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Tracking Cesarean Scar Morphology by Sonohysterography After Consecutive Cesarean Deliveries with Endometrium-Free Closure

Antoine, Clarel; Ibietatorremendia, Olivia; Timor-Tritsch, Ilan E
OBJECTIVE:To evaluate the impact of an endometrium-free closure on uterine scar morphology by comparing sonohysterograms in the same women, first after a cesarean with a standard or an endometrium-free closure, and then after a subsequent cesarean with an endometrium-free closure. MATERIALS AND METHODS/METHODS:This small retrospective longitudinal study used saline infusion sonohysterography to assess uterine scar morphology in 25 asymptomatic women who underwent 2 to 5 sonographic examinations following 2 to 9 consecutive cesarean deliveries. Forty paired consecutive procedures in which the second delivery used an endometrium-free closure technique met the inclusion criteria, categorized as "Transition Group" (n=9), in which a standard closure was followed by an endometrium-free closure, and "Successive Group" (n=31), in which women received the endometrium-free closure technique in two successive deliveries. Paired sonohysterographic analyses were performed after each cesarean delivery and longitudinally compared to evaluate niche development and scar morphology. Niche depth and residual myometrial thickness were measured; a niche depth greater than 2 mm was considered sonographically significant. A change greater than ±2 mm in depth or residual myometrial thickness was operationally defined as morphologically significant and not clinically validated. Generalized estimating equations (GEE) with robust standard errors were used to account for within-patient correlation (p-value < 0.05). RESULTS:By GEE analysis, the Transition Group had 4.67-fold higher odds of new niche development compared to the Successive Group (OR = 4.67; 95% CI: 0.71-30.77; p = 0.109). This difference did not reach statistical significance. Mean depth change was 1.31 mm greater in the Transition Group (B = 1.31; 95% CI: -0.25 to 2.87; p = 0.099). Transition Group pairs showed larger depth increases (median 4.6 mm, range: 3.0-5.0 mm) compared with Successive Group pairs (median 3.6 mm, range: 2.6-5.3 mm). These findings should be interpreted as hypothesis-generating only, not as evidence of clinical significance. Across both groups, 22/40 pairs (55.0%) ended without a niche after the second endometrium-free closure, including 21 (21/22, 95.5%) that initially presented without a niche and 1 (1/22, 4.5%) that initially presented with a niche. Ten pairs (10/40, 25.0%) that presented with pre-existing niches showed stable or improved niche depth, and nine pairs (9/40, 22.5%) of these cases showed stable or improved residual myometrial thickness, 3/40 (7.5%) worsened in depth, 2/40 (5.0%) simultaneously worsened in residual myometrial thickness, 6/40 (15.0%) developed a de novo niche, mean depth 4.2 mm (2.6 mm-6.5 mm), and mean residual myometrial thickness of 5.72 mm (3.50 mm -7.30 mm). CONCLUSION/CONCLUSIONS:In this small retrospective intraindividual cohort, the endometrium-free closure maintains favorable sonographic scar morphology in most women, with morphology reflecting both prior scar status and the technique at delivery. Repeated surgery may limit the benefit of closure technique in some women, although many maintained scar morphology even at higher-order cesareans. Results are limited by single observer measurements without reproducibility assessment, use of ±2 mm threshold, and absence of clinical outcomes. These paired observations warrant prospective evaluation in larger studies.
PMID: 42471172
ISSN: 1097-6868
CID: 6067522

Endometrium-free closure technique for hysterotomy incision at cesarean delivery

Antoine, Clarel; Timor-Tritsch, Ilan E; Bujold, Emmanuel; Young, Bruce K; Reece, E Albert
Cesarean deliveries are associated with uterine scar defects that significantly impact women's health and future pregnancy outcomes. The methods used for hysterotomy closure following cesarean delivery have undergone significant evolution. Commonly used techniques, which are relatively rapid and maintain hemostasis, include the endometrium in a single-layer or "bulk" closure. Such endometrium-inclusive cesarean closure has been linked to an increased risk of scar defects and long-term complications. However, the available data show no difference in outcomes related to cesarean closure technique, leading to widespread adoption of single-layer closure. The debate over the best method for uterine closure as well as the etiology of scar defects remains unresolved. We present the endometrium-free closure technique, an approach that requires in-depth knowledge of uterine anatomy, including the ability to distinguish the 3 layers of the uterine wall, and employs reapproximation of these layers. A 30-year retrospective study of consecutive cesarean deliveries using this closure method reports a reduction in abnormal implantation in subsequent pregnancies. Key findings from sonohysterographic studies demonstrate a clinically significant reduction in the development and size of scar defects when the endometrium is excluded from the closure, in women with one or multiple cesarean deliveries. While formal changes in surgical guidelines may require further randomized trials, we believe that this technique has the potential to reduce adverse events and provide long-term benefits for women's reproductive health.
PMID: 41485813
ISSN: 1097-6868
CID: 5980492

