The Impact of Conservative Surgical Treatment of Adenomyosis on Fertility and Perinatal Outcomes.

Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: "adenomyosis", "surgery", "radiofrequency", "infertility", "pregnancy", "sterility", "conception", "miscarriage", and "endometrial receptivity". Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines.

The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review.

Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.

Assisted Reproductive Technology and Breech Delivery: A Nationwide Cohort Study in Singleton Pregnancies.

Since essential factors have changed in recent years in assisted reproduction technologies (ARTs), this study reassessed the association between ART and breech presentation. We primarily aimed to estimate the correlation between ART and breech at delivery. Secondary purposes were to evaluate the correlation between other subfertility treatments (OSTs) and breech and to assess possible confounding factors and temporal trends. This study investigated the 31,692,729 live birth certificates from US states and territories in the 2009-2020 period. The inclusion criteria were singleton births reporting the method of conception and the presentation at delivery. The outcome was the breech presentation at delivery, while the primary exposure was ART, the secondary exposure was OST, and the potential confounding factors from the literature were considered. ART (OR 2.32 CI.95 2.23-2.41) and OST (OR 1.79 CI.95 1.71-1.87) were independent and significant risk factors for breech at delivery (p < 0.001). This study confirmed breech presentation risk factors maternal age, nulliparity, tobacco smoke, a previous cesarean delivery (CD), neonatal female sex, gestational age, and birth weight. Black race and Hispanic origin were verified to be protective factors. We found breech prevalence among ART and OST to be stable during the study period. Meanwhile, newborn birth weight was increased, and the gap between breech and other presentations in ART was reduced. Our results indicate that singleton pregnancies conceived by ART or OST were associated with a higher risk of breech at delivery. Well-known risk factors for the breech presentation were also confirmed. Some of these factors can be modified by implementing interventions to reduce their prevalence (e.g., tobacco smoke and previous CD).

Adenomyosis: An Updated Review on Diagnosis and Classification.

Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations.

Anthropometric Features and Third-Fourth Degree Perineal Tears.

The main objective of this study was to evaluate the association between maternal and fetal anthropometric characteristics and third- and fourth-degree perineal tears. This retrospective cohort study considered all consecutive pregnancies from 2011 to 2017 at a single Institution. The inclusion criteria were: singletons who delivered vaginally during the study period, the presence of information on maternal pre-pregnancy weight, maternal height, and weight of the newborn. The feto-maternal body-mass index (BMI) was calculated as neonatal weight in kg on maternal height in squared meters (kg/m2). In total, 5397 singleton-term pregnancies were included; the prevalence of third-fourth-degree perineal tears was 0.47%. The most predictive factors were: nulliparity, feto-maternal BMI, neonatal weight, gestational age at delivery, and neonatal head circumference. After adjustment in multivariate analysis, the only independent predictors were nulliparity and fetomaternal BMI. The AUC of the final multivariate model was 73.54% (95% CI 65.65-81.42). Furthermore, feto-maternal BMI and gestational age had a significant direct correlation. Nulliparity and feto-maternal BMI are the two best predictors for third and fourth-degree perineal tears in our setting. Confirming this association in future research and integrating it into a decision algorithm on delivery timing could reduce obstetric damage to the anal sphincter.

Editorial: Precision Medicine in Obstetrics: Pregnancy Complication.

Millions of women give birth every year worldwide [...].

Trial of Labor after Three or More Previous Cesarean Sections: Systematic Review and Meta-Analysis of Observational Studies.

AIMS: To assess the success rate and prevalence of maternal or neonatal complications in women undergoing a trial of labor after three or more (≥3) previous cesarean sections (CSs). METHODS: A systematic literature review and meta-analysis was conducted from inception to May 2022 in Medline, Scopus, ENBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials and Reviews. Items detailing success rate and complications in women with a history of≥3 previous CSs were considered. Selected articles were evaluated for quality, heterogeneity, and publication bias. A pooled prevalence or odds ratio was calculated. FINDINGS: Twelve articles were included for a total of 540 women with a history of≥3 CSs, accounting for the 2% (CI 95% 1-4%) of the whole cohort of trial of labor. Our findings show a 0.67 (CI 95% 0.53-0.78) rate of successful vaginal delivery. A higher success rate was observed in women having a history of a prior vaginal delivery (0.90, CI 95% 0.77-0.96) and when prostaglandins, peridural anesthesia or oxytocin were allowed (respectively 0.73, CI 95% 0.62-0.83, 0,73, CI 95% 0.57-0.85 and 0.73, CI 95% 0.64-0.81). Uterine rupture rate was 0.01 (CI 95% 0.00-0.01). No cases of fetal asphyxia or maternal or neonatal death were registered. CONCLUSIONS: The success rate and low frequency of severe complications observed seem to support a trial of labor in selected patients desiring a natural birth. However, a potential underestimation of serious maternal and neonatal complications should be considered in the decision-making process.

