Agenesis of the ductus venosus and fetal growth restriction: Is there a relation? A tertiary care center experience and systematic review of the literature.

An update on the antenatal diagnosis of agenesis of ductus venosus (ADV) by differentiating the various possible types of shunts, focusing on the associated fetal anomalies, and predicting neonatal outcomes. This study reviewed the experience of two tertiary referral centers and literature. An unfavorable outcome was detected in preterm fetuses (p = 0.017), fetuses with a genetic anomaly (p = 0.046) or other associated malformations (p < 0.001). 71% of ADVs with other anomalies had an extrahepatic ADV (p = 0.002). 76% of fetuses with Fetal Growth Restriction (FGR) had an extrahepatic ADV (p = 0.025). ADV may negatively influence fetal growth in cases with extrahepatic vein drainage.

The Role of Micronutrients in Human Papillomavirus Infection, Cervical Dysplasia, and Neoplasm.

There is evidence that diet and nutrition are modifiable risk factors for several cancers. In recent years, attention paid to micronutrients in gynecology has increased, especially regarding Human papillomavirus (HPV) infection. We performed a review of the literature up until December 2022, aiming to clarify the effects of micronutrients, minerals, and vitamins on the history of HPV infection and the development of cervical cancer. We included studies having as their primary objective the evaluation of dietary supplements, in particular calcium; zinc; iron; selenium; carotenoids; and vitamins A, B12, C, D, E, and K. Different oligo-elements and micronutrients demonstrated a potential protective role against cervical cancer by intervening in different stages of the natural history of HPV infection, development of cervical dysplasia, and invasive disease. Healthcare providers should be aware of and incorporate the literature evidence in counseling, although the low quality of evidence provided by available studies recommends further well-designed investigations to give clear indications for clinical practice.

Effects of neuraxial analgesia technique on labor and maternal-fetal outcomes: a retrospective study.

PURPOSE: To compare the effects of epidural analgesia (EA) and combined spinal epidural analgesia (SEA) on labor and maternal-fetal outcomes. METHODS: We retrospectively identified and included 1499 patients with a single cephalic fetus who delivered at the study center from January 2015 to December 2018 and received neuraxial analgesia at the beginning of the active phase of labor (presence of regular painful contractions and cervical dilatation between 4 and 6 cm). Data including analgesia, labor characteristics, and maternal-fetal outcomes were retrieved from the prospectively collected delivery room database and medical records. RESULTS: SEA was associated with a shorter first stage of labor than EA, with a median difference of 60 min. On multivariable ordinal logistic regression analysis, neuraxial analgesia, gestational age, fetal weight, labor induction, and parity were independently associated with the first stage length: patients in the EA group were 1.32 times more likely to have a longer first stage of labor (95% CI 1.06-1.64, p = 0.012) than those in the SEA group. Additionally, a significantly lower incidence of fundal pressure was performed among patients who underwent SEA (OR 0.55, 95% CI 0.34-0.9, p = 0.017). No associations were observed between the used neuraxial analgesia technique and other outcomes. CONCLUSIONS: SEA was associated with a shorter length of the first stage of labor and a lower rate of fundal pressure use than EA. Further studies confirming the effects of SEA on labor management and clarifying differences in maternal-fetal outcomes will allow concluding about the superiority of one technique upon the other.

Tranexamic acid for the prevention and the treatment of primary postpartum haemorrhage: a systematic review.

Tranexamic acid (TA) has been proposed for preventing or treating primary postpartum haemorrhage (PPH), which is the leading cause of maternal morbidity and mortality worldwide. We conducted a systematic literature search to the TA role in managing PPH in vaginal and caesarean delivery. Twenty-seven randomised controlled trials (RCTs) (33,302 women) were identified. Three RCTs investigated TA for preventing PPH after vaginal delivery and 22 after caesarean section. None demonstrated a preventive effect on secondary clinical outcomes related to blood loss. Two trials evaluated TA for treating PPH after vaginal and caesarean delivery. Only the WOMAN trial showed that 1 g of TA is effective. In conclusion, TA is considered useful and is recommended or advised for treating PPH. Conversely, available evidence on the prophylactic role is still limited, and this use is not supported. Further investigation is recommended. In this regard, stronger and more reliable outcomes than blood loss should be considered.

The Ex utero intrapartum treatment (EXIT) procedure: case report of a multidisciplinary team approach.

