Hepatocellular carcinoma treated with transarterial chemoembolization: Evaluation with parametric contrast-enhanced ultrasonography.

Aim: To evaluate the response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) using a simplified protocol of parametric contrast-enhanced ultrasound (pCEUS).

Methods: Eighteen patients with HCC (18 target tumors, diameter: 2.8-12 cm) were evaluated before, and 20 d after TACE.

The expression of receptivity markers in the fallopian tube epithelium.

Pinopodes represent the morphological and integrins, the biomolecular markers of endometrial receptivity. We studied using scanning electron microscopy, the expression of pinopodes on tubal samples and their corresponding endometria, from 21 women of reproductive age (7 from proliferative phase, 7 from day LH +5 and 7 from day LH +7). In addition, we examined the immunohistochemical staining of integrins alpha v beta 3, alpha v beta 5 and their ligands, fibronectin (FN) and osteopontin (OPN) in the same tubal epithelium samples.

Hormonal and cytokine regulation of early implantation.

Implantation of the blastocyst into the endometrium is a delicately controlled process and a prerequisite for the furtherance of the mammalian species. A complex network of molecules is involved in preparing both the endometrium and blastocyst for a successful interaction. However, the exact molecular steps are poorly understood.

Gene expression profiles and structural/functional features of the peri-implantation endometrium in natural and gonadotropin-stimulated cycles.

It has been speculated that controlled ovarian hyperstimulation (COH), as performed during in vitro fertilization therapy, may negatively affect embryo implantation. The objective of this prospective and randomized study was to investigate gene expression profiles of the human endometrium during the window of implantation of gonadotropin-stimulated COH cycles compared with temporally matched natural cycles (d 21). Analysis was performed with high-density oligonucleotide microarrays.

Clinical value of endometrial pinopodes detection in artificial donation cycles.

The aim of the study was to investigate the clinical value of pinopode detection in women with a history of multiple implantation failures after participation in assisted reproduction programmes. Forty-six women with primary infertility, three or more previous implantation failures in assisted reproduction programmes and indication for the use of donated oocytes underwent a mock cycle of endometrial preparation, based on a standard protocol. Endometrial samples were taken on days 6 and 8 of progesterone administration, and were examined under scanning electron microscope for detection and evaluation of pinopodes.

Endometrial pinopodes and uterine receptivity.

The human endometrium is an extremely sensitive target for steroid hormones. During the menstrual cycle, this tissue undergoes dynamic changes which are reflected on the surface morphology of the epithelium, and which can be followed by scanning electron microscopy. The morphological changes peak at the midsecretory phase, with the formation of the so-called pinopodes.

Synchronous expression of pinopodes and alpha v beta 3 and alpha 4 beta 1 integrins in the endometrial surface epithelium of normally menstruating women during the implantation window.

Objective: To use histology, scanning electron microscopy (SEM) and immunohistochemistry to examine the expression of pinopodes, and alpha v beta 3 and alpha 4 beta 1 integrins in the same endometrial biopsies.

Study Design: A prospective observational study. Fifteen consecutive regularly menstruating women with normal hormone profiles were followed for detection of ovulation and then biopsied twice, on postovulatory days luteinizing hormone (LH) +6 and LH +8.

Molecules in blastocyst implantation. Role of matrix metalloproteinases, cytokines and growth factors.

Initiation of implantation is due not to passive growth pressure but to an active biochemical process that requires a blastocyst to interact with a carefully prepared endometrium. This versatile and dynamic process requires a variety of different molecules secreted by human trophoblast as well as endometrial cells that play a unique role. Several molecules have been shown to regulate, by an autocrine and paracrine manner, the cross-talk between the implanting blastocyst and the endometrial epithelium.

Endometrial pinopodes: some more understanding on human implantation?

Endometrial receptivity is a prerequisite for blastocyst implantation. During receptivity, the hairy-like epithelial cell microvilli transiently fuse to a single flower-like membrane projection called the 'pinopode'. Scanning electron microscopy in sequential endometrial biopsies shows that pinopodes appear about 1 week after ovulation, and they develop and regress within just 2 days.

Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors.

Objective: To investigate the relation between the development of endometrial pinopodes and the serum concentration of hormones and the distribution of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and progesterone receptor B.

Design: Prospective clinical study.

Setting: Hospital-based unit of reproductive health and university-affiliated reproductive research laboratories.

Endometrial receptivity in terms of pinopode expression is not impaired in women with endometriosis in artificially prepared cycles.

Objective: To assess endometrial receptivity in terms of pinopode expression in women with endometriosis.

Design: Prospective, observational study.

Setting: Oocyte donation program at the Instituto Valenciano de Infertilidad.

Endometrial receptivity: changes in cell-surface morphology.

Ovulation and fertilization trigger embryonic development and endometrial differentiation by corpus luteum progesterone production. These two synchronous processes couple about 1 week later, when the blastocyst begins to implant in the now receptive endometrium (implantation window). Receptivity is a state of endometrial differentiation marked by a change in epithelial morphology: the hairy-like cell microvilli fuse to a single flower-like membrane projection called the "pinopode.

Detection of endometrial pinopodes by light microscopy.

Objective: To study the value of light microscopy (LM) in the assessment of endometrial pinopodes.

Design: Comparative histologic study.

Setting: Outpatient infertility clinic in an academic teaching institution.

