C-section technique vs minilaparotomy after minimally invasive uterine surgery: a retrospective cohort study.

PURPOSE: Uterine leiomyomas are benign uterine tumors. The choice of surgical treatment is guided by patient's age, desire to preserve fertility or avoid "radical" surgical interventions such as hysterectomy. In laparotomy, the issue of extracting the fibroid from the cavity does not arise. However, in laparoscopy and robotic surgery, this becomes a challenge. The aim of the present study was to determine the optimal surgical approach for fibroid extraction following laparoscopic or robotic myomectomy in terms of postoperative pain, extraction time, overall surgical time, scar size, and patient satisfaction. METHODS: A total of 51 patients met the inclusion criteria and were considered in our analysis: 33 patients who had undergone the "ExCITE technique" (Group A), and 18 patients a minilaparotomy procedure (Group B), after either simple myomectomy, multiple myomectomy, supracervical hysterectomy, or total hysterectomy. The diagnosis of myoma was histologically confirmed in all cases. RESULTS: Regarding the postoperative pain evaluation, at 6 h, patients reported 4 [3-4] vs 6 [5.3-7] on the VAS in Group A and B, as well as at 12 h, 2 [0-2] vs 3.5 [2.3-4] in Group A and B, respectively: both differences were statistically significant (p < 0.001). No statistically significant difference at 24 h from surgery was found. All patients in Group A were satisfied with the ExCITE technique, while in Group B only 67% of them. The length of the hospital stay was significantly shorter in Group A as compared to Group B (p = 0.007). In terms of the operative time for the extraction of the surgical specimen, overall operative time, and the scar size after the surgery, there was a statistically significant difference for those in Group A. CONCLUSION: The ExCITE technique does not require specific training and allows the surgeon to offer a minimally invasive surgical option for patients, with also an aesthetic result. It is a safe and standardized approach that ensures tissue extraction without the need for mechanical morcellation.

Laparoscopic oocyte retrieval for fertility preservation in a patient with squamous cell carcinoma of the vagina.

OBJECTIVE: To describe a feasible fertility preservation strategy in a woman with vaginal carcinoma. DESIGN: Video case report demonstrating the diagnostic work-up and laparoscopic oocyte retrieval performed under regional anesthesia. SETTING: University tertiary care hospital. PATIENT(S): A 35-year-old nulliparous woman presented with vaginal bleeding and foul-smelling vaginal discharge. After a comprehensive diagnostic work-up, a final diagnosis of squamous cell carcinoma of the vagina stage II (Federation International Obstetrics and Gynecology classification) was made. As per the patient's desire, before undergoing chemoradiotherapy, the patient underwent oocyte cryopreservation. Transvaginal retrieval of oocytes was not feasible because of stenosis of the vaginal introitus and the potential risk of intracavitary tumor cell spillage. Transabdominal ultrasound-guided oocyte retrieval was not possible because of the body's habitus. INTERVENTION(S): The patient underwent ovarian stimulation for in vitro fertilization. To minimize estrogen levels, letrozole was used during controlled ovarian stimulation. Laparoscopic oocyte retrieval was performed under spinal anesthesia. MAIN OUTCOME MEASURE(S): Successful laparoscopic egg retrieval and cryopreservation in a woman with squamous cell carcinoma of the vagina. RESULT(S): A total follicular count of nine was estimated before the oocyte retrieval. Eight oocytes were retrieved at laparoscopy, and eight mature oocytes were successfully cryopreserved. No complications were encountered, and the patient was discharged on the same day of surgery. CONCLUSION(S): To our knowledge, this is the first published case of fertility preservation using the laparoscopic approach in a patient with vaginal cancer. Letrozole is a valuable strategy to reduce high estrogen in patients with gynecological cancer undergoing controlled ovarian stimulation. Laparoscopy oocyte retrieval, performed under regional anesthesia, can be performed in an ambulatory setting and should be considered an effective fertility preservation strategy in patients with large vaginal tumors.

Is There Still a Place for Surgery in Patients with PCOS? A Review.

