"RAIL BIOPSY" A Novel and Useful Technique for Hysteroscopic Endometrial Target Biopsy.

STUDY OBJECTIVE: Endometrial biopsy (EB) is one of the most common gynecologic procedures. Office-based EB has replaced procedures involving general/loco-regional anesthesia and cervical dilatation performed in the operating room [1-3]. The Grasp Biopsy seems to be the most appropriate EB technique for reproductive-aged women [1,2,4]. Recently, the Visual D&C performed with hysteroscopic tissue removal devices has shown to be a valid alternative [5]. However, it is often difficult to obtain an adequate specimens in peri/post-menopausal women with hypo/atrophic endometrium [2]. Our aim is to show a novel hysteroscopic EB technique called "Rail Biopsy" which requires widespread and cheap instruments. DESIGN: A step-by-step explanation of surgical techinque with narrated video footage. SETTING: Tertiary Level Academic Hospital "IRCCS Azienda Ospedaliero-Universitaria di Bologna" Bologna, Italy. INTERVENTIONS: We performed the "Rail Biopsy" technique with a 5.0 mm Continuous Flow Operative Hysteroscope with a 30° Lens and a 5Fr operative channel. We identify the endometrial target area (ETA), and we create a first track cutting through the endometrium in a caudo-cranial direction using cold scissors. We repeat the procedure, creating a second parallel track, thus completing our "rail" and isolating a wide ETA. Then, in the caudo-cranial direction, we cut through the stromal layer beneath the ETA. With a 5Fr cold grasping forceps, we clench the cranial edge of the ETA, and we remove it from the uterine cavity. A high-quality specimen, even in the case of hypo/atrophic endometrium or focal sessile lesions, can be obtained with this technique. The crucial aspect of the "Rail Biopsy" indeed is cutting through the stromal tissue while the endometrium is minimally touched, avoiding thermal damage deriving from electrosurgery. The instruments required are widespread and cheap. Moreover, this technique can be performed on any wall of the uterus, under vision, and, in the majority of patients, in an office-setting without cervical dilatation or general/loco-regional anesthesia, making it an attractive alternative to hysteroscopy performed in the operating room setting. Further studies comparing "Rail Biopsy" to other EB techniques are needed. CONCLUSION: We showed a novel approach for hysteroscopic EB that may be particularly useful in patients with hypo/atrophic endometrium, easy to learn and with low costs. VIDEO ABSTRACT.

Comparison of perioperative surgical outcomes between contained and free manual vaginal morcellation of large uteruses following total laparoscopic hysterectomy.

OBJECTIVE: To compare contained and free manual vaginal morcellation of large uteruses after total laparoscopic hysterectomy (TLH) in women at low risk of uterine malignancy in terms of feasibility and safety. METHODS: A single-center, observational, retrospective, cohort study was carried out including all patients undergoing TLH requiring manual vaginal morcellation for specimen extraction of large uteruses from January 2015 to August 2021 at the Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy. Patients were divided into two groups according to the type of manual vaginal morcellation (contained or free), and compared in terms of demographic, clinical, and perioperative data. RESULTS: In all, 271 patients were included: 186 (68.6%) in the contained morcellation group and 85 (31.4%) in the free morcellation group. The mean operative time was significantly lower in the contained morcellation group compared with the free morcellation group (median [interquartile range] 130 [45] vs. 155 [60] min; P < 0.001). No significant difference was found in complications related to the morcellation step, overall, intraoperative and postoperative complications, estimated blood loss, length of hospital stays, uterine weight, and rate of occult malignancy between the two groups. CONCLUSION: Contained vaginal manual morcellation of the uterus after total laparoscopic hysterectomy using a specimen retrieval bag appears to be a safe procedure with significantly lower operative time than free vaginal manual morcellation.

Not All Bad Comes to Harm: Enhanced Recovery After Surgery for Rectosigmoid Endometriosis.

