Conservative Surgery in Endometrial Cancer

Endometrial cancer (EC) is the sixth most common female cancer worldwide. The median age of diagnosis is 65 years. However, 4% of women diagnosed with EC are younger than 40 years old, and 70% of these women are nulliparous. These data highlight the importance of preserving fertility in these patients, at a time when the average age of the first pregnancy is significantly delayed and is now firmly established at over 30 years of age. National Comprehensive Cancer Network (NCCN guidelines state that the primary treatment of endometrial endometrioid carcinoma, limited to the uterus, is a total hysterectomy, bilateral salpingo-oophorectomy and surgical staging. Fertility-sparing treatment is not the standard of care, and patients eligible for this treatment always have to undergo strict counselling. Nowadays, a combined approach consisting of hysteroscopic resection, followed by oral or intrauterine-released progestins, has been reported to be an effective fertility-sparing option. Hysteroscopic resection followed by progestins achieved a complete response rate of 95.3% with a recurrence rate of 14.1%. The pregnancy rate in women undergoing fertility-sparing treatment is 47.8%, but rises to 93.3% when only considering women who tried to conceive during the study period. The aim of the present review is to provide a literature overview reflecting the current state of fertility-sparing options for the management of EC, specific criteria for considering such options, their limits, the implications for reproductive outcomes and the latest research trends in this direction

New technologies in the surgical management of endometriosis

Introduction: Endometriosis is a very common disease that affects up to 10% of the female population. Although medical therapy represents the first-line treatment for endometriosis, it does not always manage to control symptoms. Laparoscopy represents the standard surgical treatment in endometriosis. Robotic-assisted laparoscopy is an innovative mini-invasive surgical technique. Its application in gynecological surgery and in endometriosis has increased in the last decade. Our purpose is to offer an overview of the role of robotic-assisted laparoscopy in the surgical treatment of endometriosis. Methods: We evaluated studies dealing with the new technique in surgery for endometriosis with a focus on robotic surgery. We performed a compressive literature research on PubMed and the Cochrane Library in December 2022. Expert opinion: Robotic-assisted surgery is a feasible and safe approach to endometriosis surgery and is superimposable to laparoscopy in terms of complication rate, blood loss, hospitalization, and long-term improvement of symptoms. The effect of robotic-assisted surgery on operative time is still contradictory and needs to be further investigated. Robotic-assisted laparoscopic surgery can provide particular benefit in the management of women with severe endometriosis secondary to its advantage in surgical precision and ergonomics. Indocyanine green fluorescence angiography could be useful to assist in the vascularization of ureters and bowel anastomosis, to prevent postoperative complication and leakage

Chronic Endometritis

Chronic endometritis is a persistent inflammation of the inner lining of the uterine cavity. Several studies have demonstrated that it is a condition frequently associated with repeated unexplained implantation failure at in vitro fertilization, recurrent miscarriage, as well as poor obstetric outcomes such as preterm labor

Review of the safety, efficacy and patient acceptability of the combined dienogest/estradiol valerate contraceptive pill

The aim of this review is to define the role of the combined dienogest (DNG)/estradiol valerate (E2V) contraceptive pill, in terms of biochemistry, metabolic and pharmacological effects and clinical application as well. E2V is the esterified form of 17β-estradiol (E2), while dienogest is a fourth-generation progestin with a partial antiandrogenic effect. The cycle stability is achieved with 2 to 3 mg DNG, supporting contraceptive efficacy. In this new oral contraceptive, E2V is combined with DNG in a four-phasic dose regimen (the first two tablets contain 3 mg E2V; the next five tablets include 2 mg E2V + 2 mg DNG, followed by 17 tablets with 2 mg E2V + 3 mg DNG; followed by two tablets with 1 mg E2V only, and finally two placebo tablets). Duration and intensity of scheduled withdrawal bleeding are lower with this contraceptive pill, whereas the incidence and the intensity of intra-cyclic bleeding are similar to the other oral contraceptive. With this new pill the levels of high density lipoprotein increased, while the levels of prothrombin fragment 1 + 2 and D-dimer remained relatively unchanged; the levels of sex hormone binding globulin, cortisol binding globulin, thyroxine binding globulin increased. The most frequently reported adverse events are: breast pain, headache, acne, alopecia, migraine, increase of bodyweight. The satisfaction rate is about 79.4%

Glucose regulates insulin mitogenic effect by modulating SHP-2 activation and localization in JAr cells.

The glucose effect on cell growth has been investigated in the JAr human choriocarcinoma cells. When JAr cells were cultured in the presence of 6 mm glucose (LG), proliferation and thymidine incorporation were induced by serum, epidermal growth factor, and insulin-like growth factor 1 but not by insulin. In contrast, at 25 mm glucose (HG), proliferation and thymidine incorporation were stimulated by insulin, serum, epidermal growth factor, and insulin-like growth factor 1 to a comparable extent, whereas basal levels were 25% lower than those in LG. HG culturing also enhanced insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine phosphorylations while decreasing basal phosphorylations. These actions of glucose were accompanied by an increase in cellular tyrosine phosphatase activity. The activity of SHP-2 in HG-treated JAr cells was 400% of that measured in LG-treated cells. SHP-2 co-precipitation with IRS1 was also increased in HG-treated cells. SHP-2 was mainly cytosolic in LG-treated cells. However, HG culturing largely redistributed SHP-2 to the internal membrane compartment, where tyrosine-phosphorylated IRS1 predominantly localizes. Further exposure to insulin rescued SHP-2 cytosolic localization, thereby preventing its interaction with IRS1. Antisense inhibition of SHP-2 reverted the effect of HG on basal and insulin-stimulated insulin receptor and IRS1 phosphorylation as well as that on thymidine incorporation. Thus, in JAr cells, glucose modulates insulin mitogenic action by modulating SHP-2 activity and intracellular localization

