Obstetrics — drughealth A number of abnormalities can affect each of these processes and lead to infertility or pregnancy loss. In most women, spontaneous, cyclical ovulation at to day intervals continues throughout almost 40 years between the time of menarche and menopause. For women who never use contraception, there are approximately opportunities for pregnancy, which may occur with sexual intercourse on any of days the day of ovulation and the 2 preceding days. This narrow window available for fertilization is controlled by tightly regulated production of ovarian steroids that cause the optimal regeneration of endometrium that begins with the ending of menstruation. Should fertilization occur, the events that unfold after the initial implantation of the blastocyst onto the surface of the endometrium through to parturition result from a unique interaction between the trophoblasts of the fetus and the endometrium—decidua of the mother. The ability of mother and fetus to coexist as two distinct immunological systems results from endocrine, paracrine, and immunological modification of fetal and maternal tissues in a manner not seen elsewhere. The placenta mediates a unique fetal—maternal communication system, which creates a hormonal environment that helps initially to maintain pregnancy and eventually initiates the events leading to parturition.
The Endometrial Cycle
Inadequate uterine receptivity is responsible for approximately two-thirds of implantation failures, whereas the embryo itself is responsible for only one-third of these failures Slide 6 Human embryo implantation is a three-stage process apposition, adhesion and invasion Implantation involves embryo apposition and adhesion to the endometrial epithelium penetration through the epithelium and invasion of the embryonic trophoblast through the endometrial stroma. On the blastocyst, on the other hand, it occurs at a location where there has been enough lysis of the zona pellucida to have created a rupture to enable direct contact between the underlying trophoblast and the decidua of the endometrium.
Slide 9 Endometrial morphological features classical work describing the dating of the endometrium is done by Noyes et al. Pinopod expression is limited to a brief period of maximum 2 days in the menstrual cycle corresponding to the putative window of implantation Pinopods appear progesterone dependant Slide 12 Function of Pinopods the receptors required for blastocyst adhesion are located on the pinopod surface. Association between mid-luteal increase of progesterone level and the first appearance of pinopods throughout the menstrual cycle was noted Stavreus-Evers et al.
The secretory cells are slightly bulging, covered with dense microvilli.
Predictive value of endometrial thickness, Different strategies have been developed to evaluate endometrial receptivity, such as the histologic dating of an endometrial biopsy, Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril ; 2.
Journal of Histology , , DOI: The male reproductive system of fruit bat Eidolon helvum was studied histologically using light microscope. Thirty males 17 adults and 13 juveniles were captured using net, weighed, aged using relative ossification of the wing bone, and dissected and reproductive tissue was processed for histomorphometry. On the basis of histological sections, the structures of a pair of testis containing the seminiferous tubules of adults were compacted in organization with spermatogenic cells.
The epididymis has a thinner muscular region than the vas deferens with longitudinal folds on the mucosal lining. Two portions were observed in the prostate gland, while seminal vesicle has numerous trabeculae and bulbourethral gland was observed to have multiacini. There was increase in thickness of muscular region, epithelial height, and luminal diameter of epididymis and vas deferens between adults and juveniles. This work has documented the histology of the male reproductive system in bats, and ultrastructure and histochemistry are recommended for further insight into the reproductive biology.
Human Endometrial Transcriptomics: Implications for Embryonic Implantation
Uterine fibroids are the most common benign tumors of the female genital tract. The management of symptomatic fibroids has traditionally been surgical; however, alternative pharmacological approaches have been proposed to control symptoms. To date, gonadotropin-releasing hormone analogs are the only available drugs for the preoperative treatment of fibroids.
Objective To compare the assessment of endometrial maturation parameters in endometrial secretion samples obtained by a novel minimally invasive technique with those assessed in tissue biopsies. Design Prospective study. Setting University Hospital. Population Healthy female volunteers.