OBJECTIVE: The surgical management of polycystic ovary syndrome (PCOS) represents an unclear option compared to medical therapy, and it is necessary to deepen the role of minimally invasive surgery, represented by laparoscopic ovarian drilling (LOD) and transvaginal hydrolaparoscopy (THL), for the treatment of PCOS in infertile women resistant to drug therapy and to establish its success in terms of ovulation and pregnancy rates. METHODS: A search was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and the Cochrane Library) from 1994 to October 2022 in order to evaluate the role of surgery in patients with PCOS resistant to pharmacological treatment. Only original scientific articles in English were included. RESULTS: Seventeen studies were analyzed in this review. In all analyzed studies, more than 50% of the population underwent spontaneous ovulation after surgical treatment without great differences between the two surgical techniques (LOD and THL). More than 40% of patients delivered, with a higher rate after LOD, although eight ectopic pregnancies and sixty-three miscarriages were reported. A lower risk of adhesion formation after THL has been reported. No clear data regarding the effect of surgery on the regularization of the menstrual cycle has been described. A reduction in LH and AMH serum levels as well as the LH/FSH ratio compared to preoperative levels for both surgical techniques has been described. CONCLUSIONS: Despite the scarcity and heterogeneity of data, surgical therapy could be considered an effective and safe approach in the management of PCOS patients with resistance to pharmacological treatment who desire to become pregnant.

Myomectomy in infertile women: More harm than good?

Adhesion formation following gynecological surgery remains a challenge. The adoption of minimally invasive surgical approaches, such as conventional or robotic-assisted laparoscopy combined with meticulous microsurgical principles and the application of adhesion-reducing substances, is able to reduce the risk of de novo adhesion formation but do not eliminate it entirely. Myomectomy is the most adhesiogenic surgical procedure and postoperative adhesions can have a significant impact on the ability to conceive. Therefore, when surgery is performed as infertility treatment, attention should be paid to whether the benefits outweigh the risks. Among several factors, the size and the location of fibroids are the most accountable factors in terms of adhesion development and post surgical infertility; therefore, the search for effective strategies against adhesion formation in this setting is of paramount importance. The purpose of this review is to evaluate the incidence and factors of adhesion formation and the best preventive measures current available.

Laparoscopic treatment of advanced interstitial pregnancy: key steps for a successful management.

OBJECTIVE: To describe a conservative laparoscopic treatment of an advanced case of interstitial pregnancy diagnosed in a woman at 14 weeks of gestational age. DESIGN: A video case report with demonstration of diagnostic workup and laparoscopic management of rare subtypes of ectopic pregnancy. SETTING: University tertiary care hospital. PATIENT(S): A 32-year-old nulliparous woman at 14 weeks of gestational age, presented with moderate abdominal pain. She reported a history of irregular periods; however, no risk factor for ectopic pregnancy was identified. The human chorionic gonadotropin level was 7,345 mIU/mL. Transvaginal ultrasound revealed an empty uterine cavity and a complex heterogeneous mass of 6 cm on the left cornual region. The myometrial thickness surrounding the gestational sac was 4 mm. INTERVENTION(S): There were several critical strategies for this laparoscopic approach. To reduce intraoperative bleeding, the peritoneum was opened, the ureters were identified, and bulldog clamps were used to temporarily reduce uterine vascularization. An intramyometrial injection of vasopressin was performed. After the first cornuostomy attempt, we had to perform a cornual resection to achieve complete removal of the ectopic mass. Multilayer uterine sutures and anatomical restoration to prevent adhesion were then accomplished. Institutional review board approval was not required for this case report as per our institution's policy; patient consent was obtained for publication of the case. MAIN OUTCOME MEASURE(S): Description of laparoscopic management of huge interstitial pregnancy. RESULT(S): The overall operation time was 55 minutes, and the estimated blood loss was 55 mL. A successfully conservative treatment was achieved with no short-term complications. Postoperative ultrasound showed a normal uterus, and complete regression of human chorionic gonadotropin level was achieved 2 weeks after surgery. CONCLUSION(S): Interstitial ectopic pregnancy presents a high risk of maternal mortality considering that the interstitial part of the tube, because of its thickness, has a great capacity to expand before rupture. Despite the dimension of the lesion, in our case, the tube was still intact and the patient was in a stable clinical condition. Although cornuostomy is a more conservative solution, in these cases, cornual resection should be preferred. Through the accomplishment of reproducible key steps, laparoscopic removal of interstitial pregnancy is a feasible method and can be proposed even for advanced cases of interstitial pregnancies.

