Géraldine Brichant

Persistence of an Intact Endometrial Matrix and Vessels Structure in Women Exposed to VA-2914, a Selective Progesterone Receptor Modulator

BACKGROUND VA-2914 is a selective progesterone receptor modulator with potential contraceptive activity that induces amenorrhea, whereas progestins cause endometrial spotting and bleeding. This abnormal bleeding due to progestins is a consequence of focal stromal proteolysis by an increase in naked vessel size and density. OBJECTIVE Our objective was to quantify the effects of VA-2914 on endometrial vascularization, fibrillar matrix, and vascular endothelial growth factor (VEGF)-A expression in endometrial biopsies from 41 women before and after 12 wk daily treatment with a placebo, or 2.5, 5, or 10 mg VA-2914. METHODS Collagen fibrillar network was stained by silver impregnation. Vessel area, density, and structure were quantified with a computer-assisted image analysis system after double immunostaining using an anti-von Willebrand factor (endothelial cells) and an anti-alpha smooth muscle actin (vascular smooth muscle cells) marker antibody. VEGF-A mRNAs were quantified by RT-PCR and localized by immunohistochemistry. RESULTS The endometrial vessels, collagen network, and mRNA levels of VEGF-A were identical during the luteal phase at baseline and in VA-2914 treated women. VEGF-A distribution was unchanged. CONCLUSIONS VA-2914 does not alter the endometrial matrix and cells, and does not modify the endometrial vessel morphology as compared with baseline biopsies.

Management of severe preeclampsia

Abstract Features of severe preeclampsia include severe proteinuric hypertension and symptoms of central nervous system dysfunction, hepatocellular injury, thrombocytopenia, oliguria, pulmonary oedema, cerebrovascular accident and severe intrauterine growth restriction. Women with severe preeclampsia must be hospitalized to confirm the diagnosis, to assess the severity of the disease, to monitor the progression of the disease and to try to stabilize the disease. Severe preeclampsia may be managed expectantly, in selected cases. The objective of expectant management in these patients is to improve neonatal outcome. Expectant management is based on antihypertensive treatment and prevention of end organ dysfunction. Antihypertensive treatment improves maternal outcome but has the potential to be deleterious for the foetus. Plasma volume expansion has been suggested for severe preeclampsia but trials failed to show any benefit. Magnesium sulfate is the anticonvulsivant of choice to treat or prevent eclampsia when indicated. Antenatal corticosteroids are recommended in severely preeclamptic women with 26-34 weeks gestation. Timing of delivery is based upon gestational age, severity of preeclampsia, maternal and foetal risks.

Chronic pelvic pain and the role of exploratory laparoscopy as diagnostic and therapeutic tool: a retrospective observational study

BackgroundForty percent of exploratory laparoscopies are performed for chronic pelvic pain (CPP). However, a final diagnosis is still unreported in 35% of the patients. We decided to evaluate the identification of pathological lesions and the improvement of painful symptoms in patients with CPP and normal physical examination and imaging and who are scheduled for exploratory laparoscopy. The prospective study was designed in a tertiary referral center for endometriosis. Forty-eight patients complaining of CPP and scheduled for exploratory laparoscopy were included. Pelvic pain intensity was assessed using the visual analogue pain scale (VAS), and at inclusion, negative clinical and imaging assessments were required. During exploratory laparoscopy, the recognized lesions were reported and different surgical treatment options were performed depending on the location of the lesion.ResultsIn 98% of the cases, exploratory laparoscopy demonstrated the presence of pelvic anomalies that had not been diagnosed at the time of clinical and imaging examination. After surgery, a significant improvement of CPP has been demonstrated in 24 (59%) patients with VAS < 5 postoperatively. ConclusionsExploratory laparoscopy is reasonable in patients complaining of CPP, allowing a final diagnosis in a high percentage of patients and a significant improvement in pain symptom in 59% of the cases. This study was retrospectively registered by our local Ethics Committee on February 7, 2018 (B412201835729).

Heterogeneity of estrogen receptor alpha and progesterone receptor distribution in lesions of deep infiltrating endometriosis of untreated women or during exposure to various hormonal treatments.

Abstract Deep infiltrating endometriosis (DIE) responds variably to hormonal therapy. Mutations in cancer driver genes have been identified in a fraction of the ectopic endometrial epithelial cells, suggesting a functional heterogeneity of these lesions. To evaluate the phenotype heterogeneity of cells in DIE, we measured the expression of estrogen receptor α (ERα) and of progesterone receptor (PR) in DIE of untreated women or under various treatments. We analyzed the luminal epithelial height (LEH), immunoreactive epithelial staining (IRS) and stromal staining intensity (SSI) of ERα and PR. We observed a high variability in the same gland, among distinct glands in the same sample and among distinct patients receiving the same treatment. LEH variability was primarily due to epithelial cells heterogeneity in a gland, secondarily to the glands randomly evaluated on the same section, and tertiary to the patient category. Variability in IRS and SSI scores was primarily the consequence of their heterogeneity in the same woman and to a lesser extent to variability among patients. LEH and SSI were not modified according to treatment. IRS for PR was lower in treated patients. This heterogeneity of ERα and PR distribution could explain why endocrine treatments are unable to cure this condition.