Reproductive outcomes after vaginal repair of isthmocele: A preliminary study and systematic review of the literature.

OBJECTIVE: Although vaginal repair of isthmocele is an effective and safe surgical option, data on reproductive and obstetrical outcomes are lacking. The aim of this study is to evaluate reproductive outcomes of women undergone vaginal repair of isthmocele. We also systematically reviewed the existent literature to offer a general view of available data. STUDY DESIGN: Retrospective analysis of a database prospectively collected between January 2018 and January 2022 at San Raffaele Hospital, Milan, Italy. We included secondary infertile women with ultrasound documented isthmocele who undergone vaginal repair. Post-surgical clinical, reproductive and obstetric outcomes were recorded. An advanced systematic search of the literature up to January 2023 was conducted. RESULTS: 17 women were included. The mean age of the included patients was 37.2 ± 2.7 years. The median of previous caesarian sections was 1 (1-2). One intra-operative complication (5.9 %) was reported (bladder injury, repaired at the time of surgery). At follow up, bleeding was successfully treated in 8 women (8/10; 80 %). Pregnancy was obtained in 7 women (7/17; 41.2 %): the conception was spontaneous in 4 women (4/7; 57.1 %) and trough assisted reproductive technology in 3 patients (3/7; 42.9 %). The mean time from surgery to pregnancy was 10.8 (±6.7) months. One spontaneous abortion was reported (1/7; 14.3 %), while live birth was achieved in 6 pregnancies (6/7; 85.7 %). All deliveries were by caesarian section at a median gestational age of 37.5 (36-38.25) weeks. No obstetrical complications were reported. At the time of caesarean section, no defects on the lower segment were retrieved. Regarding the systematic research, among the 21 studies screened, only 4 articles were included in the review. Pregnancy rate was around 60-70 % with very few obstetrical complications (0.01 %) such as abnormal placentation or preterm birth. CONCLUSIONS: Vaginal repair of isthmocele is a minimally invasive, safe and effective surgical approach in terms of postsurgical residual myometrium tichness. Systematic review to date has found low-quality evidences on the impact of vaginal surgery in the management of secondary infertility and obstetrics outcomes in women with isthmocele.

Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together-A Review.

Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.

Menopause: a trigger for simultaneous development of ulcerative colitis in sigmoid neovagina and residual colorectum?

Vaginoplasty using sigmoid colon is a common technique used for the creation of a neovagina. However, the risk of adverse neovaginal bowel events is a common mentioned disadvantage. We report the case of a woman submitted to intestinal vaginoplasty for Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome at the age of 24 years who, with the onset of menopause, developed blood-stained vaginal discharge. Almost simultaneously, the patients complained chronic abdominal pain in lower left quadrant and prolonged diarrhea. General exams, Pap smear test, microbiological tests and viral test for HPV were negative. Neovaginal biopsies were suggestive for inflammatory bowel disease (IBD) of moderate activity and colonic biopsies were suggestive for ulcerative colitis (UC). The development of UC in the sigmoid neovagina and, almost simultaneously, in the remaining colon with onset of menopause raises important questions about etiology and pathogenesis of these diseases. Our case suggests that menopause may consider a trigger for the development of UC, due to the changes in the colon surface permeability related to menopause.

CO2 fiber laser vaporization for endometrioma treatment results in preserved ovarian responsiveness and improved embryo quality in infertile women undergoing ART.

BACKGROUND: Infertile women carrying ovarian endometriomas can be managed either with surgery or by in-vitro fertilization (IVF). The aim of this study was to compare ovarian responsiveness to controlled ovarian stimulation (COS) in assisted reproduction techniques (ART) in infertile women carrying small intact endometriomas and those managed by endometrioma cystectomy or CO2 fiber laser ablation. METHODS: Retrospective case-control study of prospectively collected data including women underwent ART for endometriosis-related infertility. The study group consisted of infertile women undergoing endometriomas CO2 fiber laser vaporization before ART ("ART after laser CO2" group). Controls were infertile women with endometrioma managed by cystectomy before ART ("ART after cystectomy" group) and infertile women with small endometriomas undergoing ART as first approach ("ART only" group). RESULTS: Of the 86 included patients, 27 (31.4%) belonged to "ART after laser CO2" group, 37 (43%) to "ART after cystectomy" group and 22 (25.6%) to "ART only" group. Surgical groups had larger endometriomas than patients referred to "ART only" group. No between-groups differences were observed in terms of COS protocol, gonadotropins starting and total doses and length of COS. While women belonged to "ART after cystectomy" group had fewer recruited follicles (P=0.014), oocytes (P=0.042), MII oocytes (P=0.042) and formed embryos (P=0.004) compared to women of "ART only" group, no significant differences were found between patients of "ART only" group "ART after laser CO2" group. A greater number of good-quality embryos were observed in surgical groups. No between-groups differences were found in clinical pregnancy rates. CONCLUSIONS: Our results demonstrate encouraging findings on IVF/ICSI outcomes after laser CO2 endometrioma ablation in terms of both quantity and quality of developed embryos.

