Incidence of pre-neoplastic and neoplastic lesions of the cervix before and after the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic had significant effects on healthcare systems worldwide, including the disruption of routine screening programs for cervical cancer. This study aimed to compare the incidence of cervical intra-epithelial neoplasia (CIN)2 and CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix before and after the COVID-19 pandemic. METHODS: A retrospective analysis was performed using archive data from the Policlinico di Bari, Unit of Gynecology and Obstetrics. The study included patients who tested positive for high-risk human papillomavirus (HPV) at the level I screening test (HPV test) and were subsequently referred to level II screening, which involves the Papanicolaou (Pap) test and colposcopic examination. We excluded individuals who did not comply with the recommended follow-up, patients with low-risk HPV infection, those with autoimmune diseases, oncologic diseases, or those undergoing immunosuppressive therapies. The time period spanned from January 2020 to December 2022. The incidence of CIN2/CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix was compared between the pre-screening period (2017-2019) and the post-screening period (2020-2022). RESULTS: The study comprised a cohort of 1558 consecutive European sexually active women with a median age of 34 years (range 25-65) who underwent colposcopic evaluation of the uterine cervix as a level II screening program. The comparison between the pre-screening and post-screening periods showed an increase in the incidence of CIN2/CIN3 lesions, rising from 23.9 to 63.3 per 100 000 (HR 2.62, 95% CI 1.64 to 4.20; p<0.001). Additionally, although there was an absolute increase in the incidence of cervical carcinoma and adenocarcinoma, the comparison did not reach statistical significance (squamous carcinoma: 2017-2019, 2.5 per 100 000; 2020-2022 3.4 per 100 000, p=0.72; adenocarcinoma: 2017-2019, 3.5 per 100 000; 2020-2022 7.6 per 100 000, p=0.24). CONCLUSION: This study showed a significant increase in the incidence rate of CIN2/CIN3 lesions after the COVID-19 pandemic. Our findings may be attributed to the temporary suspension of follow-up programs during the pandemic, although the study does not rule out direct effects of SARS-CoV-2 on the risk of pre-neoplastic and neoplastic conditions of the cervix.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

Contraception as chemoprevention of ovarian cancer in BRCA1 and BRCA2 women.

Ovarian cancer is the seventh most common cancer in women in the world, with an estimated worldwide mortality of over 207'000 women every year. This cancer, due to the current lack of adequate screening techniques, is commonly diagnosed late and has a poor prognosis. The oral contraceptive pill is considered the most effective prevention strategy for ovarian cancer in the general population, being associated with a decreased incidence while also having a substantial positive impact on the mortality rate, which is reduced by up to 50%. BRCA1 and BRCA2 germline mutated women have an augmented risk of ovary and breast cancer: despite international guidelines that consider prophylactic surgery as the gold standard for ovarian cancer prevention, there are currently no effective non-invasive preventive methods. In BRCA1\2 mutated patients, clinicians should weigh the benefits of contraceptive pills against the risk of long-term thromboembolic side effects and hormonal malignancies such as breast and cervical cancer. A multidisciplinary team should counsel patients on the most appropriate risk-reduction strategy tailored to their needs and expectations, proposing the oral contraceptive pill to selected patients after balancing the risks of adverse effects and the benefits on both contraception and chemoprevention.

Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis: A Systematic Review and Meta-Analysis.

Importance: Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue. Objective: To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation. Data Sources: In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom. Study Selection: Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes. Data Extraction and Synthesis: Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted. Main Outcomes and Measures: The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI. Results: This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97). Conclusions and Relevance: This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis.

Diagnostic, Management, and Neonatal Outcomes of Colorectal Cancer during Pregnancy: Two Case Reports, Systematic Review of Literature and Metanalysis.

OBJECTIVE: Colorectal cancer (CRC) during pregnancy is a rare occurrence, with a reported incidence of 0.8 cases per 100,000 pregnancies. Managing CRC during pregnancy poses substantial challenges for clinicians: the diagnosis is often complicated and delayed due to symptom overlap with pregnancy-related manifestations, and medical imaging is constrained by safety concerns for the foetus. METHODS: This article presents two cases of advanced CRC diagnosed and managed during pregnancy. Additionally, we conducted a systematic review of the literature to assess diagnostic and prognostic factors involved in CRC in pregnant individuals. The systematic review, with pre-registration and approval through Prospero, involved an extensive search of medical databases (Pubmed, Web of Science, Scopus and Scholar) and statistical analysis using t-test for continuous variables and chi square for dichotomous variables. RESULTS: A total of 1058 studies were identified. After applying exclusion criteria, sixty-six studies were included. Women whose initial symptoms were severe abdominal pain not responsive to common medical treatments and constipation (acute abdomen) had a mean gestational age at delivery lower than those who presented with paucisymptomatic onset. In our study groups, women who underwent chemotherapy during pregnancy had a higher mean gestational age at delivery and did not experience worse neonatal outcomes compared to those who did not undergo chemotherapy. CONCLUSIONS: CRC during pregnancy poses unique diagnostic and therapeutic challenges. Collaborative efforts among various medical disciplines are essential to manage CRC during pregnancy.