To review the literature for studying the mechanisms of influence of superovulation on the receptivity of the endometrium in vitro fertilization IVF , which is largely due not only to the quality of the embryo, but with the condition of the endometrium, its maturity and readiness for implantation. In the course of acquaintance with the publication presents the morphological characteristics of the endometrium in stimulated cycles.
Presents current views on endometrial receptivity and the molecular mechanisms regulation of implantation. The features of the expression of estrogen and progesterone receptors, as well as other markers of endometrial receptivity pinopodii, leukemia inhibitory factor, integrins in natural and stimulated cycles. Patients with a history of failure of implantation prior to IVF ART program is necessary to analyze all inducers affecting the endometrium, endometrial morphological landscape, E2 receptor expression and progesterone pinopodii, integrins, molecular and genetic aspects of the endometrium in stimulated cycles.
The analysis of numerous publications showing an adverse effect on superovulation endometrial receptivity in assisted reproduction programs. Undetermined noninvasive markers to assess the receptivity of the endometrium, including in stimulated cycles. Not evaluated linically significant endometrial threshold level of progesterone on the day of ovulation trigger and insufficiently studied the possible mechanisms of the effect of a premature increase of progesterone on the outcomes of IVF.
Therefore, further study and development of the best approaches for the prevention and correction of the negative impact of ovarian stimulation function on the endometrium in assisted reproduction programs. Keywords IVF; premature luteinization stimulated cycle; endometrial receptivity; receptors estradiol; progesterone receptors; integrins; pinopodii; leukemia inhibitory factor expression of Noja Full Text: Assisted reproductive technology in Europe, European Society of Human Reproduction and Embriology:
Luteal Phase Dysfunction
Department of Clinical Science, Division of Ob. During the time of implantation, pinopodes appear on the endometrial surface. The precise function of these structural markers of endometrial receptivity is not known, but it is generally believed that they play a role in the implantation process.
who did endometrial dating according to the Noyes criteria,(2) considering as out-of-phase a delay of 3 days or Filho JH, Cedenho AP, Freitas V. Correlation between endometrial dating of luteal phase days 6 and 10 of the same menstrual cycle. Rev Paul Med ;(3)
Received Sep 2; Accepted Nov 6. Materials and methods Prospective, self-controlled study. The thirty-five volunteers were studied for two cycles: Endometrial biopsy was performed on day 6 after ovulation for histological dating and morphometric study. Results No statistical differences between histological dating and the endometrial thickness in the control and GnRH antagonist-treated cycles. All morphometric parameters were also not different. Conclusion GnRH antagonist has no effect on the endometrium of regularly menstruating women as assessed by either histological dating or morphometric analysis.
The role of GnRH agonist is to prevent premature LH surge which is associated with cycle cancellation.
The Endometrial Cycle
Abstract Aims and Objectives: To evaluate the role of endometrial thickness, pattern and sub-endometrial blood flows measured by 2D power Doppler ultrasound to predict pregnancy during in-vitro fertilization IVF treatment. Prospective, non-randomized clinical study. This was a prospective observational study. Women with tubal factor, male factor and unexplained infertility were included in the study.
The mean age was 35 years and mean duration of infertility was 8 years.
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Provisional Patent Application No. What is claimed is: The method of claim 1, wherein the presence of NCSs indicates that the endometrium is in a state that is receptive for implantation of an embryo. The method of claim 1, wherein the tissue sample is obtained from the endometrium of a woman between day 18 and day 24 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo.
The method of claim 1, wherein the tissue sample is obtained from the endometrium of a woman between day 19 and day 22 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo.
The method of claim 1, wherein the tissue sample is obtained from the endometrium of a woman between day 4 and day 9 of the luteal phase of the menstrual cycle, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo. The method of claim 1, wherein the tissue sample is obtained from the endometrium of a woman between day 5 and day 8 of the luteal phase of the menstrual cycle, and wherein the absence of NCSs indicates that the endometrium is not in a state that is receptive for implantation of an embryo.