Endometriosis and Impaired Placentation: A Prospective Cohort Study Comparing Uterine Arteries Doppler Pulsatility Index in Pregnancies of Patients with and without Moderate-Severe Disease.

The aim of this study was to evaluate if moderate-severe endometriosis impairs uterine arteries pulsatility index (UtA-PI) during pregnancy when compared to unaffected controls. In this prospective cohort study, pregnant women with stage III-IV endometriosis according to the revised American Fertility Society (r-AFS) classification were matched for body mass index and parity in a 1:2 ratio with unaffected controls. UtA-PIs were assessed at 11-14, 19-22 and 26-34 weeks of gestation following major reference guidelines. A General Linear Model (GLM) was implemented to evaluate the association between endometriosis and UtA-PI Z-scores. Significantly higher third trimester UtA-PI Z-scores were observed in patients with r-AFS stage III-IV endometriosis when compared to controls (p = 0.024). In the GLM, endometriosis (p = 0.026) and maternal age (p = 0.007) were associated with increased third trimester UtA-PI Z-scores, whereas conception by in-vitro fertilization with frozen-thawed embryo transfer significantly decreased UtA-PI measures (p = 0.011). According to these results, r-AFS stage III-IV endometriosis is associated with a clinically measurable impaired late placental perfusion. Closer follow-up may be recommended in pregnant patients affected by moderate-severe endometriosis in order to attempt prediction and prevention of adverse pregnancy and perinatal outcomes due to a defective late placental perfusion.

A Systematic Review of Atypical Endometriosis-Associated Biomarkers.

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

Consistency and Reliability Analyses of a Comprehensive Index for the Evaluation of Teeth Alignment Performance.

(1) Introduction: The purpose of this work was to describe a method and propose a novel accuracy index to assess orthodontic alignment performance. (2) Methods: Fifteen patients who underwent orthodontic treatment using directly printed clear aligners were recruited. The study sample included 12 maxillary and 10 mandibular arches, whose pre-treatment, predicted and post-treatment digital models were superimposed on the untreated posterior teeth by means of a best-fit surface-based registration, which was also used to transfer three anatomical landmarks, digitally labeled on the crown of each anterior moving tooth, from the pre-treatment to the predicted and post-treatment models. The Teeth Alignment Performance (TAP) index, quantifying how close the final landmarks were to their expected final position, was proposed as an accuracy index of both individual tooth and group of teeth movement, and its inter-examiner repeatability was tested. (3) Results: No systematic inter-rater discrepancy associated with TAP was observed (p > 0.05), not even when a slight systematic inter-rater difference in landmark labelling was detected (for the upper central incisors, p < 0.001). In addition, all Intra-class Correlation Coefficient (ICC) values showed excellent inter-rater agreement (>0.95), and the small Random Error of Measurement (REM), ranging from 1% for the arch TAP to 3% for the lower canine TAP, indicated that this accuracy index is highly repeatable. (4) Conclusions: The TAP index was proven to be comprehensive, consistent and reliable in assessing the performance of teeth alignment according to a digital plan. The proposed method is also suitable to be implemented in the clinical digital workflow.

COVID-19 Vaccination Does Not Affect Reproductive Health Parameters in Men.

