Laparoscopic subtotal hysterectomy followed by in-bag transvaginal corpus uteri morcellation and extraction: A case series.

OBJECTIVES: Laparoscopic subtotal hysterectomy (LSH) is a possible treatment for patients with benign uterine disease. Once the hysterectomy has been completed, morcellation and extraction of the corpus uteri is a crucial step of the procedure. We here present a case series to evaluate the feasibility of the in-bag transvaginal specimen retrieval following LSH. STUDY DESIGN: We report a case series of consecutive patients who underwent LSH followed by in-bag transvaginal specimen retrieval. LSH was accomplished in a standard fashion. Once the uterus was detached from the cervix, a 2 cm posterior colpotomy was performed laparoscopically with a monopolar hook under direct view to insert a specimen retrieval bag into the abdomen. The corpus uteri was placed into the bag and transvaginal contained manual morcellation was performed. The colpotomy was then sutured transvaginally. Baseline patients' characteristics and surgical data were collected. Postoperative complications, same-hospital readmissions, and reoperations were registered if occurred within 30 days from surgery. RESULTS: Patients' median age and BMI were 45,5 and 22,7, respectively. Median operative time was 71.5 min (range 34-143) and uterus weight ranged from 60 g to 470 g (median 210 g). The estimated blood loss was 100 mL (median) and no blood transfusion was required. No conversions to open surgery, nor intraoperative complications occurred. Median hospital stay was 2 days (1-3) and no postoperative complications within 30 days from surgery were recorded. CONCLUSIONS: LSH followed by in-bag transvaginal specimen extraction is a promising technique and might be considered a reliable and safe option to further reduce the invasiveness of the procedure.

Pregnancy outcomes in women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrinological disease of reproductive-aged women, with an estimated incidence ranging from 5% to 15%. The clinical manifestations of PCOS are heterogeneous and vary according to the age of the patient. Insulin resistance (IR), hyperandrogenism, and obesity are widely assumed to play a pivotal role in the pathophysiological mechanism of PCOS. As previously stated by many conducted meta-analyses, PCOS can cause a rising risk of pregnancy complications, including maternal, fetal, and neonatal complications. Pregnancy-induced hypertension (PIH), preeclampsia (PE), gestational diabetes mellitus (GDM), spontaneous preterm birth (PTB), and an increased necessity for a cesarean section (CS) are the most documented maternal implications. Regarding fetal outcomes, PCOS has also been correlated with elevated neonatal morbidity, prematurity, fetal growth restriction (FGR), birth weight variations (large for gestational age [LGA] and small for gestational age [SGA]), and transfer to the Neonatal Intensive Care Unit (NICU). Owing to the variability of the studies performed, the association of PCOS with an elevated risk of adverse pregnancy outcomes is still controversial. This variability is found in the diagnosis and clinical presentations of PCOS, and can be influenced by prepregnancy circumstances and therapies as well as particular population and environmental features. The Amsterdam Consensus Guidelines confirm that obesity and IR can worsen maternal and fetal complications; thus, a closer follow-up should be offered to PCOS women during pregnancy.

Role of surgical treatment in endometriosis.

Endometriosis can take one of three forms depending on its clinical presentation and management: endometriotic ovarian cyst (ovarian endometrioma), superficial or peritoneal endometriosis and deep infiltrating endometriosis (DIE).1Among them, DIE is considered the most aggressive, and the patient is often affected by more than one type together. The therapeutic methodology should not be influenced by a combination of different types of endometriotic lesion. According to the clinical context and the patient's needs, the treatment of this pathology can be medical or surgical. Although medical therapy could improve endometriosis-associated symptoms, it never offers a definite treatment for symptomatic patients, who often require surgical treatment. The rationale behind endometriosis surgical treatment is to achieve the complete removal of all lesions through a one-step surgical procedure; to obtain promising long-term results for pelvic pain, recurrence rate, and fertility; and to protect the functionality of the involved organs. Achieving these results depends on the total removal of the pathology from the pelvis, in an attempt to preserve, as much as possible, the healthy tissues surrounding the site of the disease. The choice of a surgical approach rather than medical therapy is subject to the patient's expectations, such as pregnancy desire, the effectiveness of treatment compared to possible complications, the type of pain and its intensity, and the location and severity of the disease. In this context, surgical management using a multidisciplinary endometriosis team is an important factor for achieving good outcomes.

Possible role of microbiome in the pathogenesis of endometriosis.

INTRODUCTION: There is an urgent necessity to explore the complex pathophysiological nature of endometriosis, which may enable the rationale for new diagnostic and therapeutic strategies to be discovered. This systematic review aimed to clarify the bidirectional relationship between endometriosis and the microbiome and evaluate if the microbiome may be involved in endometriosis's pathogenesis, establishing a potential connection between the different studies. EVIDENCE ACQUISITION: Studies were identified through a systematic literature search of papers that evaluated the microbiomes of human or other animal species with endometriosis and of those without in the electronic database PubMed/Medline, and Embase without a date restriction. We included all cohort studies focusing on the interaction between endometriosis and the microbiomes of humans or other mammals, evaluating if the microbiome may be involved in endometriosis's pathogenesis. EVIDENCE SYNTHESIS: Endometriosis appears to be associated with elevated levels of different microorganisms across various microbiome sites. An ineffective immune response seems to play a key role in endometriosis pathogenesis, and there is some scientific proof to state that the immune response may be modulated by the microbiome. Interestingly, nine studies of our review detected species belonging to the phyla Proteobacteria, Bacteroidetes, and Negativicutes characterized by Gram-negative staining, that were significantly increased in endometriosis cohorts. CONCLUSIONS: Laboratory and clinical investigations indicate that hosts' microbiome profiles with and without endometriosis can be significantly different. To further our understanding of the relationships between endometriosis and the host microbiome, more studies are necessary.