Three-dimensional imaging reconstruction and laparoscopic robotic surgery: a winning combination for a complex case of multiple myomectomy.

OBJECTIVE: To demonstrate the intraoperative use of three-dimensional (3D) imaging reconstruction for a complex case of multiple myomectomy assigned to robot-assisted laparoscopic surgery. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: University tertiary care hospital. PATIENT(S): A 36-year-old nulliparous infertile woman with multiple uterine myomas (>20) presented with menorrhagia and pelvic discomfort for many months. Because of the huge number of fibroids present, the patient was considered eligible for laparoscopic robotic-assisted myomectomy. INTERVENTION(S): A robotic-assisted laparoscopic myomectomy was performed with the use of intraoperative 3D imaging reconstruction. After opening the retroperitoneum through the adnexal triangle and identifying the ureters, to reduce intraoperative bleeding, bulldog clamps were used to temporarily reduce uterine vascularization. A multiple myomectomy was then performed with the use of tenaculum and Maryland bipolar forceps. During the intervention, the surgeon used the 3D uterine reconstruction to adapt its surgical strategy. Multilayer running closure was achieved using a bidirectional barbed suture ensuring introflexion of the serosa. Patients' consent was obtained for publication of the case; institutional review board approval was not required for this case report as per our institution's policy. MAIN OUTCOME MEASURE(S): Description of a robotic-assisted myomectomy with the intraoperative use of 3D imaging reconstruction. RESULT(S): The total operative time was 105 minutes. A total of 21 fibroids were removed with 150 mL of intraoperative blood loss. The patient was discharged the day after. CONCLUSION(S): The application of 3D imaging technology could overcome one of the limitations of robot-assisted minimally invasive surgery, the lack of haptic feedback, enabling the surgeon to rapidly locate myomas and guide the intraoperative plan to optimize the results. Additional studies evaluating the clinical impact of this technique and its improvement are required.

Fertility-Sparing Approach in Patients with Endometrioid Endometrial Cancer Grade 2 Stage IA (FIGO): A Qualitative Systematic Review.

Background: Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease. Objective: (1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment. Materials and Methods: A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors' judgments were categorized as "low risk," "high risk," or "unclear risk" of bias. Results: Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be "low." 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice. Conclusions: The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.

Is intracrinology of endometriosis relevant in clinical practice? A systematic review on estrogen metabolism.

Endometriosis is a chronic, multifactorial, estrogen-dependent disease. The abnormal endocrine microenvironment of endometriosis lesions is considered a main feature and multiple enzymatic pathways leading to local increased synthesis of estrogens have been identified. However, the relevance of intracrinology in clinical practice is still lacking. Medline, Embase, Scopus database were systematically searched for studies reporting on local estrogens metabolism of endometriotic lesions. The main enzymatic pathways involved in the intracrinology of endometriosis such as aromatase (CYP19A1), 17ß-hydroxysteroid dehydrogenase (HSD17B) type 1, type 2 and type 5, steroid sulfatase (STS), estrogen sulfotransferase (SULT1E1) were assessed with a critical perspective on their role in disease endocrine phenotyping, drug resistance and as therapeutic targets. Overall, studies heterogeneity and missing clinical data affect the interpretation of the clinical role of these enzymes. Although the use of some drugs such as aromatase inhibitors has been proposed in clinical practice for two decades, their potential clinical value is still under investigation as well as their modality of administration. A closer look at new, more realistic drug targets is provided and discussed. Altered expression of these key enzymes in the lesions have far reaching implication in the development of new drugs aimed at decreasing local estrogenic activity with a minimal effect on gonadal function; however, given the complexity of the evaluation of the expression of the enzymes, multiple aspects still remains to be clarified. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311329, identifier CRD42022311329.