BACKGROUND AND AIM OF THE WORK: The EXIT-to-airway procedure is aimed to provide the time required to secure airways when an extrinsic or intrinsic fetal mass raise concerns about airways control at delivery. Due to the rarity of the procedure, we aim to provide a summary of the appropriate prenatal planning by a multidisciplinary team. METHODS: Report of a case of EXIT-to-airway procedure. RESULTS: A 30 years-old woman, G2P1 with previous cesarean section, was referred to our Unit at 34 gestational weeks due to a fetal cervical mass of 7cm. An EXIT-to-airways procedure was performed by a multidisciplinary team after accurate preoperative planning and the practice simulations. The partial fetal extraction and the amnioinfusion of pre-heated saline were used to prevent fetal complications. The use of supplemental intravenous anesthesia with remifentanil and better control of uterine tone with nitroglycerin allowed to reduce the exposure to volatile halogen for both the mother and the fetus. The accurate preoperative planning and the practice simulations allowed us to perform the treatment safely in urgency due to the onset of spontaneous labor at 37 weeks and 6 days. CONCLUSIONS: The strong cooperation among specialists, accurate prenatal planning, and adopting all the required procedures and precautions are of paramount importance to successfully perform the EXIT-to-airway procedure.

The Psychological Impact of COVID-19 on Healthcare Providers in Obstetrics: A Cross-Sectional Survey Study.

Objective: To assess the psychological distress of healthcare providers (HCPs) working in the field of obstetrics during the coronavirus disease 2019 (COVID-19) pandemic and to identify factors associated with psychological distress at the individual, interpersonal, and organizational level. Design: Cross-sectional survey study. Setting: Four University hospitals in Italy. Participants: HCPs working in obstetrics, including gynecologists, residents in gynecology and obstetrics, and midwives. Methods: The 104-item survey Impatto PSIcologico COVID-19 in Ostetricia (IPSICO) was created by a multidisciplinary expert panel and administered to HCPs in obstetrics in May 2020 via a web-based platform. Main Outcome Measures: Psychological distress assessed by the General Health Questionnaire-12 (GHQ-12) included in the IPSICO survey. Results: The response rate to the IPSICO survey was 88.2% (503/570), and that for GHQ-12 was 84.4% (481/570). Just over half (51.1%; 246/481) of the GHQ-12 respondents reported a clinically significant level of psychological distress (GHQ-12 ≥3). Psychological distress was associated with either individual (i.e., female gender, stressful experience related to COVID-19, exhaustion, and the use of dysfunctional coping strategies), interpersonal (i.e., lower family support, limitations in interactions with colleagues), and organizational (i.e., reduced perception of protection by personal protective equipment, perceived delays on updates and gaps in information on the pandemic) factors in dealing with the pandemic. Conclusions: Results confirm the need for monitoring and assessing the psychological distress for HCPs in obstetrics. Interventions at the individual, interpersonal, and organizational level may relieve the psychological distress during the COVID-19 pandemic and foster resilience skills in facing emotional distress.

Needlestick injuries among obstetrics and gynecology trainees: A survey study.

OBJECTIVE: To assess characteristics, incidence, risk factors, and reporting rate of needlestick injuries (NSIs) among Obstetrics and Gynecology trainees. STUDY DESIGN: We performed a nationwide cross-sectional survey study. The 40-items survey Obstetrics Needlestick Injury Questionnaire (ONSI-Q) was used to investigate the prevalence of NSIs, participant attitudes, associated factors, and the NSI reporting rate among trainees in Obstetrics and Gynecology. The target responders were all trainees of Obstetrics and Gynecology training programs in Italy. The trainees were invited between September 2018 and December 2018 via a web-based platform. RESULTS: Among 1049 trainees, 1041 (99.2%) completed the survey. Out of 1041 trainees, 639 (61.4%) had at least one NSI, and 90.9% (581/639) experienced at least one during obstetric surgery. The number of NSIs increased with the year of training, with 2.48 NSIs per trainee in the fifth year. 90.6% (579/639) reported details about the most recent NSI, which was during obstetric surgery in 95.3% (552/579) of cases. 57.1% (315/552) experienced the most recent NSI during cesarean section, which was mainly inflicted by someone else (72.4%; 228/315). 42.9% (237/552) of NSIs were during perineal suture, and 84% (199/237) of them were self-inflicted. 77.9% (417/535) of trainees did not report the NSI. Associated factors were non-high-risk patients, self-inflicted NSI, and the first NSI. CONCLUSIONS: NSIs are frequent among Obstetrics and Gynecology trainees but not reported, and obstetric surgery is the primary source. These data support the European efforts to improve working practices' safety. The education about protective strategies and reporting should be a priority.

