Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: A multicentric Italian study.

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high-grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin-fixed paraffin-embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2 and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2 and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2 and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2 and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine-valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia.

Vaginal metastasis of lung cancer: A case report.

Lung adenosquamous carcinoma (ASC) is a rare biphasic malignant tumor with squamous cell carcinoma (SCC) and adenocarcinoma (AC) components. ASC is reported to be aggressive; the most common metastatic sites are the regional lymph nodes and surrounding areas. A 46-year-old woman was referred to the emergency department with a persistent dry cough. She underwent fibro-bronchoscopy and was diagnosed with an adenosquamous lung carcinoma. Other than pulmonary and lymphatic findings, a total-body computed tomography (CT) examination highlighted a hypodense formation, of about 9 mm, with a cystic appearance, at the level of the vaginal region. A biopsy performed in the posterior vaginal wall highlighted a vaginal wall flap with subepithelial localization of neoplasia, compatible with the pulmonary ASC. Oncologists took charge of the case and the patient commenced medical therapy with entrectinib. Four months later, she developed dyspnea, and high-resolution CT highlighted an increase in the pathological tissue causing bronchial occlusion. The patient underwent endobronchial stent placement and thereafter restarted therapy with entrectinib, previously stopped because of the new symptoms, and was closely monitored. Apparently only one case of vaginal metastasis from pulmonary tumor has been previously reported, and this is the first report of vaginal metastasis from ASC. Although extremely rare, the presence of such metastasis should be considered in women with suspected vaginal neoformations.

A twin pregnancy with partial hydatidiform mole and a coexisting normal fetus delivered at term: A case report and literature review.

Hydatiform mole occurs in 1/1000 singleton and 1/20000-100,000 twin pregnancies. Although the pregnancy often ends in a miscarriage or presents with many obstetric complications such as preeclampsia, vaginal bleeding, hyperthyroidism, prematurity, or fetal malformations, in some cases of twin pregnancy, one of the fetuses can develop normally. Coexistence of a viable fetus in a twin molar pregnancy is more commonly described for cases of complete hydatiform moles than partial hydatiform moles. A partial hydatiform mole coexisting with a normal fetus was suspected in a 40-year-old woman, G2P1, at twelve weeks of gestation of a twin dichorionic diamniotic pregnancy. Serial antenatal ultrasound scans and serial evaluations of human chorionic gonadotropin were performed, and a healthy baby was delivered at term without any obstetric or neonatal complications. A twin pregnancy with partial hydatidiform mole and a coexisting normal fetus is a rare obstetric condition that can result, under proper management, in the delivery of a healthy baby without any sequelae for the mother or child.

Hysteroscopy in the new media: quality and reliability analysis of hysteroscopy procedures on YouTube™.

BACKGROUND: Hysteroscopy plays a crucial role in diagnosing and managing various intrauterine pathologies. However, its execution can be influenced by patients' perception and understanding, which are often shaped by digital resources such as YouTubeTM. Given its popularity and accessibility, YouTubeTM has the potential to greatly influence patients' knowledge and expectations about this procedure, highlighting the need for accurate and reliable information. PURPOSE: This study aims to assess the reliability and quality of hysteroscopy information available to patients on YouTubeTM. Understanding the nature of information patients' access can help address their fears and potential misunderstandings about the procedure, consequently reducing the likelihood of suspension or postponement due to anxiety. METHODS: A comprehensive analysis of YouTubeTM was conducted, simulating the search process of a patient seeking information about hysteroscopy. The study evaluated the reliability and quality of 90 out of the first 100 hysteroscopy-related videos on YouTubeTM, scored by four gynecologists-two experienced hysteroscopists and two trainees. The videos were assessed for reliability and quality using the mDISCERN and Global Quality Scale (GQS) scores. RESULTS: The average mDISCERN and GQS scores for the evaluated videos were below the optimal three points, highlighting the lack of fluency, comprehensiveness, and reliability of the available information. Notably, while videos produced by experts, including doctors and professional channels, had higher scores, they still fell short of the minimum score of 3. These videos also were not considered more suitable for either patients or trainees. Videos that were assessed as reliable (mDISCERN ≥ 3) were observed to be longer and were more frequently produced by doctors. These videos were suggested more to trainees rather than patients. Similarly, videos deemed as fluent and comprehensive (GQS ≥ 3) were longer and were more often recommended to patients. CONCLUSIONS: While YouTubeTM is a widely used source of medical information, the quality and reliability of hysteroscopy videos on the platform are poor. The strategic use of selected, high-quality hysteroscopy videos can enhance procedure success and alleviate patient fears. However, the unsupervised discovery of information by patients could potentially lead to procedure failure or an elevated level of stress due to misleading or incorrect information.