The challenging management of borderline ovarian tumors (BOTs) in women of childbearing age.

Borderline ovarian tumors (BOTs) account for approximately 15% of all epithelial ovarian cancers. In 80% of cases the diagnosis of BOTs is done at stage I and more than a third of BOTs occurs in women younger than 40 years of age wishing to preserve their childbearing potential; the issue of conservative surgical management (fertility-sparing treatment) is thus becoming of paramount importance. At early stages, the modalities of conservative treatment could range from mono-lateral cystectomy to bilateral salpingo-oophorectomy. Although cystectomy is the preferred method to promote fertility it can lead to an elevated risk of recurrence; therefore, an appropriate counseling about the risk of relapse is mandatory before opting for this treatment. Nevertheless, relapses are often benign and can be treated by repeated conservative surgery. Besides the stage of the disease, histological subtype is another essential factor when considering the proper procedure: as most mucinous BOTs (mBOTs) are more commonly unilateral, the risk of an invasive recurrence seems to be higher, compared to serous histotype, therefore unilateral salpingo-oophorectomy is recommended. In the appraisal of current literature, this review aims to gain better insight on the current recommendations to identify the right balance between an accurate staging and an optimal fertility outcome.

Ovarian Drilling: Back to the Future.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. The complex metabolic dysregulation at the base of this syndrome often renders infertility management challenging. Many pharmacological strategies have been applied for the induction of ovulation with a non-negligible rate of severe complications such as ovarian hyperstimulation syndrome and multiple pregnancies. Ovarian drilling (OD) is currently being adopted as a second-line treatment, to be performed in case of medical therapy. Laparoscopic ovarian drilling (LOD), the contemporary version of ovarian wedge resection, is considered effective for gonadotropins in terms of live birth rates, but without the risks of iatrogenic complications in gonadotropin therapy. Its endocrinal effects are longer lasting and, after the accomplishment of this procedure, ovarian responsiveness to successive ovulation induction agents is enhanced. Traditional LOD, however, is burdened by the potential risks of iatrogenic adhesions and decreased ovarian reserve and, therefore, should only be considered in selected cases. To overcome these limits, novel tailored and mini-invasive approaches, which are still waiting for wide acceptance, have been introduced, although their role is still not well-clarified and none of them have provided enough evidence in terms of efficacy and safety.

Minimally invasive anesthesia for laparoscopic hysterectomy: a case series.

PURPOSE: Regional anesthesia (RA) is considered as a "minimally invasive technique" to achieve anesthesia. To assess the feasibility and the perioperative outcomes of laparoscopic hysterectomy in regional anesthesia from the point of view of the surgeon, anesthesiologist and patient. METHODS: A retrospective search was performed to identify patients who underwent laparoscopic hysterectomy under RA from April 2020 to September 2021. Five patients affected by benign gynecological disease (atypical endometrial hyperplasia or uterine leiomyomas) were included. RESULTS: The postoperative pain, nausea, and vomiting (PONV) and the antiemetic/analgesic intake were evaluated. Postoperative surgical and anesthesiological variables were recorded. Duration of surgery was 84 ± 4.18 and no conversion to GA was required. According to VAS score, the postoperative pain during the whole observation time was less than 4 (median). A faster resumption of bowel motility (≤ 9 h) and patient's mobilization (≤ 4 h) were observed as well as a low incidence of post-operative nausea and vomit. Early discharge and greater patient's satisfaction were recorded. Intraoperatively pain score was assessed on Likert scale during all the stages of laparoscopy in RA, with only 2 patients complaining scarce pain (= 2) at pneumoperitoneum. CONCLUSION: RA showed to have a great impact on surgical stress and to guarantee a quicker recovery without compromising surgical results. RA technique could be a viable option for patients undergoing laparoscopic hysterectomy.

Uterine fibroids morcellation: a puzzle topic.

