Gonadotrophin stimulation reduces follicular fluid hormone concentrations and disrupts their quantitative association with cumulus cell mRNA.

Research Question: Do follicular fluid hormone concentrations and the mRNA expression of LHCG, FSH and androgen receptors, aromatase and anti-Müllerian hormone (AMH) in cumulus granulosa cells differ in naturally matured and stimulated follicles?

Design: Cross-sectional study involving 57 natural cycle IVF (NC-IVF) and 36 conventional gonadotrophin-stimulated IVF (cIVF) cycles performed between 2014 and 2016. cIVF was performed by ovarian stimulation with human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonists. Hormone concentrations were determined in the follicular fluid of the leading follicle, and mRNA concentrations were quantified by reverse transcription polymerase chain reaction in RNA extracted from granulosa cells of the cumulus oophorus complex obtained from these fluids.

The endocrine milieu in naturally matured follicles is different in women with high serum anti-Müllerian hormone concentrations.

Research Question: Is the endocrine milieu different in women with low serum anti-Müllerian hormone (AMH) concentration compared with women with high concentration?

Design: Cohort study of 84 women (four groups) classified according to AMH concentration and age undergoing natural cycle IVF treatment. Concentrations of LH, oestradiol, testosterone, androstenedione and AMH were determined in follicular fluid (FF), associations analysed and clinical outcome parameters evaluated.

Results: A positive correlation between serum and FF AMH concentrations was confirmed.

Association of endocannabinoids with pain in endometriosis.

Endocannabinoid (eCB) levels fluctuate in inflammatory conditions and as such may take part in endometriosis-associated pain or even in endometriosis pathogenesis. In this case-control (23 cases and 19 controls) study, targeted lipids were measured in the serum and peritoneal fluid collected during laparoscopy. Endometriosis was confirmed histologically.

Gonadotropin Stimulation Has Only a Limited Effect on the Concentration of Follicular Fluid Signalling Proteins: An Antibody Array Analysis.

Objective: The follicular fluid (FF) plays an essential role in the physiology of the follicle and the oocyte. Gonadotropin stimulation affects the FF steroid hormone and anti-Mullerian hormone (AMH) concentrations, which has been suggested to be the reason for lower oocyte competence in conventional gonadotropin stimulated fertilisation (cIVF) compared to natural cycle IVF (NC-IVF). To analyse the effect of gonadotropin stimulation on a broad spectrum of signalling proteins, we ran proteomic antibody arrays on FF of women undergoing both treatments NC-IVF and cIVF.

Ultra-high sensitive C-reactive protein during normal pregnancy and in preeclampsia: a pilot study.

Introduction: Angiogenic and inflammatory factors have been shown to play an important role in the pathogenesis of preeclampsia. However, there is little information on their interaction. The aims of this study were to investigate the longitudinal pattern of inflammatory markers, such as interleukin-6 (IL-6) and C-reactive protein (CRP) using a novel ultra-high sensitive assay method (uhsCRP), and to explore their relationship with angiogenic factors such as placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) in normal pregnancies and pregnancies complicated by preeclampsia.

Serum and follicular fluid testosterone concentrations do not correlate, questioning the impact of androgen supplementation on the follicular endocrine milieu.

Basic research into a possible link between serum and follicular fluid androgen concentrations to detemine whether androgen supplementation in low responders affects follicular endocrine milieu is still lacking. Ninety-seven women (aged 28-43 years) undergoing one natural IVF cycle without any hormone stimulation were analysed. Serum and follicular fluid were collected at the time of follicle aspiration, and the concentrations of LH, total testosterone, oestradiol, dehydroepiandrosterone and anti-Mullerian hormone (AMH) were determined.

TNFα-induced IKKβ complex activation influences epithelial, but not stromal cell survival in endometriosis.

Study Question: Can the activity of the IκB kinase (IKKβ) complex in endometriotic cells contribute to endometriotic lesion survival?

Summary Answer: There is a constitutive activity of the IKKβ catalytic complex in peritoneal and deeply infiltrating lesions that can influence epithelial, but not stromal cell viability.

What Is Known Already: Endometriotic lesions exist in an inflammatory microenvironment with higher local concentrations of cytokines, such as tumour necrosis factor α (TNFα). TNFα stimulates the activation of the IKKβ complex, an important nodal point in multiple signalling pathways that influence gene transcription, proliferation and apoptosis.

Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis.

Endometriosis is an estrogen-dependent disease characterised by the growth of endometrial epithelial and stromal cells outside the uterus creating a chronic inflammatory environment that further contributes to disease progression. The first choice treatment for endometriosis is currently progestin mediated hormone modulation. In addition to their progestogenic activity however, progestins also have the potential to bind to other nuclear receptors influencing their local activity on endometriotic cells.

Kinase signalling pathways in endometriosis: potential targets for non-hormonal therapeutics.

Background: Endometriosis, the growth of endometrial tissue outside the uterine cavity, is associated with chronic pelvic pain, subfertility and an increased risk of ovarian cancer. Current treatments include the surgical removal of the lesions or the induction of a hypoestrogenic state. However, a reappearance of the lesion after surgery is common and a hypoestrogenic state is less than optimal for women of reproductive age.

Does dienogest influence the inflammatory response of endometriotic cells? A systematic review.

Objective And Design: A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells.

Main Outcome Measures: In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human).

Results: After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue.

Comparison of ovarian cancer markers in endometriosis favours HE4 over CA125.

Endometriosis is a gynaecological condition with an associated chronic inflammatory response. The ectopic growth of 'lesions', consisting of endometrial cells outside the uterine cavity, stimulates an inflammatory response initiating the activation of macrophages, and resulting in increased cytokine and growth factor concentrations in the peritoneal fluid (PF). Endometriosis‑associated inflammation is chronic and long lasting.

