A blood-based multi-biomarker approach reveals different physiological responses of common kestrels to contrasting environments.

The increase of urbanization and agricultural activities is causing a dramatic reduction of natural environments. As a consequence, animals need to physiologically adjust to these novel environments, in order to exploit them for foraging and breeding. The aim of this work was to compare the physiological status among nestling common kestrels (Falco tinnunculus) that were raised in nest-boxes located in more natural, rural, or urban areas in a landscape with a mosaic of land uses around Rome in Central Italy. A blood-based multi-biomarker approach was applied to evaluate physiological responses at multiple levels, including antioxidant concentrations, immunological functions, genotoxicity, and neurotoxicity. We found lower concentrations of glutathione and GSH:GSSG ratio values and higher proportions of monocytes in urban birds compared to the other areas. We also found higher DNA damage in rural compared to urban and natural krestels and inhibition of butyrylcholinesterase activity in urban and natural birds compared to rural area. Finally, we found similar values among study areas for respiratory burst, complement system, bactericidal capacity, and plasma non-enzymatic antioxidant capacity. These results suggest that (i) city life does not necessarily cause physiological alterations in kestrels compared to life in other habitats, and (ii) environmental pressures are likely to differ in typology and intensity across habitats requiring specific responses that a multi-biomarker approach can help to detect. Further studies are needed to assess which factors are responsible for the physiological differences among city, rural, and natural birds, and whether these differences are consistent across time and space.

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.

Efficacy and safety of therapies for COVID-19 in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Clinical evidence suggests that pregnant women are more vulnerable to COVID-19, since they are at increased risk for disease progression and for obstetric complications, such as premature labor, miscarriage, preeclampsia, cesarean delivery, fetal growth restriction and perinatal death. Despite this evidence, pregnant women are often excluded from clinical trials, resulting in limited knowledge on COVID-19 management. The aim of this systematic review and meta-analysis is to provide better evidence on the efficacy and safety of available COVID-19 treatment in pregnant women. METHODS: Four authors searched major electronic databases from inception until 1 st November-2022 for controlled trials/observational studies, investigating outcomes after the administration of anti-SARS-CoV-2 treatments in pregnant women affected by COVID-19. The analyses investigated the cumulative incidence of delivery and maternal outcomes in pregnant women, comparing those taking active medication vs standard care. Risk ratios (RRs) with 95% confidence intervals were calculated. Statistical significance was assessed using the random effects model and inverse-variance method. This systematic review and meta-analysis was conducted in accordance with the updated 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol has been registered in Prospero (number registration: CRD42023397445). RESULTS: From initially 937 non duplicate records, we assessed the full texts of 40 articles, finally including ten studies. In six studies, including 1627 patients, the use of casirivimab/imdevimab (CAS/IMD), remdesivir, and IFN-alpha 2b significantly decreased the need of cesarean section ((RR = 0.665; 95%CI: 0.491-0.899; p = 0.008; I 2 = 19.5%;) (Table 1, (Fig. 1). Treatments did not decrease the risk of preterm delivery, admission to neonatal ICU, or stillbirth/perinatal loss (p-values > 0.50 for all these outcomes) and did not prevent the progression of disease towards severe degrees (k = 8; 2,374 pregnant women; RR = 0.778; 95%CI: 0.550-1.099; p = 0.15; I 2 = 0%). Moreover, the use of medications during pregnancy did not modify the incidence of maternal death in two studies (Table 2). CONCLUSIONS: To our analysis, CAS/IMD, remdesivir, and IFN alpha 2b reduced the number of cesarean sections but demonstrated no effect on disease progression and other obstetric and COVID-19 related outcomes. The inability to evaluate the influence of viral load on illness development in pregnant women was attributed to lack of data. In our systematic review, no major side effects were reported. Though, it is essential for the medical community to focus more on clinical trials and less on episodic case reports and case series, with standardization of fetal and maternal outcomes.

