Gestational diabetes mellitus is associated with in vivo platelet activation and platelet hyperreactivity.

BACKGROUND: Gestational diabetes mellitus is associated with obstetrical and long-term cardiovascular complications. Although platelet hyperresponsiveness in type-2 diabetes mellitus has been well characterized and has been shown to play a crucial role in cardiovascular complications, this aspect has been little studied in gestational diabetes mellitus. OBJECTIVE: We aimed to evaluate platelet reactivity, in vivo platelet activation, and endothelial function in gestational diabetes mellitus in comparison with normal pregnancy. STUDY DESIGN: This was a prospective, case-control study of 23 women with gestational diabetes mellitus and 23 healthy pregnant women who were studied at 26 to 28 and 34 to 36 weeks of gestation and at 8 weeks postpartum. Platelet reactivity and in vivo platelet activation, including light transmission aggregometry, PFA-100, platelet activation antigen expression, platelet adhesion under flow, platelet nitric oxide and reactive oxygen species production, and endothelial dysfunction markers, were assessed. RESULTS: The study of platelet function showed a condition of platelet hyperreactivity in cases with gestational diabetes mellitus when compared with healthy pregnant women at enrollment, which was further enhanced at the end of pregnancy and tended to decrease 2 months after delivery, although it still remained higher in gestational diabetes mellitus. In vivo platelet activation was also evident in gestational diabetes mellitus, especially at the end of pregnancy, in part persisting up to 8 weeks after delivery. Finally, women with gestational diabetes mellitus showed defective platelet nitric oxide production and endothelial dysfunction when compared with healthy pregnancies. CONCLUSION: Our data showed that gestational diabetes mellitus generates a condition of platelet hyperreactivity that in part persists up to 2 months after delivery. Impaired platelet sensitivity to nitric oxide and reduced platelet and endothelial nitric oxide production may contribute to the platelet hyperreactivity condition. Platelet hyperreactivity may play a role in the long-term cardiovascular complications of gestational diabetes mellitus women.

Health-related quality of life after hysterectomy for endometrial cancer: the impact of enhanced recovery after surgery (ERAS) shifting paradigm.

OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols provide well-known benefits in the immediate recovery with a shorter length of stay (LOS) also in gynecological surgery. However, the impact of ERAS has not been clearly showed yet regarding long-term consequences and health-related quality of life (HRQL). The aim of this study is to investigate the impact of ERAS on HRQL after hysterectomy for endometrial cancer. DESIGN: Observational retrospective study with propensity score matching (PSM). Participants We administered the SF-36 validated questionnaire to women underwent hysterectomy and lymph nodal staging before and after introducing ERAS protocol, getting, respectively, a standard practice (SP) and ERAS group Settings Academic hospital Methods We collected demographic, clinical, surgical and postoperative data and performed a PSM of the baseline coufouders. We administered the questionnaire four weeks after the surgery. The SF-36 measures HRQL using eight scales: physical functioning (PF), role physical (RLP), bodily pain (BP), general health (GH), vitality (Vt), social functioning (SF), role emotional (RLE) and mental health (MH). Results After PSM, we enrolled a total of 154 patients, 77 in each group (SP and ERA). The two groups were similar in terms of age, BMI, anaesthesiologic risk, Charlson comorbidity index (CCI) and surgical technique (minimally invasive versus open access). Median LOS was shorter for ERAS group (5 versus 3 days; p = 0.02), while no significant differences were registered in the rates of postoperative complications (16.9% versus 17.4%; p = 0.66). Response rates to SF-36 questionnaire were 89% and 92%, respectively, in SP and ERAS group. At multivariate analyzes, the mean scores of SF-36 questionnaire, registered at 28 days weeks after surgery (range 26-32 days), were significantly higher in ERAS group for PF (73.3 vs 91.6; p < 0.00), RLP (median 58.3 vs 81.2; p = 0.02) and SF (37.5 versus 58.3; p = 0.01) domains, when compared to SP patients. Limitations Further follow-up was not possible due to the anonymized data derived from clinical audit. Conclusions ERAS significantly increases HRQL of women underwent surgery for endometrial cancer. HRQL assessment should be routinary implemented in the ERAS protocol.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