Evaluation of circ_100219 and miR-135b in serum and exosomes of healthy pregnant women.

AIM: Circular RNAs (circRNAs) are recently discovered and highly stable noncoding RNAs acting as gene regulators. These circRNAs can function as miRNA sponges, thereby upregulating or downregulating miRNA target gene expression. MiR-135b is expressed in placenta tissue and can be found in maternal circulation, thus playing a functional role in pregnancy. This miR is a target of circ_100219. This preliminary study was aimed to evaluate circ_100219 and miR-135b expression in pregnant and nonpregnant women, and explore the relationship between circ_100219 and miR-135b in serum and exosomes. METHODS: Total RNA was isolated from serum and exosomes of 30 healthy pregnant women (32.9 ± 5.1 years) between 23-27 gestational weeks and 30 healthy nonpregnant women (31.3 ± 5.4 years). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_100219 and miR-135b expression. GAPDH and U6 snRNA were chosen as reference for normalizing expression levels. The differences between pregnant and nonpregnant women were assessed with Mann-Whitney test and correlation with Spearman's test. RESULTS: The circ_100219 expression levels were significantly lower both in serum and exosomes of second trimester pregnant women compared to the control group (p < .0001), whilst Mir-135b expression levels were significantly higher in pregnant than in the control group (p < .0001). A significant negative correlation was observed between circ_100219 and miR-135b expression levels in both serum and exosomes (r = -0.34 and p = .009; r = -0.31 and p = .01, respectively). The circ_100219:miR-135b ratio was significantly increased in nonpregnant women compared to the pregnant group, in both serum and exosomes (49.0 versus 1.1, p < .0001 and 2042.4 versus 28.5, p < .0001, respectively). CONCLUSIONS: Our results confirm a role for circ_100219 and miR-135b in physiological pregnancy. Further studies are needed to investigate the circ_100219:miR-135b ratio in pregnancy complications.

Fertility and reproductive outcome after tubal ectopic pregnancy: comparison among methotrexate, surgery and expectant management.

PURPOSE: To compare fertility and reproductive outcome after surgical, medical, and expectant management for tubal ectopic pregnancy (EP). METHODS: 133 of 228 patients, who were managed between January 2012 and December 2017 for a tubal EP, tried to conceive immediately after treatment: 86 out of 173 (49.7%) underwent surgical treatment; 38 (21.9%) were treated with methotrexate (MTX), and 49 (28.3%) had expectant management. Clinical data were retrieved by medical records, fertility outcomes were obtained by phone follow-up. The cumulative incidence (CI) of intrauterine clinical pregnancy (CP), miscarriage, live birth (LB), and recurrent EP, and the time between treatment and first intrauterine CP were compared between women treated with MTX, surgery and expectant management. RESULTS: The CI of intrauterine CP starting from 12 months after the EP was 65.3% for the expectant management, 55.3% for the MTX group, and 39.5% for surgery (p = 0.012). Post-hoc analysis showed expectant management having higher intrauterine CP and LB, and shorter time between treatment and first intrauterine CP compared to surgery (p < 0.05). The CI of recurrent EP was comparable between the 3 groups. The analysis stratified per ßhCG cut-off of 1745 mUI/mL and EP mass cut-off of 25 mm reported consistent results. CONCLUSIONS: Women successfully managed by expectation appear to have better reproductive outcomes compared to women who underwent surgery, with the shortest time to achieve a subsequent intrauterine CP. Therefore, if safely applicable the expectant management should be considered in the case of tubal EP. The fact that the chosen treatment was primarily guided by the ßhCG value and EP mass diameter based on the protocol, which is intrinsically related to the characteristics of the EP, represents the main limitation of the present study. Indeed, we cannot completely exclude that the observed differences between treatments are related to the EP itself instead of the treatment.

Novel drug delivery methods for improving efficacy of endometriosis treatments.