Patients' Use of Virtual Reality Technology for Pain Reduction during Outpatient Hysteroscopy: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize evidence from randomized controlled trials (RCTs) on the effectiveness of virtual reality technology (VRT), as used by patients, for reducing pain during outpatient hysteroscopy. DATA SOURCES: Electronic databases and clinical registers were searched until June 21, 2023. The review protocol was registered in PROSPERO before the data extraction (CRD42023434340). METHODS OF STUDY SELECTION: We included RCTs of patients receiving VRT compared with controls receiving routine care during outpatient hysteroscopy. TABULATION, INTEGRATION, AND RESULTS: The primary outcome was average pain during hysteroscopy. Pooled results were expressed as mean differences (MDs) with 95% confidence interval (CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. Five RCTs were included (435 participants). The comparison between the intervention and control groups showed a borderline difference in perceived pain during hysteroscopy (MD -0.88, 95% CI -1.77 to 0.01). Subgroup analysis based on the type of VRT (active or passive) indicated that active VRT potentially reduced the perception of pain (MD -1.42, 95% CI -2.21 to -0.62), whereas passive VRT had no effect (MD -0.06, 95% CI -1.15 to 1.03). CONCLUSION: Patients' use of active VRT may be associated with a reduction in pain during outpatient hysteroscopy (evidence Grading of Recommendations Assessment, Development, and Evaluation 2/4). Future research should focus on conducting methodologically robust studies with larger sample sizes and more homogeneous populations.

Pregnancy by Oocyte Donation: Reviewing Fetal-Maternal Risks and Complications.

Oocyte donation (OD) has greatly improved over the last three decades, becoming a preferred practice of assisted reproductive technology (ART) for infertile women wishing for motherhood. Through OD, indeed, it has become possible to overcome the physiological limitation due to the ovarian reserve (OR) exhaustion as well as the poor gamete reliability which parallels the increasing age of women. However, despite the great scientific contribution related to the success of OD in the field of infertility, this practice seems to be associated with a higher rate of major risky events during pregnancy as recurrent miscarriage, infections and placental diseases including gestational hypertension, pre-eclampsia and post-partum hemorrhage, as well as several maternal-fetal complications due to gametes manipulation and immune system interaction. Here, we will revisit this questioned topic since a number of studies in the medical literature focus on the successful aspects of the OD procedure in terms of pregnancy rate without, however, neglecting the risks and complications potentially linked to external manipulation or heterologous implantation.

Prolonged Dystocic Labor in Neuraxial Analgesia and the Role of Enkephalin Neurotransmitters: An Experimental Study.

The investigation studied the enkephalinergic neuro fibers (En) contained in the Lower Uterine Segment (LUS) during the prolonged dystocic labor (PDL) with Labor Neuraxial Analgesia (LNA). PDL is generally caused by fetal head malpositions in the Occiput Posterior Position (OPP), Persistent Occiput Posterior Position (POPP), in a transverse position (OTP), and asynclitism (A), and it is detected by Intrapartum Ultrasonography (IU). The En were detected in the LUS samples picked up during cesarean section (CS) of 38 patients undergoing urgent CS in PDL, compared to 37 patients submitted to elective CS. Results were statistically evaluated to understand the differences in En morphological analysis by scanning electron microscopy (SEM) and by fluorescence microscopy (FM). The LUS samples analysis showed an important reduction in En in LUS of CS for the PDL group, in comparison with the elective CS group. The LUS overdistension, by fetal head malpositions (OPP, OTP, A) and malrotations, lead to dystocia, modification of vascularization, and En reduction. The En reduction in PDL suggests that drugs used during the LNA, usually local anesthetics and opioids, cannot control the "dystocic pain", that differs from normal labor pain. The IU administration in labor and the consequent diagnosis of dystocia suggest stopping the numerous and ineffective top-up drug administration during LNA, and to shift the labor to operative vaginal delivery or CS.

The Role of Hormonal Replacement Therapy in BRCA Mutated Patients: Lights and Shadows.

