Low-Risk and High-Risk NSMPs: A Prognostic Subclassification of No Specific Molecular Profile Subtype of Endometrial Carcinomas.

(1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we collected data on 51 patients diagnosed with NSMP EC following the introduction of molecular profiling at our institution. Patients were retrospectively analyzed for estrogen receptor (ER) status, histotype, and grade to identify potential prognostic subgroups. (3) Results: Our analysis identified two distinct subgroups within NSMP EC: low-risk and high-risk, based on ER status, histotype, and grade. The low-risk NSMP group demonstrated significantly better survival outcomes compared to the high-risk group. With a median follow-up time of 16 moths (IQR 13.0-29.7), the disease-free survival (DFS) and overall survival (OS) for the low-risk group were 100%. For the high-risk group, the DFS and OS were 71.4% and 78.6%, respectively, which showed a statistically significantly difference (Log-Rank Mantel-Cox < 0.001). In the high-risk group, four patients experienced recurrence, and three of these patients died. (4) Conclusions: Stratifying NSMP EC into low-risk and high-risk categories based on ER status, histotype, and grade can lead to more accurate prognostic assessments. In time, it may require tailored adjuvant therapies and a personalized treatment.

Salpingectomy before assisted reproductive technologies: a systematic literature review.

Salpingectomy is largely used in case of hydrosalpinx in infertile women scheduled for assisted reproductive technologies (ART), whereas there is no consensus on its role in absence of hydrosalpinx. The current is a systematic literature review to collate all available evidence regarding salpingectomy as fertility enhancement procedure before ART in infertile patients. Our primary endpoint was to assess the impact of the surgical procedure on ovarian reserve, and secondary outcomes were to evaluate its benefits and harms on ART outcomes. We identified 29 papers of which 16 reporting data on the impact of tubal surgery on ovarian reserve and 24 (11 previously included) on ART outcomes. Available data suggested an absence of variation in ovarian reserve markers after unilateral salpingectomy while contradictory results were reported for bilateral surgery. Considering ART outcomes, data reported a significant improvement in ongoing pregnancy/live-birth rate in treated subjects without significant reduction in ovarian response to gonadotropin stimulation. In case of tubal disease, a surgical approach based on unilateral salpingectomy may be considered safe, without negative effects on ovarian reserve and ovarian response to controlled ovarian stimulation whilst having a positive effect on pregnancy rate. Data regarding bilateral salpingectomy and ovarian reserve are conflicting. Further trials are needed to confirm both the benefits of salpingectomy before ART and the safety of bilateral salpingectomy on ovarian reserve, and to clarify the role of uni- or bilateral surgery in case of tubal blockage without hydrosalpinx.

The Potential Role of GnRH Agonists and Antagonists in Inducing Thyroid Physiopathological Changes During IVF.

We conducted an observational cohort study to evaluate whether drugs used for hypothalamic inhibition may impact thyroid function of infertile women scheduled for fresh nondonor in vitro fertilization/intracytoplasmic sperm injection treatment. We considered eligible for inclusion in the study only women with normal thyroid function (serum thyroid-stimulating hormone [TSH] range: 0.2-4.0 mIU/L, serum thyroxin values: 9-22 pmol/L) and negative personal history for previous thyroid disorders. According to which protocols were implemented to gain hypothalamic inhibition, patients were assigned to group A (70 women treated by long gonadotropin-releasing hormone [GnRH] agonist protocol) or to group B (86 women treated by flexible GnRH antagonist protocol). Before initiating controlled ovarian stimulation (COS), both groups were further stratified into 4 subgroups: A1 (46 of the 70 women) and B1 (61 of the 86 women) in women with a baseline TSH value <2.5 mIU/L, whereas those with a baseline value ≥2.5 mIU/L were assigned to groups A2 (24 of the 70 women) and B2 (25 of the 86 women). Prior to initiating stimulation (T-0), 17-ß-estradiol (E(2)) and TSH serum values were dosed in all women and repeated on T-5 (day 5 of COS) and subsequently every 2 days until T-ov-ind (ovulation induction day) and T-pick-up (oocytes retrieval day). In case of detection of TSH levels above the cutoff, patients were screened for thyroxin and thyroid autoantibody serum values. In group A, E(2) at T-ov-ind was significantly increased compared to group B (P < .01), whereas TSH values showed an opposite trend (not significantly modified in group A, whereas significantly increased in group B; P < .001). A total of 64 women were found to have TSH values above the cutoff during COS: 7 in group A (11%) and 57 in group B (89%). Among them, 5 (71.4%) of the 7 in group A displayed hypothyroidism (and 4 of the 5 autoantibody positivity), whereas in group B, 6 (10.5%) of the 57 displayed hypothyroidism (and 2 of the 6 autoantibody positivity; P < .001). No pregnancies were observed in women with hypothyroidism, whereas in the 53 women with "isolated" increased TSH (normal T4, negative antibodies), we reported a 20.7% clinical pregnancy rate and a 54.5% ongoing pregnancy rate. Our preliminary data, despite requiring further confirmation, seem to suggest that the various drugs used for gaining hypothalamic control during COS could interfere through different mechanisms with physiological function of thyroid axis, potentially affecting its regulation.

