Development of a coordinated registry network for pelvic organ prolapse technologies.

Baird CE, Chughtai B,, Kobashi K, Jung M, Sedrakyan A, Andrews S, Ferriter A, Cornelison T, Marinac-Dabic D.

BMJ Surg Interv Health Technol. 2022 Nov 11;4(Suppl 1):e000076. doi: 10.1136/bmjsit-2020-000076. PMID: 36393893; PMCID: PMC9660621.

Objectives: The accumulation of data through a prospective, multicenter Coordinated Registry Network (CRN) could be a robust and cost-effective way to gather real-world evidence on the performance of pelvic organ prolapse (POP) technologies for device-based and intervention-based studies. To develop the CRN, a group of POP experts consisting of representatives from professional societies, the Food and Drug Administration, academia, industry, and the patient community, was convened to discuss the role and feasibility of the CRN and to identify the core data elements important to assess POP technologies.

• A Delphi method approach was employed to achieve consensus on a core minimum dataset for the CRN. A series of surveys were sent to the panel and answered by each expert anonymously and individually. Results from the surveys were collected, collated, and analyzed by the study design team from Weill Cornell Medicine. Questions for the next round were based on the analysis process and discussed with group members via conference call. This process was repeated twice over a 6-month time period during which consensus was achieved.

Results: Twenty-one experts participated in the effort and proposed 120 data elements. Participation rates in the first and second round of the Delphi survey were 95.2% and 71.4%, respectively. The working group reached final consensus among responders on 90 data elements capturing relevant general medical and surgical history, procedure and discharge, short-term and long-term follow-up, device factors, and surgery and surgeon factors.

• The CRN successfully developed a set of core data elements to support the study of POP technologies through convening an expert panel on POP technologies and using the Delphi method. These standardized data elements have the potential to influence patient and provider decisions about treatments and include important outcomes related to efficacy and safety.

The American Urogynecologic Society Pelvic Floor Disorders Registry Bears Fruit.

Barber MD, Bradley CS.

Urogynecology (Hagerstown). 2022 Dec 1;28(12):797-799. doi: 10.1097/SPV.0000000000001290. PMID: 36409636.

Outcomes of Pessary Use at 1 Year in Women Treated for Pelvic Organ Prolapse in a Large Multicenter Registry: Developed by the Pelvic Floor Disorders Registry.

Yurteri-Kaplan LA, Meyn L, Moalli PA, Foster RT Sr, Andy UU, Guaderrama N, Gutman RE, Anger JT, Hull A, Propst K, Shippey SS, Brown HW.

Urogynecology (Hagerstown). 2022 Dec 1;28(12):800-810. doi: 10.1097/SPV.0000000000001279. PMID: 36409637.

• There is a lack of high-quality long-term follow-up regarding pessary treatment. Most studies are case series or retrospective with a small sample size and short-term follow-up.

Objectives: This study aimed to evaluate differences in women who continue versus discontinue pessary use and the effectiveness, quality of life, and safety associated with pessary management at 1 year.

Study design: This study analyzed a multicenter national registry following women for 3 years with vaginal prolapse treated with a pessary or surgery. The primary outcome of this analysis was to compare the difference in characteristics among those who continue versus discontinue pessary use at 12 months.

• Among 1,153 participants enrolled, 376 (32.6%) opted for a pessary, and 296 (78.7%) were successfully fitted. Data were available for 240 participants (81%). At 1 year, 62% (n = 148) were still using pessaries, and 38% (n = 92) had stopped with 25% opting for surgery. Most commonly reported de novo adverse effects were urinary leakage (16%), feeling or seeing a bulge (12%), and vaginal discharge (11%). There was no difference in baseline characteristics among women who continued versus discontinued pessary use. At 12 months, subjective symptoms were similar between groups, with similar change in symptoms from baseline on most validated instruments. Those who continued to use a pessary reported worse urinary symptoms due to de novo urinary leakage ( P = 0.01).
• At 1 year, most women successfully fitted with a pessary continued pessary use. Although there was a significant improvement in condition-specific quality of life and low rates of complications, approximately 40% of women discontinued pessary use by 12 months. We were unable to identify any baseline characteristics associated with pessary discontinuation.   

Effects of maternal hypertension on cord blood Arginine vasopressin receptor expression.

Gumusoglu S, Davis L, Schickling B, Devor E, Von Tersch L, Santillan M, Santillan D.

Pregnancy Hypertens. 2022 Nov 18;31:1-3. doi: 10.1016/j.preghy.2022.11.005. Epub ahead of print. Epub 2022 Nov 18. PMID: 36435036; PMCID: PMC9974773.

Arginine vasopressin (AVP) signaling is altered in preeclampsia and physiologic stress. AVP is implicated in fluid homeostasis and cardiovascular (CV) function, which is disrupted in some progeny from preeclamptic pregnancies. However, whether altered fetal AVP signaling occurs in preeclampsia is unknown. Here, we measured CV-related transcripts (e.g., AVP receptors) in cord blood via quantitative PCR. Chronic hypertension decreased AVPR1b, AVPR2, OXTR, LNPEP, and CUL5. AVPR1a, AVPR1b, and AVPR2 were decreased while OXTR was increased in preeclamptic cord blood. In sum, we found prenatal exposure to hypertension in pregnancy alters fetal AVP signaling and may thereby prime offspring CV disease risk.

Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium.

Barber EL, Chen S, Pineda MJ, Robertson SE, Teoh D, Schilder J, O'Shea KL, Kocherginsky M, Zhang B, Matei D.

Cancer Res Commun. 2022 Oct;2(10):1293-1303. doi: 10.1158/2767-9764.crc-22-0147. Epub 2022 Oct 28. PMID: 36388466; PMCID: PMC9648489.

• The objective of this study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in patients with advanced endometrial cancer (EC).

Patients and methods: This single-arm, open-label, multi-center phase II study enrolled patients with RECIST measurable advanced EC. Patients could have received < 1 prior platinum-based regimen and < one non-platinum chemotherapy. The primary endpoint was objective response rate (ORR). Planned sample size of 46 subjects provided 80% power to detect 15% ORR improvement compared to historical control rate of 50%.

Results: 46 patients were enrolled, and 43 were evaluable for ORR. Median age was 66 (range: 43-86). Thirty-four (73.9%) patients had recurrent and 12 (26.1%) primary metastatic EC. Patients received carboplatin AUC 6, paclitaxel 175mg/m2 and pembrolizumab 200mg IV every 3 weeks for up to 6 cycles. ORR was 74.4% (32/43), higher than historic controls (p = 0.001). Median PFS was 10.6 months (95% CI 8.3-13.9 months). The most common grade 1-2 treatment related adverse event (TRAEs) included anemia (56.5%), alopecia (47.8%), fatigue (47.8%) and neuropathy (13%), while the most common grade 3-4 TRAEs were lymphopenia, leukopenia, and anemia (19.6% each). High-dimensional spectral flow cytometry (CyTEK) identified enrichment in peripheral CD8+ and CD4+ T cell populations at baseline in responders. The CD8+ T cell compartment in responders exhibited greater expression levels of PD-1 and PD-L1 and higher abundance of effector memory CD8+ cells compared to non-responders.

• Addition of pembrolizumab to carboplatin and paclitaxel for advanced EC was tolerated and improved ORR compared to historical outcomes.

Patients in Iowa Counties Lacking Hospitals With Labor and Delivery Services Disproportionately Receive Care at Level III Maternal Care Hospitals When Undergoing Cesarean Delivery: A Retrospective Longitudinal Study.

Thenuwara KN, Dexter F, Ledolter J, , Epstein RH.

Cureus. 2022 Oct 25;14(10):e30683. doi: 10.7759/cureus.30683. PMID: 36439612; PMCID: PMC9691387.

• Many obstetrical patients from rural areas in the United States lack hospitals that provide labor and delivery care. Our objective was to examine the effects of such patients on caseloads of cesarean deliveries at Iowa hospitals with level III maternal care, as defined by the Iowa Department of Public Health (e.g., with obstetric anesthesiologists).

Methods: This retrospective longitudinal study included every discharge with cesarean delivery in the state of Iowa from October 2015 through June 2021. There were N=60,534 such deliveries from 76 hospitals, of which three were level III, and the rest were level I or II. Poisson regression models with robust variance estimation and controlling for geography, maternal risk factors, and insurance, were used to evaluate the binary outcome of whether patients received care at the university level III hospital in Eastern Iowa, or not. Similar models were also developed for care at the two private level III hospitals in Central Iowa, or not. Differences in the mean probabilities of receiving care at the level III hospitals were then estimated using logistic regression, with results reported in units of changes in cases per week at the hospitals.

Results: Statewide, the university level III hospital performed 7.4% of the cesarean deliveries, and the two private level III hospitals performed 23.4%. Patients from counties in which no cesarean deliveries were performed during the quarter of the year when they underwent a cesarean delivery disproportionately received care at level III hospitals versus levels I and II hospitals. Lower 99% confidence limits for incremental risk ratios were 1.46 and 4.20, respectively. Cesarean deliveries among patients residing in counties where no hospital had a labor and delivery ward were distributed unequally between the counties of the hospitals with level III maternal care. There were approximately 1.09 (standard error 0.10) extra cesarean deliveries per week at the university hospital versus 5.81 (standard error 0.11) at the private hospitals. The 1.09 vs 5.81 difference was caused, in part, by the effects of insurance and other hospitals with similar services.

• Patients residing in counties without labor and delivery care disproportionately go to level III hospitals. These results can help anesthesiologists, obstetricians, and analysts at hospitals with large tertiary (level III) programs interpret their annual increases in total obstetric anesthesia activity.

Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line.

Rush CM, Blanchard Z, Polaski JT, Osborne KS, Osby K, Vahrenkamp JM, Yang CH, Lum DH, Hagan CR, Leslie KK, Pufall MA, , Gertz J.

Sci Rep. 2022 Nov 17;12(1):19731. doi: 10.1038/s41598-022-24211-8. PMID:

36396974; PMCID: PMC9672046.

Most endometrial cancers express the hormone receptor estrogen receptor alpha (ER) and are driven by excess estrogen signaling. However, evaluation of the estrogen response in endometrial cancer cells has been limited by the availability of hormonally responsive in vitro models, with one cell line, Ishikawa, being used in most studies. Here, we describe a novel, adherent endometrioid endometrial cancer (EEC) cell line model, HCI-EC-23. We show that HCI-EC-23 retains ER expression and that ER functionally responds to estrogen induction over a range of passages. We also demonstrate that this cell line retains paradoxical activation of ER by tamoxifen, which is also observed in Ishikawa and is consistent with clinical data. The mutational landscape shows that HCI-EC-23 is mutated at many of the commonly altered genes in EEC, has relatively few copy-number alterations, and is microsatellite instable high (MSI-high). In vitro proliferation of HCI-EC-23 is strongly reduced upon combination estrogen and progesterone treatment. HCI-EC-23 exhibits strong estrogen dependence for tumor growth in vivo and tumor size is reduced by combination estrogen and progesterone treatment. Molecular characterization of estrogen induction in HCI-EC-23 revealed hundreds of estrogen-responsive genes that significantly overlapped with those regulated in Ishikawa. Analysis of ER genome binding identified similar patterns in HCI-EC-23 and Ishikawa, although ER exhibited more bound sites in Ishikawa. This study demonstrates that HCI-EC-23 is an estrogen- and progesterone-responsive cell line model that can be used to study the hormonal aspects of endometrial cancer.

Stimulated whole blood cytokine/chemokine responses are associated with interstitial cystitis/bladder pain syndrome phenotypes and features of nociplastic pain: a MAPP research network study.

Schrepf A, Kaplan C, Harris RE, Williams DA, Clauw DJ, As-Sanie S, Till S, Clemens JQ, Rodriguez LV, Van Bokhoven A, Landis R, Gallop R, Naliboff B, Pontari M, O'Donnell M, Luo Y, , Harte SE; See MAPP masthead.

Pain. 2022 Oct 19. doi: 10.1097/j.pain.0000000000002813. Epub ahead of print. PMID: 36279178; PMCID: PMC10106356.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the multidisciplinary approach to the study of chronic pelvic pain research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex vivo toll-like receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS. Here, we attempt to confirm these findings in the multisite multidisciplinary approach to the study of chronic pelvic pain Symptom Patterns Study using TLR4-stimulated whole blood (female IC/BPS patients with COPC n = 99; without n = 36). Samples were collected in tubes preloaded with TLR4 agonist, incubated for 24 hours, and resulting supernatant assayed for 7 cytokines/chemokines. These were subject to a principal components analysis and the resulting components used as dependent variables in general linear models. Controlling for patient age, body mass index, and site of collection, we found that greater ex vivo TLR4-stimulated cytokine/chemokine release was associated with the presence of COPCs ( P < 0.01), extent of widespread pain ( P < 0.05), but not experimental pain sensitivity ( P > 0.05). However, a second component of anti-inflammatory, regulatory, and chemotactic activity was associated with reduced pain sensitivity ( P < 0.01). These results confirm that the IC/BPS + COPCs subtype show higher levels of ex vivo TLR4 cytokine/chemokine release and support a link between immune priming and nociplastic pain in IC/BPS.

Biobehavioral factors predict an exosome biomarker of ovarian carcinoma disease progression.

Lutgendorf SK, Thaker PH, , Arevalo JMG, Chowdhury MA, Noble AE, Dahmoush L, Slavich GM, Penedo FJ, Sood AK, Cole SW.

Cancer. 2022 Oct 17. doi: 10.1002/cncr.34496. Epub ahead of print. PMID:

36251340; PMCID: PMC9744596.

Background: Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors.

• Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6 months) versus more extended disease-free intervals following initial treatment. Samples from a second subgroup of 24 patients were analyzed by mixed-effects linear models to determine whether the progression-predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms).
• An RNA-based molecular signature was identified that discriminated between individuals who had disease progression in ≤6 months versus >6 months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates.

Conclusion: These data identified a novel exosome-derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring.

SSRI use in pregnancy: Moving towards collaborative, evidence-based decision-making.

Gumusoglu SB, Santillan MK.

Pregnancy Hypertens. 2022 Oct 7;30:146-147. doi: 10.1016/j.preghy.2022.10.001. Epub ahead of print.2022 Oct 7. PMID: 36219941; PMCID: PMC10158533.

Foreword: Maternity Care in Rural America.

Hunter SK.

Clin Obstet Gynecol. 2022 Dec 1;65(4):786-787. doi: 10.1097/GRF.0000000000000764. Epub 2022 Oct 20. PMID: 36260012.