Patients' Use of Virtual Reality Technology for Pain Reduction during Outpatient Hysteroscopy: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize evidence from randomized controlled trials (RCTs) on the effectiveness of virtual reality technology (VRT), as used by patients, for reducing pain during outpatient hysteroscopy. DATA SOURCES: Electronic databases and clinical registers were searched until June 21, 2023. The review protocol was registered in PROSPERO before the data extraction (CRD42023434340). METHODS OF STUDY SELECTION: We included RCTs of patients receiving VRT compared with controls receiving routine care during outpatient hysteroscopy. TABULATION, INTEGRATION, AND RESULTS: The primary outcome was average pain during hysteroscopy. Pooled results were expressed as mean differences (MDs) with 95% confidence interval (CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. Five RCTs were included (435 participants). The comparison between the intervention and control groups showed a borderline difference in perceived pain during hysteroscopy (MD -0.88, 95% CI -1.77 to 0.01). Subgroup analysis based on the type of VRT (active or passive) indicated that active VRT potentially reduced the perception of pain (MD -1.42, 95% CI -2.21 to -0.62), whereas passive VRT had no effect (MD -0.06, 95% CI -1.15 to 1.03). CONCLUSION: Patients' use of active VRT may be associated with a reduction in pain during outpatient hysteroscopy (evidence Grading of Recommendations Assessment, Development, and Evaluation 2/4). Future research should focus on conducting methodologically robust studies with larger sample sizes and more homogeneous populations.

Biochemical and Anthropometric Parameters for the Early Recognition of the Intrauterine Growth Restriction and Preterm Neonates at Risk of Impaired Neurodevelopment.

BACKGROUND: S100B and Tau are implicated with both brain growth and injury. Their urinary levels in 30-to-40-day-old full-term, preterm, IUGR, and preterm-IUGR subjects were measured to investigate their possible relationship with future delayed neurodevelopment. METHODS: Values were related to the neuro-behavioral outcome at two years of age, as well as to brain volumes and urinary NGF assessed at the same postnatal time point. RESULTS: Using the Griffiths III test, cognitive and motor performances were determined to establish subgroups characterized by either normal or impaired neuro-behavior. The latter included preterm, IUGR, and preterm-IUGR individuals who exhibited significantly higher and lower S100B and Tau levels, respectively, along with markedly reduced cerebral volumes and urinary NGF, as previously demonstrated. Contrary to NGF, however, Tau and S100B displayed a weak correlation with brain volumes. CONCLUSIONS: Delayed cognitive and motor performances observed in two-year-old preterm and IUGR-born individuals were also found to be associated with anomalous urinary levels of S100B and Tau, assessed at 30-40 days of the postnatal period, and their changes did not correlate with brain growth. Thus, our data suggests that, in addition to cerebral volumes and NGF, urinary S100B and Tau can also be considered as valuable parameters for the early detection of future neurodevelopmental abnormalities.

Training in Diagnostic Hysteroscopy: The "Arbor Vitae" Method.

Background and Objectives: Diagnostic hysteroscopy is the gold standard in the diagnosis of intrauterine pathology and is becoming an essential tool in the daily practice of gynecology. Training programs for physicians are necessary to ensure adequate preparation and learning curve before approaching patients. The aim of this study was to describe the "Arbor Vitae" method for training in diagnostic hysteroscopy and to test its impact on the knowledge and skills of trainees using a customized questionnaire. Materials and Methods: A three-day hysteroscopy workshop combining theory and practical "hands on "sessions with dry and wet labs has been described. The aim of the course is to teach indications, instruments, the basic principles of the technique by which the procedure should be performed, and how to recognize and manage the pathologies that can be identified by diagnostic hysteroscopy. To test this training method and its impact on the knowledge and skills of the trainees, a customized 10-question questionnaire was administered before and after the course. Results: The questionnaire was administered to 34 participants. All trainees completed the questionnaire, and no missing responses were recorded. Regarding the characteristics of the participants, 76.5% had less than 1 year of experience in performing diagnostic hysteroscopy and 55.9% reported performing fewer than 15 procedures in their career. For 9 of the 10 questions embedded in the questionnaire, there was a significant improvement in the scores between pre- and post-course, demonstrating a perceived significant improvement in theoretical/practical skills by the trainees. Conclusions: The Arbor Vitae training model is a realistic and effective way to improve the theoretical and practical skills required to perform correct diagnostic hysteroscopy. This training model has great potential for novice practitioners to achieve an adequate level of proficiency before performing diagnostic hysteroscopy on live patients.