New development on hysteroscopy for endometrial cancer diagnosis: state of the art.

Endometrial cancer (EC) is the most common gynecologic cancer diagnosed in developed countries and represents the second most frequent gynecologic cancer-related cause of death following ovarian cancer. There are 2 subtypes of EC. Type I tumors (endometrioid adenocarcinoma) representing 85-90% of the cases. They are likely to be low-grade tumors and are thought to have a link to estrogen exposure. Type II tumors represent 10-15% of EC. They are characterized as high-grade carcinomas, with serous or clear cell histology type, and carry poor prognoses. The benefits of hysteroscopy in achieving a targeted endometrial biopsy under direct visualization over blind biopsy techniques are widely accepted. Hysteroscopic endometrial biopsy is performed under direct visualization and is the only technique that allows for the selective biopsy of targeted areas of the endometrium. There is no screening protocol for the early detection of EC. Among the general population, advanced age, obesity, nulliparity and the use of exogenous hormones are known as risk factors for EC. There are additional situations that portend an increased risk of EC that deserve special consideration such as in patients diagnosed with Lynch Syndrome, using tamoxifen, obese, or the young patient with a desire for future fertility. We presented a narrative review of the current role of hysteroscopy for the diagnosis of endometrial cancer.

Vilaprisan, a New Selective Progesterone Receptor Modulator in Uterine Fibroid Pharmacotherapy-Will it Really be a Breakthrough?

BACKGROUND: Vilaprisan (VPR) is a new orally available selective progesterone receptor modulator (SPRM), with anti-proliferative activity against uterine fibroids (UFs). It definitively causes suppression of ovulation and inhibition of proliferation of endometrial, myometrial and UF cells. PURPOSE: This review aims to summarize current knowledge on VPR from all studies, including clinical trials, conducted to date and to contextualize the potential role of VPR in future medical regimens for the treatment of UFs. METHODS: We performed a literature search in PubMed US National Library of Medicine and Google Scholar databases. Both databases were extensively searched for all original and review articles/book chapters as well as congress abstracts published in English until July 2019. The use of VPR for UF therapy was identified by using the keywords: "uterine fibroids" and "vilaprisan". RESULTS: In phase I and II clinical trials, VPR was shown to be effective in ameliorating UF-related clinical symptoms, especially abnormal or excessive uterine bleeding and in shrinking UFs. The tolerability of VPR is roughly similar to that of ulipristal acetate (UPA) and it tends to be more favorable than that of GnRH-agonists. CONCLUSION: Presently, all trials examining the utility of VPR for the treatment of UF are halted; likely, due to the recently reported cases of hepato-toxicity with UPA, in addition to non reassuring toxicology results from preclinical long-term testing on rodents, carried out in parallel with late stage testing on humans. An accurate summary of robust data related to the safety of VPR is urgently needed to draw definitive conclusions on the future clinical development of this drug for UF therapy.

Ovulation induction in infertile women with endometriotic ovarian cysts: current evidence and potential pitfalls.

Endometriosis is a chronic benign gynecological disease with symptoms that can severely impact quality of life and well-being. Women affected by endometriotic ovarian cyst could have associated infertility problems. Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, due to the disease pathophysiologic mechanisms. Generally, infertility management include surgical procedure (usually with minimally invasive approach) and ovulation induction with intrauterine insemination or in vitro fertilization. Fertility preservation technologies also include oocyte or embryo freezing and ovarian tissue cryopreservation. Approach to patients with endometriotic cysts still remains controversial, and a multidisciplinary approach is a key factor to achieve the best outcome with appropriate patient counselling. Such management by a multidisciplinary team is a key factor in achieving the successful outcome.

Psychological stress levels in women with endometriosis: systematic review and meta-analysis of observational studies.