All cancers develop as a result of mutations in genes. DNA damage induces genomic instability and subsequently increases susceptibility to tumorigenesis. Women who carry mutations of BRCA 1 and BRCA2 genes have an augmented risk of breast and ovarian cancer and a markedly augmented probability of dying because of cancer compared to the general population. As a result, international guidelines recommend that all BRCA1\2 mutation carriers be offered risk-reducing bilateral salpingo-oophorectomy at an early age to reduce the risk of cancer and decrease the mortality rate of this high-risk population. NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy in pre-menopausal women, between 35-40 years in BRCA1 mutation carriers and between 40-45 years in BRCA2 mutation carriers. Unfortunately, the well-documented reduction of cancer risk is counterbalanced by early sterility and premature ovarian failure with an early onset of secondary menopausal syndromes such as neuromotor, cardiovascular, cognitive and urogenital deficiency. Hormonal replacement therapy significantly compensates for hormonal deprivation and counteracts menopausal syndrome morbidity and mortality; however, some data suggest a possible correlation between hormonal medications and cancer risk, especially in BRCA1\2 carriers who undergo long-term regimens. Conversely, short-term treatment before the age of natural menopause does not appear to increase the cancer risk in BRCA1 mutation carriers without a personal history of breast cancer after prophylactic surgery. Few data are available on BRCA2 mutation carriers and more well-designed studies are needed. In conclusion, clinicians should propose short-term hormone replacement therapy to BRCA 1 carriers to counteract hormonal deprivation; personalized counselling should be offered to BRCA2 mutation carriers for a balance between the risks and benefits of the treatment.

Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation?

One emerging problem for onco-gynecologists is the incidence of premenopausal patients under 40 years of age diagnosed with stage I Endometrial Cancer (EC) who want to preserve their fertility. Our review aims to define a primary risk assessment that can help fertility experts and onco-gynecologists tailor personalized treatment and fertility-preserving strategies for fertile patients wishing to have children. We confirm that risk factors such as myometrial invasion and The International Federation of Gynecology and Obstetrics (FIGO) staging should be integrated into the novel molecular classification provided by The Cancer Genome Atlas (TCGA). We also corroborate the influence of classical risk factors such as obesity, Polycystic ovarian syndrome (PCOS), and diabetes mellitus to assess fertility outcomes. The fertility preservation options are inadequately discussed with women with a diagnosis of gynecological cancer. A multidisciplinary team of gynecologists, oncologists, and fertility specialists could increase patient satisfaction and improve fertility outcomes. The incidence and death rates of endometrial cancer are rising globally. International guidelines recommend radical hysterectomy and bilateral salpingo-oophorectomy as the standard of care for this cancer; however, fertility-sparing alternatives should be tailored to motivated women of reproductive age, establishing an appropriate cost-benefit balance between childbearing desire and cancer risk. New molecular classifications such as that of TCGA provide a robust supplementary risk assessment tool that can tailor the treatment options to the patient's needs, curtail over- and under-treatment, and contribute to the spread of fertility-preserving strategies.

Office intrauterine morcellation for retained products of conception.

OBJECTIVE: Proposing hysteroscopic morcellation (HM) as a surgical-therapeutic approach in the treatment of retained products of conception (RPOC) to prevent intrauterine adhesions (IUAs). DESIGN: Prospective analysis. SETTING: A teaching and university hospital. PATIENTS: Women with RPOC. INTERVENTIONS: Office -HM with 'Truclear 5 C'. MATERIAL AND METHODS: Twenty-two consecutive patients presenting with trophoblastic residue retention after miscarriage and interruption of pregnancy or placenta remnants after cesarean section or delivery were enrolled. These women underwent office-HM with 'Truclear 5 C'. Primary outcomes were median time and rate of hospitalization. The quality of the specimen was also analyzed. A hysteroscopic second look for IUAs was performed. RESULTS: Mean procedure time was six minutes (SD ± 5). Tissue samples had a mean collection size 2.5 cm3+0.9. 38% of the samples had spotting or abnormal vaginal discharge. Dilatation of the cervical canal was not performed in any case. Second-look hysteroscopy did not show any de novo IUAs in any of the enrolled patients. CONCLUSIONS: In the hysteroscopic treatment of RPOC, HM is a valid choice in an office setting without the use of cervical dilatation. Removal of RPOC was uneventful in all cases, simple and carried out faster without any adverse outcomes.

Outcomes of Bleomycin-based electrochemotherapy in patients with repeated loco-regional recurrences of vulvar cancer.

