Contraception and sterilization selection at delivery among pregnant patients with malignancy.

INTRODUCTION: Since malignancy during pregnancy is uncommon, information regarding contraception selection or sterilization at delivery is limited. The objective of this study was to examine the type of long-acting reversible contraception or surgical sterilization procedure chosen by pregnant patients with malignancy at delivery. MATERIAL AND METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample in the USA. The study population was vaginal and cesarean deliveries in a hospital setting from January 2017 to December 2020. Pregnant patients with breast cancer (n = 1605), leukemia (n = 1190), lymphoma (n = 1120), thyroid cancer (n = 715), cervical cancer (n = 425) and melanoma (n = 400) were compared with 14 265 319 pregnant patients without malignancy. The main outcome measures were utilization of long-acting reversible contraception (subdermal implant or intrauterine device) and performance of permanent surgical sterilization (bilateral tubal ligation or bilateral salpingectomy) during the index hospital admission for delivery, assessed with a multinomial regression model controlling for clinical, pregnancy and delivery characteristics. RESULTS: When compared with pregnant patients without malignancy, pregnant patients with breast cancer were more likely to proceed with bilateral salpingectomy (adjusted odds ratio [aOR] 2.30) or intrauterine device (aOR 1.91); none received the subdermal implant. Pregnant patients with leukemia were more likely to choose a subdermal implant (aOR 2.22), whereas those with lymphoma were more likely to proceed with bilateral salpingectomy (aOR 1.93) and bilateral tubal ligation (aOR 1.76). Pregnant patients with thyroid cancer were more likely to proceed with bilateral tubal ligation (aOR 2.21) and none received the subdermal implant. No patients in the cervical cancer group selected long-acting reversible contraception, and they were more likely to proceed with bilateral salpingectomy (aOR 2.08). None in the melanoma group chose long-acting reversible contraception. Among pregnant patients aged <30, the odds of proceeding with bilateral salpingectomy were increased in patients with breast cancer (aOR 3.01), cervical cancer (aOR 2.26) or lymphoma (aOR 2.08). The odds of proceeding with bilateral tubal ligation in pregnant patients aged <30 with melanoma (aOR 5.36) was also increased. CONCLUSIONS: The results of this nationwide assessment in the United States suggest that among pregnant patients with malignancy, the preferred contraceptive option or method of sterilization at time of hospital delivery differs by malignancy type.

Concurrent Minimally Invasive Gynecologic Procedures at the Time of Laparoscopic Cholecystectomy.

In this cross-sectional study including 1,722,479 women who underwent laparoscopic cholecystectomy between January 2016 and December 2019 identified in the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample, the prevalence rate of gynecologic diagnoses was 11.3 per 1,000. Among presumed elective laparoscopic cholecystectomy, the highest performance rate of concurrent gynecologic procedure per gynecologic diagnosis was laparoscopic adnexectomy among patients with benign ovarian tumor (652/1,000 diagnoses), followed by laparoscopic adnexectomy for endometrioma (386/1,000 diagnoses) and cervical conization for cervical carcinoma in situ (304/1,000 diagnoses). The measured surgical morbidity rates for patients who had concurrent gynecologic surgery and those who did not were 2.8 per 1,000 and 1.9 per 1,000, respectively (adjusted odds ratio 1.39, 95% CI 0.75-2.59). These results suggest that minimally invasive gynecologic surgeries are being performed at the time of outpatient laparoscopic cholecystectomy in the United States.

Alternative end-joining results in smaller deletions in heterochromatin relative to euchromatin.

Pericentromeric heterochromatin is highly enriched for repetitive sequences prone to aberrant recombination. Previous studies showed that homologous recombination (HR) repair is uniquely regulated in this domain to enable 'safe' repair while preventing aberrant recombination. In Drosophila cells, DNA double-strand breaks (DSBs) relocalize to the nuclear periphery through nuclear actin-driven directed motions before recruiting the strand invasion protein Rad51 and completing HR repair. End-joining (EJ) repair also occurs with high frequency in heterochromatin of fly tissues, but how alternative EJ (alt-EJ) pathways operate in heterochromatin remains largely uncharacterized. Here, we induce DSBs in single euchromatic and heterochromatic sites using a new system that combines the DR- white reporter and I-SceI expression in spermatogonia of flies. Using this approach, we detect higher frequency of HR repair in heterochromatin, relative to euchromatin. Further, sequencing of mutagenic repair junctions reveals the preferential use of different EJ pathways across distinct euchromatic and heterochromatic sites. Interestingly, synthesis-dependent microhomology-mediated end joining (SD-MMEJ) appears differentially regulated in the two domains, with a preferential use of motifs close to the cut site in heterochromatin relative to euchromatin, resulting in smaller deletions. Together, these studies establish a new approach to study repair outcomes in fly tissues, and support the conclusion that heterochromatin uses more HR and less mutagenic EJ repair relative to euchromatin.