STUDY OBJECTIVE: To assess the impact of implementing an enhanced recovery after surgery (ERAS) protocol on the length of hospitalization in women undergoing laparoscopy for rectosigmoid deep infiltrating endometriosis (DIE). DESIGN: A retrospective cohort study. SETTING: An academic referral center for endometriosis and minimally invasive gynecologic surgery. PATIENTS: Women aged between 18 and 50 years scheduled for laparoscopic excision (shaving, full-thickness anterior wall resection, segmental resection) of rectosigmoid endometriosis between February 2017 and February 2023. INTERVENTIONS: We divided patients into 2 groups (non-ERAS and ERAS) based on the timing of surgery (before or after March 5, 2020). Starting from this day, restrictions were issued to limit the spread of the coronavirus disease 2019 pandemic, inducing our group to implement an ERAS protocol for patients hospitalized after surgery for posterior DIE. MEASUREMENTS AND MAIN RESULTS: We included 579 patients in the analysis, 316 (54.6%) in the non-ERAS group and 263 (45.4%) in the ERAS group. In the ERAS group, we observed a shorter length of hospital stay (5.8 ± 3.1 days vs 4.8 ± 2.9 days; p <.001) and lower complications rates (33, 12.5% vs 60, 19.0%; p = .04), despite a decreased frequency of conservative surgical approaches (shaving procedures 121 vs 196; p <.001). Repeated surgery or hospital readmissions owing to postdischarge complications were infrequent, with no significant differences between the 2 groups. The multiple linear regression analysis strengthened our results given the higher prevalence of bowel resection surgeries (both full-thickness anterior wall or segmental), showing that patients managed with a multimodal protocol had an overall reduction of hospital stay by 1.5 days. CONCLUSION: The implementation of an ERAS program in patients undergoing laparoscopic surgery for DIE is associated with a significant reduction in hospital stay, without an increase in perioperative or postoperative complication rates.

Clinical and laboratory key performance indicators in IVF: A consensus between the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) and the Italian Society of Embryology, Reproduction and Research (SIERR).

PURPOSE: Infertility is increasing worldwide, and many couples seek IVF. Clinical management and laboratory work are fundamental in the IVF journey. Therefore, the definition of reliable key performance indicators (KPIs) based on clinical and laboratory parameters, is essential for internal quality control (IQC). Laboratory performance indicators have been identified and a first attempt to also determine clinical ones has been recently published. However, more detailed indicators are required. METHODS: An Italian group of experts in Reproductive Medicine from both public and private clinics on behalf of SIFES-MR and SIERR was established to define IVF indicators to monitor clinical performance. RESULTS: The working group built a consensus on a list of KPIs, performance indicators (PIs) and recommendation indicators (RIs). When deemed necessary, the reference population was stratified by woman age, response to ovarian stimulation and adoption of preimplantation genetic testing for aneuploidies (PGT-A). Each indicator was scored with a value from 1 to 5 and a weighted average formula - considering all the suggested parameters-was defined. This formula generates a center performance score, indicating low, average, good, or excellent performance. CONCLUSION: This study is intended to provide KPIs, PIs and RIs that encompass several essential aspects of a modern IVF clinic, including quality control and constant monitoring of clinical and embryological features. These indicators could be used to assess the quality of each center with the aim of improving efficacy and efficiency in IVF.

COVID-19 and ART: the view of the Italian Society of Fertility and Sterility and Reproductive Medicine.

The COVID-19 pandemic is an unprecedented global situation. As assisted reproductive technology (ART) specialists, we should be cautious, carefully monitoring the situation while contributing by sharing novel evidence to counsel our patients, both pregnant women and would-be mothers. Time to egg collection and drop-out rates are critical parameters for scheduling treatments once the curve of infections has peaked and plateaued in each country. In order to reduce the values for these two parameters, infertile patients now require even more support from their IVF team: urgent oocyte collection for oncology patients must be guaranteed, and oocyte retrievals for women of advanced maternal age and/or reduced ovarian reserve cannot be postponed indefinitely. This document represents the position of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) in outlining ART priorities during and after this emergency.

The use of ovarian reserve markers in IVF clinical practice: a national consensus.