Risk factors for non-adherent retained placenta after vaginal delivery: a systematic review.

BACKGROUND: Retained placenta represents a cause of maternal morbidity and mortality affecting 0.5-3% of all vaginal deliveries. The unpredictability of this condition makes difficult to develop predictive and preventive strategies to apply in clinical practice. This analysis collected and analyzed all known risk factors related to this obstetric complication. METHODS: A systematic literature review for all original research articles published between 1990 and 2020 was performed. Observational studies about retained placenta risk factors published in English language were considered eligible. Conference abstracts, untraceable articles and studies focused on morbidly adherent placenta were excluded. The included articles were screened to identify study design, number of enrolled patients and retained placenta risk factors investigated. All stages of the revision followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. RESULTS: Thirty-five studies met the inclusion criteria. The reported retained placenta prevalence ranged from 0.5 to 4.8%. Maternal age, previous cesarean sections, previous dilation and curettage, previous retained placenta, labor induction, resulted as the most recurrent, independent risk factors for retained placenta. Previous estro-progestins therapy, morphological placental features (weight, shape, insertion of umbilical cord, implantation site), endometriosis, Assisted Reproductive Technologies, Apgar score are fascinating new proposal risk factors. CONCLUSIONS: Old and new data are not enough robust to draw firm conclusions. Prospective and well-designed studies, based on a well agreed internationally retained placenta definition, are needed in order to clarify this potential dramatic and life-threatening condition.

The Technique of Vaginal Septum as Uterine Septum: A New Approach for the Hysteroscopic Treatment of Vaginal Septum.

STUDY OBJECTIVE: To evaluate the outcomes of a new hysteroscopic technique for the treatment of a longitudinal vaginal septum. DESIGN: A retrospective study. SETTING: Arbor Vitae Center for Endoscopic Gynecology, Rome, Italy. PATIENTS: Thirty women who underwent hysteroscopic treatment for a vaginal septum. INTERVENTION: All enrolled patients underwent pelvic examination, hysteroscopy, and 2-dimensional ultrasound. In case of a diagnosis of a partial or complete uterine septum, magnetic resonance imaging or 3-dimensional ultrasound were performed, and surgical procedures were performed after diagnostic laparoscopy was used to better visualize the uterine fundus. All patients were treated with the technique using vaginal septum as uterine septum or the same methodology applied for a uterine septum. MEASUREMENTS AND MAIN RESULTS: The procedure was successfully accomplished in all patients, and longitudinal vaginal septa were totally resected. There were no perioperative complications, and in only 1 case, vaginal bleeding occurred because of an erroneous identification of the excision line that was easily remedied with coagulation by resectoscope. Dyspareunia has improved or completely disappeared in all patients. CONCLUSION: The technique of vaginal septum as uterine septum for the resectoscope of a longitudinal vaginal septum appears to be safe and effective with good outcomes, even in terms of dyspareunia.

Hysteroscopic Evaluation of Endometrial Changes in Breast Cancer Women with or without Hormone Therapies: Results from a Large Multicenter Cohort Study.