Sodium concentrations in municipal drinking water are associated with an increased risk of preeclampsia

Thompson DA, Cwiertny DM, Davis HA, Grant A, Land D, Landsteiner SJ, Latta DE, , Jones MP, Lehmler H,

Environmental Advances, Volume 9, October 2022, 100306. doi: 10.1016/j.envadv.2022.100306

Chronic ingestion of excess sodium has been associated with high blood pressure, heart disease, and stroke. Limited research has suggested a relationship between increased sodium intake and the development of preeclampsia. This study investigated the association between elevated sodium in drinking water with preeclampsia using a hospital-based case-control study of 10,114 pregnant women in Iowa in the United States. Health records of women who delivered at the University of Iowa Hospitals and Clinics in Iowa City, Iowa, USA, between May 2009 and August 2020 were obtained from the Intergenerational Health Knowledgebase. Water quality data for community water systems from Safe Drinking Water Act compliance reporting and Consumer Confidence Reports (CCR) were used to estimate maternal exposure to sodium in drinking water. Logistic regression models were calculated to estimate the odds of preeclampsia based on median sodium concentrations reported by public water systems from 2000 to 2019. Preeclampsia was associated with a 38% increased odds (adjusted odds ratio (aOR) 1.38, 95% confidence interval (CI) 1.13-1.69) when women were exposed to concentrations between 20-69 milligrams per liter (mg/L), above EPA's recommendation for individuals on a very low sodium diet. Increased odds of 5% and 16% were also found at concentrations between 70-102 mg/L and greater than 256 mg/L but were not statistically significant. The lower odds at higher sodium concentrations may be due to consumers using alternative drinking water sources due to taste issues that are noted to arise between 30-60 mg/L. Preeclampsia diagnosis was strongly associated with gestational age, parity, newborn count, and body mass index. Better data on individual exposure through drinking water is needed to account for factors like home softeners, which can greatly increase sodium levels at the tap, or those users seeking out alternative water supplies (like bottled water) due to taste issues arising from greater salinity.

Rural Maternal Health Care Outcomes, Drivers, and Patient Perspectives.

Anglim AJ, Radke SM.

Clin Obstet Gynecol. 2022 Dec 1;65(4):788-800. doi: 10.1097/GRF.0000000000000753. Epub 2022 Oct 3. PMID: 36260013.

Rural communities are a vital segment of the US population; however, these communities are shrinking, and their population is aging. Rural women experience health disparities including increased risk of maternal morbidity and mortality. In this article, we will explore these trends and their determinants both within and external to the health care system. Health care providers, public health professionals, and policymakers should be aware of these social and structural factors that influence health outcomes and take action to reduce generational cycles of health disparity. Opportunities to improve the health and pregnancy outcomes for rural women and rural populations are highlighted.

A Case of Persistent Human Pegivirus Infection in Two Separate Pregnancies of a Woman.

Garand M, Huang SSY, Goessling LS, Brar A, Wylie TN, Wylie KM, Eghtesady P.

Microorganisms. 2022 Sep 28;10(10):1925. doi: 10.3390/microorganisms10101925. PMID: 36296201; PMCID: PMC9610878.

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in the maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no clear indication of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus.

Need for Improved Collection and Harmonization of Rural Maternal Healthcare Data

Santillan DA, Davis HA, Faro EZ, Knosp BM, Santillan MK.

Clin Obstet Gynecol. 2022 Dec 1;65(4):856-867. doi: 10.1097/GRF.0000000000000752. Epub 2022 Oct 20. PMID: 36260014; PMCID: PMC9586468.

Representation in data sets is critical to improving healthcare for the largest possible number of people. Unfortunately, pregnancy is a very understudied period of time. Further, the gap in available data is wide between pregnancies in urban areas versus rural areas. There are many limitations in the current data that is available. Herein, we review these limitations and strengths of available data sources. In addition, we propose a new mechanism to enhance the granularity, depth, and speed with which data is made available regarding rural pregnancy.

Reply to De Giorgi et al. Comment on "Kesić et al. Early Diagnostics of Vulvar Intraepithelial Neoplasia. Cancers 2022, 14, 1822".

Kesić V, Vieira-Baptista P,

Cancers (Basel). 2022 Oct 18;14(20):5088. doi: 10.3390/cancers14205088. PMID: 36291873; PMCID: PMC9600382.

Group B Streptococcus Screening and Treatment Adherence in Pregnancy: A Retrospective Cohort Study and Opportunities for Improvement.

Santillan DA, Hubb AJ, Nishimura TE, Rosenfeld-O'Tool S,  Schroeder KJ, Conklin JM, Karras AE, Gumusoglu SB, Brandt DS, Miller E, Hunter SK, Santillan MK.

AJPM Focus 2022;1(2):100028.

• Pregnancy is a time of increased healthcare screening, and past adherence to evolving guidelines informs best practices. Although studies of Group B Streptococcus guideline adherence have focused primarily on treatment of Group B Streptococcus carriers, this study broadly evaluated long-term adherence to both Group B Streptococcus screening and treatment guidelines. Adherence was evaluated across provider types (obstetrics and gynecology, certified nurse midwives, and family medicine).

Methods: We conducted a retrospective cohort study. Demographic and clinical information were extracted from all prenatal care and delivery patients at a single institution in a single year. Vancomycin prescriptions in pregnancy were tracked for 10 years to determine long-term adherence. Adherencewas defined as no deviation from 2010 Group B Streptococcusscreening and treatment guidelines.

Results: Adherence occurred in 89% (1,610/1,810) of patients. Reasons for deviations from guidelines could not always be determined. There was no significant difference in maternal age, race, prenatal provider type, provider type at delivery, gestational age at delivery, delivery mode, or whether antibiotic sensitivities were performed between compliant and noncompliant groups. Significant differences in adherence were found between obstetric clinics (high-risk obstetrics clinic, maternal‒fetal medicine fellows clinic, continuity of care clinic, and faculty private clinic) (p<0.0001) and between the faculty family medicine clinic and resident family medicine clinic (p=0.001). Vancomycin prescription practice did not change significantly over the10-year period.

Conclusions: High rates of adherence to Group B Streptococcus screening and treatment guidelines in pregnancy have positive implications for reducing antibiotic resistance. Given evolving guidelines, there is a need to periodically evaluate adherence and to re-educate providers about standard practices and best documentation practices.

Comparing clinical bladder diaries and recalled patient reports for measuring lower urinary tract symptoms in the symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

Flynn KE, Wiseman JB, Helmuth ME, Smith AR, , Cameron AP, Henry Lai H, Kirkali Z, Kreder KJ, Geynisman-Tan J, Merion RM, Weinfurt KP; LURN Study Group.

Neurourol Urodyn. 2022 Sep 6. doi: 10.1002/nau.25030. Epub ahead of print.

Purpose: Bladder diaries are a key source of information about lower urinary tract symptoms (LUTS); however, many patients do not complete them as instructed. Questionnaire-based patient-reported outcome measures (PROMs) are another option for reporting LUTS but may have recall bias. We assessed the strength of the associations between PROMs and a 3-day bladder diary.

Materials and methods: Symptomatic adults from 6 tertiary care sites completed a 3-day paper bladder diary and 3-, 7-, and 30-day electronic PROMs. We assessed the linear associations between mapped pairs of diary variables and responses to PROM items using biserial and polyserial correlation coefficients with 95% confidence intervals.

Results: Of 290 enrolled participants, 175 (60%) completed the bladder diary as instructed and at least one corresponding PROM. Linear associations were strongest between the diary and 3-day recall of daytime frequency (r = 0.75) and nighttime frequency (r = 0.69), followed by voids with urgency sensations (r = 0.62), and an item reporting any incontinence (r = 0.56). Linear associations between bladder diary and specific incontinence variables (e.g., stress, urgency) were low to negligible (ranging from r = 0.16-0.39). Linear associations were consistent across the 3-, 7-, and 30-day recall periods.

Conclusions: Missing and unusable bladder diary data were common, highlighting the patient burden associated with this method of data collection. A questionnaire-based PROM is a reasonable alternative to a diary for reporting voiding frequency and may offer an easier option for reporting some symptoms.

American Journal of Obstetrics & Gynecology appoints Wanda K. Nicholson, MD, MPH, MBA, as Editor for Health Equity, Diversity, and Inclusion.

Bradley CS, Romero R.

Am J Obstet Gynecol. 2022 Aug 27:S0002-9378(22)00630-5. doi: 10.1016/j.ajog.2022.07.059. Epub ahead of print.

CNM/CMs Fill the Gap in Rural Maternal Care.

Coleman LNG.

Clin Obstet Gynecol. 2022 Sep 26. doi: 10.1097/GRF.0000000000000751. Epub ahead of print.

The United States is in the midst of a maternity care crisis. A key driver is workforce shortages, which impacts maternity care service delivery in rural areas significantly. The midwifery model of care remains underutilized. Midwifery care delivered by certified nurse-midwives and certified midwives is heavily endorsed and supported in the extant literature, but no firm national actions have been taken to move recommendations into funding or practice. Certified nurse-midwives and Certified Midwives are able to care for low-risk pregnancies and are uniquely situated to address factors associated with social determinants of health in rural areas. One of the solutions to the rural maternity care crisis is scaling up the midwifery workforce. Individual, institutional, state, and federal factors are discussed.

Association of Distance to Gynecologic Oncologist and Survival in a Rural Midwestern State.

Ulmer KK, Greteman B, McDonald M, Gonzalez Bosquet J, Charlton ME, Nash S.

Womens Health Rep (New Rochelle). 2022 Aug 4;3(1):678-685.

Objectives: Rural ovarian cancer patients experience worse survival compared to urban patients. We assessed whether distance to gynecologic oncology specialists was associated with survival for patients in a rural state.

Methods: Demographic, tumor, and treatment characteristics were extracted from the Iowa Cancer Registry for patients diagnosed between 1990 and 2018. Data were linked to the county-level 2018-2019 Area Health Resource File (number of surgeons and hospital beds per 100,000 population). Rurality was defined using 2013 Rural-Urban Continuum Codes; distance to the nearest gynecologic oncologist was calculated from the centroid of the county of residence to the centroid of the nearest county with a high volume health care center with a gynecologic oncologist. Associations with survival were assessed using multivariable Cox proportional hazards models.

Results: Analyses included 1,562 ovarian cancer patients. Mean distance to gynecologic oncology was 60.8 miles, and median survival was 23 months. Unadjusted models showed increased distance from gynecologic oncology had progressively greater risk of death 30-49 miles (hazard ratio [HR] = 1.09, confidence interval [CI]: 1.04-1.15), 50-69 miles (HR = 1.19, CI: 1.07-1.32), 70+ miles (HR = 1.30, CI: 1.11-1.51). In adjusted models, association of distance to gynecologic oncology with risk of death was not significant; however, more advanced cancer stage and age, unmarried status, and higher county-level poverty were independently associated with increased risk of death.

Conclusions: Above and beyond demographics and stage, distance to gynecologic oncology care was not an independent predictor of ovarian cancer survival. Further studies are needed to determine how to mitigate the factors contributing to worsened ovarian cancer survival among rural patients.

Proposed Solutions for Improving Maternal Health Care in Rural America.

Garcia KK,

Clin Obstet Gynecol. 2022 Sep 27. doi: 10.1097/GRF.0000000000000754. Epub ahead of print.

Increasing hospital and labor & delivery (L&D) closures have led to declining access to hospital obstetric care in rural areas across the country. These closures increase the burden on women and families living in rural communities, who often must drive long distances for prenatal visits and delivery. The lack of maternal health care in rural America can also result in several adverse maternal and infant outcomes including premature birth, low birth weight, out of hospital births, maternal and infant morbidity and mortality, and increased risk of postpartum depression. The reasons for these closures are multifactorial, and include, workforce shortages, financial viability, low volume of patients, concerns over maintaining the knowledge base and skill sets of the obstetrical health care team required to provide high quality and safe care, as well as medical-legal concerns. The problems of providing and accessing quality maternal and obstetrical care in rural America have not happened overnight, Likewise, the solutions to these problems will also not occur overnight and must also address the multifactorial nature of the problem. However, there are several opportunities to improve access to maternal health care in rural communities. Programs, policies, and funding need to be designed and provided to make these opportunities a reality.

Low oocyte maturity ratio is associated with a reduced in vitro fertilization and intracytoplasmic sperm injection live birth rate

Capper E, Krohn M, Summers K, Mejia R, Sparks A, Van Voorhis BJ.

• To determine whether a low oocyte maturity ratio in a cohort of oocytes from an in vitro fertilization cycle predicts outcomes and to examine clinical factors associated with oocyte maturity.
• A retrospective cohort study.
• An academic medical center.

Intervention(s): Determination of oocyte maturity immediately after the retrieval and 6 hours later if intracytoplasmic sperm injection was performed.

Main outcome measure(s): The primary outcome was live birth rate after the first embryo transfer. Secondary outcomes included clinical pregnancy, miscarriage, and fertilization rates.

Result(s): After adjusting for age, preimplantation genetic testing, and number of embryos transferred, we found that a low oocyte maturity ratio was associated with a decreased live birth rate (adjusted odds ratio [AOR], 0.41; 95% confidence interval [CI], 0.22-0.77) and clinical pregnancy rate (AOR, 0.32; 95% CI, 0.17-0.61). We did not find a relationship between oocyte maturity and miscarriage rate (AOR, 0.25; 95% CI, 0.03-1.91) or fertilization rate (Welch test). The number of 2 pronuclei embryos per retrieved oocyte was found to be associated with the maturity ratio at retrieval. Patients with anovulation had slightly reduced oocyte maturity compared with other diagnostic groups.

Conclusion(s): Low oocyte maturity ratio is an important factor related to poor in vitro fertilization outcomes, including decreased pregnancy and live birth rates.

Fertil Steril. 2022 Sep 6:S0015-0282(22)00457-5. doi: 10.1016/j.fertnstert.2022.07.008. Epub ahead of print.

A Case of Persistent Human Pegivirus Infection in Two Separate Pregnancies of a Woman.

Garand M, Huang SSY, Goessling LS, Brar A, Wylie TN, Wylie KM, Eghtesady P.

Microorganisms 2022, 10(10), 1925; https://doi.org/10.3390/microorganisms10101925.

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in the maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no clear indication of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus.

Reply to E. Guerra et al.

Leslie KK,

J Clin Oncol. 2022 Sep 16:JCO2201656. doi: 10.1200/JCO.22.01656. Epub ahead of print.

End of an endometrial receptivity array?

Raff M, Jacobs E, Voorhis BV.

Fertil Steril. 2022 Sep 5:S0015-0282(22)00489-7. doi: 10.1016/j.fertnstert.2022.07.031. Epub ahead of print.

Implementation of a Maternal Child Knowledgebase.

Santillan DA, Santillan MK, Davis HA, Crooks M, Flanagan PJ, Ortman CE, Faro EZ, Hunter SK, Knosp BK.

AMIA Annu Symp Proc. 2022 May 23;2022:432-438.

To advance the application of clinical data to address maternal health we developed and implemented a Maternal Child Knowledgebase (MCK). The MCK integrates data from every pregnancy that received care at the University of Iowa Hospitals & Clinics (UIHC) and links information from the pregnancy episode to the delivery episode and between the mother and child. This knowledgebase contains integrated information regarding diagnoses, medications, mother and child vitals, hospital admissions, depression screenings, laboratory value results, and procedure information. It also collates information from the electronic health record (EPIC), the Social Security Death Index, and the Medication Administration Record into one knowledgebase. To enhance usability, we designed a custom viewer with several pre-designed queries and reports that eliminates the need for users to be proficient in SQL coding. The recent implementation of the MCK has supported multiple projects and reduced the number of Obstetrics-related data queries to the Biomedical Informatics group.