Assessment of placenta accreta spectrum at vaginal birth after cesarean delivery.

BACKGROUND: Previous cesarean delivery is a risk factor for developing placenta accreta spectrum in a subsequent pregnancy and patients with antenatally suspected placenta accreta spectrum frequently undergo planned cesarean hysterectomy. There is a paucity of data regarding unsuspected placenta accreta spectrum among patients undergoing trial of labor after cesarean delivery for attempted vaginal birth after cesarean delivery. OBJECTIVE: This study aimed to investigate the incidence, characteristics, and delivery outcomes of patients with placenta accreta spectrum diagnosed at the time of vaginal birth after cesarean delivery. STUDY DESIGN: The Healthcare Cost and Utilization Project's National Inpatient Sample was retrospectively queried to examine 184,415 patients with a history of low transverse cesarean delivery who had vaginal delivery in the current index hospital admission between 2017 and 2020. Those with placenta previa, previous vertical cesarean delivery, other uterine scars, and uterine rupture were excluded. This study identified placenta accreta spectrum cases using the World Health Organization International Classification of Disease, Tenth Revision, codes of O43.2. Coprimary outcomes were (1) the incidence rate of placenta accreta spectrum at vaginal birth after cesarean delivery; (2) clinical and pregnancy characteristics related to placenta accreta spectrum, assessed with multivariable binary logistic regression model; and (3) delivery outcomes associated with placenta accreta spectrum by fitting propensity score adjustment. The secondary outcome was to conduct a systematic literature review using 3 public search engines (PubMed, Cochrane, and Scopus). Data on incidence rate and maternal morbidity related to placenta accreta spectrum at vaginal birth after cesarean delivery were evaluated. RESULTS: The incidence rate of placenta accreta spectrum at vaginal birth after cesarean delivery was 8.1 per 10,000 deliveries. Most placenta accreta spectrum cases were placenta accreta (83.3%). In a multivariable analysis, older maternal age, tobacco use, preeclampsia, multifetal pregnancy, fetal anomaly, preterm premature rupture of membrane, chorioamnionitis, low-lying placenta, and preterm delivery were associated with an increased risk of placenta accreta spectrum (all, P<.05). Of these factors, low-lying placenta had the largest odds for placenta accreta spectrum (526.3 vs 7.3 per 10,000 deliveries; adjusted odds ratio, 35.02; 95% confidence interval, 18.19-67.42). Patients in the placenta accreta spectrum group were more likely to have postpartum hemorrhage (80.0% vs 5.5%), blood product transfusion (23.3% vs 1.0%), shock or coagulopathy (20.0% vs 0.2%), and hysterectomy (43.3% vs <0.1%) than those without placenta accreta spectrum (all, P<.001). In a systematic literature review, a total of 212 studies were screened, and none of these studies examined the incidence and morbidity of placenta accreta spectrum at vaginal birth after cesarean delivery. CONCLUSION: This nationwide assessment suggests that although placenta accreta spectrum with vaginal birth after cesarean delivery is uncommon (1 of 1229 cases), the diagnosis of placenta accreta spectrum at vaginal birth after cesarean delivery is associated with significant maternal morbidity. In addition, the data suggest that low-lying placenta in the setting of previous low transverse cesarean delivery warrants careful evaluation for possible placenta accreta spectrum before a trial of labor.

Uptake and Outcomes of Neoadjuvant Chemotherapy Among US Patients With Less Common Epithelial Ovarian Carcinomas.

