Prevalence of fetal anomalies, stillbirth, neonatal morbidity, or mortality in pregnancies complicated by placenta accreta spectrum disorders.

INTRODUCTION: Placenta accreta spectrum disorders (PAS) lead to major complications in pregnancy. While the maternal morbidity associated with PAS is well known, there is less information regarding neonatal morbidity in this setting. The aim of this study is to describe the neonatal outcomes (fetal malformations, neonatal morbidity, twin births, stillbirth, and neonatal death), using an international multicenter database of PAS cases. MATERIAL AND METHODS: This was a prospective, multicenter cohort study based on prospectively collected cases, using the international multicenter database of the International Society for PAS, carried out between January 2020 and June 2022 by 23 centers with experience in PAS care. All PAS cases were included, regardless of whether singleton or multiple pregnancies and were managed in each center according to their own protocols. Data were collected via chart review. Local Ethical Committee approval and Data Use Agreements were obtained according to local policies. RESULTS: There were 315 pregnancies eligible for inclusion, with 12 twin pregnancies, comprising 329 fetuses/newborns; 2 cases were excluded due to inconsistency of data regarding fetal abnormalities. For the calculation of neonatal morbidity and mortality, all elective pregnancy terminations were excluded, hence 311 pregnancies with 323 newborns were analyzed. In our cohort, 3 neonates (0.93%) were stillborn; of the 320 newborns delivered, there were 10 cases (3.13%) of neonatal death. The prevalence of major congenital malformations was 4.64% (15/323 newborns), most commonly, cardiovascular, central nervous system, and gastrointestinal tract malformations. The overall prevalence of major neonatal morbidity in pregnancies complicated by PAS was 47/311 (15.1%). There were no stillbirths, neonatal deaths, or fetal malformations in reported twin gestations. CONCLUSIONS: Although some outcomes may be too rare to detect within our cohort and data should be interpreted with caution, our observational data supports reassuring neonatal outcomes for women with PAS.

Opportunities for, and barriers to, uterus-preserving surgical techniques for placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making. MATERIAL AND METHODS: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered. RESULTS: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%). CONCLUSIONS: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.

Uterine scars after caesarean delivery: From histology to the molecular and ultrastructural level.

Uterine rupture during a trial of labor after caesarean delivery (CD) is a serious complication for mother and fetus. The lack of knowledge on histological features and molecular pathways of uterine wound healing has hindered research in this area from evolving over time. We analysed collagen content and turnover in uterine scars on a histological, molecular and ultrastructural level. Therefore, tissue samples from the lower uterine segment were obtained during CD from 16 pregnant women with at least one previous CD, from 16 pregnant women without previous CD, and from 16 non-pregnant premenopausal women after hysterectomy for a benign disease. Histomorphometrical collagen quantification showed, that the collagen content of the scar area in uterine wall specimens after previous CD was significantly higher than in the unscarred myometrium of the same women and the control groups. Quantitative real-time PCR of uterine scar tissue from FFPE samples delineated by laser microdissection yielded a significantly higher COL3A1 expression and a significantly lower COL1A2/COL3A1 ratio in scarred uteri than in samples from unscarred uteri. Histological collagen content and the expression of COL1A2 and COL3A1 were positively correlated, while COL1A2/COL3A1 ratio was negatively correlated with the histological collagen content. Transmission electron microscopy revealed a destroyed myometrial ultrastructure in uterine scars with increased collagen density. We conclude that the high collagen content in uterine scars results from an ongoing overexpression of collagen I and III. This is a proof of concept to enable further analyses of specific factors that mediate uterine wound healing.

Intraoperative ultrasound during repeat cesarean delivery facilitates sampling of uterine scar tissue.