What's new on female genital mutilation/cutting? Recent findings about urogynecologic complications, psychological issues, and obstetric outcomes.

Female genital mutilation/cutting (FGM/C or FGM) are injuries to the female genital organs for non-medical reasons. Every year, over 4 million girls are at risk of FGM. Complications of this practice are very common and some of them are still under investigation. The purpose of this short narrative review is to highlight and summarize the main ones. Psychologic and psychiatric sequelae, chronic vulvar pain, urogenital symptoms, pelvic organs prolapse, sexual disfunction, cervical dysplasia and infections resulted as chronic sequalae of FGM. Severe pain, excessive bleeding, and tissues swelling are acute consequences of FGM. Rates of caesarean section, time of second stage of delivery, post-partum blood loss (but not major hemorrhage), peri-clitoral and perineal injuries and episiotomy rates are higher in pregnant women with FGM, when compared with those non victims of mutilation. The female genital mutilation practice is often cause of severe urogynecologic, psychologic and obstetrics sequelae. Although several studies have been carried out on FMG complications and treatments, long term sequelae are still very common and deserve major attention and further research.

Aggressive Pelvic Angiomyxoma in a Patient with Twin Pregnancy: Diagnosis, Treatment, and Clinical Complications in Light of the Literature.

(1) Background: Aggressive angiomyxoma is a mesenchymal cancer that is rare during pregnancy. It is a neoplasm that relapses and infiltrates the nearest structures. Our aim is to evaluate the management and outcomes of an observed case, in light of the current literature. (2) Methods: We observed this condition at the "Maggiore della Carità" Hospital in Novara (Italy) in a patient with an initial twin pregnancy and a suspected pelvic mass. The words "angiomyxoma" and "pregnancy" were searched on the main online scientific search sources (PubMed, Google Scholar, Scopus, WES, and Embase, etc.). (3) Results: The patient underwent surgery with a complicated follow-up, but recent negative controls. We analyzed the literature about the topic and found only 24 similar clinical cases. (4) Conclusions: Considering the current literature, it is useful to assess an aggressive angiomyxoma in the differential diagnosis of soft masses in pregnant women. The treatment of choice is surgical excision, and vaginal delivery is feasible. The therapeutic decision depends on each case.

Contraception in cancer survivors: insights from oncofertility follow-up visits.

OBJECTIVE: Current literature suggests that cancer survivors are less likely to receive adequate contraception counseling. However, limited data existed on barriers to contraception usage in this population and on the efficacy of dedicated consultations. This study aims to describe how contraception is perceived by cancer survivors after counseling and acceptance rates of highly effective contraceptives. METHODS: We retrospectively analyzed clinical records from 313 consecutive cancer survivors at their first follow-up visit at the Oncofertility Unit of a tertiary hospital, from 2014 to 2019. Contraception acceptance and choice were examined stratified for the type of malignancy (hormone-sensible or not). A multivariate logistic regression model was used to evaluate possible predictors of acceptance. RESULTS: Thity-three women were excluded from the analysis because trying to conceive or already pregnant. Out of the remaining 280, only 9 (3.2%) asked spontaneously for contraception, in all the other visits the issue was brought up by the physician. After counseling 44.3% of the women without contraindications still opted out effective methods for fear of hormones or refusal of more medications. Age < 33 years and being in a relationship were correlated with acceptance. CONCLUSIONS: Even after a complete counseling in a dedicated service, fears of hormones and refusal of more medications remain strong issues for these patients. Family planning needs to be discussed with cancer survivors, preferably in the context of a long-term healthcare relationship. The Oncofertility Unit should become a privileged place for this type of counseling.

Steroids receptors immunohistochemical expression in different sites of endometriosis.

BACKGROUND: A better characterization of steroid intracrine pathways in endometriosis lesions may lead to a better understanding of the pathogenesis of the disease and insights on the mechanism of resistance to medical therapy. The study aims to evaluate the expression of steroid receptors in endometriosis lesions, including for the first-time androgen receptors, both in glandular and stromal tissue, and to describe the differences, in any, in receptor expression in the different subtypes. BASIC PROCEDURES: This is a retrospective analysis of 76 specimens from 51 women, that underwent laparoscopic surgery for endometriosis at a tertiary hospital between 2015 and 2019. Immunohistochemical detections of estrogen, progesterone and androgen receptors positive cells was performed and the results described in terms of both density and intensity. The density and intensity scores were combined to obtain a final Histological Score (HS). Non-parametric Kruskal-Wallis test or Mann-Whitney U-test were used to compare continuous data, chi square test for categorical data. MAIN FINDINGS: Estrogen receptor α expression was moderate/high in almost all specimens, regardless of the site. Samples from endometriomas presented lower progesterone receptor expression in the epithelium, compared to pelvic sites. Androgen receptor density was higher in stromal cells compared to epithelial cells and in pelvic sites compared to ovarian ones. CONCLUSIONS: The roles of nuclear receptors in endometriosis, including differences in their expression, could help in defining the pathogenesis of the disease and in explaining different responsivity to therapies. The intracrine regulation of steroids plays a relevant role in the metabolic and inflammatory pathogenetic paths of endometriosis: if better understood, its manipulation could be a relevant therapeutic target for treatment.

