Michelle Nisolle

Estrogen receptors and estetrol-dependent neuroprotective actions: a pilot study

Estetrol (E4) has strong antioxidative, neurogenic and angiogenic effects in neural system resulting in the attenuation of neonatal hypoxic–ischemic encephalopathy. We aimed to define the role of estrogen receptors in E4-dependent actions in neuronal cell cultures and prove the promyelinating effect of E4. In vitro the antioxidative and cell survival/proliferating effects of E4 on H2O2-induced oxidative stress in primary hippocampal cell cultures were studied using different combinations of specific inhibitors for ERα (MPP dihydrochloride), ERβ (PHTTP), GPR30 (G15) and palmytoilation (2-BR). LDH activity and cell survival assays were performed. In vivo the promyelinating role of different concentrations of E4 (1u2009mg/kg/day, 5u2009mg/kg/day, 10u2009mg/kg/day, 50u2009mg/kg/day) was investigated using the hypoxic–ischemic brain damage model in the 7-day-old immature rats before/after the induction of hypoxic–ischemic insult. Myelin basic protein (MBP) immunostaining was performed on brain coronal sections. Our results show that LDH activity is significantly upregulated in cell cultures where the E4’s effect was completely blocked by concomitant treatment either with ERα and ERβ inhibitors (MPP and PHTPP, respectively), or ERα and ERβ inhibitors combined with 2-BR. Cell survival is significantly downregulated in cell cultures where the effect of E4 was blocked by ERβ inhibitor (PHTTP) alone. The blockage of GRP30 receptor did affect neither LDH activity nor cell survival. MBP immunostaining is significantly upregulated in E4-pretreated groups at a concentration of 5u2009mg/kg/day and 50u2009mg/kg/day E4, whereas the MBP-positive area OD ratio is significantly increased in all the E4-treated groups. E4’s antioxidative actions mostly depend on ERα and ERβ, whereas neurogenesis and possibly promyelinating activities might be realized through ERβ.

Comparison between paraffin and mineral oil covering on early human embryo culture: a prospective randomized study

ABSTRACT The oil overlay in microdrop culture systems prevents medium evaporation, helps to maintain appropriate pH and osmotic conditions and protects from microbial contamination. In the present study, we prospectively compared covering by Ovoil™, a paraffin oil, and LiteOil®, a mineral oil, on the in vitro development of human embryos and their suitability for transfer/freezing at day 3 and live birth rate. One hundred and one patients undergoing in vitro fertilization (IVF) treatment by intracytoplasmic sperm injection (ICSI) were enrolled in our study. After ICSI, 1237 oocytes were 1:1 randomly allocated into 2 groups according to the type of overlaying oil: Ovoil™ (616 oocytes) or LiteOil® (621 oocytes). Fertilization rate was assessed around 18 hours post-insemination (hpi) and embryos were checked for early cleavage at 25 hpi. Embryo morphology was recorded on days 2 and 3. A total of 437 (Ovoil™) and 438 day 3 embryos (LiteOil®) were analyzed. There were no differences between the two groups in terms of fertilization rate and occurrence of early cleavage. The proportion of top quality embryos (41.7% vs. 41.2%) and the final utilization rates (92.2% vs. 92.0%) were similar in Ovoil and LiteOil groups, respectively, at day 3. Live birth rate per transfer was essentially the same with Ovoil™ overlay (26.9%) when compared to LiteOil® (26.2%). Live birth rate in patients who simultaneously received embryos from both overlay types was 17.2%. Despite the different characteristics of these two oils regarding hydrocarbon saturation, packing and temperature storage, Ovoil™ and LiteOil® can be used in parallel in the same IVF protocol. Abbreviations: ART: assisted reproductive technologies; hpi: hours post-insemination; hSA: human serum albumin; HTF: human tubal fluid; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; MII: metaphase II; MEA: mouse embryo assay; RT: room temperature.

Low omega-3 index values and monounsaturated fatty acid levels in early pregnancy: an analysis of maternal erythrocytes fatty acids

BackgroundIt is unanimously recognized that the maternal nutritional status at the pregnancy onset influence both short-term and long-term health of the mother and offspring. Among several nutrients, LCPUFA, particularly from the omega-3 family, are of utmost importance. This study was carried out to determine fatty acids profile of maternal erythrocyte membranes in early pregnancy and to identify potential determinants impacting on this status.MethodsA cohort of 122 healthy women with a singleton pregnancy was included. Fatty acids were analyzed using gas chromatography. Because of the lack of cutoff values, reference ranges were used to determine fatty acids categories.ResultsOf concern, our data revealed low monounsaturated and long-chain omega-3 fatty acid status in most participants. More than 75% of Belgian pregnant women exhibited Pal, AO and EPA levels as well as IOM3 values below the laboratory reference ranges. Higher DHA concentrations and IOM3 values were found among foreign-nationality participants, non-smokers and physically active women. With regard to dietary factors, omega-3 supplements and diet seem to be complementary since DHA from supplements (but not from diet) and EPA from diet (but not from supplements) were found to be associated with higher concentrations of DHA and EPA, respectively.ConclusionsOur study presents evidence demonstrating that the fatty acid status of most early pregnant women is far from being optimal based on the admitted general reference values. Clinicians should be advice to carefully evaluate and improve this status to guarantee the best possible outcome for both the mother and the baby.