STUDY OBJECTIVE: The primary aim of our study was to investigate the incidence of endometrial pathologies, especially endometrial cancer, in women with breast cancer treated with tamoxifen (TAM), aromatase inhibitors (AIs), or receiving no treatment (NT). The secondary aim was to identify, in this cohort, ultrasonographic findings that represent robust indications for hysteroscopy and endometrial biopsy, to avoid unnecessary second-level diagnostic procedures. DESIGN: Multicenter retrospective cohort study (Clinical Trial ID: NCT03898947). SETTING: Data were collected from different Italian centers: Regina Elena National Cancer Institute of Rome, Arbor Vitae Centre of Rome, Gaetano Martino University Hospital of Messina, and Villa Sofia-Cervello Hospital of Palermo. PATIENTS: We selected and consecutively included patients with a history of breast cancer who had undergone hysteroscopy for ultrasonographic or clinical indications between January 2007 and December 2016. INTERVENTIONS: Diagnostic hysteroscopy with endometrial biopsy or operative hysteroscopy, when clinically indicated. MEASUREMENTS AND MAIN RESULTS: A higher percentage of patients in the TAM and AI groups had a normal endometrium compared with those in the NT group, whereas the incidence of endometrial polyps was higher in the NT group than in the others; no significant differences were observed among the 3 groups for other benign conditions or for premalignant and malignant uterine diseases, such as endometrial atypical hyperplasia and adenocarcinoma. CONCLUSION: TAM treatment does not seem to be associated with a higher rate of endometrial cancer in women with breast cancer compared with women treated with AIs or NT.

Effects of Sodium Hyaluronate on Symptoms and Quality of Life in Women Affected by Pregnancy Rhinitis: A Pilot Study.

AIMS: To investigate sodium hyaluronate (SH) efficacy in the treatment of pregnancy rhinitis. METHODS: A single-center, prospective, open-label, 2 parallel-group study was carried out. Pregnant women affected by pregnancy rhinitis were randomly assigned to 1 of 2 groups: Group A was treated with SH, while Group B did not receive any treatment. Pregnancy rhinitis symptoms and quality of life (QOL) during pregnancy were investigated by administering a questionnaire and carrying out an otorhinolaryngoiatric visit. RESULTS: A significant reduction in the intensity of headache, snoring and insomnia in the Group A compared to the Group B were demonstrated. In the Group A, a significant lower presence of amount of secretions (Group A 0.88, 95% CI 0.57-1.18 vs. Group B 2.00, 95% CI 1.69-2.31, p < 0.001), turbinate hypertrophy (Group A 1.70, 95% CI 1.46-1.94 vs. Group B 2.53, 95% CI 2.29-2.77, p < 0.001), and mucosal congestion/hyperemia (Group A 1.41, 95% CI 1.14-1.68 vs. Group B 2.26, 95% CI 1.99-2.53, p < 0.001) was observed. No adverse events were reported in patients treated with SH. CONCLUSIONS: SH is a safe and effective therapeutic alternative for the treatment of pregnancy rhinitis symptoms, improving patients' QOL.

Treatment of genitourinary syndrome of menopause: the potential effects of intravaginal ultralow-concentration oestriol and intravaginal dehydroepiandrosterone on quality of life and sexual function.

The climacteric is considered a natural phase in a woman's aging process and is defined as the period starting from the decline in ovarian activity until after the end of ovarian function. Genitourinary syndrome of menopause (GSM) is commonly observed in menopausal women and is characterised by a collection of symptoms resulting from changes to the internal and external genitalia as well as the lower urinary tract. Several studies have demonstrated the close association between sexual dysfunction and symptoms related to GSM. Many medications, at different doses, have been studied over the years for the treatment of the symptoms of GSM. More specifically, ultralow-dose intravaginal oestriol and intravaginal dehydroepiandrosterone (DHEA) are reported to improve symptoms, signs, and quality of life of women with GSM, and they are safe owing to their specific local effect. While the dosage and the administration of intravaginal DHEA are well defined, the literature on intravaginal oestriol is less uniform: different doses and times of administration are proposed with different possible combinations with other non-pharmacological therapies, although a more standardised treatment may be necessary. The aim of this review is to summarise the available data about the effects of ultralow-concentration oestriol and intravaginal DHEA on the menopause-related symptoms, quality of life, and sexual function of women affected by GSM.