Objective To evaluate the safety, local tumor efficacy and relief of symptoms of electrochemotherapy (ECT) treatment in patients affected by recurrence of vulvar cancer (VC), unsuitable for standard treatments. Methods Ten patients were recruited with histological diagnosis of recurrence of VC. Intravenous bleomycin was injected, after an accurate mapping of all lesions and ECT was performed. Response to therapy was evaluated and quality of life (QoL) was evaluated via questionnaires. Results Diagnosis stage of primary tumors, according to the FIGO system, was: four patients respectively at stage IB (40%), and at stage II (40%), one patient at stage IIIA (10%), one patient with Paget cancer (10%). Mean age was 76 years (SD ± 7) at time of enrollment. Eight patients (80%) were previously submitted to surgery and/or radio-chemotherapy. Mean treatment time was 20 (range 10-20) min. After a median follow-up of 12 (3-22) months, six patients (60%) were alive. Conclusions Objective responses (ORs) with local control of the tumor were obtained in 80%. After a mean follow-up of 12 (3-22) months six patients (60%) were alive. The favorable outcome of this study, indicates that ECT is a reliable treatment option that may improve their functioning, thus enhancing the care provided in the palliative setting.

Robotic Shaving Technique in 25 Patients Affected by Deep Infiltrating Endometriosis of the Rectovaginal Space.

Minimally invasive surgery represents the gold standard for the management of deep infiltrating endometriosis (DIE) involving the rectovaginal septum (RVS). This analysis aimed to evaluate the feasibility of robotic-assisted laparoscopy (RAL) and clinical outcomes in terms of long-term complications, pain relief, and recurrence rate for the treatment of DIE of the RVS. A prospective cohort study of robotic procedures was performed between October 2010 and July 2014, including removal of endometriotic nodules from the RVS with rectal shaving alone or in combination with accessory procedures. In all cases, the revised American Society for Reproductive Medicine (rASRM) score for endometriosis was >40 points (stage IV). Twenty-five consecutive patients underwent RAL, with a successful complete nodule debulking by the wall shaving technique. Pathology confirmed the adequacy of the surgical specimen and the median largest endometriotic nodule was of 21 mm (range, 10-60 mm), with free margins in all cases. The median operative time from skin opening to closure was 174 minutes (range, 75-300 minutes), and blood loss was close to 0 mL. The median revised Enzian score for location A (RVS) was 2 (range, 1-3). The most frequent Enzian class was A2B0C0 (48%), followed by A3B0C0 (12%). In 3 cases (12%), partial vaginal resection was required to remove endometriotic nodules of the RVS (1 each in classes A3B0C1FI, A3B0C0FO, and A3B0C0). No intraoperative complications occurred. This series has a median long-term follow up of 22 months (range, 6-50 months) currently available with an optimal operative time, demonstrating good long-term outcomes. Our data support robotics as a safe and attractive alternative for comprehensive surgical treatment of DIE.

Blood transcriptome analysis of common kestrel nestlings living in urban and non-urban environments.

Urbanisation is one of the main anthropogenic forms of land cover affecting an ever-increasing number of wild animals and their habitats. Physiological plasticity represents an important process through which animals can adjust to the novel conditions of anthropogenic environments. Relying on the analysis of gene expression, it is possible to identify the molecular responses to the habitat conditions and infer possible environmental factors that affect the organismal physiology. We have quantified for the first time the blood transcriptome of common kestrel (Falco tinnunculus) nestlings living in urban sites and compared it to the transcriptome of kestrel nestlings inhabiting rural and natural environments. We found mild differences in the expression of genes among sites, indicating adaptability or acclimation of the birds to the urban habitat. We identified 58 differentially expressed genes between urban and natural kestrels, and 12 differentially expressed genes between urban and rural kestrels. The most striking differences among sites involved inflammatory-immunological, metabolic, apoptosis, DNA repair and development genes. In particular, we found that (i) urban kestrel nestlings had higher expression of genes linked to inflammation, repair of DNA damage, or apoptosis than natural kestrel nestlings, and (ii) natural and rural kestrel nestlings had higher expression of genes linked to the development and activation of immune cells, type I interferon response, or major histocompatibility complex than urban kestrel nestlings. Finally, the KEGG enrichment analysis identified the insulin signalling as the main pathway that differed between natural and urban kestrel nestlings. This is one of a limited number of studies on vertebrates that revealed habitat-associated differences in the transcriptome. It paves the way for further in-depth studies on the links between physiological variation and habitat structure at different spatial and temporal scales.

