Continuous adaptation of conversation aids for uterine fibroids treatment options in a four-year multi-center implementation project.

BACKGROUND: Fibroids are non-cancerous uterine growths that can cause symptoms impacting quality of life. The breadth of treatment options allows for patient-centered preference. While conversation aids are known to facilitate shared decision making, the implementation of these aids for uterine fibroids treatments is limited. We aimed to develop two end-user-acceptable uterine fibroids conversation aids for an implementation project. Our second aim was to outline the adaptations that were made to the conversation aids as implementation occurred. METHODS: We used a multi-phase user-centered participatory approach to develop a text-based and picture-enhanced conversation aid for uterine fibroids. We conducted a focus group with project stakeholders and user-testing interviews with eligible individuals with symptomatic uterine fibroids. We analyzed the results of the user-testing interviews using Morville's Honeycomb framework. Spanish translations of the conversation aids occurred in parallel with the English iterations. We documented the continuous adaptations of the conversation aids that occurred during the project using an expanded framework for reporting adaptations and modifications to evidence-based interventions (FRAME). RESULTS: The first iteration of the conversation aids was developed in December 2018. Focus group participants (n = 6) appreciated the brevity of the tools and suggested changes to the bar graphs and illustrations used in the picture-enhanced version. User-testing with interview participants (n = 9) found that both conversation aids were satisfactory, with minor changes suggested. However, during implementation, significant changes were suggested by patients, other stakeholders, and participating clinicians when they reviewed the content. The most significant changes required the addition or deletion of information about treatment options as newer research was published or as novel interventions were introduced into clinical practice. CONCLUSIONS: This multi-year project revealed the necessity of continuously adapting the uterine fibroids conversation aids so they remain acceptable in an implementation and sustainability context. Therefore, it is important to seek regular user feedback and plan for the need to undertake updates and revisions to conversation aids if they are going to be acceptable for clinical use.

Long-term health-related quality of life and symptom severity following hysterectomy, myomectomy, or uterine artery embolization for the treatment of symptomatic uterine fibroids.

BACKGROUND: Few studies have directly compared different surgical procedures for uterine fibroids with respect to long-term health-related quality of life outcomes and symptom improvement. OBJECTIVE: We examined differences in change from baseline to 1-, 2-, and 3-year follow-up in health-related quality of life and symptom severity among patients who underwent abdominal myomectomy, laparoscopic or robotic myomectomy, abdominal hysterectomy, laparoscopic or robotic hysterectomy, or uterine artery embolization. STUDY DESIGN: The COMPARE-UF registry is a multiinstitutional prospective observational cohort study of women undergoing treatment for uterine fibroids. A subset of 1384 women aged 31 to 45 years who underwent either abdominal myomectomy (n=237), laparoscopic myomectomy (n=272), abdominal hysterectomy (n=177), laparoscopic hysterectomy (n=522), or uterine artery embolization (n=176) were included in this analysis. We obtained demographics, fibroid history, and symptoms by questionnaires at enrollment and at 1, 2, and 3 years posttreatment. We used the UFS-QoL (Uterine Fibroid Symptom and Quality of Life) questionnaire to ascertain symptom severity and health-related quality of life scores among participants. To account for potential baseline differences across treatment groups, a propensity score model was used to derive overlap weights and compare total health-related quality of life and symptom severity scores after enrollment with a repeated measures model. For this health-related quality of life tool, a specific minimal clinically important difference has not been determined, but on the basis of previous research, a difference of 10 points was considered as a reasonable estimate. Use of this difference was agreed upon by the Steering Committee at the time when the analysis was planned. RESULTS: At baseline, women undergoing hysterectomy and uterine artery embolization reported the lowest health-related quality of life scores and highest symptom severity scores compared with those undergoing abdominal myomectomy or laparoscopic myomectomy (P<.001). Those undergoing hysterectomy and uterine artery embolization reported the longest duration of fibroid symptoms with a mean of 6.3 years (standard deviation, 6.7; P<.001). The most common fibroid symptoms were menorrhagia (75.3%), bulk symptoms (74.2%), and bloating (73.2%). More than half (54.9%) of participants reported anemia, and 9.4% women reported a history of blood transfusion. Across all modalities, total health-related quality of life and symptom severity score markedly improved from baseline to 1-year with the largest improvement in the laparoscopic hysterectomy group (Uterine Fibroids Symptom and Quality of Life: delta= [+] 49.2; symptom severity: delta= [-] 51.3). Those undergoing abdominal myomectomy, laparoscopic myomectomy, and uterine artery embolization also demonstrated significant improvement in health-related quality of life (delta= [+]43.9, [+]32.9, [+]40.7, respectively) and symptom severity (delta= [-]41.4, [-] 31.5, [-] 38.5, respectively) at 1 year, and the improvement persisted from baseline for uterine-sparing procedures during second (Uterine Fibroids Symptom and Quality of Life: delta= [+]40.7, [+]37.4, [+]39.3 SS: delta= [-] 38.5, [-] 32.0, [-] 37.7 and third year (Uterine Fibroids Symptom and Quality of Life: delta= [+] 40.9, [+]39.9, [+]41.1 and SS: delta= [-] 33.9, [-]36.5, [-] 33.0, respectively), posttreatment intervals, however with a trend toward decline in degree of improvement from years 1 and 2. Differences from baseline were greatest for hysterectomy; however, this may reflect the relative importance of bleeding in the Uterine Fibroids Symptom and Quality of Life, rather than clinically meaningful symptom recurrence among women undergoing uterus-sparing treatments. CONCLUSION: All treatment modalities were associated with significant improvements in health-related quality of life and symptom severity reduction 1-year posttreatment. However, abdominal myomectomy, laparoscopic myomectomy and uterine artery embolization indicated a gradual decline in symptom improvement and health-related quality of life by third year after the procedure.