Factors influencing the effect of external cephalic version: a retrospective nationwide cohort analysis.

OBJECTIVE: This study aims to assess the factors associated with the success and failure rate of the external cephalic version (ECV) in breech fetuses. Secondary outcomes were fetal presentation in labor and mode of delivery. METHODS: This cross-sectional study examined the live birth certificates from 2003 through 2020 from US states and territories that implemented the 2003 revision. A total of 149,671 singleton pregnancies with information about ECV success or failure were included. The outcome was ECV success/failure, while the exposures were possible factors associated with the outcome. RESULTS: The successful ECV procedures were 96,137 (64.23%). Among the successful ECV procedures, the prevalence of spontaneous vaginal delivery was 71.63%. Among the failed ECV procedures, 24.74% had a cephalic presentation at delivery, but 63.11% of these pregnancies were delivered by cesarean section. Nulliparity, female sex, low fetal weight centile, high pre-pregnancy BMI, high BMI at delivery, and high maternal weight gain during pregnancy were associated with an increased ECV failure (p < 0.001). African American, American Indian and Alaska Native race categories were significant protective factors against ECV failure (p < 0.001). Maternal age had a U-shape risk profile, whereas younger maternal age (< 25 years) and old maternal age (> 40 years) were significant protective factors against ECV failure (p < 0.001). CONCLUSIONS: A high prevalence of successful ECV procedures and subsequent spontaneous vaginal delivery were found. The present results found nulliparity, maternal race, maternal age, female fetal sex, low fetal weight, and maternal anthropometric features correlated to ECV results. These findings can potentially improve the knowledge about the factors involved in ECV, allowing more informed counseling to the women undergoing this procedure.

Ruptured ectopic pregnancy as complete hydatidiform mole: Case report and review of the literature.

Usually, a hydatidiform mole (HM) develops inside the uterus. The occurrence of HM in ruptured tubal pregnancy is exceptional. Cases reported in the literature are scarce. In this article, a case of haemoperitoneum secondary to a ruptured fallopian tube by a complete mole is reported. A 50-year-old gravida 2, para 1 was admitted to the emergency department for acute abdominal pain. After the clinical examination, an abdominal sonography and CT scan were done, revealing the presence of an adnexal left mass associated with an important haemoperitoneum. A urine pregnancy test was done and was positive, indicating an immediate laparoscopic exploration. The laparoscopy revealed a haemoperitoneum secondary to a ruptured tubal mass. The pathological exam concluded a complete hydatidiform mole (CHM) invading the wall of the fallopian tube. Any acute abdominal pain in a potentially pregnant woman imposes first the routine realization of a pregnancy test. The occurrence of CHM in a ruptured fallopian tube is particularly rare and has exceptionally been diagnosed before the laparoscopic exploration.

Short-term neonatal outcomes in vaginal breech delivery: Results of a retrospective single-centre study.

BACKGROUND: Vaginal breech delivery (VBD) has been widely discouraged over the last two decades due to associated neonatal risks. However, many gynaecologists are still challenging this approach, at least in selected settings. OBJECTIVE: To study short-term neonatal outcomes in singleton pregnancies undergoing VBD. MATERIALS AND METHODS: Retrospective cohort study conducted on singleton pregnancies who delivered in breech presentation between 2012 and 2019. Neonatal complications in terms of mortality, umbilical artery (UA) pH, 5-min Apgar score, and postnatal admission to neonatal intensive care unit (NICU) were evaluated. RESULTS: Overall, 804 breech deliveries were considered. Of these, 53.86 % had VBD, 26.62 % had emergency caesarean sections (CS) and 19.53 % had elective CS. No perinatal deaths were reported. After multivariate adjustment, VBD was associated with higher incidence of UA pH < 7.10 compared with both elective and emergency CS. No significant associations were found between VBD and UA pH < 7.00 or 5-min Apgar score < 3 or < 7. No significant differences in NICU hospitalization were observed for different modes of delivery. Gestational age was inversely correlated with UA pH < 7.00, 5-min Apgar score < 3 and < 7, and NICU hospitalization. CONCLUSIONS: VBD in an experienced setting does not increase the risk of negative short-term perinatal outcomes significantly. Gestational age was the most important risk factor for low UA pH or 5-min Apgar score and NICU hospitalization, independent of mode of delivery.

