physiological and molecular information. Here we review the essential features of the stereological approach, identify useful structural quantities and provide some examples of their application. The problems associated with the quantification of immunocytochemistry are illustrated with the use of immunoreactivity to insulin-like growth factor I receptor in normal placentae and in pre-eclampsia. Although stereology can provide useful quantitative information about the structure of this dynamic tissue, other anatomical methods that could be applied to better define the relationships between structure and function will be discussed. These include confocal microscopy, to examine the dynamic physiological interactions of the different tissue compartments, and low-temperature electron microscopy techniques such as cryosubstitution, to allow better access to the biochemical information resident in the tissue. The complex and dynamic nature of the tissue requires a multidisciplinary approach; central to these investigations is a comprehensive understanding of its fine structure.

Estradiol↗
PubMed2000

Glycodelin: a pane in the implantation window.

Glycodelin is an endometrial protein with proposed immunomodulatory activity during human embryonic nidation. In this review we describe the effects of ovarian hormones on glycodelin transcription, synthesis, and secretion by human epithelial cells and focus on the importance of glycodelin in implantation. We demonstrate that glycodelin transcription, synthesis, and secretion by human epithelial cells are stimulated by progestins and antiprogestins but not by estrogen. Sequences localized within a 403-base-pair region flanking the 5' human glycodelin gene promoter appear to be responsible for transcriptional activation of this gene mediated by progesterone receptor-ligand complexes. Relaxin, purported to enhance glycodelin production in vivo and in prior in vitro studies, had no stimulatory effect on the expression of this gene in vitro in our models.

Cells, Cultured↗
PubMed2001

Luteal phase of the menstrual cycle in young healthy women is associated with decline in interleukin 2 levels.

The aim of this study was to look at the possible changes in the blood levels of Interleukin 2 (IL2) during the sexual cycle in generally healthy, young, regularly menstruating women. The concentrations of progesterone and 17beta-estradiol were measured using radioimmunological assay. The bioactivity of interleukin 2 was measured using a biological test on the IL2-sensitive CTLL cell line. The percentage of lymphocytes with intracellular IL2 was determined by flow cytometry. Eighteen healthy volunteers (19-29 years old) were examined on days 5, 8, 14, 18 and 25 of the same cycle. All women were characterised by a regular menstrual cycle as per physiological levels of 17beta-es-tradiol and progesterone. The luteal phase of the cycle was characterised by both a decrease of IL2 blood levels and a decrease in the percentage of intracellular 1L2-containing lymphocytes stimulated in vitro. The IL2 level fluctuations observed during the menstrual cycle may be one factor causing pre-menstrual infections observed in young women. On the other hand, the decrease of IL2 may be seen as a start of the immune suppression necessary for an embryo's nidation.

Adult↗
PubMed1996

[Benzoporphyrin derivative mono acid for photodynamic therapy of the endometrium].

The aim was to study the impact of photodynamic therapy (PDT) on the endometrium after local intrauterine application of photosensitiser (Ps) and laser light without sensitising the skin. To our knowledge Benzoporphyrin Derivative Mono Acid (BPD) was used for the first time for this purpose in the rat model. The advantage of using BPD is the fact that light of 690 nm (maximum absorption) penetrates deeper into tissue and shows less absorption by haemoglobin. Low-light level tissue fluorescence imaging revealed a distinct positive endometrium-to-myometrium ratio within the first 12 hours. Relative fluorescence was highest in the endometrial glands and lowest in the myometrium. After 12 hours the intensity of fluorescence levelled off in all compartments and values of the glands approached close to those of the other layers. REPRODUCTIVE PERFORMANCE AFTER PDT: There was a significant difference in nidations (p < 0.03) in the treated left uterine horn as compared to the untreated right horn and the control animals (light/no drug and drug/no light). HISTOLOGICAL CHANGES: Following PDT a marked atrophy of the endometrial layer was observed in most animals leaving just a single cell epithelial layer covering the myometrium. SKIN PHOTOSENSITIVITY: None of the animals showed any alterations in the light treated skin area at any time. These promising results show that PDT of the endometrium is possible after topical application of the photosensitising drug and the laser light without provoking skin sensitivity.

Animals↗
PubMed1985

[Premature detachment of an at the uterine septum implanted placenta. Case report].

In the context of a report on a case in which the placenta was implanted at the uterine septum, the diagnosis, course of pregnancy, and obstetric management are described and discussed. In the case reported here this extremely rare nidation site led to premature detachment of the placenta during the last expulsive pain in a delivery with a vaginal breech presentation (43-year-old patient with four previous unproblematic term births).

Adult↗
PubMed1982

[The significance of alpha-feto-protein (AFP) and human chorionic gonadotrophin (HCG) during the first half of pregnancy (author's transl)].

The determination of AFP and HCG was used as a diagnostic parameter for the functional integrity of the feto-placental unit during the first 20 weeks of normal and disturbed pregnancies. In contrast to HCG which can already be detected very shortly after nidation and reaches a maximum between the 10th and 12th week of gestation, AFP does not begin to rise discernibly before the 8th and 9th week and attains the highest values in the third trimester. The assay of AFP did not contribute relevant data when carried out before the 10th week of pregnancy. Contrary to that, an irreversibly damaged pregnancy has to be expected when lower than normal AFP values are found after the 10th week, even in the presence of a normal level of HCG. Likewise, higher than normal values should be taken as a reliable sign of embryonal demise after the 14th week of pregnancy, as long as a multiple gestation, a previous amniocentesis or a neural tube defect can be excluded. Serum AFP did not only increase markedly in many cases after interruption of pregnancy, but even after amniocentesis or premature rupture of the amniotic sac when fetal cells having a high content of AFP enter the maternal circulation.

