Recent Research Publications- July 2022
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.