Ultrasound techniques in the diagnosis of deep pelvic endometriosis: algorithm based on a systematic review and meta-analysis.

OBJECTIVE: To collate all available evidence with respect to ultrasound techniques in the management of deep pelvic endometriosis (DPE) and compare the sensitivity and specificity of each to determine the most suitable site-specific method. We aim to provide clinicians with information to improve the diagnosis and management of patients with DPE. DESIGN: Systematic review of the literature and meta-analysis. SETTING: Not applicable. PATIENT(S): None. INTERVENTIONS(S): Review of MEDLINE, EMBASE, ScienceDirect, Cochrane Library. MAIN OUTCOME MEASURE(S): For each study we calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and positive/negative likelihood ratio regarding DPE sites. We then compared the specificity and sensitivity of each technique. Forest plots with the corresponding 95% confidence interval using fixed/random effects for each approach (both separately and summarized according to the weight of any single study) were used. RESULT(S): A key word search strategy identified 441 manuscripts, 35 of which were eligible for the review (32 for meta-analysis). Standard transvaginal sonography (TVS) showed specificity greater than 85% for all DPE sites, despite sensitivity ranging between 50% (bladder, vaginal wall, and rectovaginal septum) and 84% (rectosigmoid). Modified techniques such as bladder site tenderness-guided TVS showed a value of 97.4% for both sensitivity and specificity. Rectal endoscopy-sonography and rectal water contrast TVS were both superior to TVS in detecting rectosigmoid endometriosis with sensitivities and specificities over 92%. Promising data were reported by using rectal water contrast TVS for rectovaginal septum disease (sensitivity, 97.1%; specificity, 99.3%). CONCLUSION(S): The summary of data regarding diagnostic specificity and sensitivity of TVS in women undergoing surgery for deep endometriosis may allow us to conclude that TVS should remain the first-line method in the evaluation of patients with suspicion of DPE. When TVS is insufficient, second-line "modified-techniques" should be considered. Choosing the most effective technique is a challenge and should be based on patient history and clinical signs/symptoms.

Intrauterine Morcellator Devices: The Icon of Hysteroscopic Future or Merely a Marketing Image? A Systematic Review Regarding Safety, Efficacy, Advantages, and Contraindications.

The aim of this study was to analyze all available evidence regarding the use of intrauterine morcellator (IUM), for treatment of the most prevalent intrauterine benign lesions, compared to both traditional resectoscopy and conventional outpatient operative hysteroscopy in terms of safety, efficacy, contraindications, perioperative complications, operating time, and estimated learning curve. We reported data regarding a total of 1185 patients. Concerning polypectomy and myomectomy procedures, IUM systems demonstrated a better outcome in terms of operative time and fluid deficit compared to standard surgical procedures. Complication rates in the inpatient setting were as follows: 0.02% for IUM using Truclear 8.0 (Smith & Nephew Endoscopy, Andover, Massachusetts) and 0.4% for resectoscopic hysteroscopy. No complications were described using Versapoint devices. Office polipectomy reported a total complication rate of 10.1% using Versapoint device (Ethicon Women's Health and Urology, Somerville, New Jersey) and 1.6% using Truclear 5.0 (Smith & Nephew Endoscopy). The reported recurrence rate after polypectomy was 9.8% using Versapoint device and 2.6% using Truclear 8.0. Finally, the reported intraoperative and postoperative complication rate of IUM related to removal of placental remnants using Truclear 8.0 and MyoSure (Hologic, Marlborough, Massachusetts) was 12.3%. The available evidence allows us to consider IUM devices as a safe, effective, and cost-effective tool for the removal of intrauterine lesions such as polyps, myomas (type 0 and type 1), and placental remnants. Evidence regarding Truclear 5.0 suggests that it may represent the best choice for office hysteroscopy. Further studies are needed to confirm the available evidence and to validate the long-term safety of IUM in procedures for which current data are not exhaustive (placental remnants removal).