Hysteroscopic and ultrasound evaluation of a novel degradable polymer film for the prevention of intrauterine adhesion formation after hysteroscopic surgery

•Womed Leaf is a degradable polymer film barrier for the prevention of intrauterine adhesions.•We captured a set of images for the first time that illustrates the behavior of DPF after insertion.•None of our participants reported adverse events in relation to Womed Leaf use.•Six weeks post hysteroscopic surgery and Womed Leaf insertion no film or synechiae were present. To collect information on the application and behavior of a novel degradable polymeric film (DPF) developed to prevent intra-uterine adhesions (IUAs) after hysteroscopic surgery. A prospective observational study conducted in a university hospital in Naples, Italy. Women undergoing hysteroscopic myomectomy, metroplasty or adhesiolysis, were eligible for the study. Women had their uterine cavity assessed by transvaginal ultrasound scan before their hysteroscopic surgery, which was followed by the DPF insertion. Ultrasonographic and hysteroscopic assessments were undertaken immediately after insertion then at 2 h, 2–5 days, and 6 weeks postoperative. The main outcome of interest was to assess the behavior of the DPF, from insertion to degradation, by ultrasound and hysteroscopy. Other outcomes included ease of DPF insertion, any patient reported adverse events and the presence of IUAs at 6 weeks. A total of 15 patients were enrolled into the study. The DPF insertion was reported to be very easy in almost all the cases and was visualized immediately and 2 h after insertion in all patients. At the 2–5 day follow-up 5 and 2 of the 15 participants still had the entire or partially hydrolyzed film respectively. By 6 weeks there was no evidence of the DPF in all women. No adverse events were reported at the time of insertion or follow-up. None of the study participants had IUAs at the 6-week assessment. According to this pilot study, the solid degradable polymer film, Womed Leaf, is a promising, easy to apply and well tolerated novel option for the prevention of intrauterine adhesion formation after hysteroscopic surgery

Endometrial scratch injury for women with one or more previous failed embryo transfers: a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE: To investigate endometrial scratch injury (ESI) as an intervention to improve IVF outcome in women with a history of ET failure. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing IVF after one or more failed ET. INTERVENTION(S): We included all randomized controlled trials of women undergoing IVF after one or more failed ET, where the intervention group received ESI and controls received placebo or no intervention. Pooled results were expressed as relative risk (RR) with a 95% confidence interval (95% CI). The review protocol was registered in PROSPERO before starting the data extraction (CRD42017082777). MAIN OUTCOME MEASURE(S): Live birth rate (LBR), clinical pregnancy rate (PR), multiple PR, miscarriage rate, ectopic pregnancy (EP) PR. RESULT(S): Ten studies were included (1,468 participants). The intervention group showed higher LBR (RR 1.38, 95% CI 1.05-1.80) and clinical PR (RR 1.34, 95% CI 1.07-1.67) in comparison to controls, without difference in terms of multiple PR, miscarriage rate, and EP PR. Double luteal ESI with pipelle was associated with the greatest effect on LBR (RR 1.54, 95% CI 1.10-2.16) and clinical PR (RR 1.30, 95% CI 1.03-1.65). The ESI was beneficial for patients with two or more previous ET failure, but not for women with a single previous failed ET. No effect was found in women undergoing frozen-thawed ET cycles. CONCLUSION(S): The ESI may improve IVF success in patients with two or more previous ET failures undergoing fresh ET. The ESI timing and technique seem to play a crucial role in determining its effect on embryo implantatio

Assessment of DNA Damage by RAPD in Paracentrotus lividus Embryos Exposed to Amniotic Fluid from Residents Living Close to Waste Landfill Sites

The aim of this study was to assess the genotoxic effects of environmental chemicals on residents living near landfills. The study was based on samples of amniotic fluid from women living in the intensely polluted areas around the Campania region of Italy compared to a nonexposed control group. We evaluated the genetic effects that this amniotic fluids collected in contaminated sites had on Paracentrotus lividus embryos. DNA damage was detected through changes in RAPD (Random Amplified Polymorphism DNA) profiles. The absence of the amplified DNA fragments indicated deletions in Paracentrotus lividus DNA exposed to the contaminated amniotic fluids when compared to equal exposure to uncontaminated fluids. These results show the ability of RAPD-PCR to detect and isolate DNA sequences representing genetic alterations induced in P. lividus embryos. Using this method, we identified two candidate target regions for DNA alterations in the genome of P. lividus. Our research indicates that RAPD-PCR in P. lividus embryo DNA can provide a molecular approach for studying DNA damage from pollutants that can impact human health. To our knowledge, this is the first time that assessment of DNA damage in P. lividus embryos has been tested using the RAPD strategy after exposure to amniotic fluid from residents near waste landfill sites