With the implementation of COVID-19 vaccine up-take, doubts regarding the impact of immunization on future fertility have begun to emerge. We have examined vaccine safety on male reproductive health. We set up a multicentre (three infertility centers), retrospective study in order to assess semen parameters and fertilization rate of one hundred-six men in a pairwise comparison between the first and second assisted reproduction technology (ART) attempt, performed respectively before and after COVID-19 vaccination. Median time (range) between the first vaccine dose and the second ART cycle was 75 days (39-112). Semen parameters did not change before and after the exposure. Fertilization rate was also similar before and after vaccination. Twenty-five patients (24%) were oligozoospermic before the vaccination while 26 (25%) after the exposure (P = 0.87). Severe asthenozoospermia were present in 11 patients before as well as after the exposure. No difference was observed even after considering different types of vaccines (mRNA or viral vector). COVID-19 vaccination did not affect sperm quality and fertilization capacity of men undergoing ART treatments and should be considered safe for men's reproductive health.

Salivary biomarkers of neurodegenerative and demyelinating diseases and biosensors for their detection.

Salivary analysis is gaining increasing interest as a novel and promising field of research for the diagnosis of neurodegenerative and demyelinating diseases related to aging. The collection of saliva offers several advantages, being noninvasive, stress-free, and repeatable. Moreover, the detection of biomarkers directly in saliva could allow an early diagnosis of the disease, leading to timely treatments. The aim of this manuscript is to highlight the most relevant researchers' findings relatively to salivary biomarkers of neurodegenerative and demyelinating diseases, and to describe innovative and advanced biosensing strategies for the detection of salivary biomarkers. This review is focused on five relevant aging-related neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Multiple Sclerosis) and the salivary biomarkers most commonly associated with them. Advanced biosensors enabling molecular diagnostics for the detection of salivary biomarkers are presented, in order to stimulate future research in this direction and pave the way for their clinical application.

Effects of Composite Attachments on Orthodontic Clear Aligners Therapy: A Systematic Review.

This systematic review aims to highlight the differences between different clear aligner therapies that differ in the presence of attachments or in attachment configuration. Eight electronic databases were searched up to March 2020. Two authors independently proceeded to study selection, data extraction, and risk of bias assessment. The analysis of the results was carried out examining six groups of movements (mesio-distal tipping/bodily movement; anterior bucco-lingual tipping/root torque; posterior bucco-lingual tipping/expansion; intrusion; extrusion; rotation). Five clinical trials were selected and all of them showed a medium risk of bias. Literature showed that attachments mostly increase the effectiveness of orthodontic treatment with clear aligners, improving anterior root torque, rotation, and mesio-distal (M-D) movement; they are also important to increase posterior anchorage. However, some articles showed contradictory or not statistically significant results. Attachments also seem to improve intrusion, but the evidence about this movement, as well as extrusion, is lacking. No studies evaluated posterior bucco-lingual tipping/expansion. Further clinical trials are strongly suggested to clarify the influence of attachments and their number, size, shape, and position on each orthodontic movement.

Malignancies and Biosensors: A Focus on Oral Cancer Detection through Salivary Biomarkers.

Oral cancer is among the deadliest types of malignancy due to the late stage at which it is usually diagnosed, leaving the patient with an average five-year survival rate of less than 50%. The booming field of biosensing and point of care diagnostics can, in this regard, play a major role in the early detection of oral cancer. Saliva is gaining interest as an alternative biofluid for non-invasive diagnostics, and many salivary biomarkers of oral cancer have been proposed. While these findings are promising for the application of salivaomics tools in routine practice, studies on larger cohorts are still needed for clinical validation. This review aims to summarize the most recent development in the field of biosensing related to the detection of salivary biomarkers commonly associated with oral cancer. An introduction to oral cancer diagnosis, prognosis and treatment is given to define the clinical problem clearly, then saliva as an alternative biofluid is presented, along with its advantages, disadvantages, and collection procedures. Finally, a brief paragraph on the most promising salivary biomarkers introduces the sensing technologies commonly exploited to detect oral cancer markers in saliva. Hence this review provides a comprehensive overview of both the clinical and technological advantages and challenges associated with oral cancer detection through salivary biomarkers.

In vitro studies evaluating the efficacy of mouth rinses on Sars-Cov-2: A systematic review.

