Intrafetal Laser Therapy Is a Feasible Treatment for Different Fetal Conditions: A Systematic Review.

INTRODUCTION: Over the past years, intrafetal laser (IFL) therapy has been increasingly used in the management of various prenatal conditions. The aim of our research was to clarify the effectiveness and safety of this technique. METHODS: A systematic review of the literature was carried out using MEDLINE/PubMed over a period of 20 years (2001-2021). RESULTS: A total of forty-one articles were selected in the literature search, including 194 cases of twin reversed arterial perfusion (TRAP) sequence, 56 cases of bronchopulmonary sequestrations (BPSs), 5 cases of placental chorioangiomas (PCA), 11 cases of sacrococcygeal teratoma (SCT), and 103 cases of embryo reduction (ER) managed using IFL. In TRAP sequence, perfusion of the acardiac twin was successfully disrupted in all cases. However, preterm premature rupture of membranes (P-PROMs) occurred in 6 out of 79 pregnancies (7.5%), and preterm birth (PTB) occurred in 36 out of 122 pregnancies (29.5%). In BPS, IFL was successfully performed in all cases with no significant fetal-maternal complications. The rates of P-PROM and PTB were, respectively, 3.2% and 12.5%. All PCA IFL-treated cases resulted in successful pregnancy outcomes; no cases of P-PROM were reported, but the rate of PTB reached a peak of 60% due to complications such as severe fetal growth restriction and fetal Doppler abnormalities. In SCT cases, complete cessation of blood flow was achieved in 4 patients (36.4%); P-PROM occurred in 2 cases (18.2%), whereas the rate of PTB was 87.5%. In ER, no intraoperative or major maternal complications were described in the literature. Rates of miscarriage and PTB differed between initial trichorionic triamniotic and dichorionic triamniotic triplet pregnancies. CONCLUSION: Our analysis suggests that IFL is a safe and feasible technique for the management of different fetal conditions. However, the overall risk of PTB, and its related morbidity and mortality, ranges from 12.5% in BPS to 87.5% in SCT IFL-treated cases. This information could aid in decision-making during prenatal counseling. However, final perinatal outcome depends on the severity of the disease itself.

Use of pentoxifylline during ovarian stimulation to improve oocyte and embryo quality: A retrospective study.

OBJECTIVE: This study aims to investigate if the administration of pentoxifylline during ovarian stimulation have an impact on the quantity and quality of oocytes recovered for in vitro fertilization (IVF), the quality of zygotes and embryos resulting from IVF, the serum estradiol and progesterone concentrations, the endometrial thickness and pregnancy outcomes after embryo transfer. METHODS: Retrospective crossover study including 18 women with recurrent implantation failur, defined as having a history of at least two consecutive cycles of implantation failure and 25-45 years of age at the time of embryo transfer. Pentoxifylline was added during their following IVF attempt aiming to improve endometrial function. Oocyte, zygote and embryo quality, serum estradiol and progesterone concentrations, endometrial thickness and IVF outcomes were compared between the two sequential attempts. RESULTS: Compared to the first attempt, the outcomes of the second attempt, with the addition of pentoxifylline administration, resulted in higher numbers of total and mature oocytes, better oocyte, zygote and embryo quality, higher serum estradiol concentrations, thicker endometrium and better clinical IVF outcomes. CONCLUSIONS: The administration of pentoxifylline during ovarian stimulation seems to improve IVF outcomes, not only by the generating a thicker endometrial lining, but also by producing a higher number of oocytes, with better oocyte, zygote and embryo quality, and higher serum estradiol concentrations.

Lacticaseibacillus rhamnosus CA15 (DSM 33960) strain as a new driver in restoring the normal vaginal microbiota: A randomized, double-blind, placebo-controlled clinical trial.