Importance: Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied. Objective: To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer. Design, Setting, and Participants: A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed from July 2022 to April 2023. The evaluation included patients with stage III to IV ovarian cancer with clear cell, mucinous, or low-grade serous histologic subtypes who received multimodal treatment with surgery and chemotherapy. Exposures: Exposure assignment per the sequence of treatment: primary debulking surgery (PDS) followed by chemotherapy (PDS group) or NACT followed by interval surgery (NACT group). Main Outcomes and Measures: Temporal trends and characteristics of NACT use were assessed using multivariable analysis, and overall survival (OS) was assessed with the inverse probability of treatment weighting propensity score. Results: A total of 3880 patients were examined in the National Cancer Database including 1829 women (median age, 56 [IQR, 49-63] years) with clear cell, 1156 women (median age, 53 [IQR, 42-64] years) with low-grade serous, and 895 women (median age, 57 [IQR, 48-66] years) with mucinous carcinomas. NACT use increased in patients with clear cell (from 10.2% to 16.2%, 58.8% relative increase; P < .001 for trend) or low-grade serous (from 7.7% to 14.2%, 84.4% relative increase; P = .007 for trend) carcinoma during the study period. This association remained consistent in multivariable analysis. NACT use also increased, but nonsignificantly, in mucinous carcinomas (from 8.6% to 13.9%, 61.6% relative increase; P = .07 for trend). Across the 3 histologic subtypes, older age and stage IV disease were independently associated with NACT use. In a propensity score-weighted model, the NACT and PDS groups had comparable OS for clear cell (4-year rates, 31.4% vs 37.7%; hazard ratio [HR], 1.12; 95% CI, 0.95-1.33) and mucinous (27.0% vs 26.7%; HR, 0.90; 95% CI, 0.68-1.19) carcinomas. For patients with low-grade serous carcinoma, NACT was associated with decreased OS compared with PDS (4-year rates, 56.4% vs 81.0%; HR, 2.12; 95% CI, 1.55-2.90). Increasing NACT use and histologic subtype-specific survival association were also found in the Surveillance, Epidemiology, and End Results Program cohort (n = 1447). A meta-analysis of 4 studies, including the current study, observed similar OS associations for clear cell (HR, 1.13; 95% CI, 0.96-1.34; 2 studies), mucinous (HR, 0.93; 95% CI, 0.71-1.21; 2 studies), and low-grade serous (HR, 2.11; 95% CI, 1.63-2.74; 3 studies) carcinomas. Conclusions and Relevance: Despite the lack of data on outcomes of NACT among patients with less common carcinomas, this study noted that NACT use for advanced disease has gradually increased in the US. Primary chemotherapy for advanced-stage, low-grade serous ovarian cancer may be associated with worse survival compared with PDS.

The Positive Predictive Value of Hospital Discharge Data for Identifying Severe Maternal Morbidity With and Without Blood Transfusion.

BACKGROUND: Blood transfusion is 1 of the 21 indicators for severe maternal morbidity (SMM) as defined by the Centers for Disease Control and Prevention (CDC) using administrative data. The CDC SMM definition is being prepared to measure hospital quality of care; however, transfusion coding reliability has been questioned. The authors assessed the positive predictive value (PPV) of administrative data for identifying gold standard SMM using the CDC SMM definition, with and without the transfusion indicator. METHODS: A retrospective cohort study of one hospital's childbirth admissions (2016-2019) was performed. Data were screened for CDC SMM, and subgroups were created for those with transfusion as the sole indicator for SMM (transfusion-only SMM) versus those with at least one other SMM indicator (other SMM). Medical chart review classified CDC SMM cases based on gold standard SMM criteria. Gold standard SMM was defined by validated indicators identified by internal hospital quality reviews and confirmed by expert consensus. The PPV was calculated for all CDC SMM cases and the subgroups. RESULTS: Of 4,212 eligible people, 278 (6.6%) had CDC SMM. Chart review identified 110 gold standard SMM cases among screen-positive cases, yielding an overall PPV of the CDC SMM definition for gold standard SMM of 39.6%. CDC SMM cases identified solely by administrative coding for transfusion were half as likely to meet gold standard criteria, compared to cases identified by other SMM administrative codes (25.9% vs. 49.4%). CONCLUSION: Blood transfusion, coded as an independent risk factor, had a poor PPV for gold standard SMM. Given efforts to use CDC SMM for quality comparisons, more research is needed to reliably identify cases of SMM without relying on blood transfusion codes.

Pregnancy with retained intrauterine device: national-level assessment of characteristics and outcomes.