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.

Isthmocele, not cesarean section per se, reduces in vitro fertilization success: a systematic review and meta-analysis of over 10,000 embryo transfer cycles.

IMPORTANCE: Previous reviews have shown that a history of cesarean section (CS) is associated with a worse in vitro fertilization (IVF) prognosis. To date, whether the decline in the IVF chances of success should be attributed to the CS procedure itself or to the presence of isthmocele remains to be clarified. OBJECTIVE: To summarize the available evidence regarding the impact of isthmocele on IVF outcomes. DATA SOURCES: Electronic databases and clinical registers were searched until May 30, 2023. STUDY SELECTION AND SYNTHESIS: Observational studies were included if they assessed the effect of isthmocele on IVF outcomes. Comparators were women with isthmocele and women without isthmocele with a previous CS or vaginal delivery. Study quality was assessed using the modified Newcastle-Ottawa Scale. MAIN OUTCOMES: The primary outcome was the live birth rate (LBR). The effect measures were expressed as adjusted odds ratios (aORs) and unadjusted odds ratios (uORs) with 95% confidence intervals (95% CIs). The body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation working group methodology. RESULTS: Eight studies (n = 10,873 patients) were included in the analysis. Women with isthmocele showed a lower LBR than both women with a previous CS without isthmocele (aOR, 0.62; 95% CI, 0.53-0.72) and those with a history of vaginal delivery (aOR, 0.55; 95% CI, 0.42-0.71). The LBRs in women with a previous CS without isthmocele and those with a history of vaginal delivery were similar (aOR, 0.74; 95% CI, 0.47-1.15). Subgroup analysis suggested a negative effect of the intracavitary fluid (ICF) in women with isthmocele on the LBR (uOR, 0.36; 95% CI, 0.18-0.75), whereas the LBRs in women without ICF and those without isthmocele were similar (uOR, 0.94; 95% CI, 0.61-1.45). CONCLUSION AND RELEVANCE: We found moderate quality of evidence (Grading of Recommendations Assessment, Development and Evaluation grade 3/4) supporting a negative impact of isthmocele, but not of CS per se, on the LBR in women undergoing IVF. The adverse effect of isthmocele on IVF outcomes appears to be worsened by ICF accumulation before embryo transfer. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023418266.

Uterine rupture following prostaglandins use in second trimester medical abortion: Fact or fiction? A systematic review.

BACKGROUND: Prostaglandins (PGs) have emerged as key drugs in second trimester medical abortion (STMA) and are currently a cornerstone in obstetric practice. Nevertheless, the application of PGs, integral to labor and abortion procedures, is not risk-free, and has been associated with several complications, particularly maternal fever and uterine rupture (UR). OBJECTIVES: The main outcome of the present systematic review was to assess the safety of PGs use in STMA, particularly in scarred uterus (SC). SEARCH STRATEGY: The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We performed a comprehensive systematic review by searching multiple databases, including MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database, and the research registers of Web of Science during the years 1990-2022. SELECTION CRITERIA: Only articles regarding cases of UR occurred after the use of PGs for STMA were included in the article. We excluded papers regarding UR during first trimester abortion induction of labor or pregnancy or unrelated to PGs use for STMA. Risk of bias was assessed employing a modified version of the "Newcastle-Ottawa Scale" (NOS). DATA COLLECTION AND ANALYSIS: A total of 178 studies were initially identified as potentially meeting the criteria for inclusion in the review. After full text evaluation, 110 other articles were excluded and 67 studies that suited the inclusion criteria were included. A total of 19 of the included studies were judged to have a high risk of bias. Given the heterogeneous nature of the findings, we opted for a narrative synthesis of the results. MAIN RESULTS AND CONCLUSIONS: PGs appear to be an effective pharmacologic tool for STMA; however, their use is not entirely risk-free. STMA requires well-equipped obstetric centers with skilled clinicians and surgeons prepared for emergencies. Ultrasonographic scans should be routinely performed during STMA management, since a UR can also be silent during the induction of labor. Intrapartum transabdominal, transperineal, and transvaginal ultrasound may have the diagnostic potential to early recognize this obstetric emergency, to facilitate rapid medical and surgical treatment, improving the outcome.