Surface morphology of the human endometrium. Basic and clinical aspects.

The human endometrium is an extremely sensitive target for steroid hormones. During the menstrual cycle, this tissue undergoes dynamic changes that are reflected on the surface morphology of the epithelium and that can be followed by scanning electron microscopy. The morphologic changes peak at the midsecretory phase, with the formation of the so-called pinopodes.

Pinopodes as markers of endometrial receptivity in clinical practice.

Clinical evidence indicates the existence in the human of a narrow window of uterine receptivity which opens during the mid-luteal phase. At the same time, formation of pinopodes on the apical membranes of the endometrial epithelial cells occurs. To develop a specific marker for receptivity in clinical practice, the kinetics of pinopode formation has been investigated through sequential endometrial biopsying in natural, hormone replacement and stimulated cycles.

Cell-surface morphological events relevant to human implantation.

Morphological evidence on early stages of human implantation is limited to very few sporadic observations. The nature of implantation which requires the presence of both maternal and embryonic tissues, combined with the currently existing ethical constraints on human studies, appear to preclude generation of new data. However, research on relevant animal and in-vitro models as well as studies on human endometrium and in-vitro embryos, allow some indirect insights to this phenomenon.

Coculture of human embryos with autologous human endometrial epithelial cells in patients with implantation failure.

We have developed a coculture system with autologous human endometrial epithelial cells (AEEC) that retained many features of human endometrial epithelium. Implantation failure (IF; >3 previous cycles failed with 3-4 good quality embryos transferred) is a distressing condition in which 2-day embryo transfer repetition is the routine option. The objective of this study was to investigate the basics and to evaluate prospectively the clinical value of embryo coculture on AEEC and blastocyst transfer with their own oocytes [in vitro fertilization (IVF) patients] or with donated oocytes (oocyte donation patients) compared to a routine day 2 embryo transfer for patients with IF.

Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles.

The formation of endometrial pinopodes detected by scanning electron microscopy may be a specific marker for uterine receptivity. Aiming to assess the effects of ovarian stimulation on pinopode formation, we examined sequential endometrial biopsies from 17 oocyte donors. Seven normally menstruating women served as controls.

Uterine pinopodes in peri-implantation human endometrium. Clinical relevance.

Current clinical studies indicate the existence in the human of an "implantation/nidation window," similar to that observed in animal models. During this short period of uterine receptivity, the formation of pinopodes on the apical cell membrane of the endometrial epithelium is a consistent morphological event, observed in a number of species studies including the human. In order to develop a specific marker of the implantation window in clinical practice, we have investigated the kinetics of pinopode formation through sequential endometrial sampling under various hormonal conditions.

Compaction and surface polarity in the human embryo in vitro.

The surface morphology of the human ovum fertilized and cultured in vitro to the morula stage was studied by scanning electron microscopy with the specific aim of investigating embryo compaction and polarity. Unfertilized oocytes examined one day after attempted insemination (Day 0) were evenly and densely covered by long microvilli. The length and density of microvilli appeared to decrease in fertilized polypronuclear oocytes; a further decrease was observed in Day 2 and Day 3 embryos with 2-12 cells.

Hormonal anti-implantation agents: antiprogestins.

Oestrogens and progestogens separately or in combination are able to prevent implantation with high efficiency, thus acting as interceptive agents. Current interceptive medical regimens include high-dose oestrogens, the association of oestrogens with progestogens or progestogens alone. Compounds with antiprogesterone properties, such as RU 486 (mifepristone) or ZK 98734 (lilopristone), also exhibit a strong interceptive action which, as shown in animal models, is proportional to the dose and the day(s) of administration.

The role of prostaglandins in blastocyst implantation.

This review summarizes the information available on the involvement of prostaglandins in blastocyst implantation, and examines their interactions with three other inflammatory mediators, platelet-activating factor (PAF), interleukin (IL-1) and corticotrophin-releasing factor (CRF). Essential elements of this information, consistent with the assumption that prostaglandins play an important role in implantation, appear to be: (i) the burst of endometrial prostaglandin production, following the blastocyst signal(s) or an artificial stimulus; (ii) the main localization of this production at the luminal epithelium and release towards the stroma; and (iii) the presence at the stromal level of specific progesterone-dependent binding sites for prostaglandin E2. In addition, accumulated data indicate a paracrine interaction at the endometrial level between PAF and prostaglandin E2, which could serve, among others, to amplify the embryonic signal(s).

Uterine pinopodes as markers of the 'nidation window' in cycling women receiving exogenous oestradiol and progesterone.

In 14 cycling women participating in an in-vitro fertilization (IVF) donation programme, we examined the timing of the 'nidation window' using as a stage-specific 'marker' the presence of fully developed pinopodes on the apical surface of the luminal uterine epithelium. Each woman received exogenous oestradiol from the second day of their cycle and progesterone starting on day 8 or day 15 of the oestrogenic treatment. The women underwent two biopsies during the same artificial cycle, on either days 6 and 9 or days 8 and 10 of the progesterone treatment.

Corticotropin-releasing hormone (CRH) is expressed at the implantation sites of early pregnant rat uterus.

We have shown previously that the epithelial cells of human endometrium produce CRH. The biological role of endometrial CRH is not yet known. Among other things, CRH appears to be involved in the inflammatory process, acting as an autocrine/paracrine proinflammatory regulator.