BACKGROUND: Although intrauterine devices provide effective contraceptive protection, unintentional pregnancy can occur. Previous studies have shown that a retained intrauterine device during pregnancy is associated with adverse pregnancy outcomes but there is a paucity of nationwide data and analysis. OBJECTIVE: This study aimed to describe characteristics and outcomes of pregnancies with a retained intrauterine device. STUDY DESIGN: This serial cross-sectional study used data from the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population comprised 18,067,310 hospital deliveries for national estimates from January 2016 to December 2020. The exposure was retained intrauterine device status, identified by the World Health Organization's International Classification of Diseases, Tenth Revision, code O26.3. The co-primary outcome measures were incidence rate, clinical and pregnancy characteristics, and delivery outcome of patients with a retained intrauterine device. To assess the pregnancy characteristics and delivery outcomes, an inverse probability of treatment weighting cohort was created to mitigate the prepregnant confounders for a retain intrauterine device. RESULTS: A retained intrauterine device was reported in 1 in 8307 hospital deliveries (12.0 per 100,000). In a multivariable analysis, Hispanic individuals, grand multiparity, obesity, alcohol use, and a previous uterine scar were patient characteristics associated with a retained intrauterine device (all P<.05). Current pregnancy characteristics associated with a retained intrauterine device included preterm premature rupture of membrane (9.2% vs 2.7%; adjusted odds ratio, 3.15; 95% confidence interval, 2.41-4.12), fetal malpresentation (10.9% vs 7.2%; adjusted odds ratio, 1.47; 95% confidence interval, 1.15-1.88), fetal anomaly (2.2% vs 1.1%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.85), intrauterine fetal demise (2.6% vs 0.8%; adjusted odds ratio, 2.21; 95% confidence interval, 1.37-3.57), placenta malformation (1.8% vs 0.8%; adjusted odds ratio, 2.12; 95% confidence interval, 1.20-3.76), placenta abruption (4.7% vs 1.1%; adjusted odds ratio, 3.24; 95% confidence interval, 2.25-4.66), and placenta accreta spectrum (0.7% vs 0.1%; adjusted odds ratio, 4.82; 95% confidence interval, 1.99-11.65). Delivery characteristics associated with a retained intrauterine device included previable loss at <22 weeks' gestation (3.4% vs 0.3%; adjusted odds ratio, 5.49; 95% confidence interval, 3.30-9.15) and periviable delivery at 22 to 25 weeks' gestation (3.1% vs 0.5%; adjusted odds ratio, 2.81; 95% confidence interval, 1.63-4.86). Patients in the retained intrauterine device group were more likely to have a diagnosis of retained placenta at delivery (2.5% vs 0.4%; adjusted odds ratio, 4.45; 95% confidence interval, 2.70-7.36) and to undergo manual placental removal (3.2% vs 0.6%; adjusted odds ratio, 4.81; 95% confidence interval, 3.11-7.44). CONCLUSION: This nationwide analysis confirmed that pregnancy with a retained intrauterine device is uncommon, but these pregnancies may be associated with high-risk pregnancy characteristics and outcomes.

Unsuspected placenta accreta spectrum at vaginal delivery: assessment of incidence, characteristics, and maternal morbidity.