Endometrium-Free Closure Technique During Cesarean Delivery for Reducing the Risk of Niche Formation and Placenta Accreta Spectrum Disorders

Antoine, Clarel; Meyer, Jessica A; Silverstein, Jenna; Buldo-Licciardi, Julia; Lyu, Chen; Timor-Tritsch, Ilan E
OBJECTIVE:To examine the prevalence and severity of postcesarean residual niche, evaluated using saline infusion sonohysterography, in an expanded cohort of women with one prior cesarean delivery and to assess the effect of uterine closure technique on the risk of placenta accreta spectrum (PAS) disorders. METHODS:This secondary analysis includes 70 patients who underwent saline infusion sonohysterography after one prior cesarean delivery. Patients were grouped according to hysterotomy closure technique: two-layer endometrium-free closure (technique A), and two- or one-layer routine closures (technique B). Niche dimensions and residual myometrial thickness were measured. The primary outcome was clinically significant niche (depth larger than 2 mm), a risk factor for PAS. Groups were compared using χ2, unpaired t test, Kruskal-Wallis, and logistic regression with significance at P<.05. RESULTS:There were 33 patients in the technique A group and 37 patients in the technique B group. Technique A was associated with smaller niche dimensions (P=.018 for width, .005 for depth, and .002 for length), and exhibited thicker residual myometrial thickness (8.5 mm vs 5.5 mm, P=.041) and a lower incidence of clinically significant niches. The odds of having a clinically significant niche were 27 times higher in the technique B group (adjusted odds ratio 27.1, 95% CI, 4.35-168.81, P<.001). CONCLUSION/CONCLUSIONS:Uterine closure techniques are associated with the development and size of postcesarean residual niches, which are critical risk factors for PAS disorders. Use of an endometrium-free closure technique during primary cesarean delivery is associated with a reduced risk of future niche formation and PAS complications.
PMID: 39787602
ISSN: 1873-233x
CID: 5782042

The broadening spectrum of niche and insights for improved outcomes [Letter]

Antoine, Clarel; Timor-Tritsch, Ilan
PMID: 39923872
ISSN: 1097-6868
CID: 5793082

Beyond Single- vs Double-Layer Closure: Optimizing Uterine repair in Cesarean Delivery with Endometrium-Free Technique [Letter]

Antoine, Clarel
PMID: 39428032
ISSN: 1097-6868
CID: 5739412

Reply to: "Optimal closure of the uterus during cesarean section: beyond the two layers" commenting on "The Effect of Uterine Closure Technique on Cesarean Scar Niche Development After Multiple Cesarean Deliveries" [Letter]

Meyer, Jessica A; Silverstein, Jenna; Timor-Tritsch, Ilan E; Antoine, Clarel
PMID: 38282351
ISSN: 1619-3997
CID: 5627762

Clinical potential of human amniotic fluid stem cells

Martin, Monique M; Chan, Michael; Antoine, Clarel; Bar-El, Liron; Bornstein, Eran; Young, Bruce K
PMID: 38164020
ISSN: 1619-3997
CID: 5633102

The effect of uterine closure technique on cesarean scar niche development after multiple cesarean deliveries

Meyer, Jessica A; Silverstein, Jenna; Timor-Tritsch, Ilan E; Antoine, Clarel
OBJECTIVES/OBJECTIVE:To use saline infusion sonohysterography (SIS) to evaluate the effect of uterine closure technique on niche formation after multiple cesarean deliveries (CDs). METHODS:Patients with at least one prior CD were evaluated for niche via SIS. Subgroups of any number repeat CD (>1 prior), lower-order CD (<4 prior), and higher-order CD (≥4 prior) were analyzed, stratifying by hysterotomy closure technique at last cesarean preceding imaging; techniques included Technique A (endometrium-free double-layer closure) and Technique B (single- or double-layer routine endo-myometrial closure). Niche defects were quantified (depth, length, width, and residual myometrial thickness). The primary outcome was clinically significant niche, defined as depth >2 mm. Statistical analysis was performed using chi-square, ANOVA, t-test, Kruskal-Wallis, and multiple logistic regression, with p-values of <0.05 were statistically significant. RESULTS:A total of 172 post-cesarean SIS studies were reviewed: 105 after repeat CDs, 131 after lower-order CDs, and 41 after higher-order CDs. Technique A was associated with a shorter interval to imaging and more double-layer closures. Technique B was associated with more clinically significant niches across all subgroups, and these niches were significantly longer and deeper when present. Multiple logistic regression demonstrated a 5.6, 8.1, and 11-fold increased adjusted odds of clinically significant niche following Technique B closure in the repeat CD (p<0.01), lower-order CD (p<0.001), and higher-order CD (p=0.04) groups, respectively. CONCLUSIONS:While multiple CDs are known to increase risk for niche defects and their sequelae, hysterotomy closure technique may help to reduce niche development and severity.
PMID: 38081042
ISSN: 1619-3997
CID: 5589642