Endometriosis and Infertility: Prognostic Value of #Enzian Classification Compared to rASRM and EFI Score.

This study's objective was to compare the predictive validity of the three most utilized classification scores for endometriosis, #Enzian, EFI, and rASRM, in achieving a spontaneous pregnancy or pregnancy via assisted reproductive technology (ART) after surgery for endometriosis. The monocentric retrospective study was carried out from January 2012 to December 2021 at the gynaecology department of the cantonal hospital of Fribourg. Patients consulting for infertility and operated on for endometriosis with histological confirmation were included. The predictive value of #Enzian, rASRM, and EFI was evaluated and compared concerning the prediction of fertility after surgery, both spontaneous and ART, during the following 12 months. A total of 58 women (mean age 33.1 ± 4.57 years) were included. Overall, 30 women achieved a pregnancy, seven spontaneously. Among all women who achieved a pregnancy, there was a lower prevalence of rASRM stage III−IV (16.67% vs. 39.29%, p = 0.054). Women achieving a pregnancy had a significantly higher EFI score than others (p < 0.05). No significant differences were observed concerning the #Enzian score. In conclusion, the revised #Enzian score is not correlated with pregnancy achievement; EFI score is the only score significantly associated with the pregnancy outcome in women affected by endometriosis.

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review.

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies.

Fetal Growth Restriction: Comparison of Biometric Parameters.

The aim of this study was to identify growth-restricted fetuses using biometric parameters and to assess the validity and clinical value of individual ultrasound parameters and ratios, such as transcerebellar diameter/abdominal circumference (TCD/AC), head circumference/abdominal circumference (HC/AC), and femur length/abdominal circumference (FL/AC). In a retrospective single-center cross-sectional study, the biometric data of 9292 pregnancies between the 15th and 42nd weeks of gestation were acquired. Statistical analysis included descriptive data, quantile regression estimating the 10th and 90th percentiles, and multivariable analysis. We obtained clinically noticeable results in predicting small-for-gestational-age (SGA) and fetal growth restriction (FGR) fetuses at advanced weeks of gestation using the AC with a Youden index of 0.81 and 0.96, respectively. The other individual parameters and quotients were less suited to identifying cases of SGA and FGR. The multivariable analysis demonstrated the best results for identifying SGA and FGR fetuses with an area under the curve of 0.95 and 0.96, respectively. The individual ultrasound parameters were better suited to identifying SGA and FGR than the ratios. Amongst these, the AC was the most promising individual parameter, especially at advanced weeks of gestation. However, the highest accuracy was achieved with a multivariable model.

Trial of Labor and Vaginal Birth after Three Previous Cesarean Sections: Report of Two Special Cases.

BACKGROUND: Natural childbirth could represent a deeply rooted need for many women, even in exceptional situations such as after 3 previous caesarean sections. CASE PRESENTATION: The first patient, a 28-year-old 6th gravida and 3rd para, first presented in the 40+3 week of pregnancy desiring a vaginal birth, after all the other hospitals in the area had refused her request. A detailed explanation of potential risks was given and, when 2 days later contractions started, she gave birth to a newborn of 4450 g spontaneously, without complications. A month later, a second woman, 42 years old, 5th gravida, 3rd para, read about the above-mentioned case on social media and decided to attempt a natural delivery after 3 caesarean sections at our hospital as well. She presented herself for the first time in the 41+1 week of pregnancy in our delivery room with an onset of labor after rupture of the membranes and gave birth on the same day, spontaneously without complications, to a 4150 g heavy healthy newborn. CONCLUSIONS: The wish to attempt a spontaneous birth after 3 previous caesarean sections can be deeply anchored and should be professionally approached by obstetricians, even if counseling and management can be challenging.

Low Back Pain during Pregnancy and Delivery Outcomes.