Influence of age on response to controlled ovarian stimulation in women with low levels of serum anti-Müllerian hormone.

This study aims at detecting and evaluating differences in quantitative response to controlled ovarian stimulation (COS) with high doses of gonadotropins in women with low serum anti-Müllerian hormone (AMH). About 369 first cycles in a real-life scenario in women between 21 and 43 years old and with AMH ≤0.9 ng/ml were analyzed. Older women had a significantly worse outcome with respect to young women, not only qualitatively, but also in terms of quantitative ovarian response to COS [odd ratio (OR) to obtain at least three MII oocytes with each increasing year of female age: 0.89, 95% CI: 0.85 - 0.94; p < .001]. This study endorses that age is a significant factor when counseling patients with low AMH. AMH levels per se are not a reason to exclude patients from a COS treatment, since pregnancy and live birth can be achieved, especially in younger patients. However, with an AMH equally low, the ovarian response worsens with age, making questionable the effectiveness of a stimulation with high-dose gonadotropins in the older subgroup.

Beyond fertility preservation: role of the oncofertility unit in the reproductive and gynecological follow-up of young cancer patients.

STUDY QUESTION: Are there reasons that motivate young cancer survivors to ask for follow-up visits at an oncofertility unit? SUMMARY ANSWER: Cancer survivors request oncofertility follow-up visits for the management of treatment-related side effects or ovarian reserve evaluation, even if not (or not yet) wishing for a pregnancy. WHAT IS KNOWN ALREADY: Personalised oncofertility counselling before gonadotoxic therapies is considered standard of care for young women with newly diagnosed cancer. However, the long-term follow-up of these patients in an oncofertility unit is not described in the literature other than for the use of cryopreserved material. STUDY DESIGN, SIZE, DURATION: We retrospectively examined rates and reasons for the first follow-up visits of 154 consecutive young female cancer patients (age range: 18-40 years) who underwent a pre-treatment consultation between January 2012 and June 2017. Demographic and clinical data were collected, as well as information about the chosen fertility preservation method, if any. PARTICIPANTS/MATERIALS, SETTING, METHODS: Rates and reasons for follow-up visits were collected and expressed as percentages. Different reasons were examined in the whole cohort and stratified for type of malignancy. Possible predictive factors for return to the follow-up visit (age, nulliparity, presence of a partner, neoplasm, having cryopreserved material) were investigated through logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 154 patients, 74 returned to the oncofertility unit (48.1%) for a follow-up visit. The first visit was requested mostly at the end of anticancer therapies (51.3% versus 40.5% during therapies and 8.1% after cancer relapse). Among these patients, only 10.8% returned for the first time because they were actively desiring a pregnancy. For the others, the most common reasons for consultations were management of gynecological adverse effects of therapies (29.7%) and evaluation of ovarian reserve not linked to an immediate desire for a pregnancy (39.2%). Other patients asked for contraception (4.1%), menopause counselling (5.4%), or new fertility preservation counselling because of cancer relapse (10.8%). None of the examined factors were significantly predictive of return to the oncofertility unit. LIMITATIONS, REASONS FOR CAUTION: These findings represent the experience of a single centre. A longer duration of follow-up would be needed to provide more precise information on this regard. WIDER IMPLICATION OF THE FINDINGS: The role of an oncofertility unit should not be limited to proposing fertility preservation procedures. In the management of young adult cancer patients, the reproductive medical specialist should be considered a key figure not only before but also during and after anticancer treatments to explore salient aspects of gynecological and reproductive health. STUDY FUNDING/COMPETING INTEREST(S): This research did not receive any specific funding. M.L. served as a consultant for Teva and received honoraria from Theramex outside the submitted work. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N.A.

Giant Hepatic Hemangioma and Placental Chorangiosis: A Unique Case of Stillbirth?

INTRODUCTION: Hepatic hemangiomas (HH) are benign vascular tumors, and when large, may contribute to fetal morbidity/mortality. Chorangiosis is placental villus capillary hypervascularity, probably linked with fetal hypoxia. CASE REPORT: We present a macrosomic stillbirth at 39 + 3 weeks of gestation with congestive heart failure (CHF) and myocardial infarction. A giant right hepatic lobe HH was present, along with placental chorangiosis. CONCLUSION: A common pathogenetic pathway between congenital HH and placental chorangiosis has not been reported. Our case suggests that the effects of HH and chorangiosis increase the risk of late fetal loss due to the high-output CHF.