Probiotics play a key role in maintaining the health of the female reproductive tract, representing a promising alternative to safeguard or restore the homeostasis of the vaginal microbiota. The present randomized double-blind placebo-controlled study was performed to evaluate the ability of the potential probiotic Lacticaseibacillus rhamnosus CA15 (DSM 33960) strain, orally administrated, to balance the vaginal microbiota of women with vaginal dysbiosis. Sixty women, with signs and symptoms of vaginal dysbiosis, were recruited and randomly allocated to receive oral capsules containing the L. rhamnosus CA15 (DSM 33960) strain at 1.0 × 1010 colony-forming units or placebo once daily for 10 days. Clinical and microbiological parameters were evaluated in three scheduled appointments: at baseline (T0), 10 days after the start of the treatment (T1), and 30 days after the end of the treatment (T2). In addition, the quality of life, through the WHO quality of life assessment questionnaire, was assessed at baseline (T0) and 30 days after the end of the treatment (T2). The probiotic was well tolerated and no side effects were reported. The oral consumption of the potential probiotic L. rhamnosus CA15 (DSM 33960) strain determined a significant improvement of both clinical signs and symptoms not only 10 days after the start of the treatment (T1) but also 30 days after the end of the treatment (T2). A significant reduction of potential pathogens and a concomitant increase of lactobacilli was revealed, by microbial count, at both T1 and T2 sampling times. In addition, the enhancement of the perceived physical health, social relations, and environment was reported. Differently, in placebo group clinical and microbiological parameters as well as quality of life remained almost unchanged. The potential probiotic L. rhamnosus CA15 (DSM 33960) strain could be a safe and effective approach to restore and maintain a balanced vaginal microbiota.

Liposomal ferric pyrophosphate and ascorbic acid supplementation in pregnant women with iron deficiency anaemia: haematochemical, obstetric, neonatal and psychological outcomes in a prospective observational study.

This study aimed to determine the effects of liposomal iron pyrophosphate/ascorbic acid on clinical and psychological outcomes in pregnant women. Women at the 11th-13th weeks of gestation with iron deficiency anaemia assuming Sideremil™ from April 2018 to May 2019 were recruited. Haematochemical, obstetric, neonatal and psychological outcomes were investigated at the enrolment, 21-23 weeks of gestation, 30-32 weeks of gestation and after 6 weeks from childbirth. Results showed significant positive effects on haemoglobin, ferritin, sideremia and transferrin levels, compared to baseline data. A significant improvement of anxiety and depression levels was also observed. Regarding the quality of life, all the domains significantly improved, especially the Physical Role domain. Our results indicate that Sideremil™ may be a valid treatment for iron deficiency anaemia in pregnant women, since it significantly improves haematological and mental health outcomes. However, further studies are needed to confirm these results.

The Role of Genital Tract Microbiome in Fertility: A Systematic Review.

The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.

Scoring systems for the evaluation of adnexal masses nature: current knowledge and clinical applications.

Adnexal masses are a common finding in women, with 20% of them developing at least one pelvic mass during their lifetime. There are more than 30 different subtypes of adnexal tumours, with multiple different subcategories, and the correct characterisation of the pelvic masses is of paramount importance to guide the correct management. On that basis, different algorithms and scoring systems have been developed to guide the clinical assessment. The first scoring system implemented into the clinical practice was the Risk of Malignancy Index, which combines ultrasound evaluation, menopausal status, and serum CA-125 levels. Today, current guidelines regarding female patients with adnexal masses include the application of International Ovarian Tumours Analysis simple rules, logistic regression model 1 (LR1) and LR2, OVERA, cancer ovarii non-invasive assessment of treating strategy, and assessment of Different Neoplasias in the adnexa. In this scenario, the choice of the scoring system for the discrimination between benign and malignant ovarian tumours can be complex when approaching patients with adnexal masses. This review aims to summarise the available evidence regarding the different scoring systems to provide a complete overview of the topic.

Diagnostic work-up in paediatric and adolescent patients with adnexal masses: an evidence-based approach.

Adnexal masses are rare in the young female population. The differential diagnosis includes ovarian masses, tubal/paratubal masses, masses related to the gastrointestinal tract (colon), infectious lesions, or pregnancy. Acute abdominal pain, and less commonly, precocious puberty or vaginal bleeding, are typical symptoms in these cases. The majority of adnexal masses in the paediatric and adolescent population are benign; however, a thorough preoperative assessment is essential to guide surgical intervention and optimise patient outcomes. The proper diagnosis of an adnexal mass, correct management (surgical or nonsurgical), and necessary referrals are of paramount importance. In the light of these cornerstones, this review describes the aetiologies, presenting symptoms, and appropriate diagnostic work-up for paediatric and adolescent patients affected by adnexal masses.

Endothelial cell-specific-molecule-1 (endocan) levels in women with premature ovarian insufficiency: a prospective comparative study.