All-Cause Severe Maternal Morbidity (SMM) and Transfusion-Only SMM Are Independently Associated with a Lower Likelihood of Exclusive Breastfeeding.

Green S, Ryckman KK, Anderson E,

Breastfeed Med. 2022 Jul 29. doi: 10.1089/bfm.2021.0355. Epub ahead of print.

•  The rates of severe maternal morbidity (SMM) including blood transfusions after delivery are rising, yet little is known about the impact of these experiences on breastfeeding. 

Materials and Methods: This is a single-institution retrospective cohort study examining breastfeeding rates at three time points for 1,857 first-time parents delivered at term between July 1, 2016 and June 30, 2019. Our exposure of interest was SMM, which was subdivided into SMM where transfusion was the only indicator (transfusion-only SMM) and SMM where another indicator (diagnostic or procedural) was met, which may also include transfusion (all-cause SMM). Association between transfusion-only SMM and all-cause SMM with feeding method was determined using multinomial regression modeling and adjusting for relevant sociodemographic characteristics. 

•  The majority of those with uncomplicated deliveries were exclusively breastfeeding at the 2- to 4-week and 2- to 3-month time points (59.6% and 53.6%, respectively), in contrast to 46.3% and 42.0% of those who had experienced transfusion-only SMM, and 40.9% and 30% of those who had experienced all-cause SMM. In adjusted models, receipt of a blood transfusion was found to be associated with greater risk of exclusive formula feeding at all time points. Experience of all-cause SMM was significantly associated with increased likelihood of exclusive formula feeding at hospital discharge and the 2- to 3-month time point. 
•  We identified that experience of all-cause SMM and transfusion-only SMM are independently associated with a lower likelihood of exclusive breastfeeding after adjusting for sociodemographic factors. Perinatal clinicians should be aware of these risks and offer increased support to these couplets.

Integrated Clinical and Genomic Models to Predict Optimal Cytoreduction in High-Grade Serous Ovarian Cancer.

Cardillo N, Devor EJ, Pedra Nobre S, Newtson A, Leslie K, Bender DP,

Smith BJ,

Cancers (Basel). 2022 Jul 21;14(14):3554.

Advanced high-grade serous (HGSC) ovarian cancer is treated with either primary surgery followed by chemotherapy or neoadjuvant chemotherapy followed by interval surgery. The decision to proceed with surgery primarily or after chemotherapy is based on a surgeon's clinical assessment and prediction of an optimal outcome. Optimal and complete cytoreductive surgery are correlated with improved overall survival. This clinical assessment results in an optimal surgery approximately 70% of the time. We hypothesize that this prediction can be improved by using biological tumor data to predict optimal cytoreduction. With access to a large biobank of ovarian cancer tumors, we obtained genomic data on 83 patients encompassing gene expression, exon expression, long non-coding RNA, micro RNA, single nucleotide variants, copy number variation, DNA methylation, and fusion transcripts. We then used statistical learning methods (lasso regression) to integrate these data with pre-operative clinical information to create predictive models to discriminate which patient would have an optimal or complete cytoreductive outcome. These models were then validated within The Cancer Genome Atlas (TCGA) HGSC database and using machine learning methods (TensorFlow). Of the 124 models created and validated for optimal cytoreduction, 21 performed at least equal to, if not better than, our historical clinical rate of optimal debulking in advanced-stage HGSC as a control. Of the 89 models created to predict complete cytoreduction, 37 have the potential to outperform clinical decision-making. Prospective validation of these models could result in improving our ability to objectively predict which patients will undergo optimal cytoreduction and, therefore, improve our ovarian cancer outcomes.

AUGS-PERFORM: A New Patient-Reported Outcome Measure to Assess Quality of Prolapse Care.

O'Shea M, Boyles S, Jacobs K, McFatrich M, Sung V, Weinfurt K, Siddiqui NY.

Female Pelvic Med Reconstr Surg. 2022 Aug;28(8):468-478. doi: 10.1097/SPV.0000000000001225. Epub 2022 Jun 22.

Patient-reported outcomes (PRO) are important for measuring quality of care, particularly for interventions aimed at improving symptom bother such as procedures for pelvic organ prolapse. We aimed to create a concise yet comprehensive PRO measurement tool to assess pelvic organ prolapse care in high-volume clinical environments.

Methods: The relevant concepts to measure prolapse treatment quality were first established through literature review, qualitative interviews, and a patient and provider-driven consensus-building process. Extant items mapping to these concepts, or domains, were identified from an existing pool of patient-reported symptoms and condition-specific and generic health-related quality of life measures. Item classification was performed to group items assessing similar concepts while eliminating items that were redundant, inconsistent with domains, or overly complex. A consensus meeting was held in March 2020 where patient and provider working groups ranked the remaining candidate items in order of relevance to measure prolapse treatment quality. After subsequent expert review, the revised candidate items underwent cognitive interview testing and were further refined.

• Fifteen relevant PRO instruments were initially identified, and 358 items were considered for inclusion. After 2 iterative consensus reviews and 4 rounds of cognitive interviewing with 19 patients, 11 final candidate items were identified. These items map 5 consensus-based domains that include awareness and bother from prolapse, physical function, physical discomfort during sexual activity, pain, and urinary/defecatory symptoms.
• We present a concise set of candidate items that were developed using rigorous patient-centered methodology and a national consensus process, including urogynecologic patients and providers.

​Long-term Symptom Trajectories in Urologic Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.

Bradley CS, Gallop R, Sutcliffe S, Kreder KJ, Lai HH, Clemens JQ, Naliboff BD; Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

Urology. 2022 Aug 9:S0090-4295(22)00654-9. doi: 10.1016/j.urology.2022.07.045. Epub ahead of print

• To characterize Urologic Chronic Pelvic Pain Syndrome (UCPPS) pain and urinary symptom trajectories with up to 9 years of follow-up and evaluate whether initial 1-year trajectories are associated with longer-term changes.

Materials and methods: Data were analyzed from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network's prospective observational protocols including the Epidemiology and Phenotyping Study (EPS; baseline to Year 1), EPS Extension (EXT; Years 1-5), and Symptom Patterns Study (SPS: 3-year study; Years 3-9). Adults with Interstitial Cystitis/Bladder Pain Syndrome or Chronic Prostatitis/Chronic Pelvic Pain Syndrome provided patient-reported assessments biweekly (EPS), every 4 months (EXT), or quarterly (SPS). Primary outcomes were composite pain (0-28) and urinary (0-25) severity scores. Multi-phase mixed effects models estimated outcomes over time, adjusted for baseline severity and stratified by EPS symptom trajectory.

Results: 163 participants (52% women; mean ± SD age 46.4 ± 16.1 years) completed EPS and enrolled in EXT; 67 also enrolled in SPS. Median follow-up was 4.6 years (range 1.3-9.0). After 1 year: 27.6%, 44.8% and 27.6% and 27.0%, 38.0% and 35.0% were improved, stable or worse in pain and urinary symptom severity, respectively. On average, pain and urinary symptom scores did not change further during EXT and SPS periods.

• Women and men with UCPPS showed remarkable stability in pain and urinary symptom severity for up to 9 years, irrespective of their initial symptom trajectory, suggesting UCPPS is a chronic condition with stable symptoms over multiple years of follow-up.

Natural history of lower urinary tract symptoms in treatment-seeking women with pelvic organ prolapse; the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

Kowalski JT, Wiseman JB, Smith AR, Helmuth ME, Cameron A, DeLancey JOL, Hendrickson WK, Jelovsek JE, Kirby A, Kreder K, Lai HH, Mueller M, Siddiqui N, Bradley CS.

Am J Obstet Gynecol. 2022 Aug 5:S0002-9378(22)00594-4. doi: 10.1016/j.ajog.2022.07.038. Epub ahead of print.

Background: The association of pelvic organ prolapse with overactive bladder and other lower urinary tract symptoms, and the natural history of those symptoms are not well characterized. Previous cross-sectional studies demonstrated conflicting relationships between prolapse and lower urinary tract symptoms.

Objective: This study primarily aimed to determine the baseline association between lower urinary tract symptoms and prolapse and to assess longitudinal differences in symptoms over 12 months in women with and without prolapse. Secondary aims were to explore associations between lower urinary tract symptoms and prolapse treatment. We hypothesized that: (1) prolapse is associated with the presence of lower urinary tract symptoms, (2) lower urinary tract symptoms are stable over time in patients with and without prolapse, and (3) prolapse treatment is associated with lower urinary tract symptom improvement.

Study design: Women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network Observational Cohort Study with adequate 12-month follow-up data were included. Prolapse and lower urinary tract symptom treatment during follow-up was guided by standard of care. Outcome measures included the Lower Urinary Tract Symptoms Tool total severity score (in addition to overactive bladder, obstructive, and stress urinary incontinence subscales) and Urogenital Distress Inventory-6 Short Form. Prolapse (yes or no) was defined primarily when Pelvic Organ Prolapse Quantification System points Ba, C or Bp were >0 (beyond the hymen). Mixed-effects models with random effects for patient slopes and intercepts were fitted for each lower urinary tract symptom outcome and prolapse predictor, adjusted for other covariates. The study had >90% power to detect differences as small as 0.4 standard deviation for less prevalent group comparisons (eg, prolapse vs not).

• : A total of 371 women were analyzed, including 313 (84%) with no prolapse and 58 (16%) with prolapse. Women with prolapse were older (64.6±8.8 vs 55.3±14.1 years; P<.001) and more likely to have prolapse surgery (28% vs 1%; P<.001) and pessary treatment (26% vs 4%; P<.001) during the study. Average baseline Lower Urinary Tract Symptoms Tool total severity scores were lower (fewer symptoms) for participants with prolapse compared with those without (38.9±14.0 vs 43.2±14.0; P=.036), but there were no differences in average scores between prolapse groups for other scales. For all urinary outcomes, average scores were significantly lower (improved) at 3 and 12 months compared with baseline (all P<.05). In mixed-effects models, there were no statistically significant interactions between pelvic organ prolapse measurement and visit and time-dependent prolapse treatment groups (P>.05 for all regression interaction coefficients). The Lower Urinary Tract Symptoms Tool obstructive severity score had a statistically significant positive association with Pelvic Organ Prolapse Quantification System Ba, Bp, and point of maximum vaginal descent. The Lower Urinary Tract Symptoms Tool total severity scale had a statistically significant negative association with Pelvic Organ Prolapse Quantification System Ba and point of maximum vaginal descent. No other associations between prolapse and lower urinary tract symptoms were significant (P>.05 for all regression coefficients). Symptom differences between prolapse groups were small: all regression coefficients (interpretable as additive percentage change in each score) were between -5 and 5 (standard deviation of outcomes ranged from 14.0-32.4).

Conclusion: Among treatment-seeking women with urinary symptoms, obstructive symptoms were positively associated with prolapse, and overall lower urinary tract symptom severity was negatively associated with prolapse. Lower Urinary Tract Symptoms Tool scores improved over 12 months regardless of prolapse status, including in those with treated prolapse, untreated prolapse, and without prolapse.

Subtyping of common complex diseases and disorders by integrating heterogeneous data. Identifying clusters among women with lower urinary tract symptoms in the LURN study.

Andreev VP, Helmuth ME, Liu G, Smith AR, Merion RM, Yang CC, Cameron AP, Jelovsek JE, Amundsen CL, Helfand BT,DeLancey JOL, Griffith JW, Glaser AP, Gillespie BW, Clemens JQ, Lai HH; LURN Study Group.

PLoS One. 2022 Jun 10;17(6):e0268547.

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five clusters of women with LUTS were identified using the developed methodology. None of the clusters could be characterized by a single symptom, but rather by a distinct combination of symptoms with various levels of severity. Targeted proteomics of serum samples demonstrated that differentially abundant proteins and affected pathways are different across the clusters. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. The rationale and thought process are described for the selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains.

Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia.

Vignato JA, , Davis HA, Pierce GL, Knosp BA,

Reprod Sci. 2022 Aug 19. doi: 10.1007/s43032-022-01065-z. Epub ahead of print. P

Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential. This retrospective cohort study included clinical data from 9558 SSRI-untreated and 9046 SSRI-treated pregnancies. In a subcohort of 233 pregnancies, early pregnancy (< 20 weeks) maternal plasma copeptin, an inert and stable AVP prosegment secreted 1:1 with AVP, was measured by enzyme-linked immunosorbent assay. Diagnoses and depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) were identified via medical records review. Descriptive, univariate, and multivariate regression analyses were conducted (α = 0.05). SSRI use was associated with decreased preeclampsia after controlling for clinical confounders (depression severity, chronic hypertension, diabetes, body mass index, age) (OR = 0.9 [0.7-1.0], p = 0.05). Moderate-to-severe depression symptoms were associated with significantly higher copeptin secretion than mild-to-no depression symptoms (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001). SSRIs significantly attenuated first trimester plasma copeptin (78 ± 22 users vs. 240 ± 29 ng/ml non-users, p < 0.001). In preeclampsia, SSRI treatment was associated with significantly lower copeptin levels (657 ± 164 vs. 175 ± 134 ng/mL, p = 0.04). Interaction between SSRI treatment and preeclampsia was also significant (p = 0.04). SSRIs may modulate preeclampsia risk and mechanisms, although further studies are needed to investigate the relationships between 5-HT and AVP in depression and preeclampsia.

Selective serotonin reuptake inhibitors and preeclampsia: A quality assessment and meta-analysis.

Gumusoglu SB, Schickling BM, Vignato JA, Santillan DA, Santillan MK.

Pregnancy Hypertens. 2022 Aug 6;30:36-43. doi: 10.1016/j.preghy.2022.08.001. Epub ahead of print.

Serotonin modulates vascular, immune, and neurophysiology and is dysregulated in preeclampsia. Despite biological plausibility that selective serotonin reuptake inhibitors (SSRIs) prevent preeclampsia pathophysiology, observational studies have indicated increased risk and providers may be hesitant. The objective of this meta-analysis and quality assessment was to evaluate the evidence linking SSRI use in pregnancy to preeclampsia/gestational hypertension. PubMed was searched through June 5, 2020 manually and using combinations of terms: "preeclampsia", "serotonin", and "SSRI". This review followed MOOSE guidelines. Inclusion criteria were: 1) Observational cohort or population study, 2) exposure defined as SSRI use during pregnancy, 3) cases defined as preeclampsia or gestational hypertension, and 4) human participants. Studies were selected that addressed the hypothesis that gestational SSRI use modulates preeclampsia and/or gestational hypertension risk. Review Manager Web was used to synthesize study findings. Articles were read and scored (Newcastle-Ottawa Quality Assessment Scale) for quality by two independent reviewers. Publication bias was assessed using a funnel plot and the Egger test. Of 179 screened studies, nine were included. The pooled risk ratio (random effects model) was 1.43 (95 % CI: 1.15-1.78, P < 0.001; range 0.96-4.86). Two studies were rated as moderate quality (both with total score of 6); others were high quality. Heterogeneity was high (I2 = 88 %) and funnel asymmetry was significant (p < 0.00001). Despite evidence for increased preeclampsia risk with SSRIs, shared risk factors and other variables are poorly controlled. Depression treatment should not be withheld due to perceived gestational hypertension risk. Mechanistic evidence for serotonin modulation in preeclampsia demonstrates a need for future research.