Caesarean section: could different transverse abdominal incision techniques influence postpartum pain and subsequent quality of life? A systematic review.

The choice of the type of abdominal incision performed in caesarean delivery is made chiefly on the basis of the individual surgeon's experience and preference. A general consensus on the most appropriate surgical technique has not yet been reached. The aim of this systematic review of the literature is to compare the two most commonly used transverse abdominal incisions for caesarean delivery, the Pfannenstiel incision and the modified Joel-Cohen incision, in terms of acute and chronic post-surgical pain and their subsequent influence in terms of quality of life. Electronic database searches formed the basis of the literature search and the following databases were searched in the time frame between January 1997 and December 2013: MEDLINE, EMBASE Sciencedirect and the Cochrane Library. Key search terms included: "acute pain", "chronic pain", "Pfannenstiel incision", "Misgav-Ladach", "Joel Cohen incision", in combination with "Caesarean Section", "abdominal incision", "numbness", "neuropathic pain" and "nerve entrapment". Data on 4771 patients who underwent caesarean section (CS) was collected with regards to the relation between surgical techniques and postoperative outcomes defined as acute or chronic pain and future pregnancy desire. The Misgav-Ladach incision was associated with a significant advantage in terms of reduction of post-surgical acute and chronic pain. It was indicated as the optimal technique in view of its characteristic of reducing lower pelvic discomfort and pain, thus improving quality of life and future fertility desire. Further studies which are not subject to important bias like pre-existing chronic pain, non-standardized analgesia administration, variable length of skin incision and previous abdominal surgery are required.

Could in-vitro studies on Ishikawa cell lines explain the endometrial safety of raloxifene? Systematic literature review and starting points for future oncological research.

To evaluate all the in-vitro raloxifene (RAL) mechanisms of action on normal, Ishikawa, and different endometrium-derived cell lines to explain the in-vivo RAL endometrial effects, a systematic literature search was performed in the electronic databases MEDLINE, EMBASE ScienceDirect, and the Cochrane Library for the time period between 2002 and 2012. Outcomes were considered in relation to in-vitro stimulatory, inhibitory, or neutral actions of RAL in Ishikawa cell lines compared with different endometrial-derived cell lines (both cancerous and normal endometrium). We also considered all the RAL molecular mechanisms responsible for the in-vitro effects observed. More than 150 articles were available in the scientific database literature, but only 21 fulfilled our selection criteria. Although in-vitro studies appear to yield conflicting results, most evidence has shown that RAL seems to induce endometrial cell mitochondria-mediated apoptosis, and to inhibit estrogen-related cell proliferation and endometrial carcinogenesis by inducing antiangiogenic factors, and reducing cytoskeletal reorganization. If the endometrial safety profile of RAL is confirmed, in the near future, selective estrogen receptor modulators could represent an efficient alternative adjuvant treatment to tamoxifen (TAM) in women with breast cancer considered to be at an increased risk of endometrial disease. The confirmation of the endometrial safety profile could enable the proposal of RAL by clinicians as the most appropriate treatment for BRCA1-2 patients after prophylactic salpingo-oophorectomy.

Usefulness, methods and rationale of lymph nodes HPV-DNA investigation in estimating risk of early stage cervical cancer recurrence: a systematic literature review.