INTRODUCTION: Pharmacotherapy has a key role in the management of endometriosis. However, a significant proportion of patients gains only intermittent or limited benefits. In this regard, alternative and novel drug delivery methods are of paramount importance to improve efficacy and compliance of available treatments and develop alternative medical approaches. AREAS COVERED: This review aims to provide the reader with a complete overview of available evidence about alternative and novel drug delivery methods for endometriosis pharmacotherapy and highlight new research lines. EXPERT OPINION: Progestins and estroprogestins, which represent the first-line therapy, are already available in different formulations, being employed for contraception. Nevertheless, evidence on their adoption is still limited for some drug delivery methods, such as vaginal rings, patches, and subcutaneous implants. Further research is needed to define better their clinical utility in patients with endometriosis. Nanotechnologies have been investigated as novel drug delivery methods able to target the drug at the disease level. However, data are very limited and preliminary, and further research is needed to consider a possible clinical application in endometriosis.

Aromatase inhibitors for the treatment of endometriosis: a systematic review about efficacy, safety and early clinical development.

INTRODUCTION: Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with current treatment options. Therefore, novel therapeutic approaches are necessary. AREAS COVERED: This systematic review provides an overview of the efficacy and safety of aromatase inhibitors (AIs) as monotherapies and combination therapies for endometriosis. A systematic literature search was performed from January 1990 to April 2020 in the electronic database MEDLINE, EMBASE, The Cochrane Library, and Web of Science. EXPERT OPINION: Based on the critical role of estrogens and the rate-limiting step in the production of the estrogens represented by the aromatase enzyme, AIs are a potential therapeutic option for women affected by endometriosis. Nevertheless, further research is needed to clarify the efficacy of AIs in this setting. Adverse effects need to be investigated to clarify the preventive role of add-back therapy. On that basis, AIs should be adopted only as second-line therapy in patients who are refractory to standard treatments in the setting of scientific research. Further studies should define best dosages, appropriate add-back therapies, administration routes, treatment length, and which patients may benefit more from AIs.

Secondary and tertiary ovarian cancer recurrence: what is the best management?

Ovarian cancer with complete clinical response recurs with a high rate. Recurrence is observed in almost 25% of cases with early-stage diseases and in more than 80% with more advance stages. Based on a platinum-free interval cut-off of 6 months, the first recurrence is usually classified in platinum-sensitive versus platinum-resistant, reflecting the biological characteristics underlying the clinical behavior. After this first recurrence, the patients are rarely cured, but second-line therapy can provide significant clinical responses, particularly in first platinum-sensitive recurrence. The approach to secondary and tertiary recurrence follows the same general principles applied in the first recurrence. Platinum-sensitivity based on the treatment-free interval defines the available chemotherapeutic regimens, whit less therapeutic options and a generally worse prognosis in platinum-resistant recurrent disease. Nevertheless, in this scenario, the introduction of new targeted therapies changed the prognosis of patients with both platinum-sensitive and platinum-resistant recurrence. The first introduced antiangiogenic therapy resulted able to improve prognosis in recurrent disease both as a single-agent and combined therapy, although the growing adoption in the first line therapy requires further investigation to prove their efficacy after repeated use. More recently, the approach to secondary, tertiary, and later recurrence has been changed by the introduction of PARP inhibitors, which resulted effective as maintenance monotherapy in both platinum-sensitive and platinum-resistant recurrence when the genetic background of the tumor allows their application with a significant improvement of oncological outcomes. Overall, although the growing body of promising therapeutic options to approach recurrent ovarian cancer, all the available evidence suggests that the best unique management of secondary and tertiary recurrence does not exist but should be personalized based on the disease characteristics, previous treatments, patient characteristics, and patient preference. On that basis, in this review, we report a general and complete overview of the approach at the secondary and tertiary ovarian cancer recurrence with the aim to provide a wide vision on the multiple available therapeutic options.

Hysteroscopic Metroplasty for T-Shaped Uterus: A Systematic Review and Meta-analysis of Reproductive Outcomes.

IMPORTANCE: To date, a comprehensive review on the safety and effectiveness of hysteroscopic metroplasty for T-shaped uterus is still missing. OBJECTIVE: To provide a robust synthesis of the available studies investigating reproductive outcomes after hysteroscopic metroplasty for T-shaped uterus. EVIDENCE ACQUISITION: We performed a systematic review and meta-analysis (CRD42019143291), using the proportion method with 95% confidence interval (CI). Statistical heterogeneity was assessed by Higgins test (I2). RESULTS: We included 11 cohort studies embedding 937 women who underwent hysteroscopic metroplasty. After surgery, the pooled percentage of live birth was 44.54% (95% CI, 36.12%-53.12%; I2 = 46.22%) and 56.88% (95% CI, 46.48%-66.98%; I2 = 36.38%) in women with primary infertility and recurrent miscarriage, respectively. In women with recurrent miscarriage, the pooled proportion of miscarriage was 21.46% (95% CI, 15.09%-28.61%; I2 = 30.18%). The pooled clinical pregnancy proportion in women with primary infertility was 57.19% (95% CI, 43.83%-70.03%; I2 = 77.81%). The pooled rate of surgical complications was 0.65% (95% CI, 0.20%-1.33%; I2 = 11.44%). CONCLUSIONS: The hysteroscopic correction of T-shaped uteri was associated with high live birth rate and low miscarriage rate, both in case of primary infertility and recurrent miscarriage. RELEVANCE: Hysteroscopic metroplasty can be considered a safe and effective strategy to improve reproductive outcomes in case of T-shaped uterus.