Short-term quality of life after myomectomy for uterine fibroids from the COMPARE-UF Fibroid Registry.

BACKGROUND: Uterine fibroids may decrease quality of life in a significant proportion of affected women. Myomectomy offers a uterine-sparing treatment option for patients with uterine fibroids that can be performed abdominally, laparoscopically (with or without robotic assistance), and hysteroscopically. Quality of life information using validated measures for different myomectomy routes, especially hysteroscopic myomectomy, is limited. OBJECTIVE: To compare women's perception of their short-term health-related quality of life measures and reported time to return to usual activities and return to work for different routes of myomectomy. MATERIALS AND METHODS: Comparing Options for Management: Patient-centered Results for Uterine Fibroids (COMPARE-UF) is a prospective nationwide fibroid registry that enrolled premenopausal women seeking treatment for uterine fibroids at 8 clinical sites. For this analysis, we included women undergoing hysteroscopic, abdominal, or laparoscopic myomectomy who completed the postprocedure questionnaire scheduled between 6 and 12 weeks after surgery. Health-related quality of life outcomes, such as pain, anxiety, and return to usual activitie, were assessed for each route. The hysteroscopic myomectomy group had large differences in demographics, fibroid number, and uterine size compared to the other groups; thus, a direct comparison of quality of life measures was performed only for abdominal and laparoscopic approaches after propensity weighting. Propensity weighting was done using 24 variables that included demographics, quality of life baseline measures, and fibroid and uterine measurements. RESULTS: A total of 1206 women from 8 COMPARE-UF sites underwent myomectomy (338 hysteroscopic, 519 laparoscopic, and 349 abdominal). All women had substantial improvement in short-term health-related quality of life and symptom severity scores, which was not different among groups. Average symptom severity scores decreased about 30 points in each group. Return to usual activities averaged 0 days (interquartile range, 0-14 days) for hysteroscopic myomectomy, 21 days (interquartile range, 14-28 days) for laparoscopic myomectomy, and 28 days (interquartile range, 14-35 days) for abdominal myomectomy. After propensity adjustment, quality of life outcomes in the laparoscopic and abdominal myomectomy groups were similar except for more anxiety in the laparoscopic myomectomy group and slightly more pain in the abdominal myomectomy group. After propensity weighting, return to usual activities favored laparoscopic compared to abdominal procedures; median time was the same at 21 days, but the highest quartile of women in the abdominal group needed an additional week of recovery (interquartile range,14.0-28.0 for laparoscopic versus 14.0-35.0 for abdominal, P < .01). Time to return to work was also longer in the abdominal arm (median, 22 days; interquartile range, 14-40 days, versus median, 42; interquartile range, 27-56). CONCLUSION: Women who underwent myomectomy had substantial improvement in health-related quality of life, regardless of route of myomectomy. After propensity weighting, abdominal myomectomy was associated with a nearly 2-week longer time to return to work than laparoscopic myomectomy.

The Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry: rationale and design.