Dataset describing maternal prenatal restraint stress effects on immune factors in mice.

Gumusoglu SB, Maurer SV, Stevens HE.

Data Brief. 2022 Jun 3;43:108348.

Maternal immune dysregulation, caused by gestational psychological stress, infection, and other perturbations, results in altered offspring neurodevelopment and increases risk for psychiatric disorders. Prior work has found that multiple cytokines play critical roles in shaping offspring neurodevelopment after gestational stress, though how maternal psychological stress impacts maternal, placental, and fetal cytokine levels more broadly remains unclear. The purpose of the present study was to assess changes to IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17A, IFNγ, and TNFα in a widely-used mouse prenatal restraint stress model. After repetitive restraint stress on gestational days 12-14, stressed dams had increased serum levels of IL-1β, IL-6, and IL-10. Embryonic day 14 IL-2 and IL-1β levels were decreased in prenatally stressed male fetal forebrain, while placental IL-2 was decreased by stress regardless of offspring sex. Placental and fetal forebrain IL-2 levels were negatively correlated. These data provide important insights into the immune changes that occur with prenatal restraint stress.

Vaginal Leptothrix: An Innocent Bystander?

Vieira-Baptista P, Lima-Silva J, Preti M, Sousa C, Caiano F, Bornstein J.

Microorganisms. 2022 Aug 15;10(8):1645.

Leptothrix are long bacteria of rare occurrence; although these bacteria have been implicated in causing vaginal symptoms identical to candidiasis, studies on prevalence and effect on overall vaginal health are lacking. In this study, we evaluated data of women referred to a private clinic for treating vulvovaginal symptoms (n = 1847) and reassessed data of our previous and ongoing studies (n = 1773). The overall rate of leptothrix was 2.8% (102/3620), and the mean age of affected women was 38.8 ± 10.65 years (range 18-76). The majority of the women with leptothrix had normal vaginal flora (63.7% [65/102]). Leptothrix was associated with a higher risk of candidiasis (relative risk (RR) 1.90, 95% confidence interval (CI) 1.1600-3.1013; p = 0.010) and a lower risk of bacterial vaginosis (RR 0.55, 95% CI, 0.3221-0.9398; p = 0.029) and cytolytic vaginosis (RR 0.11, 95% CI, 0.0294-0.4643; p = 0.002). No cases of trichomoniasis were observed. Human immunodeficiency virus infection increased the risk of leptothrix (RR 3.0, 95% CI, 1.6335-5.7245; p = 0.000). Among the women evaluated for vulvovaginal symptoms, 2.4% (45/1847) had leptothrix, and in 26.7% (12/45), leptothrix was considered the causative entity. This study suggests that leptothrix occurrence is rare; it remains unresolved if it can be a cause of vulvar symptoms.

Full thickness epidermal burn from a heating pad on a cesarean incision with silver dressing: a case report.

Sharp AJ,

Proc Obstet Gynecol. 2022;11(2): Article 4 [ 5 p.].

We present a case of a full thickness epidermal burn resulting from an all-natural clay-based heating pad over a cesarean incision silver dressing to bring awareness to the risks associated with nonpharmacologic management of post cesarean pain. There is limited guidance on nonpharmacological management of post cesarean pain. It is important that providers are able to advise their patients about their options, including to be wary of using heating pads on post-cesarean dressings, especially with pain in the early post-partum period.

Superficial versus deep inguinal nodal dissection for vulvar cancer staging.

Mattson J, Emerson J, Underwood A, Sun G, Mott SL, Kulkarni A, Robison K,

Gynecol Oncol. 2022 Jun 30:S0090-8258(22)00428-0. doi: 10.1016/j.ygyno.2022.06.024. Epub ahead of print.

• The objective of this study was to compare the rate of groin recurrence among women undergoing superficial or deep inguinal lymph node dissections in suspected early-stage vulvar carcinoma. Secondary objectives included comparison of overall survival and post-operative morbidity between the study groups
• A retrospective cohort of 233 patients with squamous cell carcinoma (SCC) of the vulva who underwent an inguinal lymph node dissection at two major academic institutions from 1999 to 2017 were analyzed. Demographic, surgical, recurrence, survival, and post-operative morbidity data were collected for 233 patients, resulting in a total of 400 groin node dissections analyzed.
• Rates of overall primary recurrence of disease between superficial and deep inguinal LND (42.5 vs. 39.8%, p = 0.70) and rates of inguinal recurrence (3.4 vs. 8.3%, p = 0.16) were similar. Overall rates of postoperative morbidity were significantly higher in the cohort undergoing deep LND (70.3% vs 44.3%, p < 0.01). Rates of lymphedema (42.4 vs 15.9%, p < 0.01), readmission (26.3 vs 6.8%, p < 0.01), and infection (40.7 vs 14.8%, p < 0.01) were all significantly higher among patients undergoing deep LND. There was no significant difference noted in overall survival between the study groups when adjusting for stage and age (HR 1.08, p = 0.84).
• Superficial inguinal LND had no significant difference in rate of recurrence or overall survival when compared to deep inguinal LND in patients with vulvar SCC. Those who received a deep LND had a significant increase in overall morbidity, including lymphedema, readmission, and infection. For patients who cannot undergo or fail sentinel lymph node mapping, a superficial inguinal lymph node dissection may have similar outcomes in recurrence and overall survival with a reduction in overall morbidity as compared to a complete, or deep, lymph node dissection.

Cesarean delivery availability in Iowa was not constrained by anesthesia workforce limitations: Retrospective cohort study of inpatient surgery case counts.

Kokila Thenuwara, Franklin Dexter, Richard H. Epstein

Perioperative Care and Operating Room Management, Volume 28, September 2022, 100277, epub ahead of print.

Background: Our goal was to assess whether anesthesia workforce limited surgical obstetrical care in the rural US state of Iowa. All Iowa hospitals with obstetrics have anesthesia practitioners (i.e., constraints would be functional, not related to having no anesthesia coverage). Our hypothesis #1 was that scheduling for cesarean delivery would functionally be separate from other inpatient operating room scheduling. Our hypothesis #2 was absence of systematic differences among hospitals in their distributions of cesarean deliveries between weekends and regular workdays.

• The retrospective cohort study included all inpatient surgical cases at hospitals with cesarean births in the state of Iowa October 2015 through June 2021. There were analyzed 112 hospitals ×  2100 days ×  2 numbers, counts of cesarean deliveries and counts of all other surgical cases.

Results: The incremental risk ratio between daily cesarean deliveries and other inpatient surgical cases was 1.00 per cesarean delivery (99% confidence interval 0.99 to 1.01). Thus, doing another cesarean delivery was not associated with either a proportional reduction (ratio <1) or increase (ratio >1) in other cases performed on the same day. Multiple sensitivity analyses showed the same results. In addition, there was no association in cesarean deliveries between hospitals’ percentages on weekends and overall weekly numbers (P = 0.08). Multiple sensitivity analyses showed the same results, no systematic differences between large versus small obstetrical programs in the distributions of cesareans between weekends versus workdays. Finally, among the 19/73 hospitals ending obstetrics during the study period, all continued to perform surgery.

Conclusions: Limitations in the anesthesia workforce did not constrain surgical obstetrical care statewide. Similarly, cesarean births were at most negligibly causing other inpatient surgical cases to be postponed to later days.

Integrated Clinical and Genomic Models to Predict Optimal Cytoreduction in High-Grade Serous Ovarian Cancer.

Cardillo N, Devor EJ, Pedra Nobre S, Newtson A, Leslie K, Bender DP, Smith BJ, Goodheart MJ, Gonzalez-Bosquet J.

Cancers (Basel). 2022 Jul 21;14(14):3554.

Advanced high-grade serous (HGSC) ovarian cancer is treated with either primary surgery followed by chemotherapy or neoadjuvant chemotherapy followed by interval surgery. The decision to proceed with surgery primarily or after chemotherapy is based on a surgeon's clinical assessment and prediction of an optimal outcome. Optimal and complete cytoreductive surgery are correlated with improved overall survival. This clinical assessment results in an optimal surgery approximately 70% of the time. We hypothesize that this prediction can be improved by using biological tumor data to predict optimal cytoreduction. With access to a large biobank of ovarian cancer tumors, we obtained genomic data on 83 patients encompassing gene expression, exon expression, long non-coding RNA, micro RNA, single nucleotide variants, copy number variation, DNA methylation, and fusion transcripts. We then used statistical learning methods (lasso regression) to integrate these data with pre-operative clinical information to create predictive models to discriminate which patient would have an optimal or complete cytoreductive outcome. These models were then validated within The Cancer Genome Atlas (TCGA) HGSC database and using machine learning methods (TensorFlow). Of the 124 models created and validated for optimal cytoreduction, 21 performed at least equal to, if not better than, our historical clinical rate of optimal debulking in advanced-stage HGSC as a control. Of the 89 models created to predict complete cytoreduction, 37 have the potential to outperform clinical decision-making. Prospective validation of these models could result in improving our ability to objectively predict which patients will undergo optimal cytoreduction and, therefore, improve our ovarian cancer outcomes.

Phase III Randomized Trial of Maintenance Taxanes Versus Surveillance in Women With Advanced Ovarian/Tubal/Peritoneal Cancer: A Gynecologic Oncology Group 0212:NRG Oncology Study.

Copeland LJ, Brady MF, Burger RA, Rodgers WH, Huang HQ, Cella D, O'Malley DM, Street DG, Tewari KS, Morris RT, Lowery WJ, Miller DS, Dewdney SB, Spirtos NM, Lele SB, Guntupalli S, Ueland FR, Glaser GE, Mannel RS, DiSaia PJ.

J Clin Oncol. 2022 Jun 27:JCO2200146. doi: 10.1200/JCO.22.00146. Epub ahead of print.

Purpose: To compare taxane maintenance chemotherapy, paclitaxel (P) and paclitaxel poliglumex (PP), with surveillance (S) in women with ovarian, peritoneal, or fallopian tube (O/PC/FT) cancer who attained clinical complete response after first-line platinum-taxane therapy.

• Women diagnosed with O/PC/FT cancer who attained clinical complete response after first-line platinum-taxane-based chemotherapy were randomly allocated 1:1:1 to S or maintenance, P 135 mg/m² once every 28 days for 12 cycles, or PP at the same dose and schedule. Overall survival (OS) was the primary efficacy end point.
• Between March 2005 and January 2014, 1,157 individuals were enrolled. Grade 2 or worse GI adverse events were more frequent among those treated with taxane (PP: 20%, P: 27% v S: 11%). Grade 2 or worse neurologic adverse events occurred more often with taxane treatment (PP: 46%, P: 36% v S: 14%). At the fourth scheduled interim analysis, both taxane regimens passed the OS futility boundary and the Data Monitoring Committee approved an early release of results. With a median follow-up of 8.1 years, 653 deaths were reported; none were attributed to the study treatment. Median survival durations were 58.3, 56.8, and 60.0 months for S, P, and PP, respectively. Relative to S, the hazard of death for P was 1.091 (95% CI, 0.911 to 1.31; P = .343) and for PP, it was 1.033 (95% CI, 0.862 to 1.24; P = .725). The median times to first progression or death (PFS) were 13.4, 18.9, and 16.3 months for S, P, and PP, respectively. Hazard ratio = 0.801; 95% CI, 0.684 to 0.938; P = .006 for P and hazard ratio = 0.854; 95% CI, 0.729 to 1.00; P = .055 for PP.
• Maintenance therapy with P and PP did not improve OS among patients with newly diagnosed O/tubal/peritoneal cancer, but may modestly increase PFS. GI and neurologic toxicities were more frequent in the taxane treatment arms.

Lifetime Infertility and Environmental, Chemical, and Hazardous Exposures Among Women and Men United States Veterans.

Mancuso AC, Mengeling MA, Holcomb A, Ryan GL.

Am J Obstet Gynecol. 2022 Jul 13:S0002-9378(22)00538-5. doi: 10.1016/j.ajog.2022.07.002. Epub ahead of print.

Background: Veterans experience many potentially hazardous exposures during their service, but little is known about the possible impact of these exposures on reproductive health.

• To assess the association between infertility and environmental, chemical, or hazardous material exposures among United States Veterans

STUDY DESIGN: We examined self-reported cross-sectional data from a national sample of female and male United States Veterans aged 20-45 separated from service for ≤10 years. Data were obtained via a computer-assisted telephone interview lasting an average of 1 hour 27 minutes that assessed demographics, general and reproductive health, and lifetime and military exposures. Logistic regression models were used to evaluate associations between exposures to environmental, chemical, and hazardous materials and infertility as defined by two different definitions: unprotected intercourse for 12 or more months without conception and trying to conceive for 12 or more months without conception.

• Of the Veterans included in this study, 592/1194 (49.6%) women and 727/1,407 (51.7%) men met the unprotected intercourse definition for infertility and 314/781 (40.2%) women and 270/775 (34.8%) men met the trying to conceive definition for infertility. Multiple individual exposure rates were found to be higher in women and men Veterans with self-reported infertility, including petrochemicals and polychlorinated biphenyls, which were higher in both the men and women groups reporting infertility by either definition. Importantly, there were no queried exposures self-reported at higher rates in the non-infertile groups. Veterans reporting infertility also reported a higher number of total exposures with a mean ± standard deviation of 7.61 ± 3.87 exposures for the women with infertility compared to 7.13 ± 3.67 for the non-infertile group (p=.030) and 13.17 ± 4.19 for Veteran men with infertility compared to 12.54 ± 4.10 for the non-infertile group (p=.005) using the unprotected intercourse definition, and 7.69 ± 3.79 for the women with infertility compared to 7.02 ± 3.57 for the non-infertile group (p=.013) and 13.77 ± 4.17 for the Veteran men with infertility compared to 12.89 ± 4.08 for the non-infertile group (p=.005) using the trying to conceive definition.
• These data identified an association between infertility and environmental, chemical, and hazardous materials Veterans were exposed to during military service. Although this study is limited by the self-reported and unblinded data collection from a survey, and causation between exposures and infertility cannot be proven, it does show that Veterans encounter many exposures during their service and calls for further research into the possible link between Veteran exposures and reproductive health.

Intracytoplasmic sperm injection vs. conventional in vitro fertilization in patients with non- male factor infertility.

Iwamoto A, Van Voorhis BJ, Summers KM, Sparks A, Mancuso AC.

Fertil Steril. 2022 Jul 11:S0015-0282(22)00387-9. doi: 10.1016/j.fertnstert.2022.06.009. Epub ahead of print.

Objective: To compare the cumulative live birth rates (CLBRs) and cost effectiveness of intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (cIVF) for non-male factor infertility.

• A retrospective cohort study.
• Society for Assisted Reproductive Technology clinics.
• A total of 46,967 patients with non-male factor infertility with the first autologous oocyte retrieval cycle between January 2014 and December 2015.
• None.