There is an increased risk of cardiovascular disease in women with premature ovarian insufficiency (POI). A relationship between cardiovascular disease and endocan levels has been shown. Endocan is a marker that is prominent in many diseases caused by endothelial dysfunction and can be measured in the blood. POI is also associated with endothelial dysfunction. The causes of POI include chromosomal and genetic defects, autoimmune processes, chemotherapy, radiation, infections and surgery, but many are unidentified (idiopathic). This study aimed to evaluate serum endocan levels in women with idiopathic POI. The blood for analysis was obtained at the early follicular phase of the menstrual cycle and endocan levels were measured using a commercially available enzyme-linked immunosorbent assay kit. There were 38 patients with idiopathic POI in the study group and 39 healthy subjects in the control group. The median ages of the women were not significantly different between the groups 34 [7] years vs. 34 [7] years, respectively (p = .862). The median endocan level was not different in the POI and control group 769 [727] vs. 1077 [403] pg/mL, respectively (p = .603). Endocan is not associated with the cardiovascular diseases risk linked with endothelial dysfunction in idiopathic POI. Clinical trial number: NCT03932877 (Clinicaltrials.gov)IMPACT STATEMENTWhat is already known on this subject? There is an increased risk of cardiovascular disease in premature ovarian insufficiency (POI) due to the decreased level of oestrogen, which is linked with endothelial dysfunction.What do the results of this study add? This study showed that endocan is not associated with the cardiovascular disease risk linked with endothelial dysfunction in idiopathic POI.What are the implications of these findings for clinical practice and/or further research? A marker to be used to predict the risk of cardiovascular disease in patients with POI could facilitate in improving the quality of life of these patients. Moreover, advantageous and easy-to-measure markers are needed in larger sample studies to better understand the cardiovascular diseases risk in POI.

Sexual activity and contraceptive use during social distancing and self-isolation in the COVID-19 pandemic.

OBJECTIVES: The aims of the study were to investigate the effects of social distancing during the COVID-19 pandemic on the use of hormonal contraceptives, their discontinuation and the risk of unplanned pregnancy. METHODS: The study enrolled 317 women listed in the database of the Department of General Surgery and Medical-Surgical Specialties, University of Catania, Italy, family planning clinic who were known to be using hormonal contraceptives. The women were contacted by telephone and asked whether they would like to participate in the study. If they agreed, they were then emailed a questionnaire about their social behaviour and sexual activity during the pandemic, according to their cohabiting status, i.e., whether they were continuing to use their hormonal contraception and whether they had had an unplanned pregnancy. RESULTS: The questionnaire was completed by 175 (81.8%) women who were using short-acting reversible contraception (SARC) and by 90 (87.4%) women who were using long-acting reversible contraception (LARC). All married and cohabiting women were continuing to use their contraceptive method. None had had an unplanned pregnancy. On the other hand, 51 (50.5%) non-cohabiting or single women had discontinued their SARC method while social distancing, for non-method-related reasons; however, 47 (46.5%) non-cohabiting or single women had continued their sexual activity, infringing social distancing rules, and 14.9% had had an unplanned pregnancy, for which they had sought a termination. CONCLUSION: Several non-cohabiting women using SARC had discontinued their contraceptive method during the pandemic but had continued to engage in sexual activity and had had an unplanned pregnancy. Clinicians should counsel women about what they should do in regard to contraception in the event of new, future social distancing measures.

Impact of physician attire on patients' impression of their gynecologist: Results from a large single-center survey analysis.

OBJECTIVE: To assess the impact of physician attire in a gynecology office setting on a patient's level of trust and perception regarding medical advice, performing vaginal exams, and physician's ability to perform major and minor procedures. STUDY DESIGN: Cross sectional anonymous survey at a large academic medical center. The survey was distributed to 200 patients of a single-physician gynecology office, between January 1st 2018 and March 31st 2018. The survey contained an image depicting a hypothetical gynecologist and hypothetical questions regarding clinical situations. Participants were asked to answer which doctor from the image shown they preferred for a given scenario. RESULTS: White coat was reported to be preferred physician attire in almost every clinical situation (p < 0.05). There were only two clinical scenarios, a gynecologic emergency (p < 0.01) and in the setting of major surgery (p < 0.07), in which patients did not have a preference for the gynecologist wearing a white coat. Attire did not have a significant effect on respondent's perception of the gynecologist's knowledge, level of compassion, authority, or ability to communicate. CONCLUSION: The majority of patients preferred a physician wearing a white coat in the presented gynecologic scenarios, with the exception of gynecologic emergencies and gynecologic surgery, in which surgical scrubs were preferred.

Tolerability considerations for gonadotropin-releasing hormone analogues for endometriosis.

