Measuring the composition of the tumor microenvironment with transcriptome analysis: past, present and future.

Interactions between tumor cells and immune cells in the tumor microenvironment (TME) play a vital role the mechanisms of immune evasion, by which cancer cells escape immune elimination. Thus, the characterization and quantification of different components in the TME is a hot topic in molecular biology and drug discovery. Since the development of transcriptome sequencing in bulk tissue, single cells and spatial dimensions, there are increasing methods emerging to deconvolute and subtype the TME. This review discusses and compares such computational strategies and downstream subtyping analyses. Integrative analyses of the transcriptome with other data, such as epigenetics and T-cell receptor sequencing, are needed to obtain comprehensive knowledge of the dynamic TME.

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Comparison of ECG Saline-Conduction Technique and ECG Wire-Based Technique for Peripherally Inserted Central Catheter Insertion: A Randomized Controlled Trial.

(1) Background: The peripherally inserted central catheter (PICC) is commonly used in medicine. The tip position was shown to be a major determinant in PICC function and related complications. Recent advances in ECG guidance might facilitate daily practice. This study aimed to compare two ECG techniques, in terms of their tip-position accuracy, puncture site layout, and signal quality; (2) Methods: This randomized open study (1:1) included 320 participants. One PICC guidance technique used ECG signal transmission with saline (ST); the other technique used a guidewire (WT). Techniques were compared by the distance between the catheter tip and the cavoatrial junction (DCAJ) on chest X-rays, insertion-point hemostasis time, and the extracorporeal catheter length between the hub and the insertion point; (3) Results: The mean DCAJs were significantly different between ST (1.36 cm, 95% CI: 1.22-1.37) and WT (1.12 cm, 95% CI: 0.98-1.25; p = 0.013) groups. When DCAJs were classified as optimal, suboptimal, or inadequate, the difference between techniques had limited clinical impact (p = 0.085). However, the hemostasis time at the puncture site was significantly better with WT (no delay in 82% of patients) compared to ST (no delay in 50% of patients; p < 0.001). Conversely, ST achieved optimal and suboptimal extracorporeal lengths significantly more frequently than WT (100% vs. 66%; p < 0.001); (4) Conclusions: ECG guidance technologies achieved significantly different tip placements, but the difference had minimal clinical impact. Nevertheless, each technique displayed an important drawback at the PICC insertion point: the extracorporeal catheter was significantly longer with WT and the hemostasis delay was significantly longer with ST.

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression. METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540. FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study.

BACKGROUND: In the EMPOWER-Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Patient-reported outcomes were evaluated among trial participants. METHODS: Adults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer Module (QLQ-LC13) questionnaires. Mixed-model repeated measures analysis estimated overall change from baseline for PD-L1 ≥50% and intention-to-treat populations. Kaplan-Meier analysis estimated time to definitive deterioration. RESULTS: In PD-L1 ≥50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ-C30 and QLQ-LC13 scores showed moderate-to-high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32-0.71) to 0.63 (95% CI, 0.41-0.96). Cemiplimab showed lower risk of definitive deterioration for disease-related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment-related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention-to-treat population. CONCLUSIONS: Results support cemiplimab for first-line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum-doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.

Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3.

BACKGROUND: EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non-small cell lung cancer. This study evaluated patient-reported outcomes (PROs). METHODS: PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires. Prespecified analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and proportional hazards model. RESULTS: A total of 312 patients were assigned to receive cemiplimab plus platinum-doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25-84). For pain symptoms (EORTC QLQ-C30), a statistically significant overall improvement from baseline (-4.98, 95% confidence interval [CI] -8.36 to -1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26-0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20-3.19 vs. 1.08, 95% CI, -1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ-C30 or QLQ-LC13 scale. CONCLUSION: Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer-related and lung cancer-specific symptoms and functions.

Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer-Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects.

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and-as much as possible-minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

Fertility-Sparing Strategies for Early-Stage Endometrial Cancer: Stepping towards Precision Medicine Based on the Molecular Fingerprint.

Endometrial cancer represents the fifth most common cancer in women, and the most common gynecological malignancy in developed countries [...].

Urinary incontinence and quality of life in high-performance swimmers: An observational study.