Main outcome measure(s): The primary outcomes were CLBR, defined as up to 1 live birth from an autologous retrieval cycle between 2014 and 2015, and linked fresh and frozen embryo transfers through 2016. The secondary outcomes included miscarriage rate, 2 pronuclei per oocyte retrieved, and the total number of transferred and frozen embryos. Analyses were performed on subsamples with and without preimplantation genetic testing for aneuploidy (PGT-A). A cost analysis was performed to determine the costs accrued by ICSI.

• Among cycles without PGT-A in patients with non-male factor infertility, the CLBR was 60.9% for ICSI cycles vs. 64.3% for cIVF cycles, a difference that was not significantly different after adjustment for covariates (adjusted risk ratio, 0.99; 95% confidence interval, 0.99-1.00). With PGT-A, no difference in CLBR was found between ICSI and cIVF cases after adjustment (64.7% vs. 69.0%, respectively; adjusted risk ratio, 0.97; 95% confidence interval, 0.93-1.01). The patients were charged an estimated additional amount of $37,476,000 for ICSI without genetic testing and an additional amount of $7,213,500 for ICSI with PGT-A over 2 years by Society for Assisted Reproductive Technology clinics.
• In patients with non-male factor infertility, ICSI did not improve CLBR. Given the additional cost and the lack of CLBR benefit, our data show that the routine use of ICSI in patients with non-male factor infertility is not warranted.

Prophylactic Methylergonovine and Oxytocin Compared With Oxytocin Alone in Patients Undergoing Intrapartum Cesarean Birth: A Randomized Controlled Trial.

Masse N, Dexter F, Wong CA.

Obstet Gynecol. 2022 Aug 1;140(2):181-186. doi: 10.1097/AOG.0000000000004857. Epub 2022 Jul 6.

Objective: To evaluate whether the administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents.

• This was a single-center, placebo-controlled, randomized trial of patients undergoing intrapartum cesarean birth. Patients were randomly allocated to receive intravenous oxytocin 300 mL/minute plus intramuscular methylergonovine 0.2 mg (1 mL) or intravenous oxytocin 300 mL/minute plus intramuscular normal saline (1 mL). The primary outcome was the receipt of additional uterotonic agents. Secondary outcomes included surgeon assessment of uterine tone, incidence of postpartum hemorrhage, quantitative blood loss, and blood transfusion. To detect a twofold decrease in the need for additional uterotonic agents (assuming a 42% baseline) with a two-sided type 1 error of 5% and power of 80%, a sample size of 76 patients per group was required.
• From June 2019 through February 2021, 80 patients were randomized to receive methylergonovine plus oxytocin and 80 were randomized to receive to oxytocin alone. Significantly fewer patients who were allocated to the methylergonovine group received additional uterotonic agents (20% vs 55%, relative risk [RR] 0.4, 95% CI 0.2-0.6). Participants receiving methylergonovine were more likely to have satisfactory uterine tone (80% vs 41%, RR 1.9, 95% CI 1.5-2.6), lower incidence of postpartum hemorrhage (35% vs 59%, RR 0.6, 95% CI 0.4-0.9), lower mean quantitative blood loss (967 mL vs 1,315 mL; mean difference 348, 95% CI 124-572), and a lower frequency of blood transfusion (5% vs 23%, RR 0.2, 95% CI 0.1-0.6).
• The administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents.

Occupation and Semen Parameters in a Cohort of Fertile Men.

Meyer JD, Brazil C, Redmon JB, Wang C, Swan SH.

J Occup Environ Med. 2022 Jul 19. doi: 10.1097/JOM.0000000000002607. Epub ahead of print.

Objective: We examined associations between occupation and semen parameters in demonstrably fertile men in the Study for Future Families.

• Associations of occupation and workplace exposures with semen volume, sperm concentration, motility, and morphology were assessed using generalized linear modeling.
• Lower sperm concentration and motility were seen in installation, maintenance, and repair occupations. Higher exposure to lead, and to other toxicants, was seen in occupations with lower mean sperm concentrations (prevalence ratio for lead: 4.1; pesticides/insecticides: 1.6; solvents: 1.4). Working with lead for more than 3 months was associated with lower sperm concentration, as was lead exposure outside of work.
• We found evidence in demonstrably fertile men for reduced sperm quality with lead, pesticide/herbicide, and solvent exposure. These results may identify occupations where protective measures against male reproductive toxicity might be warranted.

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts.

Welch BM, Keil AP, Buckley JP, Calafat AM, Christenbury KE, Engel SM, O'Brien KM, Rosen EM, James-Todd T, Zota AR, Ferguson KK; Pooled Phthalate Exposure and Preterm Birth Study Group, Alshawabkeh AN, Cordero JF, Meeker JD, Barrett ES, Bush NR, Nguyen RHN, Sathyanarayana S, Swan SH, Cantonwine DE, McElrath TF, Aalborg J, Dabelea D, Starling AP, Hauser R, Messerlian C, Zhang Y, Bradman A, Eskenazi B, Harley KG, Holland N, Bloom MS, Newman RB, Wenzel AG, Braun JM, Lanphear BP, Yolton K, Factor-Litvak P, Herbstman JB, Rauh VA, Drobnis EZ, Redmon JB, Wang C, Binder AM, Michels KB, Baird DD, Jukic AMZ, Weinberg CR, Wilcox AJ, Rich DQ, Weinberger B, Padmanabhan V, Watkins DJ, Hertz-Picciotto I, Schmidt RJ.

JAMA Pediatr. 2022 Jul 11:e222252. doi: 10.1001/jamapediatrics.2022.2252. Epub ahead of print.

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.

• To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.

Design, setting, and participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.

• Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated.

Main outcomes and measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth.

• The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively.

Conclusions and relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions.

Preti M, Joura E, Vieira-Baptista P, Van Beurden M, Bevilacqua F, Bleeker MCG, Bornstein J, Carcopino X, Chargari C, Cruickshank ME, Erzeneoglu BE, Gallio N, Heller D, Kesic V, Reich O, Temiz BE, Woelber L, Planchamp F, Zodzika J, Querleu D, Gultekin M.

J Low Genit Tract Dis. 2022 Jul 1;26(3):229-244. doi: 10.1097/LGT.0000000000000683. Epub 2022 Jun 21.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

Endometrial thickness: How thin is too thin?

Jacobs EA, Van Voorhis B, Kawwass JF, Kondapalli LA, Liu K, Dokras A.

Fertil Steril. 2022 Aug;118(2):249-259. doi: 10.1016/j.fertnstert.2022.05.033.

Genetic counselors' experience with reimbursement and patient out-of-pocket cost for multi-cancer gene panel testing for hereditary cancer syndromes.

Weldon CB, Trosman JR, Liang SY, Douglas MP, Scheuner MT, Kurian A, Roscow B, Erwin D, Phillips KA.

J Genet Couns. 2022 Jul 28. doi: 10.1002/jgc4.1614. Epub ahead of print.

Multi-cancer gene panels for hereditary cancer syndromes (hereditary cancer panels, HCPs) are widely available, and some laboratories have programs that limit patients' out-of-pocket (OOP) cost share. However, little is known about practices by cancer genetic counselors for discussing and ordering an HCP and how insurance reimbursement and patient out-of-pocket share impact these practices. We conducted a survey of cancer genetic counselors based in the United States through the National Society of Genetic Counselors to assess the impact of reimbursement and patient OOP share on ordering of an HCP and hereditary cancer genetic counseling. Data analyses were conducted using chi-square and t tests. We received 135 responses (16% response rate). We found that the vast majority of respondents (94%, 127/135) ordered an HCP for patients rather than single-gene tests to assess hereditary cancer predisposition. Two-thirds of respondents reported that their institution had no protocol related to discussing HCPs with patients. Most respondents (84%, 114/135) indicated clinical indications and patients' requests as important in selecting and ordering HCPs, while 42%, 57/135, considered reimbursement and patient OOP share factors important. We found statistically significant differences in reporting of insurance as a frequently used payment method for HCPs and in-person genetic counseling (84% versus 59%, respectively, p < 0.0001). Perceived patient willingness to pay more than $100 was significantly higher for HCPs than for genetic counseling(41% versus 22%, respectively, p < 0.01). In sum, genetic counselors' widespread selection and ordering of HCPs is driven more by clinical indications and patient preferences than payment considerations. Respondents perceived that testing is more often reimbursed by insurance than genetic counseling, and patients are more willing to pay for an HCP than for genetic counseling. Policy efforts should address this incongruence in reimbursement and patient OOP share. Patient-centered communication should educate patients on the benefit of genetic counseling.

Cumulative live birth rate in women aged ≤37 years after in vitro fertilization with or without preimplantation genetic testing for aneuploidy: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System retrospective analysis.

Mejia RB, Capper EA, Summers KM, Mancuso AC, Sparks AE, Van Voorhis BJ.

F S Rep. 11 May 2022. doi:  10.1016/j.xfre.2022.05.004. Epub ahead of print.

• To investigate cumulative live birth rates (CLBRs) in cycles with and without preimplantation genetic testing for aneuploidy (PGT-A) among patients aged <35 and 35–37 years.

Design: Retrospective cohort study.

Setting: Society for Assisted Reproductive Technology reporting clinics.

Patient(s): A total of 31,900 patients aged % 37 years with initial oocyte retrievals between January 2014 and December 2015 followed through December 2016.

Intervention(s): None.

Main outcome measure(s): The primary outcome was CLBR among patients aged <35 and 35–37 years. The secondary outcomes included multifetal births, miscarriage, preterm birth, perinatal mortality, and the time to pregnancy resulting in a live birth. Adjusted odds ratios (aORs) adjusting for age, body mass index, total 2 pronuclei embryos, embryos transferred, and follow-up timeframe.

Result(s): Among patients aged <35 years, PGT-A was associated with reduced CLBRs (70.6% vs. 71.1%; aOR, 0.82; 95% CI [confidence interval], 0.72–0.93). No association was found between PGT-A and CLBRs among patients aged 35–37 years (66.6% vs. 62.5%; aOR, 0.92; 95% CI, 0.83–1.01). Overall, there was no significant difference in the miscarriage rate (aOR, 0.97; 95% CI, 0.82–1.14). Multifetal birth rates were lower with PGT-A (9.5% vs. 23.1%); however, PGT-A was not an independent predictor of multifetal birth (aOR, 1.11; 95% CI, 0.91–1.36). The average time to pregnancy resulting in a live birth was 2.37 months (SD 3.20) for untested transfers vs. 4.58 months (SD 3.53) for PGT-A transfers.

Conclusion(s): In women aged <35, the CLBR was lower with PGT-A than with the transfer of untested embryos. In women aged 35–37 years, PGT-A did not improve CLBRs.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions.

Preti M, Joura E, Vieira-Baptista P, Van Beurden M, Bevilacqua F, Bleeker MCG, Bornstein J, Carcopino X, Chargari C, Cruickshank ME, Erzeneoglu BE, Gallio N, Heller D, Kesic V, Reich O, Esat Temiz B, Woelber L, Planchamp F, Zodzika J, Querleu D, Gultekin M

Int J Gynecol Cancer. 2022 Jun 21:ijgc-2021-003262. doi: 10.1136/ijgc-2021-003262. Epub ahead of print. PMID: 35728950.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

Postpartum ambulatory and home blood pressure monitoring in women with history of preeclampsia: Diagnostic agreement and detection of masked hypertension.

Nuckols VR, Stroud AK, Armstrong MK, Pierce GL.

Pregnancy Hypertens. 2022 May 10;29:23-29. doi: 10.1016/j.preghy.2022.05.003. Epub ahead of print.

Women with a history of preeclampsia (hxPE) are at a four-fold higher risk for chronic hypertension after pregnancy compared with healthy pregnancy, but 'masked' hypertension cases are missed by clinical assessment alone. Twenty-four hour ambulatory blood pressure monitoring (ABPM) is the reference-standard for confirmation of hypertension diagnoses or detection of masked hypertension outside of clinical settings, whereas home blood pressure monitoring (HBPM) may represent a well-tolerated and practical alternative to ABPM in the postpartum period. The objectives of this study were to 1) assess concordance between ABPM and HBPM postpartum in women with a hxPE compared with healthy pregnancy controls and 2) evaluate HBPM in the detection of masked postpartum hypertension. Young women with a hxPE (N = 26) and controls (N = 36) underwent in-office, 24-h ABPM and 7-day HBPM 1-4 years postpartum. Chronic hypertension was more prevalent among women with a hxPE by all three blood pressure measures, but the prevalence of masked postpartum hypertension did not differ (36% vs 37%, P = 0.97). HBPM showed excellent agreement with ABPM (systolic: r = 0.78, intraclass coefficient [ICC] = 0.83; diastolic: r = 0.82, ICC = 0.88) and moderate concordance in classification of hypertension (κ = 0.54, P < 0.001). HBPM identified 21% of masked postpartum hypertension cases without false-positive cases, and HBPM measures among those with normotensive in-office readings could detect ABPM-defined masked hypertension (area under the curve [AUC] = 0.88 ± 0.06, P < 0.0001). The findings of the present study indicate that HBPM may be a useful screening modality prior or complementary to ABPM in the detection and management of postpartum hypertension.

Common Complications of Breastfeeding and Lactation: An Overview for Clinicians.

Radke SM.

Clin Obstet Gynecol. 2022 Jun 9. doi: 10.1097/GRF.0000000000000716. Epub ahead of print.

Lactation and breastfeeding are core components of reproductive health care and obstetrical providers should be familiar with common complications that may arise in lactating individuals. While many breastfeeding challenges are best addressed by a lactation consultant, there are conditions that fall out of their scope and require care from a clinician. The objective of this chapter is to review common complications of breastfeeding and lactation including inflammatory conditions, disorders of lactogenesis, dermatologic conditions, and persistent pain with lactation.

TP53 Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study.

Thiel KW, Devor EJ, Filiaci VL, Mutch D, Moxley K, Alvarez Secord A, Tewari KS, McDonald ME, Mathews C, Cosgrove C, Dewdney S, Aghajanian C, Samuelson MI, Lankes HA, Soslow RA, Leslie KK.

J Clin Oncol. 2022 Jun 3:JCO2102506. doi: 10.1200/JCO.21.02506. Epub ahead of print.

Purpose: The status of p53 in a tumor can be inferred by next-generation sequencing (NGS) or by immunohistochemistry (IHC). We examined the association between p53 IHC and sequence and whether p53 IHC alone, or integrated with TP53 NGS, predicts the outcome.

Methods: From GOG-86P, a randomized phase II study of chemotherapy combined with either bevacizumab or temsirolimus in advanced endometrial cancer, 213 cases had p53 protein expression data measured by IHC and TP53 NGS data. An analysis was designed to integrate p53 expression by IHC with the presence or absence of a TP53 mutation. These variables were further correlated with progression-free survival (PFS) and overall survival (OS) in the chemotherapy plus bevacizumab arms versus the chemotherapy plus temsirolimus arm.