The laparoscopic approach for the treatment of uterine leiomyoma is increasingly practiced. The necessity to remove large specimens from the small laparoscopic incision has always been one of the main limits of this procedure. The unrestricted use of morcellation, to overtake this weak point of minimally invasive surgery, has opened in recent years a broad debate, especially on the risk of unintended dissemination of cells that could in some cases lead to extremely negative repercussions. This review analyzes these aspects and the principal recommendations from the major gynecological society on this topic surveying their effects. Furthermore, the purpose of this article is to provide an overview of the different morcellation techniques and how they are performed, evaluating their advantages and disadvantages. Contained morcellation seems to overcome many limits; however, based on recent data, an appropriate evaluation and selection of patients, as well as complete counseling before the surgery, are mandatory.

Laparoscopic gynecological surgery under minimally invasive anesthesia: a prospective cohort study.

The purpose of this study is to assess the feasibility and the perioperative outcomes of laparoscopic gynecological surgery in regional anesthesia (RA) from the point of view of the surgeon, anesthesiologist and patient. This is a prospective cohort study comprising sixty-six women planned to undergo gynecologic laparoscopy surgery for benign pathology at tertiary care gynecolgical center of the University Federico II of Naples. Women were assigned, according to their preference, to either RA (Group A) or general anesthesia (GA) (Group B). Surgical, anesthesiologic and postoperative recovery data were recorded. Postoperative pain was considered as the primary outcome. Secondary outcomes included mobilization, length of hospital stay, global surgeons and patient satisfaction, intraoperative pain assessment in Group A. Immediate postoperative pain was significantly lower in Group A 0 vs 2 (p < 0.001), with no significant differences at 24 h. The secondary outcome demonstrated early patient's mobilization (p < 0.001) as well as early discharge (p < 0.001) and greater patient's satisfaction for the Group A. In these patients, a maximum pain score of 3 points out of 5 was recorded through the entire surgery. RA showed to decrease the impact of surgical stress and to guarantee a quicker recovery without compromising surgical results. Although several surgical approaches can be employed to treat different conditions, RA technique could be a viable option for well-selected patients affected by gynecological diseases.

A rare case of isolated rectal laceration during parturition: consideration of the controversial role of the episiotomy and literature review.

BACKGROUND: Rectal laceration without sphincter lesion during childbirth is an unusual presentation. Like all the other severe lacerations during parturition, if left undiagnosed and untreated could hesitate in serious short and long term complications. Episiotomy once considered a routine procedure in nulliparous and a safeguard against severe tissue trauma nowadays is undergoing criticism and his effectiveness reconsidered. Currently, a policy of "selective" use of episiotomy is recommended only when an impending risk of lacerations is identified. When, according to this proposal, in the absence of risk factors episiotomy is not performed and complications occur, the medicolegal implication could arise. CASE: A 29-year-old primigravida was admitted with spontaneous onset of labor at 41 weeks after an uncomplicated pregnancy. During the second stage of labor a spurt of siero- hemorrhagic fluid was noted trough the anus. In absence of recognized risk factor episiotomy was not performed. A healthy 3650 grams female was born in a fair condition. Rectal examination immediately after delivery revealed a longitudinal laceration with un undamaged sphincter. The rectal tear was repaired and recovery was uneventful. CONCLUSIONS: In our as in the other cases here reviewed a severe laceration occurred unexpectedly and unpreventably in patients where, according to a selective regime, episiotomy was not performed. In this setting, if severe short and long term complications ensued, especially in nulliparous, the decision to withhold episiotomy could be a source of medicolegal issues. Therefore a detailed informed consent is necessary to offer to patients a full disclosure on the role of episiotomy, its recent indications as well as the possible complications stemming from both executing or withholding this procedure.

The role of endocervicoscopy in women with cervical intraepithelial neoplasia: a systematic review of the literature.