Dystrophic Epidermolysis Bullosa (DEB): How Can Pregnancy Alter the Course of This Rare Disease? An Updated Literature Review on Obstetrical Management with an Additional Italian Experience.

Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic EB (DEB) represents the most intriguing and challenging in terms of clinical management, especially with regard to pregnancy, due to the highly disabling and life-threatening phenotype. Disappointingly, in the literature little focus has been directed towards pregnancy and childbirth in DEB patients, resulting in a lack of sound evidence and guidance for patients themselves and clinicians. The current study aims to contribute to the DEB literature with an updated summary of the existing evidence regarding the obstetrical and anesthesiological management of this rare disease. Furthermore, this literature review sought to answer the question of whether, and if so, in which way, the pregnancy condition may alter the course of the underlying dermatologic skin disease. Having all this information is indispensable when counseling a patient with DEB who desires a child or is expecting one. Finally, we reported own experience with a pregnant woman with a recessive DEB whom we recently managed, with a favorable outcome.

Artificial Intelligence, Intrapartum Ultrasound and Dystocic Delivery: AIDA (Artificial Intelligence Dystocia Algorithm), a Promising Helping Decision Support System.

The position of the fetal head during engagement and progression in the birth canal is the primary cause of dystocic labor and arrest of progression, often due to malposition and malrotation. The authors performed an investigation on pregnant women in labor, who all underwent vaginal digital examination by obstetricians and midwives as well as intrapartum ultrasonography to collect four "geometric parameters", measured in all the women. All parameters were measured using artificial intelligence and machine learning algorithms, called AIDA (artificial intelligence dystocia algorithm), which incorporates a human-in-the-loop approach, that is, to use AI (artificial intelligence) algorithms that prioritize the physician's decision and explainable artificial intelligence (XAI). The AIDA was structured into five classes. After a number of "geometric parameters" were collected, the data obtained from the AIDA analysis were entered into a red, yellow, or green zone, linked to the analysis of the progress of labor. Using the AIDA analysis, we were able to identify five reference classes for patients in labor, each of which had a certain sort of birth outcome. A 100% cesarean birth prediction was made in two of these five classes. The use of artificial intelligence, through the evaluation of certain obstetric parameters in specific decision-making algorithms, allows physicians to systematically understand how the results of the algorithms can be explained. This approach can be useful in evaluating the progress of labor and predicting the labor outcome, including spontaneous, whether operative VD (vaginal delivery) should be attempted, or if ICD (intrapartum cesarean delivery) is preferable or necessary.

Reproductive and Oncologic Outcomes in Young Women with Stage IA and Grade 2 Endometrial Carcinoma Undergoing Fertility-Sparing Treatment: A Systematic Review.

BACKGROUND: Endometrial cancer (EC) is the most common gynecological malignancy in both Europe and the USA. Approximately 3-5% of cases occur in women of reproductive age. Fertility-sparing treatment (FST) options are available, but very limited evidence regarding grade 2 (G2) ECs exists in the current literature. This systematic review aimed to comprehensively evaluate reproductive and oncologic outcomes among young women diagnosed with stage IA or G2EC disease who underwent FST. METHODS: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies that reported the oncologic and reproductive outcomes of patients with stage IA and G2EC tumors who underwent FST were considered eligible for inclusion in this systematic review (CRD42023484892). Studies describing only the FST for endometrial hyperplasia or G1 EC were excluded. RESULTS: Twenty-two papers that met the abovementioned inclusion criteria were included in the present systematic review. Preliminary analysis suggested encouraging oncologic and reproductive outcomes after FST. CONCLUSIONS: The FST approach may represent a feasible and safe option for women of childbearing age diagnosed with G2EC. Despite these promising findings, cautious interpretation is warranted due to inherent limitations, including heterogeneity in study designs and potential biases. Further research with standardized methodologies and larger sample sizes is imperative for obtaining more robust conclusions.