Impact of high magnification sperm selection on neonatal outcomes: a retrospective study

PurposeThe aim of this study was to compare the effect of the deselection of spermatozoa presenting vacuole-like structures using IMSI (intracytoplasmic morphologically selected sperm injection) with ICSI (intracytoplasmic sperm injection) by means of neonatal outcomes.MethodsIn a retrospective two-center analysis, a total of 848 successful IMSI or ICSI cycles ending with a live birth, induced abortion, or intrauterine fetal death (IUFD) were included.ResultsThe IMSI and ICSI groups included 332 and 655 babies or fetuses, respectively. The parents were older in the IMSI group than in the ICSI group (mothers were 35.1 vs 32.9xa0years, and fathers were 39.1 vs 36.2xa0years). The multiple pregnancy rate was higher in the IMSI group. The mean pregnancy duration and mean birth weight were almost identical in both groups. There was no significant difference in major congenital malformations between the two groups. However, this rate was decreased in the IMSI group compared to that in the ICSI group (1.8 vs 3.2%), the difference being mainly found in singletons (1.4 vs 3.3%). Boys were more often affected than girls in both groups. The percentages of chromosomal abnormalities did not differ between the IMSI and ICSI groups (0.6 and 0.8%). The reported congenital malformations mainly affected the heart, urogenital, and musculoskeletal systems.ConclusionsIn the present study, the malformation rates observed in the IMSI and ICSI groups were not significantly different, even if slightly lower after IMSI. However, the observed difference followed the same trends observed in previous reports, indicating the possible impact of IMSI on decreasing congenital malformation occurrences. This highlights the necessity to prospectively evaluate the impact of IMSI on neonatal outcome after IVF treatment.

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 <u20095 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.

Vaginocutaneous fistula and buttock abscess formation 7 years after polypropylene transobturator tape insertion

Surgical treatment for stress urinary incontinence (SUI) using transobturator tape insertion is widely accepted. However, several postoperative complications were reported in the literature including infections, abscess and fistula formation. Here, we report a case of 57-year-old female who presented with abscess and left vaginocutaneous buttock fistula 7 years after transobturator polypropylene tape insertion. Treatment included abscess drainage with dissection of the fistulous tract and removal of the left arm of the transobturator tape along with antibiotic coverage. Sinus drainage stopped after 3 days. Stress urinary incontinence did not recur. Suspicion of fistula formation should rise in patients presenting with bothersome vaginal or cutaneous discharge after transobturator tape insertion. This case is particular since it describes a fistula complication with polypropylene tape, which is unusual with this type of tapes. Treatment of such complication should always consist of surgical removal of the mesh to allow closure of the fistulous tract.

A self-administered questionnaire to measure the painful symptoms of endometriosis: Results of a modified DELPHI survey of patients and physicians.

PURPOSEnTo develop a questionnaire based on patients verbal descriptors, to measure the painful symptoms of endometriosis.nnnMETHODSnWe performed a two-round modified DELPHI procedure mixing endometriosis patients and physicians to select a set of statements to describe the painful symptoms of endometriosis. Each panelist rated each statement based on diagnosis validity and clarity. The clinicians were experts in endometriosis management selected from various geographic regions in France. Patients were women with surgically confirmed endometriosis who volunteered from a patient association and from the recruitment of the participating physicians. The first round questions were derived from words and phrases in narratives of pain by endometriosis patients.nnnRESULTSnOverall, 76xa0experts were invited, and of these 56 (74%), comprising 33xa0patients and 23xa0gynecologists, responded to the first round questionnaire, and 40 (71.4%) to the second round. Among the 48xa0statements assessed in the first-round questionnaire, 11 were selected after completion of the two round DELPHI procedure. After discussion and rewording of some items, a total of 21xa0questions were selected during a final face-to-face meeting. The content of the final questionnaire is organized according to four dimensions: (i) spontaneous pelvic pain and dysmenorrhea, (ii) dyspareunia, (iii) painful bowel symptoms, (iv) and other symptoms. We also provide an English (UK) version produced using several steps of translation and back-translation.nnnCONCLUSIONSnThe questionnaire has content validity to measure the subjective experiences of patients with painful endometriosis and can provide a solid basis on which to develop an efficient patient-centered outcome to measure the painful symptoms in therapeutic or in diagnostic studies of endometriosis.