Each day more women around the world practice high impact physical activities and this may be a risk factor for urinary incontinence (UI) in young. We verified the prevalence of UI and the impact in quality of life (QoL) in high-performance swimmers, through a cross-sectional observational study with 9 high performance swimmers and 9 sedentary women who responded the International Consultation on incontinence Questionnaire - Short Form (ICIQ-SF), participated in a functional evaluation of pelvic floor muscles with bidigital palpation and pad test. We verifed that was present in 78% of high-performance swimmers, and the quality of life was significantly worse (p =.037) when compared to sedentary women. These findings led us to conclude that presence of UI affects the quality of life, even if it is not a factor of abandonment of the sport.

Transplacental permeability of heavy metals in relation to newborn sex - evidence from the neurodevelopment project.

Introduction: Gender medicine is an innovative medical approach that studies how some biological variables are influenced by the male or female sex and gender. This issue is under debate because it characterizes the impact of tailored or individual medicine. In this scenario, the aim of this study is to study the correlation between heavy metal exposure and pathologies of neurodevelopment, according to the sex of newborns. In particular, this is an observational study under the name of the Neurosviluppo Project, involving 217 mother-child couples. Material and methods: The correlation with phenotype small for gestational age and congenital malformations were studied, but above all we focused on the pattern of placental permeability to heavy metals. Results: Our results are specifically related to foetal medicine and investigate the impact of foetal sex in transplacental metal exposure. Our results did not show any significant differences related to foetal sex in terms of congenital malformations or the other variables taken into consideration. However, because these conclusions are the first related to the gender medicine in transplacental foetal medicine, they could be a marked background for further studies. Conclusions: Considering the lack of data in literature regarding foetal sexual medicine and transplacental exposure, these study results are pioneering in terms of sexual foetal medicine. Possibly in the future, studies regarding the correlation between foetal sex and obstetrics outcomes will be performed.

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial.

BACKGROUND: We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%. METHODS: In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing. FINDINGS: Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17·9-not evaluable) with cemiplimab (n=283) versus 14·2 months (11·2-17·5) with chemotherapy (n=280; hazard ratio [HR] 0·57 [0·42-0·77]; p=0·0002). Median progression-free survival was 8·2 months (6·1-8·8) with cemiplimab versus 5·7 months (4·5-6·2) with chemotherapy (HR 0·54 [0·43-0·68]; p<0·0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3-4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy. INTERPRETATION: Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population. FUNDING: Regeneron Pharmaceuticals and Sanofi.

The role of endoglin and its soluble form in pathogenesis of preeclampsia.

Preeclampsia remains till today a leading cause of maternal and fetal morbidity and mortality. Pathophysiology of the disease is not yet fully elucidated, though it is evident that it revolves around placenta. Cellular ischemia in the preeclamptic placenta creates an imbalance between angiogenic and anti-angiogenic factors in maternal circulation. Endoglin, a transmembrane co-receptor of transforming growth factor ß (TGF-ß) demonstrating angiogenic effects, is involved in a variety of angiogenesis-dependent diseases with endothelial dysfunction, including preeclampsia. Endoglin expression is up-regulated in preeclamptic placentas, through mechanisms mainly induced by hypoxia, oxidative stress and oxysterol-mediated activation of liver X receptors. Overexpression of endoglin results in an increase of its soluble form in maternal circulation. Soluble endoglin represents the extracellular domain of membrane endoglin, cleaved by the action of metalloproteinases, predominantly matrix metalloproteinase-14. Released in circulation, soluble endoglin interferes in TGF-ß1 and activin receptor-like kinase 1 signaling pathways and inhibits endothelial nitric oxide synthase activation, consequently deranging angiogenesis and promoting vasoconstriction. Due to these properties, soluble endoglin actively contributes to the impaired placentation observed in preeclampsia, as well as to the pathogenesis and manifestation of its clinical signs and symptoms, especially hypertension and proteinuria. The significant role of endoglin and soluble endoglin in pathophysiology of preeclampsia could have prognostic, diagnostic and therapeutic perspectives. Further research is essential to extensively explore the potential use of these molecules in the management of preeclampsia in clinical settings.

The role of vitamin D in metabolic and reproductive disturbances of polycystic ovary syndrome: A narrative mini-review.

Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance (IR) and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400-800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.