INTRODUCTION: The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may cause a not negligible rate of adverse events, in particular vasomotor symptoms and bone mineral density loss, that may limit patients' adherence and safety on long-term treatment. Several strategies have been suggested to improve the compliance to treatment. AREAS COVERED: This narrative review aims to give an overview of the safety and tolerability of GnRH-a therapy and to present the different options of steroidal and non-steroidal add-back therapies in order to reduce the hypoestrogenic side effects. EXPERT OPINION: Side effects of long term GnRH-a treatment are particularly relevant. Although it has been known the efficacy of GnRH-as for treating endometriosis-associated pain, the best schedules of therapy in terms of duration and dosages are still to be defined. The ideal treatment schedule of GnRH-a is still a matter of debate as to the optimal add-back combination.

Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition.

PURPOSE: Gynaecological cancer management in older people represents a current challenge. Therefore, in the present paper, we aimed to gather all the evidence reported in the literature concerning gynecological cancers in the elderly, illustrating the state of art and the future perspectives. METHODS: We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS and Grey literature (Google Scholar; British Library) from January 1952 to May 2017, using the terms "ovarian cancer", "endometrial cancer", "cervical cancer", "gynecological cancers" combined with 'elderly', 'cancer', 'clinical trial' and 'geriatric assessment'. RESULTS: The search identified 81 citations, of which 65 were potentially relevant after initial evaluation and met the criteria for inclusion and were analyzed. We divided all included studies into three different issue: "Endometrial cancer", "Ovarian cancer" and "Cervical cancer". CONCLUSIONS: The present literature review shows that, in spite of the higher burden of comorbidities, elderly patients can also benefit from standard treatment to manage their gynecological cancers. It is important to overcome the common habit of undertreating the elderly patients because they are more fragile and with a lower life expectancy than their younger counterpart. Further trials with elderly women are warranted.

Benign multicystic mesothelioma and peritoneal inclusion cysts: are they the same clinical and histopathological entities? A systematic review to find an evidence-based management.

PURPOSE: Peritoneal mesothelial cysts (PMC) are a clinical dilemma because of their true pathogenic nature. Many definitions have been associated with PMC, including "benign multicystic mesothelioma", "cystic mesothelioma", "multilocular peritoneal inclusion cysts", ''inflammatory cysts of the peritoneum" or "postoperative peritoneal cyst". METHODS: We herein performed a systematic review of the literature focusing on clinical and histopathological aspects of PMC, diagnosis, and therapies. Moreover, we described our experience with a case of PMC in a young female. RESULTS: Since there is often a history of prior surgery or inflammatory disease, most authors consider PMC of reactive origin. However, in some cases they occur without any documentable signs of disease or injury. A variety of clinical findings can complicate the preoperative assessment and a multitude of histological pictures may potentially lead to a misdiagnosis. The absence of a uniform treatment strategy and lack of long-term follow-up often hinder the accurate definition leading to unnecessary or unnecessarily aggressive therapy. CONCLUSIONS: PMC are more common than had previously been thought. Most authors consider them non-neoplastic; thus the designation of "peritoneal inclusion cyst" is preferable. The term "mesothelioma" should be used only in cases of histological evidences of atypia. The high rates of recurrence suggest that the goal of treatment should not be necessarily complete eradication, but symptomatic relief through individualized treatment. This is a topic of particular importance, especially in young female where recurrence rates could be lower than those reported in adults and where an improperly aggressive treatment could have repercussions on fertility.

HPV genotype determination and E6/E7 mRNA detection for management of HPV positive women.