Tracking Endometrial Malacoplakia Through the Evolution of 2D and 3D Ultrasound and Histopathological Features.

Malacoplakia is an uncommon disease characterized by chronic and granulomatous inflammation, which rarely involves the female genital tract. We describe the ecographic and histological evolution of the first case of a patient developing endometrial malacoplakia as a complication after a cesarean section. The patient, a 43-year-old woman, presented with pelvic pain one month after delivering by cesarean section and the initial suspicion was of retention of placental rests. We discuss the diagnostic challenges for this rare disease, highlighting the importance of considering endometrial malacoplakia as a possible diagnosis in patients with similar clinical presentations and the important role of 2D and 3D ultrasound in the diagnostic pathway. In literature, ultrasound findings in cases of endometrial malacoplakia are represented by hypoechoic thickening of the endometrial lining; hyperechoic thickening of the myometrium, and the presence of masses, nodules, cystic areas, or anechoic fluid within the endometrium. For the first time, we describe the evolution of endometrial malacoplakia through both ultrasound, 2D and 3D, and histopathological findings, from the acute to chronic stage of the disease.

Placental ACE2 Expression: A Possible Pathogenetic Mechanism for Infantile Hemangiomas.

ACE2 is a mono-carboxypeptidase with remarkable vasculo-protective properties, and its expression in the human placenta plays a central role in blood pressure homeostasis and fetal perfusion. Therefore, an alteration in the placental expression of ACE2 could be responsible for reduced placental perfusion and infantile hemangioma (IH) development. Study placentae were collected from patients affected by IHs who were referred to our Dermatology Clinic from 2016 to 2022, while control placentae were randomly collected while matching cases for gestational age. Immunohistochemical investigations were performed with a recombinant anti-ACE2 rabbit monoclonal antibody. A total of 47 placentae were examined, including 20 study placentae and 27 control ones. The mean placental weight was significantly lower in the study group (380.6 g vs. 502.3 g; p = 0.005), while subclinical chorioamnionitis occurred more frequently in the study group (20% vs. 0%, p = 0.03). The mean ACE2 expression was dramatically lower in the study group (χ2 = 42.1 p < 0.001), and the mean placental weight was significantly lower when ACE2 was not expressed compared to the 25-75% and >75% classes of expression (p < 0.05). This study demonstrated that ACE2, as a marker for tissue hypoxia, is dramatically hypo-expressed in placentae belonging to mothers who delivered one or more babies with IH compared to the controls.

Analogies between HPV Behavior in Oral and Vaginal Cavity: Narrative Review on the Current Evidence in the Literature.

Human genital papilloma virus infection is the most prevalent sexually transmitted infection in the world. It is estimated that more than 75% of sexually active women contract this infection in their lifetime. In 80% of young women, there is the clearance of the virus within 18-24 months. In developed countries, oral squamous cell carcinoma (OSCC) is now the most frequent human papilloma virus (HPV)-related cancer, having surpassed cervical cancer, and it is predicted that by 2030 most squamous cell carcinomas will be the HPV-related rather than non-HPV-related form. However, there are currently no screening programs for oral cavity infection. While the natural history of HPV infection in the cervix is well known, in the oropharynx, it is not entirely clear. Furthermore, the prevalence of HPV in the oropharynx is unknown. Published studies have found wide-ranging prevalence estimates of 2.6% to 50%. There are also conflicting results regarding the percentage of women presenting the same type of HPV at two mucosal sites, ranging from 0 to 60%. Additionally, the question arises as to whether oral infection can develop from genital HPV infection, through oral and genital contact or by self-inoculation, or whether it should be considered an independent event. However, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. Therefore, this literature review aims to evaluate whether there is evidence of a connection between oral and cervical HPV, while also endorsing the usefulness of the screening of oral infection in patients with high-risk cervical HPV as a means of facilitating the diagnosis and early management of HPV-related oral lesions. Finally, this review emphasizes the recommendation for the use of the HPV vaccines in primary prevention in the male and female population as the most effective means of successfully counteracting the increasing incidence of OSCC to date.

Oxytocin augmentation and neurotransmitters in prolonged delivery: An experimental appraisal.