OBJECTIVES: Histological examination of uterine scars provides insight into uterine wound healing and helps to develop prevention methods of uterine wall rupture after previous uterine surgery. Therefore, exact intraoperative scar identification is needed for specimen collection from the actual scar tissue. The aim of this study was to correlate pre- and intraoperative ultrasound measurements of the lower uterine segment (LUS) with histological findings of scar tissue and to evaluate the relevance of intraoperative ultrasound. METHODS: In a prospective observational study, preoperative and intraoperative sonographic measurements of the LUS thickness were performed in 33 women with a history of at least one cesarean delivery. Intraoperative ultrasound with a linear transducer placed directly on the uterus identified the scar area and uterotomy was performed 2 cm cranially. Tissue samples were taken after extraction of the fetus, embedded in paraffin wax, and stained according to Gomori Trichrome to identify scar tissue. Collagen content was evaluated with imaging software Fiji (NIH, Bethesda, USA). Preoperative and intraoperative sonographic measurements were correlated with histologic evidence of scar tissue. RESULTS: Histological evidence of scar tissue was found in 11 out of 33 samples with significantly lower ultrasonographic thickness of the lower uterine segment compared to the other 22 samples, both antepartum (1.4 mm [1.3-1.9] vs. 2.0 mm [1.6-2.6], p=0.03) and intrapartum (1.6 mm [1.3-1.9] vs. 3.7 mm [2.0-4.7], p<0.01). Intraoperative ultrasound had a significantly higher predictive power (AUC difference 0.18 [0.03-0.33], p=0.01). CONCLUSIONS: Intraoperative sonography identifies the uterine wall area with histologically confirmable scar tissue far better than preoperative sonography.

A Sustainable Translational Sheep Model for Planned Cesarean Delivery of Contraction-Free Ewes.

We evaluated whether the sheep constitutes a useful translational model to evaluate anatomical and surgical aspects of cesarean delivery (CD) from a human medical perspective with the aim of both maternal and neonatal well-being. Our hypothesis was that CD in contraction-free ewes is not associated with major complications. Primary endpoint was the transferability of anatomical conditions and surgical techniques of CD from the ewe to the human. Secondary endpoints were maternal and fetal survival, occurrence of retained fetal membranes, metritis, mastitis, or wound infections. Forty-eight Merino ewes were delivered by CD after 95% gestation (142-144 days). Both ewes and newborn lambs were cared for intensively after the delivery. Ovine uterine anatomy during CD appeared slightly different but comparable to the human uterus. Uterine incisions were mostly performed in the uterine horns, not in the uterine corpus. The ovine uterine wall is thinner than in humans. All ewes survived without any major complications. Seventy-seven (88.5%) out of 87 live-born lambs survived without any complications. The contraction-free ewe constitutes an appropriate and safe model to evaluate anatomical and surgical aspects of CD from a human medical perspective. We present a step-by-step manual for successfully planned cesarean delivery for sheep including the perioperative management illustrated with photographs and a five-minute video. With adequate planning and a reasonable number of staff, it is possible to safeguard both maternal and neonatal survival. This sustainable translational medicine model offers additional potential for the offspring to be used for further research studies (e.g., transgenerational inheritance research).

Optimized RNA isolation of FFPE uterine scar tissues for RNA expression analyses delineated by laser microdissection.

Samples for histological analyses are often formalin-fixed paraffin-embedded (FFPE) and slide-mounted, which complicates RNA extraction for many downstream molecular applications. Furthermore, when the region of interest is extremely small due to isolation with laser microdissection (LMD), extracting RNA of adequate quality and quantity is difficult. We describe an optimized protocol for maximizing RNA output from FFPE tissue devised to identify and analyze gene expression of human maternal uterine scar tissue obtained from uterotomy scars resulting from prior cesarean deliveries. Gomori trichrome staining allowed for region identification for LMD. Successful RNA isolation, reverse transcription and, importantly, quantitative real-time PCR (qRT-PCR) were performed. This report provides an optimized step-by-step protocol yielding sufficient RNA for qRT-PCR analyses from challenging tissue/LMD-FFPE samples.