Metastatic involvement of pelvic lymph-nodes (LNs), generally found in 0-29.3 % of early stages, is the most important prognostic factor in cervical cancer (CC). However, even in non-metastatic LNs, recurrence rate reaches 10-15 %. The role of HPV-DNA presence in pelvic LNs has been a point of debate in the last two decades. The aim of this systematic review is to collect all available data about LNs HPV-DNA detection in patients affected by early-stage CC in order to elucidate its clinical and surgical usefulness to choose the best surgical treatment, the necessity of adjuvant therapy and to estimate the overall oncological prognosis. The available data in this field results very patchy and often conflicting in the results. The high correlation between HPV-DNA genome detected in primary lesion and the one detected in LNs, as well as the high correlation between LNs metastatic involvement and HPV-DNA presence, lead to hypothesize that LNs HPV presence represents a potential risk-factor for recurrence and poor oncological prognosis. The large disparities in recurrence-rate of cases with LNs positive for HPV-DNA test and negative for metastases could be explained by the relative "inappropriateness" of PCR test to discriminate the presence of HPV-genome alone (condition necessary but not sufficient) or in association with squamous cells (condition necessary and sufficient). The use of ISH test for HPV-DNA detection in LNs, particularly if associated to CK19-assay, improve the accuracy of micro-metastasis detection, and the identification of patients with negative histology but potentially at high-risk of recurrence and poor oncological prognosis.

Female sterilization: update on clinical efficacy, side effects and contraindications.

PURPOSE: The aim of this review is to compare studies concerning female sterilization in order to define the most suitable approach and device for each patient considering timing, safety, cost-effectiveness, failure rate, complication rate and patient satisfaction. METHODS: A systematic literature search was conducted in electronic databases MEDLINE-EMBASE-Sciencedirect and Cochrane Library between 2000 and 2012. All original descriptions, case reports, retrospective and review articles on tubal sterilization methods have been considered. Outcome measures were effectiveness, tolerability, procedure complications and female satisfaction. RESULTS: The ideal female sterilization system should be a simple, safe, highly efficient, easily learned, inexpensive, one-time procedure without negative side-effects. Nowadays, the trans-cervical approach is associated with minimal postoperative pain, allowing short hospitalization and fast resumption of daily activities. Laparoscopic and laparotomic approaches are considered second choices, since, particularly in developing countries, the transcervical hysteroscopic methods will increasingly spread within gynaecological clinical practice. CONCLUSIONS: Safety issues, hospital stay, costs and surgeons' experience are important factors in decision-making of the method for female sterilization. Hysteroscopic devices should be preferred when possible. The counselling time remains a fundamental step in choice. The decision concerning method depends on the setting, the surgeon's experience, the country's economical development and the woman's preference.

Could HPV-DNA test solve the dilemma about sentinel node frozen section accuracy in early stage cervical cancer? Hypothesis and rationale.

In order to reduce the surgical invasiveness in early-stage cervical-cancer treatment, the sentinel lymph-node (SLN) technique could be considered as a possible intraoperative-guidance to lymphadenectomy decision making. Unfortunately its accuracy ranges between 33.3% and 100% in different studies. Recent manuscripts suggest that HPV-DNA presence in pelvic-lymph-nodes may represent a molecular marker of micrometastases. According to this hypothesis, the rationale in proposing the HPV-DNA-test when negative frozen-section occurs is due to the expected improvement of its diagnostic-accuracy. HPV-DNA test may represent a marker able to discriminate at frozen section the false-negative from the truth-negative tests filling the gap between optimal and real frozen-section accuracy.

High-risk human papillomavirus DNA test: could it be useful in low-grade cervical lesion triage? Five-year follow-up.

We conducted a retrospective, observational study in order to evaluate the role of high-risk human papillomavirus (hrHPV)-DNA test in patients with first diagnosis of low-grade squamous intraepithelial lesions (L-SILs).Patients were divided into group A, annual Papanicolaou test and hrHPV-DNA tests (167 patients) and group B, immediate colposcopy, followed by annual papanicolaou test and hrHPV-DNA tests (164 patients). We assessed sensitivity, specificity, negative predictive value (NPV), positive predictive value, positive-negative likelihood ratio of hrHPV-DNA test, and 5-year relative risk of cervical intraepithelial neoplasia grade 2 in hrHPV-DNA+. Colposcopy is still considered the best choice for women with L-SIL and hrHPV-DNA+ test. High sensitivity and NPV of hrHPV-DNA test permit to use it in the follow-up of L-SIL with a HPV-negative status, without necessity of referring to colposcopy.