Biomolecular and Genetic Prognostic Factors That Can Facilitate Fertility-Sparing Treatment (FST) Decision Making in Early Stage Endometrial Cancer (ES-EC): A Systematic Review.

Endometrial cancer occurs in up to 29% of women before 40 years of age. Seventy percent of these patients are nulliparous at the time. Decision making regarding fertility preservation in early stage endometrial cancer (ES-EC) is, therefore, a big challenge since the decision between the risk of cancer progression and a chance to parenthood needs to be made. Sixty-two percent of women with complete remission of ES-EC after fertility-sparing treatment (FST) report to have a pregnancy wish which, if not for FST, they would not be able to fulfil. The aim of this review was to identify and summarise the currently established biomolecular and genetic prognostic factors that can facilitate decision making for FST in ES-EC. A comprehensive search strategy was carried out across four databases; Cochrane, Embase, MEDLINE, and PubMed; they were searched between March 1946 and 22nd December 2022. Thirty-four studies were included in this study which was conducted in line with the PRISMA criteria checklist. The final 34 articles encompassed 9165 patients. The studies were assessed using the Critical Appraisal Skills Program (CASP). PTEN and POLE alterations we found to be good prognostic factors of ES-EC, favouring FST. MSI, CTNNB1, and K-RAS alterations were found to be fair prognostic factors of ES-EC, favouring FST but carrying a risk of recurrence. PIK3CA, HER2, ARID1A, P53, L1CAM, and FGFR2 were found to be poor prognostic factors of ES-EC and therefore do not favour FST. Clinical trials with bigger cohorts are needed to further validate the fair genetic prognostic factors. Using the aforementioned good and poor genetic prognostic factors, we can make more confident decisions on FST in ES-EC.

Fertility preservation in female cancer sufferers: (only) a moral obligation?

PURPOSE: Advances in cancer diagnostics and therapeutics have thankfully led to high numbers of young cancer survivors, although some interventions may sometimes threaten fertility. The authors aimed to assess how evidence-based oncofertility counselling can be adequately fulfilled for the sake of female cancer patients, in light of its complexities and multidisciplinary nature, which require thorough counselling and consent pathways. MATERIALS AND METHODS: A search has been conducted in the databases PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Google Scholar via search strings such as fertility preservation, reproductive counselling, oncofertility, cancer survivors, in order to identify relevant meaningful sources spanning the 2010-2021 period. RESULTS: Counselling needs to be implemented in compliance with international guidelines, so as to avoid medicolegal repercussions. Albeit fertility preservation is supported by most health care institutions, actual conditions at health care facilities often reflect several lingering difficulties in the oncofertility process. Oncofertility counselling should foster access to fertility preservation procedures. To best serve that purpose, it should be implemented in a manner consistent with ethical and legal standards, so that patients can make an informed decision based on comprehensive and relevant data. CONCLUSIONS: Counselling needs to be rooted in a close cooperation of oncologists, reproductive endocrinologists, mental health counsellors and clinical researchers. The provision of oncofertility services is grounded in the moral obligation to uphold individual autonomy, which is essential in a free society, unless the exercise thereof could pose a risk to the children conceived or to others.

Impact of assisted reproduction techniques on the neuro-psycho-motor outcome of newborns: a critical appraisal.

Subfertility and infertility are common problems among couples of reproductive age, and they increasingly require the use of assisted reproductive techniques (ART). Understandably, doubts about the safety of such methods are increasing among future parents. The purpose of this review is to analyse the real impact of ART, such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), on the health of the unborn baby; in particular, this work is focussed on the problems related to the neuro-psycho-motor area. Twenty-four studies were reviewed and outcomes investigated were: risk of the onset of neurodevelopmental diseases, worsening of school cognitive performance and risk of developing infantile cerebral palsy (CP) or neurological sequelae. For the first two outcomes, we did not find a correlation with ART; nevertheless, the results of the included studies about risk of CP are discordant and influenced by various confounding factors, such as pre-term birth and multiple pregnancies.IMPACT STATEMENTWhat is already known on this subject? Assisted reproductive techniques (ART) are the main answer for achieving pregnancy in infertile couples. However, a wide number of studies have tried to focus on possible different outcomes in terms of maternal and foetal/new-born health. Regarding this scenario, a peculiar importance is given to diseases affecting the neuro-psycho-motor area of the new-born. Since this group of detrimental pathologies could heavily affect the new-born's quality of life and require costly social facilities, different studies have tried to focus on possible outcomes after ART.What do the results of this study add? This manuscript provides a review of the literature regarding ART procedures and neuro-psycho-motor implication. A review is strongly required due to the importance of collecting evidence from studies with different methodologies.What are the implications of these findings for clinical practice and/or further research? This manuscript provides evidence about the need for wider and more congruent studies regarding neurodevelopment disorders in new-borns after ART procedures. Data are prone to suggest a slight correlation, but several confounding factors can heavily hamper the possibility to draw a firm conclusion about the topic.