AIM: To evaluate low back pain (LBP) incidence and impact throughout pregnancy in terms of women's well-being and delivery outcomes. MATERIAL AND METHODS: Cross-sectional prospective study conducted on singleton pregnancies at ≥37th gestational age admitted for delivery. Localization of LBP, intensity and frequency as well as derived functional disability status were assessed with a self-reported questionnaire. Main delivery outcomes including mode of delivery, and maternal or neonatal complications were recorded. RESULTS: A total of 229 women participated in the study. LBP prevalence amounted to 55.9%, with the pain already present before pregnancy in 14.0% of the cases. The pain was mostly localized in the lower back (40.6%), symphysis (23.3%), and coccyx (20.5%). Both the frequency and intensity of pain gradually increased significantly during pregnancy, reaching 20 days/month (IQR=10-30) and 6/10 points (IQR=5-8) on a visual analog scale in the 3rd trimester (p<0.05). The extent of functional impairment also progressively increased up to 39/100 points (IQR=25-55, p<0.05). Women affected by LBP during pregnancy had a higher cesarean section rate during labor than women without LBP (11.9% vs. 28.9%, p<0.05). The risk was also significant in the multivariate analysis (OR=4.0, 95%CI=1.1-15.0, p<0.05). There was no difference in the rate of operative vaginal births or in the other outcomes considered. CONCLUSIONS: LBP is a common issue in pregnant women, accounting for increasing morbidity and invalidity, and leading to an increased cesarean section risk during labor.

Antiangiogenic Therapy as a New Strategy in the Treatment of Endometriosis? The First Case Report.

Angiogenesis plays a pivotal role in implantation and development of ectopic endometrial lesions. Thus, the potential usefulness of anti-angiogenic therapies has been speculated. Several reports describe their usefulness in animal models. Nonetheless this therapy has not been tested on humans yet. Here we report the outcome of a patient treated for a severe endometriosis with Bevacizumab (Avastin®), a monoclonal antibody directed against the vascular endothelial growth (VEGF). After a first-look laparoscopy with confirmatory biopsies was performed, three doses of Bevacizumab at 2-week intervals were administered. The therapy showed a well-tolerated profile and the prompt disappearance of the therapy-refractory chronic dysmenorrhea. A suppression of metabolic activity at the PET-scan compared to the basal one performed at diagnosis was also recorded. Furthermore, compared to the diagnostic biopsies prior the treatment, we documented a shift in the hormonal receptors profile toward a higher expression of progesterone and estrogen receptors in the endometriotic lesions.

STRA6 and Placental Retinoid Metabolism in Gestational Diabetes Mellitus.

BACKGROUND: Recent reports indicate the potential role of the stimulated by retinoic acid 6 (STRA6) protein in developing insulin resistance. The study's objective was to assess placental STRA6 expression and staining pattern in human pregnancy complicated by gestational diabetes mellitus (GDM). The expression pattern of further relevant genes involved in retinoid metabolism was also evaluated. METHODS: A retrospective case-control study on paraffin-embedded placental tissue. Twenty-two human pregnancies affected by GDM, namely, 11 insulin-treated (iGDM) and 11 diet-controlled (dGDM), were compared with 22 normal-developed pregnancies (controls). An RT-PCR was performed in a random sample of 18 patients (six iGDM, six dGDM, and six controls) to assess RNA expression of STRA6 and further markers of retinoid metabolism. A semi-quantitative intensity evaluation at immunohistochemistry was performed for STRA6 in all 44 recruited patients. RESULTS: STRA6 showed a decreased placental staining (9.09% vs. 68.18% positively stained samples, p < 0.05) and augmented RNA expression in dGDM patients than controls (ΔCT expression 0.473, IQR 0.403-0.566 vs. 0.149, IQR 0.092-0.276, p < 0.05). The protein staining pattern in patients affected by iGDM was comparable to controls. A reduced RNA expression of LPL, LRP1, VLDLR, and MTTP besides an augmented expression of LDLR was found in dGDM, while overexpression of LRP1 and LPL was found in iGDM patients. Unlike in the control group, significant positive correlations were found between RXRα and the proteins involved in the intracellular uptake of ROH, such as STRA6, LRP1, LRP2, and VLDLR. CONCLUSIONS: An altered placental expression and staining pattern of STRA6 were found in pregnancies complicated by GDM compared to the controls. These changes were coupled to an altered expression pattern of several other genes involved in the retinoid metabolism.