Clinical potential of human amniotic fluid stem cells

Martin, Monique M; Chan, Michael; Antoine, Clarel; Bar-El, Liron; Bornstein, Eran; Young, Bruce K
OBJECTIVES/OBJECTIVE:To determine whether amniotic fluid derived stem cells maintain their stem cell characteristics (a) after processing by a licensed cell therapy center and (b) after the cells undergo simulated clinical application. METHODS:Amniotic fluid was collected by laparotomy - a small uterine incision was made at proposed site for delivery and a sterile catheter inserted to collect fluid into a sterile bag. After flow stopped the catheter was withdrawn, the cesarean completed and the collected fluid delivered to the cell therapy center for processing and cryostorage. A clinical setting was simulated where amniotic fluid cells received from cell therapy center were thawed at room temperature for a maximum of 3 h and passed through a clinical cell delivery device to monitor cell viability. The cells were examined for viability, stability, growth, differentiation, and markers of stemness. RESULTS:Amniotic fluid stem cells processed from a clinical cell therapy center behave similarly to amniotic fluid stem cells processed in a research laboratory with respects to viability, stability, growth, differentiation and maintain markers of stemness. There were differences due to heterogeneity of samples which were not methodological. Growth in cell culture and differentiation were satisfactory. Simulation of treating the cells in a clinical environment show a general stability in viability of amniotic fluid cells at room temperature for 3 h minimum and when passed through a clinically approved delivery device. CONCLUSIONS:The data indicate human amniotic fluid processed in a clinical facility could be used therapeutically if proven to be safe.
PMID: 35985014
ISSN: 1619-3997
CID: 5300322

Variations in uterine closure technique: an institutional survey of obstetricians and implications for patient counseling and prevention of adverse sequelae

Antoine, Clarel; Alexander, Jameshisa S; Yaghoubian, Yasaman C; Harary, Joyce M
OBJECTIVES/OBJECTIVE:To assess the diversity of uterine closure techniques (UCTs) among providers in one institution and evaluate concurrent consideration of adverse outcomes for patient counseling, provisional care, and prevention. METHODS:Forty-four obstetricians at NYU Langone Health were emailed a survey of their uterine closure technique, patient counseling, and practice experience. Results were stratified by years of practice: ≤5, 5-20, and 20-40 years. RESULTS:Thirty-nine obstetricians (88.6%) completed the survey. Among those, a blunt uterine opening was preferred by 29 (74.4%), and a mid-lower segment location was favored by 34 (87.2%). At uterine closure, the endometrium was included by 20 (51.3%), with half a centimeter or more incorporated in the myometrial closure, whereas 15 (38.5%) did not factor in the endometrium's presence. Closure duration varied from 1 to 20 min, with 21 (53.9%) lasting 1-5 min and 12 (30.8%) lasting 5-10 min. All physicians were familiar with the potential post-cesarean complications and counseled their patients accordingly; 25 (64.1%) at the first post-op visit while 14 (35.9%) did so before the next conception. Practitioners with fewer years in practice endorsed the safety of up to five consecutive cesarean births, while those with more experience approved up to ten. Thirty-two obstetricians (82.1%) stated that the risk of abnormal placentation is exclusively associated with the number of cesarean sections, whereas five (12.8%) senior obstetricians asserted that individual surgical techniques are most impactful. CONCLUSIONS:The survey illustrates that various UCTs are performed irrespective of potential adverse sequelae and without consideration for subsequent patient counseling and care. Ongoing research must study the impact of UCT on scar healing to formulate preventive strategies for post-cesarean complications.
PMID: 35538677
ISSN: 1619-3997
CID: 5214382