The method of claim 1, wherein the presence or absence of the protein is determined using a light microscope. The method of claim 9, wherein the tissue sample is obtained from the endometrium of a woman between day 18 and day 24 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss. The method of claim 9, wherein the tissue sample is obtained from the endometrium of a woman between day 19 and day 22 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss.
The method of claim 9, wherein the presence of NCSs is detected between day 18 and day 24 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss. The method of claim 9, wherein the presence of NCSs is detected between day 19 and day 22 of a 28 day menstrual cycle, where day 1 of the cycle is defined as the first day of menstrual blood loss. The method of claim 9, wherein the presence of NCSs is detected between day 4 and day 9 of the luteal phase of the menstrual cycle.
Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule ICAM Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle , but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle. The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM
For endometrial dating, the phase assignment is made based on previous histological dating by at least two independent pathologists.  Figure 1: Principal component analysis of human endometrium throughout the development of the luteal phase in natural (LH + n) and controlled ovarian stimulation cycles (human chorionic gonadotropin + n).
Some newer aspects of management of infertility. Fundamental role of folliculo-luteal function in recurrent miscarriage. Sonntag B, Ludwig M. An integrated view on the luteal phase: Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Transvaginal sonographic evaluation at different menstrual cycle phases in diagnosis of uterine lesions. Int J Womens Health. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev.
Current clinical irrelevance of luteal phase deficiency: HOX gene expression is altered in the endometrium of women with endometriosis. Corpus luteum function and regression. Regulation of HOXA expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J Clin Endocrinol Metab.
Biology of Reproduction
MicroRNAs miRNAs , a class of small noncoding RNAs that regulate gene expression, have fundamental roles in biological processes, including cell differentiation and proliferation. These small molecules mainly direct either target messenger RNA mRNA degradation or translational repression, thereby functioning as gene silencers. Epithelial cells of the uterine lumen and glands undergo cyclic changes under the influence of the sex steroid hormones estradiol beta and progesterone.
Because the expression of miRNAs in human endometrium has been established, it is important to understand whether miRNAs have a physiological role in modulating the expression of hormonally induced genes.
Talbi S, Hamilton AE, Vo KC, Tulac S, Overgaard MT, Dosiou C, et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women.
Hematoxylin end eosin-stained sections from paraffin-embedded blocks were classified as: The hormonal phases of all normal endometrium specimens were established according to the criteria of Noyes et al. The endometrial adenocarcinomas were graded according the World Health Organization grading system: The patients had not received any preoperative therapy. Immunohistochemistry was performed according to a standard streptavidin-biotin peroxidase complex method Zymed, S.
Endogenous peroxidases were quenched by incubation in 0. The secondary biotinylated antibody was incubated as previously described The reaction was revealed by adding diaminobenzidine-tetrahydrochloride DAB chromogen mixture Zymed. After hematoxylin counterstaining, slides were permanently mounted and analyzed for the presence and distribution of the immunostaining. Staining was scored based on semiquantitative assessment of the distribution pattern of staining plasma membrane and cytoplasm and number of immunoreactive epithelial cells.
Samples were considered negative when they showed no immunoreactivity.
Dating the endometrial biopsy.
Bikerdatingsite com Dating the endometrial biopsy noyes Blighted ovum was designated in cases where embryonic echoes were never visualized in the gestational sac, and embryonic death in cases where embryo heart action, which had been once identified, disappeared within 11 weeks of gestation menstrual age. Over the last decade, research to improve success rates in reproductive medicine has focused predominantly on the understanding and optimization of embryo quality.
Of pregnancies, persisted successfully to live birth, but 42 ended in early pregnancy loss.
In normal endometrium (proliferative, secretory phases and atrophic endometrium), E-cadherin and α-catenin were expressed in %, % and % of samples, respectively: a homogeneous pattern of immunostaining was observed with intense reactivity at the cell-to-cell borders, whereas a weak immunostaining was present in the cytoplasm. No.