Anti-Müllerian hormone and progesterone levels produced by granulosa cells are higher when derived from natural cycle IVF than from conventional gonadotropin-stimulated IVF.

Background: The study was designed to compare the effect of in vitro FSH stimulation on the hormone production and gene expression profile of granulosa cells (GCs) isolated from single naturally matured follicles obtained from natural cycle in vitro fertilization (NC-IVF) with granulosa cells obtained from conventional gonadotropin-stimulated IVF (c-IVF).

Methods: Lutein granulosa cells from the dominant follicle were isolated and cultured in absence or presence of recombinant FSH. The cultures were run for 48 h and six days.

Panels of cytokines and other secretory proteins as potential biomarkers of ovarian endometriosis.

Endometriosis is a gynecologic disease that is characterized by nonspecific symptoms and invasive diagnostics. To date, there is no adequate noninvasive method for the diagnosis of endometriosis. Although more than 100 potential biomarkers have been investigated in blood and/or peritoneal fluid, none of these has proven useful in clinical practice.

Inflammation and nerve fiber interaction in endometriotic pain.

Endometriosis is an extremely prevalent estrogen-dependent condition characterized by the growth of ectopic endometrial tissue outside the uterine cavity, and is often presented with severe pain. Although the relationship between lesion and pain remains unclear, nerve fibers found in close proximity to endometriotic lesions may be related to pain. Also, women with endometriosis pain develop central sensitization.

Phospholipase A2 group IIA is elevated in endometriomas but not in peritoneal fluid and serum of ovarian endometriosis patients.

Our previous gene expression analysis identified phospholipase A2 group IIA (PLA2G2A) as a potential biomarker of ovarian endometriosis. The aim of this study was to evaluate PLA2G2A mRNA and protein levels in tissue samples (endometriomas and normal endometrium) and in serum and peritoneal fluid of ovarian endometriosis patients and control women. One-hundred and sixteen women were included in this study: the case group included 70 ovarian endometriosis patients, and the control group included 38 healthy women and 8 patients with benign ovarian cysts.

Detection of the pan neuronal marker PGP9.5 by immuno-histochemistry and quantitative PCR in eutopic endometrium from women with and without endometriosis.

Purpose: To assess endometrial gene as well as protein expression of neuroendocrine and supposedly endometriosis-associated product PGP9.5 and pain symptoms in women with endometriosis and controls undergoing laparoscopy, using molecular biological and immuno-histochemical approaches in the same patients.

Methods: Biopsy of eutopic endometrium from 29 patients by sharp curettage, and preparation of paraffin blocks.

Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain.

Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis.

Increased levels of biglycan in endometriomas and peritoneal fluid samples from ovarian endometriosis patients.

In our previous low-density-array gene-expression analysis we found an increased expression of biglycan gene in ovarian endometriosis patients. In the present study we evaluated biglycan expression at the protein level in tissue, serum and peritoneal fluid (PF) from ovarian endometriosis patients, patients with benign ovarian cysts and healthy women. Twenty samples of endometriomas and 27 of control tissues (benign ovarian cysts and eutopic endometrium of healthy women) were obtained laparoscopically or by curettage.

Hormonal contraceptive use and the prevalence of endometriotic lesions at different regions within the peritoneal cavity.

Endometriosis is an estrogen-dependent disease that can lead to chronic pain and subfertility. Endometriotic lesions found in different locations are heterogeneous and may represent a collection of related but distinct conditions. Whether there is a relationship between hormonal contraceptive (HC) use and endometriosis is still controversial.

Enhanced inflammatory activity of endometriotic lesions from the rectovaginal septum.

Endometriosis is characterised by the growth of ectopic lesions at multiple locations outside the uterine cavity and may be considered a collection of distinct but related conditions. The exact aetiology of endometriosis is still not clear although a role for inflammation is increasingly accepted. We therefore investigated the inflammatory activity of eutopic tissue and that of the matching ectopic lesions from different locations by measuring the genetic expression of inflammatory chemokines and cytokines.

Glucose transporter expression in eutopic endometrial tissue and ectopic endometriotic lesions.

Endometriosis is an extremely prevalent disorder characterized by the growth of endometrial tissue at ectopic locations. Glycolysis is an energy-producing mechanism that occurs in almost all cells and requires an adequate uptake of glucose mediated by glucose transporter (GLUT) proteins. At present, however, very little is known about their expression in either the endometrium or the endometriotic lesions.

Exogenous gonadotropins do not increase the blood-follicular transportation capacity of extra-ovarian hormones such as prolactin and cortisol.

Backgrounds: In vitro fertilization involves high dosage gonadotropin stimulation, which apparently has some negative impact on follicular endocrine function. As chorionic gonadotropin stimulation has been shown to increase the blood-follicular permeability in animal models, this raises the question if such an effect also applies to gonadotropins in humans, possibly affecting the endocrine follicular milieu.

Findings: Follicular fluid and serum were collected at the time of follicular aspiration in in vitro fertilisation without (Natural cycle IVF, n = 24) and with (conventional gonadotropin stimulated IVF, n = 31) gonadotropin stimulation.

Induction of the neurokinin 1 receptor by TNFα in endometriotic tissue provides the potential for neurogenic control over endometriotic lesion growth.

Context: Endometriosis is characterized by the growth of ectopic endometrial tissue. Nerve fibers are frequently associated with ectopic lesions, and neurogenic inflammation may play a role in endometriosis.

Objective: The purpose of this study was to determine the presence of tachykinin receptors in endometriotic lesions and the role of TNFα on their expression.