Intraoperative Effect of Preoperative Gonadotropin-Releasing Hormone Analogue Administration in Women Undergoing Cold Loop Hysteroscopic Myomectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To evaluate the intraoperative effects of gonadotropin-releasing hormone (GnRH) analogue pretreatment in patients undergoing cold loop hysteroscopic myomectomy. DESIGN: Randomized controlled trial (Canadian Task Force classification I). SETTING: Arbor Vitae Center for Endoscopic Gynecology, Rome, Italy. PATIENTS: A total of 99 patients were randomized and subsequently allocated to the GnRH analogue group or to the nonpharmacologic treatment control group. Fifteen patients were lost after allocation, and 42 patients per group underwent hysteroscopic myomectomy. INTERVENTIONS: Cold loop hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: The control group accomplished the treatment in a 1-step procedure more frequently than the GnRH analogue group (92.85% and 73.8% of cases, respectively; p = .040). The completion of the treatment was more unlikely in case of G2 myomas (p = .006), whereas no differences were recorded for G1 and G0 myomas. The multivariate analysis showed a significant correlation between the multiple-step treatment and the use of GnRH analogue (odds ratio, 5.365; 95% confidence interval [CI], 1.018-28.284; p = .048), grading (odds ratio, 4.503; 95% CI, 1.049-19.329; p = .043), and size of myomas (odds ratio, 1.128; 95% CI, 1.026-1.239; p = .013). CONCLUSIONS: Preoperative GnRH analogue administration did not facilitate the completion of cold loop hysteroscopic myomectomy in a single surgical procedure in G2 myomas and was correlated with a longer duration of the surgery. No significant benefits were found for G0 and G1 myomas. (ClinicalTrials.gov: NCT01873378.).

Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease.

PURPOSE: Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14-q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-ß3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion. CONCLUSION: The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future.

Is Cold Loop Hysteroscopic Myomectomy a Safe and Effective Technique for the Treatment of Submucous Myomas With Intramural Development? A Series of 1434 Surgical Procedures.

STUDY OBJECTIVE: To assess the safety and efficacy of cold loop hysteroscopic myomectomy in a large series of cases. DESIGN: Retrospective study (Canadian Task Force Classification III). SETTING: Arbor Vitae Center for Endoscopic Gynecology, Rome, Italy. PATIENTS: A total of 1215 patients with 1 or more G1-G2 submucous myomas. INTERVENTION: Cold loop hysteroscopic myomectomy. MEASUREMENT AND MAIN RESULTS: A total of 1690 myomas were removed. A minimum of 1 to a maximum of 5 fibroids for each surgical procedure were totally removed. Out of 1215 patients, 1017 (83.7%) were treated with a single surgical procedure. Twelve intraoperative complications occurred (0.84%). No cases of uterine perforation with the thermal loop or clinical intravasation syndrome were reported. CONCLUSION: Cold loop hysteroscopic myomectomy seems to represent a safe and effective procedure for the removal of submucous myomas with intramural development, while at the same time respecting the anatomic and functional integrity of the myometrium. The use of a cold loop in resectoscopic myomectomy is associated with a low rate of minor intraoperative complications and an absence of major complications. This could be of primary relevance with a view to fertility and future pregnancies.

Is 'cold loop' hysteroscopic myomectomy a better option for reproduction in women with diffuse uterine leiomyomatosis? A case report of successful repeated pregnancies.

Diffuse uterine leiomyomatosis (DUL) is a rare clinical entity with important reproductive consequences. To date, only four pregnancies have been reported after hysteroscopic myomectomy. Here we describe the case of a 28-year-old infertile woman with diffuse uterine leiomyomatosis, who presented infertility and metrorrhagia lasting for 2 years. A countless number of subserous, intramural and submucous myomas were ultrasonographically revealed. Diagnostic hysteroscopy described a uterine cavity completely subverted by the presence of myomas. A two-step 'cold loop' hysteroscopic myomectomy was performed following the technique previously described. One month after the treatment, there were no submucous myomas. A regular uterine cavity free of synechiae was endoscopically confirmed. After the treatment, the patient carried to term three consecutive, uneventful pregnancies. This is the first report of repeated successful pregnancies following the 'cold loop' hysteroscopic technique in DUL. We believe that 'cold loop' resectoscopic myomectomy may provide new advantageous perspectives for women with DUL seeking pregnancy.