• In the analysis of p53 IHC, the most striking treatment effect favoring bevacizumab was in cases where p53 was overexpressed (PFS hazard ratio [HR]: 0.46, 95% CI, 0.26 to 0.88; OS HR: 0.31, 95% CI, 0.16 to 0.62). On integrated analysis, patients with TP53 missense mutations and p53 protein overexpression had a similar treatment effect on PFS (HR: 0.41, 95% CI, 0.22 to 0.83) and OS (HR: 0.28, 95% CI, 0.14 to 0.59) favoring bevacizumab plus chemotherapy relative to temsirolimus plus chemotherapy. Concordance between TP53 NGS and p53 IHC was 88%. Concordance was 92% when cases with TP53 mutations and POLE mutations or mismatch repair deficiency were removed.

Conclusion: IHC for p53 alone or when integrated with sequencing for TP53 identifies a specific, high-risk tumor genotype/phenotype for which bevacizumab is particularly beneficial in improving outcomes when combined with chemotherapy.

Treatment of primary infertility in McCune-Albright syndrome: a case report of a successful in vitro fertilization cycle.

Chung RK,

F S Rep. 2021 May 20;2(3):352-356. doi: 10.1016/j.xfre.2021.05.001.

Objective: To report a case in which pregnancy and live birth were achieved in an infertile patient with McCune-Albright syndrome via in vitro fertilization (IVF).

Design: Case report.

Setting: University hospital.

Patients: A 29-year-old woman with McCune-Albright syndrome who presented with primary infertility due to ovulatory dysfunction and bilateral tubal blockage.

Interventions: In vitro fertilization without unilateral oophorectomy.

Main outcome measures: Live birth after IVF treatment.

Results: Fresh IVF stimulation and bilateral oocyte retrieval yielded 12 oocytes and 4 top quality embryos. Fresh single embryo transfer did not result in pregnancy. Live birth occurred after the second frozen embryo transfer cycle.

Conclusions: In vitro fertilization can lead to ongoing pregnancy in infertile patients with McCune-Albright syndrome without requiring unilateral oophorectomy.

Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors.

Kenne KA, Wendt L, Brooks Jackson J

Sci Rep. 2022 Jun 14;12(1):9878. doi: 10.1038/s41598-022-13501-w.

Determine the prevalence of pelvic floor disorders (PFD) stratified by age, race, body mass index (BMI), and parity in adult women attending family medicine and general internal medicine clinics at an academic health system. The medical records of 25,425 adult women attending primary care clinics were queried using International Classification of Diseases-10th Revision codes (ICD-10 codes) for PFD [urinary incontinence (UI), pelvic organ prolapse (POP), and bowel dysfunction (anal incontinence (AI) and difficult defecation)]. Prevalence and odds ratios were calculated using univariate and multivariate analysis for age, race, BMI, and parity when available. Multivariate logistic regression models were used to assess the impact of age, race, BMI, and parity on the likelihood of being diagnosed with a PFD. A separate model was constructed for each of the three PFD categories (UI, POP, and bowel dysfunction) as well as a model assessing the likelihood of occurrence for any type of PFD. The percentage of women with at least one PFD was 32.0% with bowel dysfunction the most common (24.6%), followed by UI (11.1%) and POP (4.4%). 5.5% had exactly two PFD and 1.1% had all 3 categories of PFD. Older age and higher BMI were strongly and significantly associated with each of the three PFD categories, except for BMI and prolapse. Relative to White patients, Asian patients were at significantly lower risk for each category of PFD, while Black patients were at significantly lower risk for UI and POP, but at significantly greater risk for bowel dysfunction and the presence of any PFD. Higher parity was also significantly associated with pelvic organ prolapse. Using multivariate analyses, age, race, and BMI were all independently associated with PFD. PFD are highly prevalent in the primary care setting and should be screened for, especially in older and obese women. BMI may represent a modifiable risk factor.

Barriers and solutions to developing and maintaining research networks during a pandemic: An example from the iELEVATE perinatal network

Santillan DA, Brandt DS, Sinkey R, Scheib S, Peterson S, LeDuke R, Dimperio L, Cherek C, Varsho A, Granza M, Logan K, Hunter SK, Knosp BM, Davis HA, Spring JC, Piehl D, Makkapati R, Doering T, Harris S, Day L, Eder M, Winokur P, Santillan MK.

J Clin Transl Sci. 2022 Jan 17;6(1):e56. doi: 10.1017/cts.2022.5.

Introduction: To improve maternal health outcomes, increased diversity is needed among pregnant people in research studies and community surveillance. To expand the pool, we sought to develop a network encompassing academic and community obstetrics clinics. Typical challenges in developing a network include site identification, contracting, onboarding sites, staff engagement, participant recruitment, funding, and institutional review board approvals. While not insurmountable, these challenges became magnified as we built a research network during a global pandemic. Our objective is to describe the framework utilized to resolve pandemic-related issues.

Methods: We developed a framework for site-specific adaptation of the generalized study protocol. Twice monthly video meetings were held between the lead academic sites to identify local challenges and to generate ideas for solutions. We identified site and participant recruitment challenges and then implemented solutions tailored to the local workflow. These solutions included the use of an electronic consent and videoconferences with local clinic leadership and staff. The processes for network development and maintenance changed to address issues related to the COVID-19 pandemic. However, aspects of the sample processing/storage and data collection elements were held constant between sites.

Results: Adapting our consenting approach enabled maintaining study enrollment during the pandemic. The pandemic amplified issues related to contracting, onboarding, and IRB approval. Maintaining continuity in sample management and clinical data collection allowed for pooling of information between sites.

Conclusions: Adaptability is key to maintaining network sites. Rapidly changing guidelines for beginning and continuing research during the pandemic required frequent intra- and inter-institutional communication to navigate.

Foreword: Management of Breast Disorders.

Huber-Keener KJ.

Clin Obstet Gynecol. 2022 Jun 15. doi: 10.1097/GRF.0000000000000728. Epub ahead of print.

Management of Breast Cancer Survivors by Gynecologists.

Huber-Keener KJ.

Clin Obstet Gynecol. 2022 Jun 16. doi: 10.1097/GRF.0000000000000727. Epub ahead of print.

Breast cancer patients commonly present to their OBGYN during the process of diagnosis and treatment of breast cancer both for specific gynecologic needs and for primary care follow up. These patients require counseling on contraception, hormone use, and fertility at diagnosis. During treatment and survivorship, patients will face a variety of side effects from treatments leading to vasomotor symptoms, vulvovaginal discomfort, sexual dysfunction, osteoporosis, and vaginal bleeding. This chapters aims to enlighten providers on the unique range of issues a gynecologist may face when caring for breast cancer patients.

Subtyping of common complex diseases and disorders by integrating heterogeneous data. Identifying clusters among women with lower urinary tract symptoms in the LURN study.

Andreev VP, Helmuth ME, Liu G, Smith AR, Merion RM, Yang CC, Cameron AP, Jelovsek JE, Amundsen CL, Helfand BT, , DeLancey JOL, Griffith JW, Glaser AP, Gillespie BW, Clemens JQ, Lai HH; LURN Study Group.

PLoS One. 2022 Jun 10;17(6):e0268547. doi: 10.1371/journal.pone.0268547.

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five clusters of women with LUTS were identified using the developed methodology. None of the clusters could be characterized by a single symptom, but rather by a distinct combination of symptoms with various levels of severity. Targeted proteomics of serum samples demonstrated that differentially abundant proteins and affected pathways are different across the clusters. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. The rationale and thought process are described for the selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains.

Ductal-cutaneous fistula secondary to recurrent Bartholin’s cysts: a case report.

Ikoma DM, Shaffer SA.

Proc Obstet Gynecol. 2022;11(2): Article 1 [ 10 p.]. doi: 10.17077/2154-4751.31455.

Background: Disorders of the Bartholin’s duct and gland, including cyst and abscess formation, account for 2% of gynecologic visits annually. An uncommon complication of a Bartholin’s duct or gland abscess is fistula formation. Literature has described cases of recto-Bartholin’s and recto-vaginal fistulas.

Case: We present a case of fistula development between the perineum and the Bartholin’s duct and gland. The patient was successfully managed with fistulectomy and Bartholin’s gland excision.

Conclusion: Though fistula formation is a rare complication of Bartholin’s duct and gland pathology, investigation is warranted. A ductal-cutaneous fistula is possible in the setting of recurrent cysts located beyond the vaginal introitus. The best method of prevention is appropriate execution of a marsupialization. Complete removal of the fistulous tract and Bartholin’s duct and/or gland can result in resolution of symptoms.

Investigating the effect of optimal cytoreduction in the context of platinum sensitivity in high-grade serous ovarian cancer.

Cardillo N, Devor E, Calma C, Pedra Nobre S, Gabrilovich S, Bender DP, Goodheart M, Gonzalez-Bosquet J.

Acta Obstet Gynecol Scand. 2022 Jul 2. doi: 10.1111/aogs.14415. Epub ahead of print.

• The survival benefits of surgical cytoreduction in ovarian cancer are well-established. However, the surgical outcome has never been assessed while controlling for the efficacy of chemotherapy. This leaves the possibility that cytoreduction may not be beneficial for patients whose cancer does not respond well to adjuvant treatment. We sought to answer whether surgical cytoreduction independently improves overall survival when controlling for chemotherapy outcome.

Material and methods: We performed a retrospective case-control study using our institution's ovarian cancer database to evaluate the effect of optimal cytoreduction on advanced stage, high-grade serous ovarian cancer. Patients' characteristics were compared using both univariate and multivariate regression modeling to assess for independent predictors of overall survival.

Results: A total of 470 patients were assessed for inclusion; 234 responders to chemotherapy and 98 nonresponders. Significant survival characteristics were identified and included in the multivariate analysis. Independent predictors of survival in the multivariate analysis were age, responder status, optimal cytoreduction, neoadjuvant chemotherapy, and number of chemotherapy cycles. Kaplan-Meier survival curves showed improved survival for both patients who responded to chemotherapy and for those undergoing optimal cytoreduction (p < 0.001). We also demonstrated improved survival for patients receiving optimal cytoreduction among both nonresponders and responders (p < 0.001).

Conclusions: Our analysis shows that patients who undergo optimal cytoreduction have an overall survival benefit regardless of their response to chemotherapy. Therefore, cytoreduction should be considered in all patients, even in those with advanced disease, if an optimal result can be achieved. This study was underpowered to assess patients who received neoadjuvant chemotherapy as a separate subgroup, but the order of treatment was controlled for in the overall analysis.

The Effect of Financial Incentives on Adherence to Glucose Self-Monitoring during Pregnancy among Patients with Insulin-Requiring Diabetes: A Randomized Clinical Trial.

Wernimont S, , , Deonovic B, , Andrews J.

Am J Perinatol. 2022 Jul 1. doi: 10.1055/a-1889-7765. Epub ahead of print.

Objective: Glucose self-monitoring is critical for management of diabetes in pregnancy, and increased adherence to testing is associated with improved obstetrical outcomes. Incentives have been shown to improve adherence to diabetes self-management. We hypothesized that use of financial incentives in pregnancies complicated by diabetes would improve adherence to glucose self-monitoring.

Study design: We conducted a single center, randomized clinical trial from 5/2016 to 7/2019. 130 pregnant patients, <29 weeks with insulin requiring diabetes, were recruited. Participants were randomized in a 1:1:1 ratio to one of three payment groups: control, positive incentive, and loss aversion. The control group received $25 upon enrollment. The positive incentive group received 10 cents/test, and the loss aversion group received $100 for > 95% adherence and "lost" payment for decreasing adherence. The primary outcome was percent adherence to recommended glucose self-monitoring where adherence was reliably quantified using a cellular-enabled glucometer. Adherence, calculated as the number of tests per day divided by the number of recommended tests per day X 100%, was averaged from time of enrollment until admission for delivery.

Results: We enrolled 130 participants and the 117 participants included in the final analysis had similar baseline characteristics across the three groups. Average adherence rates in the loss aversion, control and positive incentive groups were 69% (SE 5.12), 57% (SE 4.60) and 58% (SE 3.75), respectively (p=0.099). The loss aversion group received an average of $50 compared to $38 (positive incentive) and $25 (control).

Conclusion: In this randomized clinical trial, loss aversion incentives tended towards higher adherence to glucose self-monitoring among patients whose pregnancies were complicated by diabetes, though did not reach statistical significance. Further studies are needed to determine whether use of incentives improve maternal and neonatal outcomes.

Differences in H3K4me3 and chromatin accessibility contribute to altered T cell receptor signaling in neonatal naïve CD4 T cells.

Bermick JR, Issuree P, denDekker A, Gallagher KA, Kunkel S, Lukacs N, Schaller M.

Immunol Cell Biol. 2022 May 24. doi: 10.1111/imcb.12561. Epub ahead of print.

Neonatal CD4+ T cells have reduced or delayed T cell receptor (TCR) signaling responses compared to adult cells, but the mechanisms underlying this are poorly understood. This study tested the hypothesis that human neonatal naïve CD4+ TCR signaling and activation deficits are related to differences in H3K4me3 patterning and chromatin accessibility. Following initiation of TCR signaling using anti-CD3/anti-CD28 beads, adult naïve CD4+ T cells demonstrated increased CD69, phosphoCD3E and IL-2, TNF-α, IFN-γ and IL-17A compared to neonatal cells. In contrast, following TCR-independent activation using PMA/ionomycin, neonatal cells demonstrated increased expression of CD69, IL-2 and TNF- α and equivalent phosphoERK compared to adult cells. H3K4me3 ChIP-seq and ATAC-seq were performed on separate cohorts of naïve CD4+ T cells from term neonates and adults, and RNA-seq data from neonatal and adult naïve CD4+ T cells was obtained from the Blueprint Consortium. Adult cells demonstrated overall increased chromatin accessibility and a higher proportion of H3K4me3 sites associated with open chromatin and active gene transcription compared to neonatal cells. Adult cells demonstrated increased mRNA expression of the TCR-associated genes FYN, ITK, CD4, LCK and LAT, which was associated with increased H3K4me3 at the FYN and ITK gene loci and increased chromatin accessibility at the CD4, LCK and LAT loci. These findings indicate that neonatal TCR-dependent defects in activation are epigenetically regulated and provide a potentially targetable mechanism to enhance neonatal CD4+ T cell responses.

Early Diagnostics of Vulvar Intraepithelial Neoplasia

Kesić V, Vieira-Baptista P,

Cancers (Basel). 2022 Apr 4;14(7):1822. doi: 10.3390/cancers14071822.

The spectrum of vulvar lesions ranges from infective and benign dermatologic conditions to vulvar precancer and invasive cancer. Distinction based on the characteristics of vulvar lesions is often not indicative of histology. Vulvoscopy is a useful tool in the examination of vulvar pathology. It is more complex than just colposcopic examination and presumes naked eye examination accompanied by magnification, when needed. Magnification can be achieved using a magnifying glass or a colposcope and may aid the evaluation when a premalignant or malignant lesion is suspected. It is a useful tool to establish the best location for biopsies, to plan excision, and to evaluate the entire lower genital system. Combining features of vulvar lesions can help prediction of its histological nature. Clinically, there are two distinct premalignant types of vulvar intraepithelial neoplasia: HPV-related VIN, more common in young women, multifocal and multicentric; VIN associated with vulvar dermatoses, more common in older women and usually unicentric. For definite diagnosis, a biopsy is required. In practice, the decision to perform a biopsy is often delayed due to a lack of symptoms at the early stages of the neoplastic disease. Clinical evaluation of all VIN lesions should be conducted very carefully, because an underlying early invasive squamous cancer may be present.