Intraovarian injection of autologous platelet-rich-plasma: myth or reality?

INTRODUCTION: The diminished ovarian reserve (DOR) relates to a condition in which the ovary experiences a decline in its typical reproductive capacity. Despite notable advancements in understanding the pathophysiology of reduced ovarian reserve in recent years, significant unresolved challenges remain, particularly concerning the optimal therapeutic approaches for this complex condition. The main aim of this study was to investigate the potential of platelet-rich plasma (PRP) in enhancing ovarian follicle numbers by assessing changes in ovarian reserve markers. EVIDENCE ACQUISITION: A comprehensive literature search was conducted on the following databases: PubMed/MEDLINE, SCOPUS, The Cochrane Library, Science Direct and Web of Science. All the relevant studies published till October 2023 were screened. After removing duplicates, and full-text evaluation, 9 articles were eventually included in the present review. EVIDENCE SYNTHESIS: The pregnancy rate (PR) among patients with poor ovarian reserve (POR) ranged from 13% to 40%, indicating the potential effectiveness of PRP as a rejuvenating treatment. The live birth rate (LBR) ranged from 13% to 20%, comparable to or not lower than the LBR of a matched healthy population aged between 38 and 42 years. Furthermore, the data presented thus far support the notion that PRP may lead to an average clinical PR of 10% in women affected by premature ovarian insufficiency (POI) and perimenopause. CONCLUSIONS: PRP can not be regarded as a gamete replacement therapy, but rather as an 'additional' therapeutic tool in the management of women with DOR or POR, as well as in peri-menopausal women. Additional qualitative studies are required to validate the existing evidence, as the literature currently lacks randomized controlled trials (RCTs) in this regard.

Four-handed Technique for Total Laparoscopic Hysterectomy: An Italian Experience.

Objectives: In our previous article, we proposed the novel four-handed technique (FHT) for total laparoscopic hysterectomy (TLH), which, according to us, is more helpful compared to the traditional TLH route. The objectives of the study were to analyze the FHT-TLH feasibility and efficiency by comparing some surgical outcomes recorded from 750 FHT-TLH performed in our hospital to literature data about the traditional TLH route and to underline the great opportunity this novel technique offers to the young specialists and residents to be more confident with gynecological laparoscopy. Materials and Methods: This was a retrospective analysis carried out by collecting data regarding patient characteristics and surgical outcomes (operative time, blood loss, surgical complications, use of analgesics, and length of hospitalization) from 750 hospital records of women who underwent FHT-TLH (with or without adnexectomy) due to benign or malignant pathology from January 2015 to December 2021 at our hospital. Results: We performed a total of 750 FHT-TLH, with or without adnexectomy. The mean skin-to-skin operative time for a FHT-TLH was 50 min, and the mean blood loss was 150 mL. No visceral damage was caused during surgeries. Only two patients underwent exploratory laparotomy with total abdominal hysterectomy due to the inability to proceed laparoscopically. Nonsteroidal anti-inflammatory drugs were administered only twice a day as analgesics, with advantage. The mean length of stay in the hospital after the procedure was 1.5 days, with discharge on the evening of the 1st day after surgery. No major postoperative complications occurred. The only minor postoperative complication described, in just three patients, was cellulitis of the vaginal vault. Conclusion: Our FHT-TLH experience represents an alternative to the traditional TLH route, which allows to apply a minimally invasive approach with some advantages for patients compared to the traditional TLH route, such as early recovery and reduced operating time, blood loss, use of analgesics, and hospital stay. Moreover, it allows young specialists and residents to be more confident with gynecological laparoscopy, particularly when operating as the first assistant, to improve their laparoscopic surgical skills faster than the traditional TLH route allows them.