BACKGROUND: Clinical management of HPV positive women is difficult since many of the infections, including high-risk oncogene genotypes (hr-HPV), are transient. Therefore only a limited number of patients have a high-grade lesion and sending all HPV positive women for colposcopy would only increase costs and unnecessary treatment, with serious psychological consequences for patients. The need has emerged to identify other HPV related markers able to correctly detect women with a high-risk of developing high-grade lesions. Genotyping and the search for E6/E7 mRNA are among the possible candidates. METHODS: The study was carried out by means of an observational analysis of the data relative to 674 HR-HPV positive women who we had observed from January 2013 to June 2015; the data had been gathered in a database at the HPV Center of the University Hospital of Catania, Italy. Women were considered eligible for this study if the following data was present in the database: Pap TEST, histologic evaluation, HPV TEST and E6/E7 mRNA detection. We calculated the Odds Ratio (OR) of woman who were mRNA positive, with CIN2+ lesions, and Odds Ratio of HPV16 positive women. RESULTS: Transcripts were detected in 23.6% (69/292) of the women with CIN1 and in 97.2% (210/220) of those with CIN2 + . Regarding genotyping, the 81,8% (180/220) of the women with CIN2+ had genotype 16, while only 18.1% (40/220) had genotype 18, 31, 33, 45. We calculated the OR in the group of HPV16 women with CIN2+ (OR = 4.62; 95% CI = 3.13 to 6.82), this value increased (OR = 106.12; 95% CI = 53.71 to 209.69) in women with CIN2+ and positive mRNA. DISCUSSION: The presence of the HPV16 genotype in our study was associated with a risk 5 times greater of developing a high-grade lesion (CIN2+) (OR = 4.62 95% CI:3.13-6.82); this supports the hypothesis that it would be opportune to have targeted protocols for the management of HPV 16 positive women. The results showed that there was an association between E6/E7 mRNA expression and histology (OR = 106.12; 95% CI = 53.71 to 209.69). The E6/E7 mRNA test showed a higher prevalence of E6 and E7 transcripts in patients with higher-grade lesions. CONCLUSION: The results of this study suggest that the HPV genotype determination and E6/E7 mRNA detection would find an important application for management of HPV positive women.

Pelvic organ prolapse: the impact on quality of life and psychological well-being.

The aim of this work is to propose a brief comment about the impact of pelvic organ prolapse on the quality of life and the psychological well-being of the affected women.

Fertility preservation in women with gynaecologic cancer: the impact on quality of life and psychological well-being.

The aim of this article is to propose a brief commentary about the impact of gynaecologic cancer treatments on the reproductive capacity of affected women and the importance of the fertility preservation treatments to improve quality of life and psychological well-being. The experience of gynaecologic cancer and treatment affects sexual function and psychological well-being of patients. Therefore, the preservation of reproductive potential is central to quality of life. Despite the importance of fertility preservation for cancer survivors' quality of life and psychological well-being, there is still little information about these treatments. We suggest that further studies about the impact on quality of life and psychological outcomes of fertility preservation counselling and fertility preservation treatments should be conducted.

[Differential diagnosis and management of abnormal uterine bleeding in adolescence].

Abnormal uterine bleeding (AUB) is defined as any atypical genital bleeding originating from the uterine cavity, without the characteristics of normal menstrual period. AUB is an important symptom both for adolescents and their parents, and it usually leads to a state of anxiety. Although about 95% of AUB could be considered as a dysfunctional disorder, AUB requires well-defined diagnostic procedures in order to detect a physical cause, ruling out complex or systemic diseases, including oncological ones. Diagnostic procedures require the acquisition of a full and detailed history, and it is also crucial to obtain as much compliance from the patient as possible. A complete gynecological evaluation (whenever possible) and a full physical examination are useful to detect any kind of general disease which can compromise the hormonal reproductive system. Auxiliary tools such as gynecological ultrasonography for pelvic examination are allowed in sexually-active women, otherwise transrectal ultrasonography could be considered, if needed. Hematic ß-hCG must be dosed in every fertile woman with AUB and laboratory tests must be tailored on each patient. The first-line treatment consists of combined oral contraceptives and, when they are contraindicated, progesterone alone, medicated intrauterine devices, GnRH-analogues, or desmopressin are the most common second-line treatments.

Hysteroscopic Morcellation of Submucous Myomas: A Systematic Review.

Hysteroscopic surgery is the actual gold standard treatment for several types of intrauterine pathologies, including submucous myomas (SMs). To date, the availability of Hysteroscopic Tissue Removal systems (HTRs) opened a new scenario. Based on these elements, the aim of this article is to review the available evidence about HTRs for the management of SMs. We included 8 papers (3 prospective studies and 5 retrospective studies). A total of 283 women underwent intrauterine morcellation of SM: 208 were treated using MyoSure and 75 using Truclear 8.0. Only 3 articles reported data about procedures performed in outpatient/office setting. Only half of the included studies included type 2 SMs. HTRs significantly reduced operative time compared to traditional resectoscopy in some studies, whereas others did not find significant differences. Despite the availability of few randomized controlled trials and the cost of the instrument, according to our systematic review, the use of HTRs seems to be a feasible surgical option in terms of operative time and complications. Nevertheless, the type of SM still remains the biggest challenge: type 0 and 1 SMs are easier to manage with respect to type 2, reflecting what already is known for the "classic" hysteroscopic myomectomy.

Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease.

PURPOSE: Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14-q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-ß3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion. CONCLUSION: The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future.