Endocervicoscopy is an alternative diagnostic tool to endocervical curettage for the diagnostic workup of repeatedly positive cervicovaginal cytology suggestive of a high-grade squamous intraepithelial lesion (HSIL) and negative or unsatisfactory colposcopy. The aim of this review is to summarize the current evidence on the diagnostic accuracy of endocervicoscopy in women with cervical intraepithelial neoplasia in the presence of nonvisible squamocolumnar junction with unsatisfactory colposcopy. A systematic review of literature was performed by searching in the main electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, ClinicalTrial.gov, OVID and Cochrane Library), from their inception to January 2021 for studies testing endocervicoscopy. Risk of Bias Assessment was performed. Four articles were included: three prospective and one retrospective cohort studies. Data on the endocervicoscopy accuracy, the accuracy and reliability correlation with definitive histology, the cone biopsy dimension after endocervicoscopy, the comparison between endocervicoscopy and curettage and the lesion missed were analyzed. Based on our results, the limit of this technique is the low predictive value that does not allow it to replace the colposcopy. Nevertheless, it could help to define the characteristics and localization of cervical-suspected lesions. However, further studies are needed to clarify its use and indication.

Spinal Anesthesia versus General Anesthesia in Gynecological Laparoscopic Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: In the last years, spinal anesthesia (SA) has been emerging as an alternative to general anesthesia (GA) for the laparoscopic treatment of gynecological diseases, for better control of postoperative pain. The aim of the review is to compare the advantages of SA compared to GA. METHODS: MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Cochrane Library, and CINAHL were searched from inception until March 2021. Randomized controlled trials (RCTs) and non-randomized studies (NRSs) about women underwent SA and GA for gynecological laparoscopic surgery were analyzed. Relevant data were extracted and tabulated. RESULTS: The primary outcomes included the evaluation of postoperative pain (described as shoulder pain), postoperative nausea and vomiting, and operative times. One hundred and eight patients were included in RCTs, 58 in NRSs. The qualitative analysis had conflicting results and for the most of parameters (hemodynamic variables, nausea, and postoperative analgesic administration) no statistically significant differences were observed: in the NRSs, contradictory results regarding the postoperative pain in SA and GA groups were reported. Regarding the quantitative analysis, in the RCTs, women who received SA had not significantly lower operative times (relative risk [RR] -4.40, 95% confidence interval [CI] -9.32-0.53) and a lower incidence of vomiting (RR 0.51, 95% CI 0.17-1.55); on the other hand, in the NRS, women who received SA had longer operative times (RR 5.05, 95% CI -0.03-10.14) and more episodes of vomiting (RR 0.56, 95% CI 0.10-2.97) compared to those with GA: anyway, the outcomes proved to be insignificant. CONCLUSIONS: Current evidence suggests no significant advantages to using SA over GA for laparoscopic treatment of gynecological diseases.

Microbiome and PCOS: State-of-Art and Future Aspects.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

Tolerability considerations for gonadotropin-releasing hormone analogues for endometriosis.

INTRODUCTION: The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may cause a not negligible rate of adverse events, in particular vasomotor symptoms and bone mineral density loss, that may limit patients' adherence and safety on long-term treatment. Several strategies have been suggested to improve the compliance to treatment. AREAS COVERED: This narrative review aims to give an overview of the safety and tolerability of GnRH-a therapy and to present the different options of steroidal and non-steroidal add-back therapies in order to reduce the hypoestrogenic side effects. EXPERT OPINION: Side effects of long term GnRH-a treatment are particularly relevant. Although it has been known the efficacy of GnRH-as for treating endometriosis-associated pain, the best schedules of therapy in terms of duration and dosages are still to be defined. The ideal treatment schedule of GnRH-a is still a matter of debate as to the optimal add-back combination.

Sentinel lymph node biopsy in endometrial cancer: state of the art.

Endometrial cancer (EC) is the most common gynecological neoplasm in developed countries. In literature, there are discordant data regarding the therapeutic value of systematic lymphadenectomy whereas the importance of lymph node status for determining prognosis and the need for adjuvant treatment is undoubted. Given the low risk of lymph-node metastases in the apparent early-stage disease and the significant surgical and postoperative risks when performing a complete pelvic lymphadenectomy, the surgical approach in these patients is controversial, ranging from no nodal evaluation to comprehensive pelvic and aortic lymphadenectomy. The recent introduction of sentinel node mapping represents the mid-way between the execution and omission of node dissection in EC patients. Indeed, the sentinel node mapping has rapidly emerged as an alternative to complete lymphadenectomy to reduce morbidity. In the present review, we discuss the role of sentinel node mapping in the surgical management of EC evaluating all aspects of this procedure.