Abortion, Spontaneous↗
PubMed1996

The evolution of new agents for ovulation induction.

The field of clinical ovulation-induction therapy has remained relatively static for over 30 years. This field promises to benefit from advances in our understanding of the biology of ovulation, and from exciting new work in the areas of molecular and cellular biology and in the biochemistry of steroids, gonadotropins, and their receptors. New therapies with recombinant gonadotropins and their analogues show promise for the near future. Advances in our ability to stimulate and suppress the reproductive axis through central mechanisms also show some promise. In the long term, our understanding of the mechanisms involved in folliculogenesis and oocyte maturation may be combined with an enhanced ability to dissect these processes that lead to disordered ovulation. Our improved understanding of the implantation process may well lead to an ability to create nearly universal nidation in women who are undergoing ART or who have implantation disorders. This article discusses some of the many new opportunities in the clinical and basic science of ovulation induction. New technologies, such as those available through the Human Genome Project, and the use of genetic manipulation of animal models will stimulate additional new avenues of research.

Female↗
PubMed1987

The progesterone antagonist RU 486. A potential new contraceptive agent.

Since progesterone supports endometrial nidation of the fertilized ovum, a progesterone antagonist would theoretically block this process and thus have contraceptive potential. We have explored the ability of RU 486, a newly developed competitive progesterone antagonist, to function as a contraceptive agent. A single oral dose of 10 mg per kilogram of body weight given in the midluteal phase consistently induced menses within 72 hours in women with normal cycles and no risk of pregnancy. Bleeding was not prevented by administration of human chorionic gonadotropin in the midluteal phase. This suggested that giving a single dose of RU 486 late in the menstrual cycle might be an effective contraceptive strategy. This concept was tested in monkeys. When given to rhesus females on day 25 of the cycle, a single intramuscular dose of RU 486 (5 mg per kilogram) prevented pregnancy. The vehicle-treated control animals had a 28 percent pregnancy rate (P less than 0.05 by chi-square analysis). No side effects were noted in women or monkeys. These data suggest that a progesterone antagonist such as RU 486 has the potential to be an effective, safe, and convenient contraceptive agent. Further work will be necessary to assess the safety of long-term monthly administration and to define the optimal dose and time of administration in women.

Adult↗
PubMed1997

Nitric oxide synthase regulation during embryonic implantation.

It has previously been demonstrated that uterine nitric oxide synthase (NOS) activity increases before embryonic implantation in rats. The aim of the present work was to investigate the regulation and the physiological relevance of the nitric oxide (NO) system in ovoimplantation. The increase in NOS activity in early pregnancy was found to be independent of the presence of embryos in the uterus. Whereas the Ca2+-dependent isoform of NOS increased gradually in the preimplantation days, the Ca2+-independent isoform increased just at the beginning of implantation (Day 5, 1800 hours); then the activity of both isoforms declined. Oestradiol, whose concentration peaks before implantation, might be regulating NOS activity in the uterus, since treatment of rats with tamoxifen, a receptor antagonist, reduces the activity of both isoforms to preimplantation levels. Intraluminal injections of L-NAME (0.5 mg kg[-1]), a competitive inhibitor of NOS, reduced by 50% the number of implanted embryos; this suggests that the NO system plays a role during implantation. The data suggest that oestradiol might be a modulator of NOS activity during nidation and that NO production is necessary to achieve a successful embryo implantation.

Animals↗
PubMed1996

Recombinant human uteroglobin suppresses cellular invasiveness via a novel class of high-affinity cell surface binding site.

The mechanism(s) that regulates invasion of trophoblasts through the uterine epithelium during embryo implantation and nidation in hemochorial placental mammals is poorly understood. While limited trophoblast invasion is essential for the establishment of normal pregnancy, dysregulation of this process may contribute to the pathogenesis of choriocarcinoma, a highly invasive and lethal form of cancer arising from the trophoblasts. We have previously demonstrated that rabbit uteroglobin (UG), a cytokine-like, antiinflammatory protein, produced by the endometrial epithelium during pregnancy, has a potent antichemotactic effect on neutrophils and monocytes in vitro. Here, we report that recombinant human UG (hUG) dramatically suppresses invasion of human trophoblasts and NIH 3T3 cells through an artificial basement membrane (Matrigel) in vitro but has no effect on that of human choriocarcinoma cells. We identified a previously unreported high-affinity, high molecular weight (approximately 190 kDa), nonglycosylated hUG-binding protein, readily detectable on human trophoblasts and NIH 3T3 cells but totally lacking on choriocarcinoma cells. Taken together, these results raise the possibility that (i) hUG plays a critical role in regulating cellular invasiveness, at least in part, via its previously unrecognized cell surface binding site, and (ii) some of the numerous biological activities of proteins of the UG family, reported so far, may be mediated via this binding site.

3T3 Cells↗