Ovarian reserve markers have been documented to perform very well in the clinical practice. While this is widely recognized, still now there is no consensus on how to use new biomarkers in the clinical practice. This study was conducted among Italian IVF centres using the Delphi technique, a validated consensus-building process. Briefly three consecutive questionnaires were developed for clinicians in charge of IVF centres. In the first rounds, participants were asked to rate the importance of a list of statements regarding the categorization of ovarian response and the diagnostic role of biomarkers. In round 3, participants were asked to rate their agreement and consensus on the list of statements derived from the first two rounds. There were 120 respondents. Consensus was achieved for many points: (a) poor ovarian response is predicted on the basis of the following: AMH < 1 ng/ml or AFC < 7, FSH ≥ 10 IU/l, age ≥ 40 yrs; (b) hyper-response is predicted on the basis of the following: AMH > 3 ng/ml or AFC > 14; (c) day 3 FSH measurement should always be associated to estradiol; (d) AMH can be measured on a random basis; (e) the measurement of the AFC with the 2D technology may be considered adequate and (f) the AFC should be measured in the early follicular phase and consists in the total number of 2-9 mm follicles in both the ovaries. The present study suggests that extensive consensus on the importance and use of new ovarian reserve markers to improve IVF safety and performance is already present among clinicians.

Gene expression profiles of cumulus cells obtained from women treated with recombinant human luteinizing hormone + recombinant human follicle-stimulating hormone or highly purified human menopausal gonadotropin versus recombinant human follicle-stimulating hormone alone.

OBJECTIVE: To evaluate cumulus cell (CC) expression profile modulation after different stimulation protocols. DESIGN: CCs transcriptome variations were evaluated by microarray in patients undergoing different treatments for ovarian stimulation, namely, r-hLH + r-hFSH and hp-hMG, compared with a control group treated with r-hFSH. SETTING: Healthy patients undergoing assisted reproduction protocols. PATIENT(S): Sixteen healthy women with regular cycles and tubal disease or unexplained infertility. INTERVENTION(S): Four patients received hp-hMG, four received r-hFSH + r-hLH, and eight received r-hFSH daily. Aspiration of the oocytes was performed 36 hours after hCG administration. Only samples derived from cumulus-oocyte complexes containing mature oocytes showing polar body were processed. MAIN OUTCOME MEASURE(S): Comparison of genes differentially expressed in both treatment groups with the use of a hierarchic clustering analysis. RESULT(S): Data clustering analysis allowed detection of four clusters containing genes differentially expressed in both treatment groups compared with control. Functional analysis of the affected transcripts revealed genes involved in oocyte development and maturation. CONCLUSION(S): r-hLH and hCG, though acting on the same receptor, produce a differential activation of intracellular pathways. It can be hypothesized that this effect depends on their different structures and specific binding affinity for the receptor.

Differential actions of FSH and LH during folliculogenesis.

In the gonadotrophin-dependent stage of follicular development, FSH- and LH-signalling pathways play an obligatory role in follicle differentiation, selection and survival. Under the effect of LH the theca-interstitial cell layer acts as an androgen producer. Thus, androgen diffusing into the mural granulosa cell layer represents the substrate for FSH-induced aromatase for follicular oestradiol synthesis. This is the landmark 'two cell-two gonadotrophin' concept in the physiology of ovarian function in mammals. The increase in plasma FSH during luteo-follicular transition is the basis for follicle selection. The rise of FSH to the threshold concentration represents a critical condition for the growth of the most sensitive follicle in a given time frame of the last 14 days of the dominant follicle odyssey. The gonadotrophin-induced follicular oestradiol secretion inhibits pituitary secretion of FSH, which in turn causes the concentration of FSH in the developing cohort follicles to drop below threshold concentrations and the arrest of the development of the less FSH-sensitive follicle (FSH threshold and window concept). In the gonadotrophin-dependent phase of follicular development, LH also seems to acts within a critical window of the hormone concentration framed between the minimal threshold and a ceiling for the normal functions of the follicle unit.