Larry J. Copeland, MD, American Journal of Obstetrics & Gynecology Editor.

Bradley CS, Romero R.

Am J Obstet Gynecol. 2022 May;226(5):603-604

Natural history of postoperative neuropathies in gynecologic surgery.

Chen E,

Int Urogynecol J. 2022 Apr 6. doi: 10.1007/s00192-022-05183-9. Epub ahead of print.

Introduction and hypothesis: Neuropathy following pelvic surgery is an uncommon but important complication. The current literature about the natural history and treatment of these neuropathies is limited. We aim to describe the characteristics, treatments and natural history of postoperative neuropathy following benign gynecologic surgery.

Methods: This retrospective case series included patients who underwent benign gynecologic surgery for ≥ 60 min in lithotomy. Patients with preexisting neurologic disease were excluded. Patient demographics, identification of postoperative neuropathy and details regarding evaluation and treatment were obtained from the medical record. Neuropathies were characterized by anatomic location and nerve/dermatome distribution. Duration of symptoms was classified as < 1 week, 1 week to 3 months or > 3 months with neuropathy symptoms grouped as resolved, persistent but improved or persistent. Data were analyzed with appropriate descriptive statistics, Pearson correlation and chi-square test.

Results: The study included 2449 patients who had undergone benign gynecologic surgery, with 78 (3.2%) patients identified as having postoperative neuropathy. Most patients with neuropathies demonstrated either complete resolution [59 (75.6%)] or persistent but improved [13 (16.7%)] symptoms. Twenty-eight (35.9%) had symptoms of ≥ 3 months. Most neuropathies were sensory only [63 (80.8%)], and the most frequently documented nerve distribution was femoral [23 (29.5%)]. Evaluation and treatment of neuropathy most commonly included physical therapy consult [17 (21.8%)] and neurology consult [8 (10.3%)].

Conclusions: The incidence of postoperative neuropathy in this large, benign gynecologic surgery population was 3.2%. Most neuropathies are sensory only and self-limited. While physical therapy was the most common treatment, most patients received no specific intervention.

Fresh Embryo Transfer Cycle Characteristics and Outcomes Following In Vitro Fertilization via Intracytoplasmic Sperm Injection Among Patients With and Without COVID-19 Vaccination.

Jacobs E, Summers K, Sparks A, Mejia R.

JAMA Netw Open. 2022 Apr 1;5(4):e228625

Trends and Outcomes for Preimplantation Genetic Testing in the United States, 2014-2018.

Hipp HS, Crawford S, Boulet S, Toner J, Kawwass JF.

JAMA. 2022 Apr 5;327(13):1288-1290.

This study uses US national surveillance data to describe preimplantation genetic testing trends and outcomes between 2014 and 2018.

Early Diagnostics of Vulvar Intraepithelial Neoplasia.

Kesić V, Vieira-Baptista P,

Cancers (Basel). 2022 Apr 4;14(7):1822.

The spectrum of vulvar lesions ranges from infective and benign dermatologic conditions to vulvar precancer and invasive cancer. Distinction based on the characteristics of vulvar lesions is often not indicative of histology. Vulvoscopy is a useful tool in the examination of vulvar pathology. It is more complex than just colposcopic examination and presumes naked eye examination accompanied by magnification, when needed. Magnification can be achieved using a magnifying glass or a colposcope and may aid the evaluation when a premalignant or malignant lesion is suspected. It is a useful tool to establish the best location for biopsies, to plan excision, and to evaluate the entire lower genital system. Combining features of vulvar lesions can help prediction of its histological nature. Clinically, there are two distinct premalignant types of vulvar intraepithelial neoplasia: HPV-related VIN, more common in young women, multifocal and multicentric; VIN associated with vulvar dermatoses, more common in older women and usually unicentric. For definite diagnosis, a biopsy is required. In practice, the decision to perform a biopsy is often delayed due to a lack of symptoms at the early stages of the neoplastic disease. Clinical evaluation of all VIN lesions should be conducted very carefully, because an underlying early invasive squamous cancer may be present.

Look before you LEEP: patient reported pain with IV sedation vs local analgesia.

Frahm AJ,

Proc Obstet Gynecol. 2022;11(1): Article 8 [ 6 p.].

Objective: Examine the effectiveness of IV sedation in addition local analgesia compared to local analgesia alone for LEEP pain management.

Methods: This quality improvement project surveyed 89 patients who underwent a LEEP procedure: 26 in the local only group and 63 in the IV + local group. Patients completed a visual analog scale and pain survey immediately following their LEEP.

Results: The local analgesia + IV sedation group reported a lower average pain score compared to the local analgesia only group (2.4 ± 2.2 v 3.6 ± 2.7). However, this was not statistically significant, p 0.47. Patients found it was helpful to know what to expect prior to the LEEP and utilized various means of pain relief in addition to the primary treatments assessed.

Conclusions: There is a need for high quality trials to determine best practices of pain management.

Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open- Label, Phase III Trial.

Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA.

J Clin Oncol. 2022 Mar 15:JCO2102011. doi: 10.1200/JCO.21.02011. Epub ahead of print.

Purpose: Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy.

Patients and methods: NRG-GY004 is an open-label, randomized, phase III trial conducted in the United States and Canada. Eligible patients had high-grade serous or endometrioid platinum-sensitive ovarian cancer. Patients were randomly assigned 1:1:1 to platinum-based chemotherapy, olaparib, or olaparib/cediranib. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included activity within germline BRCA-mutated or wild-type subgroups and patient-reported outcomes (PROs).

Results: Between February 04, 2016, and November 13, 2017, 565 eligible patients were randomly assigned. Median PFS was 10.3 (95% CI, 8.7 to 11.2), 8.2 (95% CI, 6.6 to 8.7), and 10.4 (95% CI, 8.5 to 12.5) months with chemotherapy, olaparib, and olaparib/cediranib, respectively. Olaparib/cediranib did not improve PFS versus chemotherapy (hazard ratio [HR] 0.86; 95% CI, 0.66 to 1.10; P = .077). In women with germline BRCA mutation, the PFS HR versus chemotherapy was 0.55 (95% CI, 0.32 to 0.94) for olaparib/cediranib and 0.63 (95% CI, 0.37 to 1.07) for olaparib. In women without a germline BRCA mutation, the PFS HR versus chemotherapy was 0.97 (95% CI, 0.73 to 1.30) for olaparib/cediranib and 1.41 (95% CI, 1.07 to 1.86) for olaparib. Hematologic adverse events occurred more commonly with chemotherapy; however, nonhematologic adverse events were higher with olaparib/cediranib. In 489 patients evaluable for PROs, patients receiving olaparib/cediranib scored on average 1.1 points worse on the NFOSI-DRS-P subscale (97.5% CI, -2.0 to -0.2, P = .0063) versus chemotherapy; no difference between olaparib and chemotherapy was observed.

Conclusion: Combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. Notably, in patients with a germline BRCA mutation, both olaparib and olaparib/cediranib had significant clinical activity.

Is Pelvic Floor Muscle Tenderness a Distinct Urologic Chronic Pelvic Pain Syndrome (UCPPS) Phenotype?: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Symptoms Pattern Study (SPS).

Gupta P, Gallop R, Spitznagle T, Lai H, Tu F, Krieger JN, Clemens JQ, Yang C, Sutcliffe S, Moldwin R, Kreder K, Kutch J, Rodriguez LV.

J Urol. 2022 Mar 28:101097JU0000000000002679. doi: 10.1097/JU.0000000000002679. Epub ahead of print.

Purpose: 85% of women with interstitial cystitis/bladder pain syndrome (IC/BPS) and men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have concomitant pelvic floor muscle tenderness (PFT). The significance of this finding is incompletely understood. This study examines PFT among participants in the MAPP Research Network, and its relationship with urologic chronic pelvic pain syndrome (UCPPS) symptom severity, in order to determine whether this is a phenotypic predictor in UCPPS.

Materials and methods: Participants in the MAPP Network Symptom Patterns Study (SPS) underwent a standardized pelvic examination (PEX). Trained examiners palpated six locations evaluating the pelvic musculature for PFT. Participants were assigned a 0 to 6 PEX score based on the number of areas with tenderness on PEX. Using regression tree models, PEX scores were divided into low (0-1), mid (2,3,4,5), and high (6). The relationship between PFT and UCPPS symptoms was examined using several validated questionnaires.

Results: The study cohort consisted of 562 UCCPS participants (375 females and 187 males), and 69 controls. Diagnoses included IC/BPS (n=397), CP/CPPS (n=122), both (n=34), or no diagnosis (n=9). 81% of UCPPS participants had PFT on PEX compared to 9% of controls: 107 (19%) low, 312 (56%) mid, and 143 (25%) high. Participants with higher PFT scores had more severe disease burden (worse pelvic pain and urinary symptoms), worse quality of life, and more widespread distribution of non-pelvic pain.

Conclusions: UCPPS patients with more widespread PFT have severe pain and urinary symptoms, worse quality of life, and a more centralized pain phenotype.

Prospective evaluation of genital hiatus in patients undergoing surgical prolapse repair.

Bonglack M, Maetzold E, Kenne KA, Bradley CS, Kowalski JT.

Int Urogynecol J. 2022 Mar 17:1–8. doi: 10.1007/s00192-022-05157-x. Epub ahead of print.

Introduction and hypothesis: Enlarged genital hiatus (GH) is associated with prolapse recurrence following prolapse repair. Perineorrhaphy is often performed to reduce GH. However, changes in GH between the time of surgery and follow up are poorly understood. Our primary aim was to compare the intra-operative resting GH at the conclusion of surgery with the resting GH 3 months post-operatively in patients who undergo perineorrhaphy. We hypothesized that the intra-operative resting GH would be sustained.

Methods: Patients planning apical prolapse surgery were prospectively enrolled. Perineorrhaphy was performed at the surgeon's discretion. GH was measured pre-operatively in clinic, intra-operatively before and after surgery (resting), and 3 months post-operatively (resting and Valsalva).

Results: Twenty-nine perineorrhaphy and 27 no perineorrhaphy patients completed 3-month follow-up. Groups were similar in age (63.9 y, SD 10.4), body mass index (28.3 kg/m2, SD 5.2) and prior prolapse surgery (19.6%). Median (interquartile range) baseline Valsalva GH was larger in the perineorrhaphy group (4.5 (4 - 5.5) vs 3.5 (3 - 4) cm, p < 0.01). Median resting GH at 3 months was 0.5 cm less than end of surgery in the perineorrhaphy group (p < 0.01). The median change in GH between baseline and 3-month follow up was greater with perineorrhaphy (-1.5 vs -0.5 cm, p < 0.01). This difference was not seen in the sacrocolpopexy subgroup (-1.75 vs -1.5, p = 0.14; n = 24).

Conclusions: Surgeons can be reassured that the intra-operative change in GH resulting from perineorrhaphy is sustained 3 months after surgery and similar to the more commonly measured preoperative to postoperative change in Valsalva GH.

Hemolytic disease of the fetus and newborn in the sensitizing pregnancy where anti-D was incorrectly identified as RhIG.

Walhof ML, Leon J, , Knudson CM.

J Clin Lab Anal. 2022 Mar 3:e24323. doi: 10.1002/jcla.24323. Epub ahead of print.

Background: Hemolytic disease of the fetus and newborn (HDFN) is a potentially fatal complication in Rh-incompatible pregnancies and rarely occurs in the sensitizing pregnancy. Distinguishing RhIG from true anti-D identified is challenging. A case of severe HDFN in which a sample drawn at 28 weeks showed anti-D antibody (3+ strength) attributed to RhIG is described. RBC antibody testing early in pregnancy was negative. At birth, the infant was severely anemic and maternal anti-D titer was 1:256. This case represents a clinically significant anti-D in the sensitizing pregnancy that was missed due to confusion with RhIG.

Methods: To determine if agglutination strength could be helpful, a retrospective chart-review using both electronic and paper medical records was performed on 348 samples identified as RhIG and 52 true anti-D samples. The agglutination strength of antibody was recorded for each sample.

Results: For RhIG, there was an even distribution between the weak to moderate agglutination strength (w+, 1+, and 2+) results (35%, 26%, and 33%, respectively) and just 6% had a 3+ strength. Agglutination strength in patients with high titer (≥1:16) anti-D showed they often (44.4%) have 1+ or 2+ agglutination reactivity.

Conclusions: These results show that agglutination strength alone does not provide reliable evidence to distinguish RhIG from high titer anti-D antibodies. We recommend that in cases where there is any uncertainty about whether the anti-D reactivity is due to RhIG, titers should be performed to rule out clinically significant anti-D antibody.

Health Disparities in Uterine Cancer: Report From the Uterine Cancer Evidence Review Conference.

Whetstone S, Burke W, Sheth SS, Brooks R, Cavens A, Scott DM, Worly B, Chelmow D.

Obstet Gynecol. 2022 Mar 10;139(4):645–59. doi: 10.1097/AOG.0000000000004710. Epub ahead of print.

The Centers for Disease Control and Prevention recognized the need for educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines for the development of evidence-based educational materials for women's health care clinicians about uterine cancer. This article is the evidence summary of the literature review of health disparities and inequities related to uterine cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.

Executive Summary of the Uterine Cancer Evidence Review Conference.

Chelmow D, Brooks R, Cavens A, , Scott DM, Sheth SS, Whetstone S, Worly B, Burke W.

Obstet Gynecol. 2022 Mar 10;139(4):626–43. doi: 10.1097/AOG.0000000000004711. Epub ahead of print.

The Centers for Disease Control and Prevention recognized the need for educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about uterine cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in January 2021. This article is the evidence summary of the relevant literature and existing recommendations to guide clinicians in the prevention, early diagnosis, and special considerations of uterine cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.

Cancer genetics and breast cancer.

Huber-Keener KJ.

Best Pract Res Clin Obstet Gynaecol. 2022 Jan 31:S1521-6934(22)00016-5. doi: 10.1016/j.bpobgyn.2022.01.007. Epub ahead of print.

The risk of developing breast cancer is multifactorial and, at times, modifiable. However, the risk imposed by family history and hereditary pathogenic variants in a person's genetic code is, at present, an important fixed variable. Therefore, it is imperative to identify patients at risk for hereditary breast cancer and to understand the current evidence-based approach to the management of that risk. This chapter focuses on how genes play a role in breast cancer risk, why certain genes are commonly involved in hereditary breast cancer, and what are the specific genes and genetic syndromes that put patients at risk for breast cancer. Hereditary cancer susceptibility syndromes, including Hereditary Breast and Ovarian Cancer Syndrome (HBOC - BRCA1/2), Cowden Syndrome (CS - PTEN), Li-Fraumeni Syndrome (LFS - TP53), Peutz-Jegher Syndrome (PJS - STK11), Neurofibromatosis Type 1 (NF1), and Diffuse Hereditary Gastric Cancer Syndrome (CDH1) will be discussed along with individual genes not associated with a particular syndrome (ATM, BARD1, CHEK2, and PALB2).

Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review.

Vieira-Baptista P, Pérez-López FR, López-Baena MT, , Preti M, Bornstein J.

J Low Genit Tract Dis. 2022 Mar 10. doi: 10.1097/LGT.0000000000000673. Epub ahead of print.

Objective: Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP.

Materials and methods: A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database.

Results: Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11).The risk was significantly higher in the first 1-3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use.For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively.

Conclusions: Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.

Disparity of ovarian cancer survival between urban and rural settings.

Ulmer KK, Greteman B, Cardillo N, Schneider A, McDonald M, Bender D, Goodheart MJ, Gonzalez Bosquet J.

Int J Gynecol Cancer. 2022 Feb 23:ijgc-2021-003096.

Objective: To determine if there is a difference in overall survival of patients with epithelial ovarian cancer in rural, urban, and metropolitan settings in the United States.

Methods: We performed a retrospective cohort study using 2004-2016 National Cancer Database (NCDB) data including high and low grade, stage I-IV disease. Bivariate analyses used Student's t-test for continuous variables and χ² test for dichotomous variables. Kaplan-Meier curves estimated survival of patients based on location of residence, and univariate analyses using Cox proportional HR assessed survival based on baseline characteristics. Multivariate analysis was performed to account for significant covariates. Propensity score matching was used to validate the multivariate survival model. For all tests, p<0.05 was considered statistically significant.

Results: A total of 111 627 patients were included with a mean age of 62.5 years for metroolitan (range 18-90), 64.0 years for rural (range 19-90) and 63.2 years for urban areas (range 18-90). Of all patients included, 94 290 were in a metropolitan area (counties >1 million population or 50 000-999 999), 15 386 were in an urban area (population of 10 000-49 999), and 1951 were in a rural area (non-metropolitan/non-core population). Univariate Cox proportional hazards models showed clinically significant differences in survival in patients from metropolitan, urban, and rural areas. Multivariate Cox proportional hazards models showed a clinically significant increase in HRs for patients in rural settings (HR 1.17; 95% CI 1.06 to 1.29). Increasing age and stage, non-insured status, non-white race, and comorbidity were also significant for poorer survival.

Conclusion: Patients with ovarian cancer who live in rural settings with small populations and greater distance to tertiary care centers have poorer survival. These differences hold after controlling for stage, age, and other significant risk factors related to poorer outcomes. To improve clinical outcomes, we need further studies to identify which of these factors are actionable.

Umbilical Cord Blood Leptin and IL-6 in the Presence of Maternal Diabetes or Chorioamnionitis.

Vasilakos LK, Steinbrekera B, Dagle D, Roghair RD.

Front Endocrinol (Lausanne). 2022 Feb 7;13:836541

Diabetes during pregnancy is associated with elevated maternal insulin, leptin and IL-6. Within the placenta, IL-6 can further stimulate leptin production. Despite structural similarities and shared roles in inflammation, leptin and IL-6 have contrasting effects on neurodevelopment, and the relative importance of maternal diabetes or chorioamnionitis on fetal hormone exposure has not been defined. We hypothesized that there would be a positive correlation between IL-6 and leptin with progressively increased levels in pregnancies complicated by maternal diabetes and chorioamnionitis. To test this hypothesis, cord blood samples were obtained from 104 term infants, including 47 exposed to maternal diabetes. Leptin, insulin, and IL-6 were quantified by multiplex assay. Factors independently associated with hormone levels were identified by univariate and multivariate linear regression. Unlike IL-6, leptin and insulin were significantly increased by maternal diabetes. Maternal BMI and birth weight were independent predictors of leptin and insulin with birth weight the strongest predictor of leptin. Clinically diagnosed chorioamnionitis and neonatal sepsis were associated with increased IL-6 but not leptin. Among appropriate for gestational age infants without sepsis, IL-6 and leptin were strongly correlated (R=0.6, P<0.001). In summary, maternal diabetes and birth weight are associated with leptin while chorioamnionitis is associated with IL-6. The constraint of the positive association between leptin and IL-6 to infants without sepsis suggests that the term infant and placenta may have a limited capacity to increase cord blood levels of the neuroprotective hormone leptin in the presence of increased cord blood levels of the potential neurotoxin IL-6.

Correlations between hormonal IUDs and androgenic skin conditions: a retrospective cohort study.

Munjal A, Tripathi R, Wu C, Powers JG.

J Am Acad Dermatol. 2022 Feb 24:S0190-9622(22)00152-9.

Fresh embryo transfer after in vitro insemination of fresh vs. cryopreserved anonymous donor oocytes: which has a better live birth rate? A Society for Assisted Reproductive Technology Clinic Outcome Reporting System analysis.

Whynott RM, , Ball GD,

Fertil Steril. 2022 Feb 22:S0015-0282(22)00018-8.

Objective: To determine if transfer of fresh embryos derived from fresh or cryopreserved donor oocytes yields a higher live birth rate.

• : Historical cohort study.

Setting: Society for Assisted Reproductive Technology Clinic Outcome Reporting System database.

• : A total of 24,663 fresh embryo transfer cycles of donor oocytes.
• : None.

Main outcome measure(s): The primary outcome was live births per number of embryos transferred on day 5. The secondary outcomes included number of infants per embryo transfer, surplus embryos cryopreserved, and characterization of US oocyte recipients.

• A total of 16,073 embryo transfers were from fresh oocytes and 8,590 were from cryopreserved oocytes. Recipient age, body mass index (BMI), gravidity, and parity were similar between the groups. Most recipients were of White non-Hispanic race (66.9%), followed by Asian (13.7%), Black non-Hispanic (9.3%), and Hispanic (7.2%). Fresh oocyte cycles were more likely to use elective single embryo transfer (42.5% vs. 37.8%) or double embryo transfer (53.2% vs. 50.4%) and resulted in more surplus embryos for cryopreservation (4.6 vs. 1.2). The live birth rate from fresh oocytes was 57.5% vs. 49.7% from cryopreserved oocytes. Negative predictors of live birth included the use of cryopreserved oocytes (odds ratio [OR] 0.731, 95% confidence interval [CI] 0.665-0.804), Black non-Hispanic race (OR 0.603, 95% CI 0.517-0.703), Asian race (OR 0.756, 95% CI 0.660-0.867), and increasing recipient BMI (OR 0.982, 95% CI 0.977-0.994) after controlling for recipient age, number of embryos transferred on day 5, and unexplained infertility diagnosis. The proportion of multifetal deliveries was greater in cycles utilizing fresh (26.4%) vs. cryopreserved (20.6%) oocytes.

Conclusion(s): The live birth rate is higher with use of fresh oocytes vs. cryopreserved oocytes in fresh embryo transfer cycles. Negative live birth predictors include recipient Black non-Hispanic or Asian race and increasing BMI.

Vanquishing Multiple Pregnancy for In Vitro Fertilization in the United States - a 25-year Endeavor.

Katler QS, Kawwass JF, Hurst BS,, Mcculloh DH, Wantzman E, Toner JP.

Am J Obstet Gynecol. 2022 Feb 9:S0002-9378(22)00104-1.

The practice of in vitro fertilization (IVF) has changed tremendously since the birth of the first IVF baby in 1978. With the success of early IVF programs in the U.S. there was a significant rise in twin births nationwide. In the mid-1990's, over 30% of IVF cycles resulted in twin or higher-order multiple-gestation pregnancies. Since that time, not only have we witnessed improvements in laboratory and treatment efficacy, but we have also seen a dramatic impact on pregnancy outcomes, specifically regarding twin pregnancies. As the field evolved and the risks of multi-fetal pregnancies became more salient, by 2019, the rate of twin pregnancies had dropped to below 7% of cycles. This improvement is largely due to technical advancements and revised professional guidance: culturing embryos longer before transfer, improved freezing technology, embryo preimplantation genetic testing, and revised professional guidance regarding the number of embryos to transfer. These developments have led to single embryo transfer (SET) becoming the standard of care in most scenarios. We use national IVF surveillance data of all autologous IVF cycles from 1996 to 2019 in order to illustrate trends in the following improved outcomes: autologous embryo transfer cycles involving blastocyst stage embryos, vitrified embryos, preimplantation genetic testing cycles, total number of embryos being transferred per cycle, and SET usage over time; among deliveries from autologous embryo transfers, we highlight trends in singleton births over time, and proportion of deliveries involving twins, triplets, quadruplets or greater. The significant progress in reducing the rate of multiple-gestation pregnancies with IVF is largely attributed to a series of technical and clinical actions, culminating in an 80% reduction in the incidence of multiple births without a loss in overall treatment effectiveness.

Topical Treatment of Recurrent Vulvovaginal Candidiasis: An Expert Consensus.

Phillips NA, Bachmann G, Haefner H, Martens M,

Womens Health Rep (New Rochelle). 2022 Jan 31;3(1):38-42.

Background: Recurrent vulvovaginal candidiasis (RVVC), defined as three or more confirmed infections over 1 year, occurs in up to 10% of women. In these women, the objective is often symptomatic control rather than mycologic cure. Current Centers for Disease Control and Prevention (CDC) guidelines recommend oral fluconazole as first-line maintenance, but state if this oral regimen is not feasible, intermittent topical treatments can be considered. No specific recommendations for type or frequency of topical applications are provided by the CDC.

• A panel of vulvovaginal experts convened to develop a consensus recommendation for topical maintenance dosing for RVVC.
• Data suggest that clotrimazole, miconazole, terconazole, and intravaginal boric acid are suggested recommendations for recurrent vulvovaginitis caused by both Candida albicans and nonalbicans species. Nystatin ovules may not be as effective as azoles. Identification of species will influence treatment decisions. In addition, treatment may be modified based on prior response to a specific agent, especially in nonalbicans species. Fluconazole, ibrexafungerp, and intravaginal boric acid should be avoided during pregnancy.
• The expert consensus for women with RVVC is an initial full course of treatment followed by topical maintenance beginning at one to three times weekly, based on chosen agent. Twice a week dosing was the regimen most often utilized. In some women, episodic treatment may be used, but maintenance should remain an option for this population.

COVID-19 Vaccination in Obstetrics and Gynecology: Addressing Concerns While Paving a Way Forward.

Jacobs E, Van Voorhis BJ.

Obstet Gynecol. 2022 Jan 28.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

Salvo G, Ramirez PT, Leitao MM, Cibula D, Wu X, Falconer H, Persson J, Perrotta M, Mosgaard BJ, Kucukmetin A, Berlev I, Rendon G, Liu K, Vieira M, Capilna ME, Fotopoulou C, Baiocchi G, Kaidarova D, Ribeiro R, Kocian R, Li X, Li J, Pálsdóttir K, Noll F, Rundle S, Ulrikh E, Hu Z, Gheorghe M, Saso S, Bolatbekova R, Tsunoda A, Pitcher B, Wu J, Urbauer D, Pareja R.

Am J Obstet Gynecol. 2022 Jan;226(1):97.e1-97.e16.

• Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer.
• We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy.

Study design: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental.

• Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery.
• The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Amenorrhea and pituitary human chorionic gonadotrophin production in a 38-year-old presenting as pregnancy of unknown location: case report and review of literature.

Ordog T, .

Proc Obstet Gynecol. 2022;11(1):Article 3 [ 11 p.].

Background: Amenorrhea and extraplacental production of serum human chorionic gonadotropin (hCG), particularly in young women, can mimic a pregnancy of unknown location. Elevated serum hCG in the absence of pregnancy can pose a diagnostic dilemma and has led to potentially harmful and unwarranted interventions including chemotherapeutic agents like methotrexate or have led to delay in necessary medical interventions in women.

We report a case to demonstrate that amenorrhea and extraplacental human chorionic gonadotropin (hCG) production in young women can mimic a pregnancy of unknown location. Furthermore, we performed a critical review of literature on pituitary hCG production.

Case: A 38-year-old woman with a diagnosis of Silver-Russell syndrome, a unicornuate uterus, history of right oophorectomy for a benign serous cystadenoma and a desire for pregnancy presenting with a provisional diagnosis of pregnancy of unknown location. After performing a thorough review of history, physical examination, ultrasound exams, and a review of hormone analysis [including hCG, Tumor markers, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Anti-Mullerian Hormone (AMH), Estradiol (E2) levels], we confirmed the diagnosis of premature ovarian insufficiency and pituitary hCG production.

Conclusions: In women, serum levels of hCG may increase with age, and are not always an indicator of pregnancy. Therefore, it is imperative to interpret false-positive test results and rule out the extraplacental production of hCG. This will help prevent unnecessary surgical procedures and treatment, including chemotherapy.

Cardiorespiratory management of infants born at 22 weeks' gestation: The Iowa approach.

Dagle JM, Rysavy MA, Colaizy TT, Elgin TG, Giesinger RE, McElroy SJ, Harmon HM, Klein JM, McNamara PJ, Rabe GK, Bell EF, Thomas BA, Bischoff AR, Rios DR, Lindower JB, Bermick JR, Lee SS, Wong SW, Roghair RD, Morgan-Harris AT, Niwas R, Arikat S, Boly TJ, Segar JL.

Semin Perinatol. 2021 Nov 10:151545.        

The approach to clinical care of infants born at 22 weeks' gestation must be consistent and well-designed if optimal results are to be expected. Publications from several international centers have demonstrated that, although there may be variance in aspects of care in this vulnerable population, treatment should be neither random nor inconsistent. In designing a standardized approach, careful attention should be paid to the unique anatomy, physiology, and biochemistry of this vulnerable patient population. Emerging evidence, suggesting a link between cardiopulmonary health and longer-term sequela, highlights the importance of understanding the relationship between cardiorespiratory illnesses of the 22-week infant, treatments provided, and subsequent cardiopulmonary development. In this review we will provide an overview to our approach to cardiopulmonary assessment and treatment, with a particular emphasis on the importance of early recognition of atypical phenotypes, timely interventions with evidence-based treatments, and longitudinal monitoring.

Labor & delivery unit closures most impact travel times to birth locations for micropolitan residents in Iowa.

Carrel M, Keino BC, Ryckman KK,

J Rural Health. 2022 Jan 3.

Purpose: Continued closure of rural hospitals and labor & delivery units can impact timely access to care. Iowa has lost over a quarter of its labor & delivery units in the previous decade. Calculating how travel times to labor & delivery services have changed, and where in the state the largest travel times take place, are important for understanding access to this critical service.

Methods: Using parental address and facility location from birth certificate data in Iowa from 2013 to 2019, travel times to birth facility are assessed for rural, micropolitan, and metropolitan parents, as well as for complicated versus noncomplicated births and Medicaid versus non-Medicaid recipients.

Findings: Parts of the state have travel times that are consistently greater than 30 minutes over the duration of the study. The largest increases in travel times are found among micropolitan residents, particularly those experiencing complicated births. Travel times are consistently the longest for rural residents but increased only slightly over the study time period.

Conclusions: These findings suggest that access to hospital-based obstetric care is most changed for residents of small towns rather than rural or larger city residents.