BACKGROUND: Uterine fibroids are common in premenopausal women, yet comparative effectiveness research on uterine fibroid treatments is rare. OBJECTIVE: The purpose of this study was to design and establish a uterine fibroid registry based in the United States to provide comparative effectiveness data regarding uterine fibroid treatment. STUDY DESIGN: We report here the design and initial recruitment for the Comparing Options for Management: Patient-centered REsults for Uterine Fibroids (COMPARE-UF) registry (Clinicaltrials.gov, NCT02260752), funded by the Agency for Healthcare Research and Quality in collaboration with the Patient-Centered Outcomes Research Institute. COMPARE-UF was designed to help answer critical questions about treatment options for women with symptomatic uterine fibroids. Women who undergo a procedure for uterine fibroids (hysterectomy, myomectomy [abdominal, hysteroscopic, vaginal, and laparoscopic/robotic], endometrial ablation, radiofrequency fibroid ablation, uterine artery embolization, magnetic resonance-guided focused ultrasound, or progestin-releasing intrauterine device insertion) at 1 of the COMPARE-UF sites are invited to participate in a prospective registry with 3 years follow up for postprocedural outcomes. Enrolled participants provide annual follow-up evaluation through an online portal or through traditional phone contact. A central data abstraction center provides information obtained from imaging, operative or procedural notes, and pathology reports. Women with uterine fibroids and other stakeholders are a key part of the COMPARE-UF registry and participate at all points from study design to dissemination of results. RESULTS: We built a network of 9 clinical sites across the United States with expertise in the care of women with uterine fibroids to capture geographic, racial, ethnic, and procedural diversity. Of the initial 2031 women who were enrolled in COMPARE-UF, 42% are self-identified as black or African American, and 40% are ≤40 years old, with 16% of participants <35 years old. Women who undergo myomectomy comprise the largest treatment group at 46% of all procedures, with laparoscopic or robotic myomectomy comprising the largest subset of myomectomies at 19% of all procedures. Hysterectomy is the second most common treatment within the registry at 38%. CONCLUSION: In response to priorities that were identified by our patient stakeholders, the initial aims within COMPARE-UF will address how different procedures that are used to treat uterine fibroids compare in terms of long-lasting symptom relief, potential for recurrence, medical complications, improvement in quality of life and sexual function, age at menopause, and fertility and pregnancy outcomes. COMPARE-UF will generate evidence on the comparative effectiveness of different procedural options for uterine fibroids and help patients and their caregivers make informed decisions that best meet an individual patient's short- and long-term preferences. Building on this infrastructure, the COMPARE-UF team of investigators and stakeholders, including patients, collaborate to identify future priorities for expanding the registry, such as assessing the efficacy of medical therapies for uterine fibroids. COMPARE-UF results will be disseminated directly to patients, providers, and other stakeholders by traditional academic pathways and by innovative methods that include a variety of social media platforms. Given demographic differences among women who undergo different uterine fibroid treatments, the assessment of comparative effectiveness for this disease through clinical trials will remain difficult. Therefore, this registry provides optimized evidence to help patients and their providers better understand the pros and cons of different treatment options so that they can make more informed decisions.

MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus.

Cardiac left ventricular outflow tract (LVOT) defects represent a common but heterogeneous subset of congenital heart disease for which gene identification has been difficult. We describe a 46,XY,t(1;5)(p36.11;q31.2)dn translocation carrier with pervasive developmental delay who also exhibited LVOT defects, including bicuspid aortic valve (BAV), coarctation of the aorta (CoA) and patent ductus arteriosus (PDA). The 1p breakpoint disrupts the 5' UTR of AHDC1, which encodes AT-hook DNA-binding motif containing-1 protein, and AHDC1-truncating mutations have recently been described in a syndrome that includes developmental delay, but not congenital heart disease [Xia, F., Bainbridge, M.N., Tan, T.Y., Wangler, M.F., Scheuerle, A.E., Zackai, E.H., Harr, M.H., Sutton, V.R., Nalam, R.L., Zhu, W. et al. (2014) De Novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea. Am. J. Hum. Genet., 94, 784-789]. On the other hand, the 5q translocation breakpoint disrupts the 3' UTR of MATR3, which encodes the nuclear matrix protein Matrin 3, and mouse Matr3 is strongly expressed in neural crest, developing heart and great vessels, whereas Ahdc1 is not. To further establish MATR3 3' UTR disruption as the cause of the proband's LVOT defects, we prepared a mouse Matr3(Gt-ex13) gene trap allele that disrupted the 3' portion of the gene. Matr3(Gt-ex13) homozygotes are early embryo lethal, but Matr3(Gt-ex13) heterozygotes exhibit incompletely penetrant BAV, CoA and PDA phenotypes similar to those in the human proband, as well as ventricular septal defect (VSD) and double-outlet right ventricle (DORV). Both the human MATR3 translocation breakpoint and the mouse Matr3(Gt-ex13) gene trap insertion disturb the polyadenylation of MATR3 transcripts and alter Matrin 3 protein expression, quantitatively or qualitatively. Thus, subtle perturbations in Matrin 3 expression appear to cause similar LVOT defects in human and mouse.