BACKGROUND: Placenta accreta spectrum refers to morbidly adherent trophoblastic tissue invading into the gravid uterus and is associated with significant maternal morbidity. Most cases of placenta accreta spectrum are suspected antenatally, and most patients undergo planned, late-preterm cesarean hysterectomy to reduce the risk of morbidity. Rarely, however, placenta accreta spectrum is incidentally diagnosed at vaginal delivery, but there is a scarcity of data regarding these events. OBJECTIVE: This study aimed to examine the incidence, characteristics, and outcomes of pregnant individuals with incidentally diagnosed placenta accreta spectrum at term vaginal delivery. STUDY DESIGN: This was a retrospective cohort study investigating the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population was 8,694,669 term vaginal deliveries from January 2016 to December 2019. Exclusion criteria included previous uterine scar, placenta previa, and preterm delivery. Exposure was assigned by the diagnosis of placenta accreta spectrum. The main outcomes were: (1) incidence rate, (2) clinical and pregnancy characteristics, and (3) maternal morbidity related to unsuspected placenta accreta spectrum at vaginal delivery. Multivariable binary logistic regression analysis and inverse probability of treatment weighting were fitted for statistical analysis. RESULTS: Unsuspected placenta accreta spectrum was reported in 1 in 3797 vaginal deliveries. In a multivariable analysis, the following were associated with increased likelihood of unsuspected placenta accreta spectrum (all, P<.05): (1) patient factor with older age, (2) uterine factors such as uterine anomaly and uterine myoma, (3) pregnancy factors including early-term delivery and previous recurrent pregnancy losses, and (4) fetal factors of in utero growth restriction and demise. Of those, uterine anomaly had the greatest association with unsuspected placenta accreta spectrum (adjusted odds ratio, 6.23; 95% confidence interval, 4.20-9.26). In a propensity score-weighted model, patients in the unsuspected placenta accreta spectrum group were more likely to have hemorrhage (65.2% vs 4.1%), blood product transfusion (21.3% vs 0.6%), hysterectomy (14.9% vs <0.1%), coagulopathy (2.9% vs 0.1%), and shock (2.9% vs <0.1%) compared with those without placenta accreta spectrum. Patients in the unsuspected placenta accreta spectrum group were also more likely to receive manual removal of the placenta compared with those in the non-placenta accreta spectrum group (25.1% vs 0.6%). CONCLUSION: This study suggests that although unsuspected placenta accreta spectrum among patients undergoing term vaginal delivery is rare, it is associated with significant morbidity. The observed association between uterine anomalies and placenta accreta spectrum warrants further investigation.

Gynecologic oncologists in surgery for placenta accreta spectrum: a survey for practice, experience, and interest.

OBJECTIVE: Surgery for placenta accreta spectrum is associated with significant maternal morbidity and mortality. The role of gynecologic oncologists in the surgical management of placenta accreta spectrum is currently under investigation. This study examined the practices, experiences, and interests of gynecologic oncologists in placenta accreta spectrum surgeries. METHODS: The intervention was an anonymous, cross-sectional, 20-question survey sent to 1084 members of the Society of Gynecologic Oncology in the USA. RESULTS: A total of 184 gynecologic oncologists responded to the survey (response rate 17.0%). Most participating gynecologic oncologists have been practicing for >10 years after fellowship (53.2%), practice in urban-teaching hospitals (84.8%) with delivery volumes ≥3000/year (54.3%), and have a multidisciplinary approach (82.5%). Three-quarters (78.7%) feel that the rate of placenta accreta spectrum is increasing over time. One-third (35.5%) perform ≥6 hysterectomies for placenta accreta spectrum yearly. Less than half (45.5%) practice conservative management. Approximately half are involved from the beginning of the case (49.7%) and perform the surgery in the main operating room (59.4%). Almost three-quarters (71.6%) have experienced surgical blood loss >5 L and one-third (36.6%) have experienced cases with blood loss >10 L. About half (50.3%) of participants are interested in placenta accreta spectrum surgery for future practice. Gynecologic oncologists engaging in a multidisciplinary approach are more likely to practice in an urban-teaching hospital, have higher surgical volume, be involved from the beginning of the case, and be interested in placenta accreta spectrum surgery. Those >10 years post-training and in the Southern US region are more likely to practice conservative management or delayed hysterectomy. CONCLUSION: This society-based cross-sectional survey suggests that gynecologic oncologists are actively involved in the surgical management of placenta accreta spectrum in the USA. Nearly half of gynecologic oncologists who responded to the survey expressed interest in surgery for placenta accreta spectrum.

Nuclear F-actin and myosins drive relocalization of heterochromatic breaks.

Heterochromatin mainly comprises repeated DNA sequences that are prone to ectopic recombination. In Drosophila cells, 'safe' repair of heterochromatic double-strand breaks by homologous recombination relies on the relocalization of repair sites to the nuclear periphery before strand invasion. The mechanisms responsible for this movement were unknown. Here we show that relocalization occurs by directed motion along nuclear actin filaments assembled at repair sites by the Arp2/3 complex. Relocalization requires nuclear myosins associated with the heterochromatin repair complex Smc5/6 and the myosin activator Unc45, which is recruited to repair sites by Smc5/6. ARP2/3, actin nucleation and myosins also relocalize heterochromatic double-strand breaks in mouse cells. Defects in this pathway result in impaired heterochromatin repair and chromosome rearrangements. These findings identify de novo nuclear actin filaments and myosins as effectors of chromatin dynamics for heterochromatin repair and stability in multicellular eukaryotes.