An update on treatment options for interstitial cystitis.

Interstitial cystitis or bladder pain syndrome (IC/BPS) is a chronic pelvic pain syndrome related to the urinary bladder. The ideal treatment should match as much as possible with the pathophysiologic causes of the IC/BPS, but the scarcely available evidence limits this approach, with the majority of available treatments that are primarily targeted to the control of symptoms. The treatment strategies have traditionally focused on the bladder, which is considered the primary end-organ and source of pain. Nevertheless, the growing body of evidence suggests a multifaceted nature of the disease with systemic components. In general, guidelines recommend the personalized and progressive approach, that starts from the more conservative options and then advances toward more invasive and combined treatments. The behavioral changes represent the first and most conservative steps. They can be combined with oral medications or progressively with intravesical instillation of drugs, up to more invasive techniques in a combined way. Despite the multiple available options, the optimal treatment is not easy to be found. Only further investigation on the etiopathogenetic mechanisms, taking into account the differences among subgroups, and the interaction between central and peripherical factors may allow providing a real improvement in the treatment and management of these patients.

Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer.

To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 ± 12 years) and 31 healthy controls (HC) (63 ± 13 years), excluding in both groups other oncologic and severe non-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than in HC (p < 0.0001). The diagnostic performance of cfDNA RTL was estimated with receiver operating characteristics (ROC) curve analysis, which showed a diagnostic accuracy for EC of 0.87 (95% CI: 0.79-0.95, p < 0.0001). The cutoff cfDNA RTL value of 2.505 (T/S copy ratio) reported a sensitivity of 80.0% (95% CI: 64.35-90.95) and a specificity of 80.65% (95% CI: 62.53-92.55). Significant differences of RTL among EC stages or grades (p = 0.85 and p = 0.89, respectively) were not observed. Our results suggest that cfDNA RTL analysis may be a diagnostic tool for EC detection since the early stage, whilst its diagnostic performance seems unsatisfactory for cancer progression, staging, and grading. However, further studies are needed to confirm these preliminary findings. In particular, future investigations should focus on high-risk patients (such as those with atypical endometrial hyperplasia) that may benefit from this tool, because TL shortening is not specific for EC and is influenced by other oncologic and non-oncologic diseases.

CDT reference values for monitoring chronic alcohol abuse in pregnancy.

INTRODUCTION AND AIM: Carbohydrate Deficient Transferrin (CDT) is one of the most used biomarkers for monitoring alcohol use in pregnancy. However, its effective application in this context is hampered by the demonstrated physiological progressive increase during pregnancy (even in abstinent women) of CDT values, which in the third trimester can reach values close or exceeding the cut-offs usually adopted in clinical and forensic diagnostics. The present work was aimed at the re-assessment of CDT reference values in pregnancy. MATERIALS AND METHODS: The CDT analysis was performed by a validated HPLC-UV Vis method on 284 serum samples of women with a physiological pregnancy and on 370 sera of non-pregnant woman from the general population (control group). All the samples were tested also for GGT for excluding alcohol abuse. The statistical analysis was performed using the MedCalc® Statistical Software. RESULTS: The re-definition of the specific reference concentrations was carried out according to the Horn and Pesce Robust Method. The resulting CDT upper reference values were 1.45%, 2.01% and 2.05% in the first, second, and third trimester, respectively. CONCLUSIONS: In order to prevent the development of maternal and fetal prenatal alcohol exposure complications, the use of alcohol biomarkers, including CDT, has been proposed. However, this biomarker, in the monitoring of alcohol use in pregnancy, has so far been applied adopting the same cut-off used for general population without taking into consideration the progressive physiological increase of its value throughout the pregnancy. In the present study, a specific re-assessment of the CDT reference concentrations of each trimester is reported.