Original studies on endometrial transcriptomics in assisted reproductive medicine Most of these studies investigate the transcriptomic signature in the whole endometrial tissue without separating the different compartments. However, in some studies, laser capture micro-dissection has facilitated specific compartment gene expression profiles Yanaihara et al.
Even the specific profiles for stromal cells and glands at different depths in the endometrium have been reported Gaide Chevronnay et al. Several groups have used transcriptomics to search for the molecular diagnosis of the different phases of the human endometrium Carson et al. Based on data extracted from samples taken at different cycle phases, they identified seven main groups of genes with a similar expression pattern throughout the cycle.
Each of these groups had an expression peak in one of the seven subphases menstrual, early-proliferative, mid-proliferative, late-proliferative, early-secretory, mid-secretory, and late-secretory. This finding was later reinforced by Talbi et al. There was a lack of consensus on the results obtained, which was likely caused by the variability in some of the parameters such as samples taken from the same or different patients, the decision to use a pool of samples or not, the day of the cycle on which samples were taken, or the type of data analysis undertaken Horcajadas et al.
Despite the differences among all the studies performed, they all agreed on the existence of a specific transcriptomic profile during the WOI. This characteristic profile suggested that a unique transcriptional process occurs to achieve a receptive phenotype Borthwick et al. The implantation of the blastocyst in the endometrium activates the production of cytokines that modulate receptivity by regulating the expression of adhesion molecules in mammals Simon et al.
E-Cadherin and Alpha-Catenin Expression in Normal, Hyperplastic and Neoplastic Endometrium
It is asserted that examination of the endometrium during the secretory phase yields more information about the time of ovulation, degree of progestational change, and normality of the endometrium than any other test used in sterility studies. Attention to qualitative changes in 8 morphological factors is most useful in dating the endometrial biopsy. During the 1st week of luteal activity, attention should be focused on changes occurring in gland epithelium: During the 2nd week , stromal changes including edema , predecidual reaction, stromal mitosis, and leukocytic infiltration are the key criteria.
Tissue from the fundus of the uterus gives the most reliable information. These critera were used in sterility biopsies taken from normally menstruating women over a 3-year period.
Decidualization is the combination of changes on endometrium structure and hormone profiles, along with gene expression, cell differentiation and tissue modification, that allow for implantation of the embryo.
Introduction The human endometrium undergoes cyclic growth, remodeling, and functional changes that are hormonally synchronized with the maturation and release of the ovum. During every menstrual cycle, the endometrium repairs and proliferates after menstruation, differentiates in preparation for pregnancy, and breaks down and is shed during menstruation in the absence of an implanting conceptus. Based on both morphology and gene expression Noyes et al. This progresses into the first trimester of pregnancy, when maximal decidualization is achieved.
In addition, blocking of PC6 production during decidualization of human endometrial stromal cells ESCs in vitro, significantly reduces decidualization Okada et al. Based on these characteristics, we suggested that PC6 could be used as a novel target in female contraception with an additional protective function against HIV Nie et al. PC6 belongs to the PC family of serine proteases. Thus, we aimed to determine whether PCs other than PC6 are expressed in the human endometrium during the menstrual cycle and early pregnancy, and to establish whether they are also key regulators for stromal cell decidualization.
A soluble isoform can also be produced by cleavage of the transmembrane and cytosolic region Paleyanda et al. However, the in vivo cleavage of any substrate depends on the relative activity levels of all PCs that can cleave this substrate within the microenvironment Nakayama Materials and Methods Tissue collection and processing Human endometrial tissues were obtained as previously described during the menstrual M , proliferative P , ES, MS, and LS phases of the menstrual cycle Jones et al.
Early pregnant 6—8 weeks decidua D was collected from women undergoing elective termination of pregnancy. Stage of the cycle was confirmed by histological assessment according to the criteria of Noyes et al.