The uterus is a highly innervated organ, and during labor, this innervation is at its highest level. Oxytocinergic fibers play an important role in labor and delivery and, in particular, the Lower Uterine Segment, cervix, and fundus are all controlled by motor neurofibers. Oxytocin is a neurohormone that acts on receptors located on the membrane of the smooth cells of the myometrium. During the stages of labor and delivery, its binding causes myofibers to contract, which enables the fundus of the uterus to act as a mediator. The aim of this study was to investigate the presence of oxytocinergic fibers in prolonged and non-prolonged dystocic delivery in a cohort of 90 patients, evaluated during the first and second stages of labor. Myometrial tissue samples were collected and evaluated by electron microscopy, in order to quantify differences in neurofibers concentrations between the investigated and control cohorts of patients. The authors of this experiment showed that the concentration of oxytocinergic fibers differs between non-prolonged and prolonged dystocic delivery. In particular, in prolonged dystocic delivery, compared to non-prolonged dystocic delivery, there is a lower amount of oxytocin fiber. The increase in oxytocin appeared to be ineffective in patients who experienced prolonged dystocic delivery, since the dystocic labor ended as a result of the altered presence of oxytocinergic fibers detected in this group of patients.

Endometrial Cancer: A Pilot Study of the Tissue Microbiota.

BACKGROUND: The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer. METHODS: Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure. RESULTS: ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues. CONCLUSIONS: These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.

Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review.

Objective: To evaluate the reproductive outcomes of patients bearing BRCA-1 and BRCA-2 mutations. Methods: In this retrospective observational cohort study, we assessed data from BRCA-1 and BRCA-2 carriers, analyzing demographics, oncological history, and reproductive outcomes. Statistical analysis compared BRCA-1 and BRCA-2 carriers. A thorough review of the literature was carried out. Results: Fifty-eight patients were included. BRCA-1 and BRCA-2 mutations were equally distributed. Eighty-nine pregnancies occurred in our series, hesitated in 73 live births and 19 miscarriages. Mean age at first and last pregnancy was 27.8 ± 4.8 and 31.6 ± 4.8 years old. Thirty-nine patients have had at least one live birth (67.2%). Mean number of live births was 1.9 ± 0.6. Live birth rate (LBR) was 81.1% and miscarriage rate was 32.8%. Spontaneous fertility was unaltered, as evidenced by high LBR. Subgroup analysis revealed no significant differences between BRCA-1 and BRCA-2 carriers. Conclusions: Our results shows that spontaneous reproductive outcomes in BRCA-mutated patients are reassuring. Despite evidence indicating a decrease in ovarian reserve among BRCA patients, this factor seems to not impact spontaneous fertility negatively. Further research is needed, and individuals with BRCA mutations should consider early family planning and fertility preservation in case of partner absence.

Increased Vasoactive Intestinal Peptide (VIP) in polycystic ovary syndrome patients undergoing IVF.

Introduction: Polycystic ovary syndrome (PCOS) is a common multifactorial and polygenic disorder of the endocrine system, affecting up to 20% of women in reproductive age with a still unknown etiology. Follicular fluid (FF) represents an environment for the normal development of follicles rich in metabolites, hormones and neurotransmitters, but in some instances of PCOS the composition can be different. Vasoactive intestinal peptide (VIP) is an endogenous autonomic neuropeptide involved in follicular atresia, granulosa cell physiology and steroidogenesis. Methods: ELISA assays were performed to measure VIP and estradiol levels in human follicular fluids, while AMH, FSH, LH, estradiol and progesterone in the plasma were quantified by chemiluminescence. UHPLC/QTOF was used to perform the untargeted metabolomic analysis. Results: Our ELISA and metabolomic results show: i) an increased concentration of VIP in follicular fluid of PCOS patients (n=9) of about 30% with respect to control group (n=10) (132 ± 28 pg/ml versus 103 ± 26 pg/ml, p=0,03) in women undergoing in vitro fertilization (IVF), ii) a linear positive correlation (p=0.05, r=0.45) between VIP concentration and serum Anti-Müllerian Hormone (AMH) concentration and iii) a linear negative correlation between VIP and noradrenaline metabolism. No correlation between VIP and estradiol (E2) concentration in follicular fluid was found. A negative correlation was found between VIP and noradrenaline metabolite 3,4-dihydroxyphenylglycolaldehyde (DOPGAL) in follicular fluids. Conclusion: VIP concentration in follicular fluids was increased in PCOS patients and a correlation was found with noradrenaline metabolism indicating a possible dysregulation of the sympathetic reflex in the ovarian follicles. The functional role of VIP as noradrenergic modulator in ovarian physiology and PCOS pathophysiology was discussed.