INTRODUCTION: Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, associated with chronic and inflammatory reaction. Symptoms range from dysmenorrhea, dyspareunia, chronic pelvic pain, unexplained infertility to asymptomatic. The patients' quality of life is affected by anxiety, depression and stress. We aimed to verify the prevalence and levels of psychological stress among women with endometriosis. EVIDENCE ACQUISITION: The systematic review followed the PRISMA statement and the MOOSE guideline. Databases searched were MEDLINE, EMBASE, PsychNET and SciELO. The risk of bias was assessed with a modified Newcastle-Ottawa Scale. The meta-analysis of proportions used inverse variance method for pooling and random-effects model. For the stress levels we used the restricted maximum likelihood estimator for summary effects. Heterogeneity was assessed through I2 and Q statistics. Publication bias was assessed through funnel plots. Meta-regression adopted a mixed-effects model, considering patient age, endometriosis staging, stress assessment tool and data collection as categorical moderators. EVIDENCE SYNTHESIS: We included 15 studies encompassing 4,619 women with endometriosis. The overall prevalence of mild/high stress was 68% (95%CI:57%-79%), I2=98% and τ2=0.0228. The mean level of stress was 41.78% (95%CI =34.05%-49.51%), I2=99.9% and τ2=83.35. Meta-regression showed relationship with endometriosis staging. CONCLUSIONS: This is the first meta-analysis exploring the association between endometriosis and psychological stress. The interdisciplinary management of the disease should expand the mental health support in this patient care, beyond pain management. Finally, the attitude of the medical team acknowledging the patients' psychological stress may positively affect their treatment.

[Differential diagnosis and management of abnormal uterine bleeding in adolescence].

Abnormal uterine bleeding (AUB) is defined as any atypical genital bleeding originating from the uterine cavity, without the characteristics of normal menstrual period. AUB is an important symptom both for adolescents and their parents, and it usually leads to a state of anxiety. Although about 95% of AUB could be considered as a dysfunctional disorder, AUB requires well-defined diagnostic procedures in order to detect a physical cause, ruling out complex or systemic diseases, including oncological ones. Diagnostic procedures require the acquisition of a full and detailed history, and it is also crucial to obtain as much compliance from the patient as possible. A complete gynecological evaluation (whenever possible) and a full physical examination are useful to detect any kind of general disease which can compromise the hormonal reproductive system. Auxiliary tools such as gynecological ultrasonography for pelvic examination are allowed in sexually-active women, otherwise transrectal ultrasonography could be considered, if needed. Hematic ß-hCG must be dosed in every fertile woman with AUB and laboratory tests must be tailored on each patient. The first-line treatment consists of combined oral contraceptives and, when they are contraindicated, progesterone alone, medicated intrauterine devices, GnRH-analogues, or desmopressin are the most common second-line treatments.

The prevalence of sexually transmitted infections among migrant female patients in Italy.

OBJECTIVE: To evaluate the prevalence of several sexually transmitted infections (STIs) among migrant women incoming to Italy. METHODS: A single-center, prospective, observational study was conducted of migrant women who had attended an outpatient clinic in Messina, Italy, between January 1, 2003, and December 31, 2013. Participants underwent a gynecologic examination and a cervical smear test. Patients who showed cytologic alterations underwent human papillomavirus (HPV) typing by PCR and allele-specific hybridization. Routine tests for hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, and syphilis were done for pregnant participants. RESULTS: Overall, 724 women were enrolled, of whom 320 (44.2%) were pregnant. The mean ± SD age was 33.1 ± 9.8 years. Cytologic abnormalities were recorded for 76 (10.5%) participants. Among 46 who attended a follow-up clinic, 32 (69.6%) tested positive for HPV serotypes. Among the pregnant women, 9 (2.8%) had HBV infection, 3 (0.9%) had HCV infection, and 1 (0.3%) had HIV infection. No cases of syphilis were recorded. CONCLUSION: The prevalence of STIs among migrant women in Messina is similar to that among nonmigrants.

Behavior of tumor necrosis factor-α and tumor necrosis factor receptor 1/tumor necrosis factor receptor 2 system in mononuclear cells recovered from peritoneal fluid of women with endometriosis at different stages.

During endometriosis, a breakdown occurs in endometrial and peritoneal homeostasis caused by cytokine-induced cell proliferation and dysregulation of apoptosis. We studied tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1, and TNFR2 gene expression at both messenger RNA (mRNA) and protein levels in peritoneal fluid (PF) mononuclear cells (PFMCs), the percentages of these cells bearing the same markers, and soluble TNF-α (sTNF-α) values in PF of 80 women with endometriosis. We found that TNFR1 mRNA and protein levels, the percentages of TNFR1-bearing PFMCs, and sTNF-α values decreased from minimal to severe stages of the disease. Instead, TNF-α and TNFR2 mRNA and protein levels, the percentages of membrane TNF-α (mTNF-α)- and TNFR2-bearing PFMCs increased as the disease worsened. These data allow us to hypothesize that, in early stages, the high percentages of TNFR1-bearing PFMCs and the high levels of sTNF-α could address signal toward complex I pathway, favoring the inflammatory response. With the worsening of the disease, the low percentages of TNFR1-bearing PFMCs are probably due to decreased TNFR1 mRNA transcription and protein translation rate. In early stages (minimal and mild), the percentages of both TNFR2- and mTNF-α-bearing PFMCs are so low, due to decreased mRNA transcription and protein translation rate, that subsequent cellular events may depend minimally by this interaction. The high levels of sTNF-α may be rerouted to bind TNFR1. In contrast, in the moderate and severe stages, the high percentages of TNFR2-bearing PFMCs may be saturated by high percentages of mTNF-α-bearing PFMCs, triggering death process. So, in endometriosis, each component of the TNF-α/TNFRs system may trigger opposite cellular fate.