State of the art on oocyte cryopreservation in female cancer patients: A critical review of the literature.

During the last decades, important advances in therapeutic options have led to increased survival rates in cancer patients; however, cancer treatments are associated with several potential adverse effects including infertility in those diagnosed during their reproductive years. A proper discussion about fertility preservation options before the use of therapies with potential gonadotoxicity (i.e. oncofertility counseling) is standard of care and should be offered to all patients of childbearing age. Temporary ovarian suppression with LH-RH analogs, oocyte and embryo cryopreservation are standard strategies for fertility preservation in female cancer patients. Oocyte cryopreservation should be preferred to embryo cryopreservation when this latter is prohibited by law, avoided for ethical or religious issues and in single women refusing sperm donation. Despite the increasing use of this strategy, data are still lacking about the efficacy and safety of the procedure in female cancer patients, with most of the evidence on this regard deriving from infertile non-oncologic women. This article aims at critically review the available evidence about the success of oocyte cryopreservation in female cancer patients with the final goal to further improve the oncofertility counseling of these women.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study.

OBJECTIVE: To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. STUDY DESIGN: Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas. RESULTS: All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p<.005). CONCLUSIONS: Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas.

Intraoperative Transrectal Ultrasonography for Hysteroscopic Metroplasty: Feasibility and Safety.

The primary objective of this prospective comparative nonrandomized study was to assess the feasibility and safety of intraoperative transrectal ultrasonography (TRUS) during hysteroscopic metroplasty (HM). The secondary objective of the study was to assess whether TRUS facilitates complete removal of the uterine septum. Septate uterus was diagnosed by 3-dimensional transvaginal ultrasonography (3D-TVS) and confirmed by magnetic resonance imaging. In the control group (HM group; n = 18), patients underwent HM according to the traditional standard of operative hysteroscopy. In the study group (HM+TRUS group; n = 27), HM and TRUS were performed simultaneously; the hysteroscopic procedure was continued until a normal uterine fundus was observed. At 6 to 8 weeks after HM, 3D-TVS was performed to identify the numbers of complete resections (residual septum absent or <5 mm), suboptimal resections (residual septum 5-10 mm), and incomplete resections (residual septum > 10 mm). The 2 study groups did not differ significantly in terms of demographic and clinical characteristics, or in the volume of fluid infused and absorbed. There were no severe intraoperative or postoperative complication in either group; 2 patients in the HM+TRUS group and 1 patient in the HM group experienced urinary tract infection (p = .807). At 6 to 8 weeks after HM, the number of suboptimal resections and incomplete resections was higher in the HM group than in the HM+TRUS group (p = .031). Residual septum >10 mm (incomplete resection) was seen in 1 patient in the HM group but in no patients in the HM+TRUS group. Intraoperative TRUS can be performed safely during HM, and may increase the likelihood of complete resection of the uterine septum; however, this finding should be confirmed by larger studies.

How to Manage Bowel Endometriosis: The ETIC Approach.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 35-year-old patient desiring pregnancy with a history of previous surgery for endometrioma and bowel obstruction symptoms. Many questions that this paradigmatic patient may pose to the clinician are addressed, and various clinical scenarios are discussed. A decision algorithm derived from this discussion is proposed as well.

Second surgery for recurrent unilateral endometriomas and impact on ovarian reserve: a case-control study.

OBJECTIVE: To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas. DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): This study included patients who underwent stripping of endometriomas (diameter ≥4 cm) and were followed-up at our institution. Case subjects had second surgery for recurrent unilateral endometriomas (n = 18); control subjects had no recurrence and no second surgery (n = 18). INTERVENTION(S): This case-control study was based on a retrospective analysis of a prospectively collected database including patients who underwent surgery for endometriomas at our institution. MAIN OUTCOME MEASURE(S): The primary outcome of the study was to assess the changes in antimüllerian hormone (AMH) levels in each study group and between the two study groups. The secondary outcomes of the study were to assess the changes in basal FSH, antral follicle count (AFC), and ovarian volume in each study group and between the two study groups. RESULT(S): In both study groups, primary surgery decreased AMH, increased basal FSH, and decreased the AFC of the operated ovary. Before second surgery, case subjects had AMH, basal FSH, and AFC similar to control subjects. After second surgery, case subjects had lower AMH, higher basal FSH, and lower AFC of the affected ovary than before surgery; the volume of the operated ovary was lower than that of the contralateral ovary. CONCLUSION(S): The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure. CLINICAL TRIAL REGISTRATION NUMBER: NCT02047838.