Levonorgestrel intrauterine system in adjuvant tamoxifen treatment: balance of breast risks and endometrial benefits--systematic review of literature.

Levonorgestrel intrauterine system (LNG-IUS) is used in patients with breast patients taking tamoxifen (TAM) to prevent endometrial proliferation. The benefits (on endometrium), the side effects (on breast), and the patients suitable for this treatment are not still clear. Aim of this systematic review is to define the breast risks and endometrial benefits in TAM-treated women using Mirena and to define which patients could benefit from LNG-IUS use. In all, 3 studies on LNG-IUS effects on endometrium in TAM-treated women and 4 studies on breast cancer recurrence were selected for the study. All studies described a reduction in benign endometrial pathologies among Mirena users, but controversial data showed malignant disease and breast cancer recurrence. So it is mandatory to define hormonal status before TAM treatment. In selected patients Mirena was proven to protect endometrium. Perspective clinical trials on Mirena pharmacological features are necessary to establish whether systemic levels of progesterone could increase breast cancer recurrence in such patients.

Secondary amenorrhea in severe Asherman's syndrome: step by step fertility retrieval by Bettocchi's hysteroscope: some considerations.

The aim of this report was to define the best diagnostic and therapeutic approach when secondary amenorrhea is related to undiagnosed Asherman syndrome. We present a single case of secondary amenorrhea with a previous diagnosis of alterated hypothalamic-hypophysary regulation, with a component of ovarian function in probable reduction, which was evaluated in our department and resulted affected by Asherman's syndrome IV stage. We describe step by step the diagnosis and treatment of a previously misdiagnosed case of severe Asherman's syndrome. An appropriate diagnosis and adequate treatment are mandatory to allow menses and fertility to be restored when severe Asherman's syndrome occurs.

Magnetic resonance-guided focused ultrasound myomectomy: safety, efficacy, subsequent fertility and quality-of-life improvements, a systematic review.

We performed a systematic review about studies reporting data of myomectomy performed by magnetic resonance-guided focused ultrasound (MRgFUS) technique in order to define its safety, feasibility, indications, complications, and impact on uterine fibroid symptom and health-related quality of life (UFS-QOL) and fertility. Outcomes were considered according to fibroids shrinkage, nonperfused volume (NPV), NPV ratio, and uterine fibroid symptoms assessed with UFS-QOL questionnaire (baseline 3, 4, 6, and 12 months). We analyzed 38 eligible studies reporting outcomes about 2500 patients (mean age 43.67 years). The MRgFUS results a safe, efficient, and cost-effective minimal invasive technique for treatment of uterine fibroids. Increasing experience, device improvements, and availability for a larger number of patients are enhancing the outcomes, while the obstetrical ones should be more extensively explored. The MRgFUS could be considered as a minimal invasive alternative to traditional surgical or radiological procedures for the treatment of symptomatic uterine myomas improving both QOL and subsequent fertility.

Radical trachelectomy: the first step of fertility preservation in young women with cervical cancer (Review).

Radical trachelectomy (RT) can be performed vaginally or abdominally (laparotomic, laparoscopic or robotic). The aim of this systematic review was to compare all techniques in terms of surgical complications, disease recurrence and subsequent fertility/pregnancy outcomes. A total of 1293 RTs were analyzed (FIGO-stage: IA1-IIA). The most frequent surgical complications do not differ from the ones of radical hysterectomy. The recurrence risk is approximately 3% (range 0-16.8%). The majority of women conceive spontaneously: 284 pregnancies with 173 live births. The most frequent pregnancy complication was miscarriage and chorioamnionitis. RT appears to be a safe option for eligible women who intend to maintain their future pregnancy desire.

Update on raloxifene: mechanism of action, clinical efficacy, adverse effects, and contraindications.

Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in post-menopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor-positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene.