15 years of transcriptomic analysis on endometrial receptivity: what have we learnt?


Study Design : Prospective, non-randomized clinical study. Materials and Methods : This was a prospective observational study. Women with tubal factor, male factor and unexplained infertility were included in the study. Results : The mean age was 35 years and mean duration of infertility was 8 years. Seventy five The mean endometrial thickness was 8. Overall, 27 With a thin endometrium and a good texture triple-line , other prognostic factors, such as embryo quality, should be taken into account. The endometrial vascularity has a useful predictive value on the implantation rate in IVF cycles irrespective of the morphological appearance of the endometrium. However, further study is needed to make a definitive conclusion.

Endometrial Biopsy

Steven G. Arch Pathol Lab Med 1 March ; 3 : — It is well known that a number of problematic diagnostic scenarios occur relative to these specimens. Recognition of diagnostic pitfalls and practical approaches to their resolution help improve quality. Although most diagnostic pathologists encounter numerous endometrial specimens in their daily practice, many perplexing problems are still encountered when dealing with these specimens.

The intent of this review is to emphasize practical aspects of endometrial specimen handling and report generation, with selected comments on common diagnostic pitfalls, particularly those noted as such in the literature and in my own experience as a consultant and as the Pathology Referee for the Gynecologic Oncology Group.

Endometrial assessment has become part of standard moni- toring during IVF The published research to date seems to have provided con- vincing evidence.

Providing cutting-edge scholarly communications to worldwide, enabling them to utilize available resources effectively. We aim to bring about a change in modern scholarly communications through the effective use of editorial and publishing polices. Monique Monard. E-mail : bhuvaneswari. Courtney Marsh. Katelyn Schumacher. Warren Nothnick. The female reproductive system prepares the female body for conception and pregnancy through two distinct cycles, the ovarian cycle and the endometrial cycle.

The human endometrium, under the influence of complex biological signals, undergoes cyclic changes in preparation for implantation and the initiation of pregnancy.

Endometrial Biopsy in Infertile Patients

The endometrium is typically biopsied because of abnormal bleeding. Endometrial hyperplasia and endometrial carcinoma are dealt with in separate articles. An overview of gynecologic pathology is in the gynecologic pathology article. Other indications: [2]. An increased gland density is seen focally, at the edge of one tissue fragment, in association with tearing of the stroma compression artifact.

In order to assess the adequacy of endometrial LBC specimens, the evaluation of specimen cellularity (numerical criterion) is among the most important issues. In.

Morphologically, the endometrium is one of the most dynamic target tissues in women. Its cyclic structural changes mirror changes in metabolic functions, and both are regulated by ovarian estradiol and progesterone. Because of this interplay of structure, function, and ovarian hormonal stimuli, the endometrium is considered one of the most sensitive indicators of the hypothalamic-pituitary-ovarian hormonal axis.

As a result, morphologic evaluation of the endometrium is used in diagnostic evaluation of infertile patients to determine whether ovulation is occurring Fig. Schematic representation of steroid hormone-morphologic interactions during the endometrial cycle. Estradiol promotes endometrial proliferation, whereas after ovulation, progesterone converts estradiol-primed endometrium into secretory tissue.

Postovulatory estradiol amplifies the progesterone effect, and after withdrawal of both estradiol and progesterone, the endometrial mucosa breaks down and regenerates within the period of menstruation. Steroid hormone control of endometrial, epithelial, stromal, and presumably endothelial cells is mediated by estrogen receptors and progesterone receptors.

These steroid receptors are specific proteins concentrated exclusively in the nuclei of both endometrial epithelial and stromal cells, as well as the endothelial cells of stromal capillaries. They have high affinity to bind estradiol and progesterone, respectively. This chapter contains a review of the technical procedures for handling endometrial tissues and a discussion of the morphologic aspects of the endometrium, focusing on the interpretation and understanding of the physiomorphology of the endometrial cycle.

In current practice, the device that is most often used is the Pipelle endometrial aspirator. To ensure a maximum amount of tissue for morphological reading, the specimen should be placed on a piece of lens paper or some other adhesive tissue and then immersed in the fixative. By this means, all of the tissue fragments remain tightly attached to the lens paper, rather than floating in the fixative, and no tissue will be lost for histologic examination.


Implantation occurs during a specific period of the menstrual cycle, known as the window of implantation between day 6 and day 10 of the cycle, following the luteinizing hormone surge , and is dependent on a synchronized dialogue between the embryo and endometrium. This dialogue is mediated by specific biochemical factors, including hormones, growth factors, enzymes, integrins and cytokines 1 — 3. Leukemia inhibitory factor LIF , which is a multifunctional protein that belongs to the interleukin 6 cytokine family, exerts numerous regulatory actions on various domains of cellular function 4.

LIF was initially reported to induce macrophage differentiation in M1 murine myeloid leukemic cells, and to suppress their proliferation in vitro 5.

Evaluation of the status of the endometrium in infertile patients, including histological dating. 3. Evacuation of products of conception, either.

Nevertheless, there is no consensus regarding the most suitable period of the luteal phase for performing the biopsy. OBJETIVE: This study evaluated the correlation between the histological dating of two endometrial biopsies performed in the same menstrual cycle, on luteal phase days six and ten. Dating was done according to morphometric criteria, in which an endometrium sample is considered out of phase if the minimum maturation delay is one day.

Luteal phase. Female infertility. Evaluation of the luteal phase of regularly cycling women complaining of infertility is directed towards the evaluation of corpus luteum activity and the action of progesterone on the endometrium. Endometrial maturation, whose role in human reproduction was first recognized by Jones, 1 is evaluated by the Noyes criteria.

This study evaluated the correlation between the histological dating of two endometrial samples, obtained by biopsies performed on luteal phase days 6 and 10 of the same menstrual cycle. Twenty five regularly cycling healthy women, complaining of infertility for at least one year, voluntarily agreed to participate in the study group and gave their informed written consent.

Blood samples were drawn from patients between days one and five of the menstrual cycle, for basal plasma levels of LH, FSH and prolactin, measured by immunofluorimetry normal ranges: FSH: 2.

Diagnosing uterine cancer

Engman is a fellow in reproductive endocrinology and infertility, University of Connecticut School of Medicine, Farmington, Conn. Disagreement about the cause, true incidence, and diagnostic criteria of this condition makes evaluation and management difficult. Here, 2 physicians dissect the data and offer an algorithm of assessment and treatment.

Despite scanty and controversial supporting evidence, evaluation of patients with infertility or recurrent pregnancy loss for possible luteal phase deficiency LPD is firmly established in clinical practice. Although observational and retrospective studies have reported a higher incidence of LPD in women with infertility and recurrent pregnancy losses than in fertile controls, 1 – 4 no prospective study has confirmed these findings.

Objective: To formulate clinical recommendations for the assessment of endometrial databases for relevant peer-reviewed articles dating from to.

A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens. The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies.

In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies.

Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens. The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate.

In many histopathology laboratories, endometrial specimens account for a major proportion of the workload. Most specimens are taken because of abnormal uterine bleeding or other related symptoms, and the pathologist is expected to exclude an endometrial cancer or a precancerous lesion. In some cases, a benign cause for abnormal uterine bleeding is identified, such as endometritis or endometrial polyp.

In this review, I will outline my approach to the interpretation of endometrial biopsy specimens, especially concentrating on areas which, in my experience, create difficulties for pathologists.

My approach to the interpretation of endometrial biopsies and curettings

Endometrial thickness is a commonly measured parameter on routine gynecological ultrasound and MRI. The appearance, as well as the thickness of the endometrium, will depend on whether the patient is of reproductive age or postmenopausal and, if of reproductive age, at what point in the menstrual cycle they are examined. The endometrium should be measured in the long axis or sagittal plane, ideally on transvaginal scanning, with the entirety of the endometrial lining through to the endocervical canal in view.

Care should be taken not to include hypoechoic myometrium or intrauterine fluid in this measurement.

Received date: October 18, ; Accepted date: October 26, ; Published transvaginal ultrasound was done to assess the uterine size.

Study record managers: refer to the Data Element Definitions if submitting registration or results information. This study will evaluate the utility of the endometrial biopsy as a tool for the routine evaluation of the luteal phase of women presenting for infertility evaluation. The study will establish whether the mid-luteal or late-luteal phase is the most appropriate time to perform an endometrial biopsy.

The study will be conducted through the multi-center Reproductive Medicine Network. Women with a history of infertility will be age matched to fertile women controls. Women will be randomized either to the mid-luteal phase 7 to 8 days post-ovulation endometrial biopsy group or to the late-luteal phase 12 to 13 days post-ovulation endometrial biopsy group. Endometrial specimens will be evaluated histologically by a “blinded” pathologist.

Talk with your doctor and family members or friends about deciding to join a study.

Hormonal Pathology of the Endometrium

Read terms. This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Making the distinction between hyperplasia and true precancerous lesions or true neoplasia has significant clinical effect because their differing cancer risks must be matched with an appropriate intervention to avoid undertreatment or overtreatment.

Several endometrial dating criteria have been commonly used in clinical In order to develop a diagnostic tool for human ER assessment, the.

Raga, F. Bonilla-Musoles, E. Klein, F. The aim of the present prospective study was to obtain quantitative data on endometrial volume by three-dimensional 3D ultrasound at the time of embryo transfer in an in-vitro fertilization programme and to assess its value in predicting endometrial receptivity. It is concluded that endometrial volume by 3D transvaginal ultrasound may become a new objective parameter by which to predict endometrial receptivity.

Endometrial differentiation, embryo development, and embryo-endometrial interactions leading to implantation require continuous and synchronous dialogue between these two compartments. Since the introduction of transvaginal sonography, a number of studies have attempted to define a relationship between endometrial thickness, echogenicity and endometrial receptivity. Unfortunately, the sonographic parameters used to predict uterine receptivity still lack specificity, and so the ideal method to predict endometrial receptivity by a non-invasive method has yet to be established.

With the advent and evolution of three-dimensional 3D ultrasound we now stand at a new threshold in non-invasive diagnosis. The standard method of endometrial dating is the histological evaluation of an endometrial biopsy specimen Noyes et al. Indeed, this technique has allowed the demonstration of asynchrony in endometrial development during the course of cycles of ovarian stimulation for IVF leading to cancellation of embryo transfer Frydman et al.

Obviously, the invasiveness of endometrial biopsy is not acceptable in the clinical context of assisted reproduction treatment cycles.

Uterine Cycle – The Phases of Endometrial Change

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