This systematic review aims to evaluate the evidence on the efficacy of mouth rinses on SARS-CoV-2 from in vitro studies. Five electronic databases were searched up to February 2021; no language or time restrictions were used. Two independent reviewers conducted both selection and data extraction processes. The toxicological data reliability assessment tool was used to evaluate the risk of bias. Starting from 239 articles, retrieved by the electronic search, only eight studies were included in our systematic review. Povidone Iodine (PVP-I) was effective in killing SARS-CoV-2, demonstrated higher virucidal activity than other commonly used active ingredients. Conflicting results were found about the effectiveness of Chlorhexidine (CHX) while hydrogen peroxide (H2O2) proved less effective than PVP-I. Other active ingredients, such as quaternary ammonium compounds and Ethanol (particularly when combined with essential oils), have also shown promising results in reducing viral load, with results comparable to PVP-I.

Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review.

The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.

Serological Profile of Children and Young Adults with at Least One SARS-CoV-2 Positive Cohabitant: An Observational Study.

At the end of 2019, a new disease caused by the novel coronavirus SARS-CoV-2 appeared in Wuhan Province in China. Children seemed to be infected less frequently than adults, and family clusters seemed to play an important role in the spread of the pandemic. The aim of this study is to evaluate the serological profile of children and young adults between 4 and 16 years of age in order to assess the transmission patterns of COVID-19 between cohabitants. The subjects lived with at least one cohabitant who tested positive for the disease using a nasopharyngeal swab. To avoid contact with the disease, families were interviewed by telephone. Forty-nine children and adolescents with a mean age of 11 years were then subjected to a rapid lateral flow chromatographic test. Of them, seven (14.3%) were immunoglobulin G (IgG)-positive, and four (8.2%) were immunoglobulin M (IgM)-positive. In total, 16.3% of the tested sample had antibodies against SARS-CoV-2: this may confirm the lower vulnerability of children to COVID-19, despite the small sample size. The time from the negativization of the cohabitant until the test day may have influenced the results, especially when this timeframe is wide.

Maternal Arsenic Exposure and Gestational Diabetes: A Systematic Review and Meta-Analysis.

Gestational diabetes mellitus (GDM) is a metabolic complication associated with adverse outcomes for mother and fetus. Arsenic (As) exposure has been suggested as a possible risk factor for its development. The aim of this meta-analysis was to provide a comprehensive overview of published evidence on the association between As and GDM. The systematic search from PubMed, MEDLINE, and Scopus was limited to full-length manuscripts published in peer-reviewed journals up to April 2020, identifying fifty articles. Ten studies met the inclusion criteria, nine for quantitative synthesis with a total of n = 1984 GDM cases. The overall pooled risk was 1.56 (95% Confidence Interval - CI = 1.23, 1.99) with moderate heterogeneity (χ2 = 21.95; I2% = 64). Several differences among the included studies that may account for heterogeneity were investigated. Stratification for exposure indicator confirmed a positive association for studies assessing urine As. A slightly higher risk was detected pooling studies based in Asia rather than in North America. Stratification for GDM diagnostic criteria showed higher risks when diagnosis was made according to the Canadian Diabetes Association (CDA-SOGC) or World Health Organization (WHO) criteria, whereas a lower risk was observed when adopting the American Diabetes Association (ADA) criteria. These results provide additional evidence for a possible association between As exposure and GDM, although the data need to be interpreted with caution due to heterogeneity.

Assessment of Coagulation Parameters in Women Affected by Endometriosis: Validation Study and Systematic Review of the Literature.

The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to February 2020 including n = 572 women who underwent laparoscopic surgery for endometriosis (cases, n = 324) or other benign gynecologic diseases (controls, n = 248). Inflammatory markers and coagulation parameters were determined. An advanced systematic search of the literature on the same parameters was conducted up to April 2020. A significantly higher neutrophil count was found in endometriosis patients. Patients with endometriomas and stage III-IV disease had a significantly lower absolute lymphocyte count and shortened activated partial thromboplastin time (aPTT) values. In the final regression model, aPTT retained significant predictive value for stage III-IV endometriosis (odds ratio (OR) = 0.002, 95% confidence interval (CI) = 0.00-0.445; p = 0.024). Results from the n = 14 included studies in the systematic review are characterized by a high variability, but some consistency has been found for alterations in thrombin time, platelet-to-lymphocyte ratio, and neutrophil count associated with endometriosis. Modest systemic changes of some inflammatory and coagulation parameters are associated with endometriosis. Indeed, all the modifications detected are still within the normal reference intervals, explaining the high heterogeneity among studies.