Luteinised unruptured follicle syndrome: pathophysiological background and new target therapy in assisted reproductive treatments.

Luteinised unruptured follicle syndrome (LUFS) is a cause of infertility consisting in the unruptured of the dominant follicle after the LH-surge. In fact, during assisted reproductive treatments (ART) clomiphene citrate and letrozole are frequently administered in order to achieve ovulation. However, considering the pathophysiology of LUFS, new possible therapy can be proposed. On this scenario, we performed a review of the literature searching for LUFS recurrency and its impact in infertility and ART. An inflammation theory has been proposed that can be fuel for further therapeutic possibilities. In particular, considering the increase in granulocytes accumulation, the granulocyte colony-stimulating factor (G-CSF) administration has been proposed as target therapy in IUI cycles hampered by LUFS. Although data are encouraging, randomised controlled trials are needed in order to confirm the efficacy of G-CSF administration for LUFS patients.

Neonatal Outcomes and Long-Term Follow-Up of Children Born from Frozen Embryo, a Narrative Review of Latest Research Findings.

In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.

Utero-cutaneous fistula after caesarean section delivery: diagnosis and management of a rare complication.

Utero-cutaneous fistula is an extremely rare condition characterized by an abnormal communication between the anterior wall of the uterus and the abdominal wall. The causes include multiple caesarean sections, incomplete hysterorrhaphy, miscarriages, uterine cavity revision, retention of placental material after delivery, use of drains, post-operative infections, or injuries. Herein, we report a case of a 38-year-old female, who underwent caesarean section 42 days earlier and presented to the emergency room complaining of fever, abdominal pain, and purulent discharge from the abdominal wall from 6 days. Her medical history included 2 previous term caesarean section deliveries and an hysteroscopic polypectomy 2 years earlier. A pelvic computed tomography scan with contrast medium showed fluid/super-fluid phlogistic collection reported at the anterior wall of the uterus with a continuous solution of the uterine wall itself. Magnetic resonance imaging demonstrated the presence of a probable hyperintense fistula, extended for 30 mm and 16 mm of thickness, which ended in the subcutaneous area with an abscess joint without continuous solution with the skin. A laparotomic surgical procedure was successfully performed. Histopathology confirmed the surgical suspect of utero-cutaneous fistula. Although utero-cutaneous fistula is an extremely rare complication, it should be considered if after caesarean section delivery signs and symptoms of skin inflammation and/or infection persist.

Psychological variables in medically assisted reproduction: a systematic review.

Introduction: The paths of medically assisted reproduction represent the most important scientific progress to cope with the inability to achieve spontaneous conception (SC) and to reach desired parenthood. Couples undergoing assisted reproductive technology (ART) and couples not facing ovulation induction and artificial fertilization show sufficient levels of well-being and psychological adjustment. However, in some cases couples undergoing ART show lower perceived quality of life than couples with SC.Our aim is to investigate the main psychological variables involved in the special risk condition of medically assisted reproduction and how they could direct specific guidelines to enhance mental wellbeing in dealing with infertility. Material and methods: In this regard, we performed a systematic review following the PRISMA guidelines. From all the studies included, the considered outcome measures were psychological, social, and relational variables and are presented in a systematic approach. Results: A total of 14 studies were included in this article, according to our strict inclusion criteria. Conclusions: Conflicting results have been proven by this systematic review. Even though all underlined the importance of taking charge of the psychological variables in infertility, few studies monitored and evaluated the effectiveness of these interventions. Moreover, none of the selected studies monitored the evolutionary implications of parental competence on the development of children born from ART.

Impact of lifestyle and diet on endometriosis: a fresh look to a busy corner.

Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and mono-saccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and well-designed randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.