Association between peak estradiol levels and ovarian torsion among symptomatic patients receiving gonadotropin treatment.

PURPOSE: Ovarian torsion is a surgical emergency that can be clinically challenging to diagnose. Patients who have received assisted reproductive technologies (ART) are a subset of women with an increased risk for torsion. As the ART population continues to increase, there is a need to delineate risk factors for the development of ovarian torsion in this unique population. A pilot study was performed to determine the proportion of patients with suspected ovarian torsion who have received ART and to identify possible diagnostic biomarkers for ovarian torsion among these patients. METHODS: A single institution retrospective cohort study of patients taken to surgery for suspected ovarian torsion over a 5-year period. RESULTS: During the study period, 171 patients were taken to surgery for suspected ovarian torsion. Patients receiving ART constituted 19 (11%) of these patients. Among the 19 fertility treatment patients, 16 had received treatment with gonadotropins, 10 of which had surgically confirmed ovarian torsion. These ten patients had higher preoperative peak estradiol levels (3122 versus 1875 pg/mL, p = 0.05) and a larger ovarian diameter (9.7 versus 7.6 cm, p = 0.05) than the six patients receiving gonadotropins found to not have ovarian torsion. CONCLUSIONS: These results suggest infertility treatment using gonadotropins for ovarian hyperstimulation may be an independent risk factor for ovarian torsion as suggested by the disproportionate number of such individuals represented in the study population (9% of all patients, 84% of fertility patients). Additionally, among women taking gonadotropins, an association exists between peak estradiol levels, ovarian diameter, and risk for ovarian torsion.

Contained tissue extraction using power morcellation: prospective evaluation of leakage parameters.

BACKGROUND: Safe tissue removal is a challenge for minimally invasive procedures such as myomectomy, supracervical hysterectomy, or total hysterectomy of a large uterine specimen. There is concern regarding disruption or dissemination of tissue during this process, which may be of particular significance in cases of undetected malignancy. Contained tissue extraction techniques have been developed in an effort to mitigate morcellation-related risks. OBJECTIVE: The objective of the study was to quantify perioperative outcomes of contained tissue extraction using power morcellation, specifically evaluating parameters of tissue or fluid leakage from within the containment system. STUDY DESIGN: This was a study including a multicenter prospective cohort of adult women who underwent minimally invasive hysterectomy or myomectomy using a contained power morcellation technique. Blue dye was applied to the tissue specimen prior to removal to help identify cases of fluid or tissue leakage from within the containment system. RESULTS: A total of 76 patients successfully underwent the contained power morcellation protocol. Mean time for the contained morcellation procedure was 30.2 minutes (±22.4). The mean hysterectomy specimen weight was 480.1 g (±359.1), and mean myomectomy specimen weight was 239.1 g (±229.7). The vast majority of patients (73.7%) were discharged home the same day of surgery. Final pathological diagnosis was benign in all cases. Spillage of dye or tissue was noted in 7 cases (9.2%), although containment bags were intact in each of these instances. CONCLUSION: Findings are consistent with prior work demonstrating the feasibility of contained tissue extraction; however, further refinement of this technique is warranted.

Targeting NGF but not VEGFR1 or BDNF signaling reduces endometriosis-associated pain in mice.

INTRODUCTION: Endometriosis is a chronic inflammatory disease that affects âˆ¼10 % of women. A significant fraction of patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting that disease pathology involves neurotrophic activity and angiogenesis. OBJECTIVES: We aim to evaluate the potential for key tyrosine-kinase-receptor-coupled neurotrophic molecules to contribute to endometriosis-associated pain in mice. METHODS: Peritoneal fluid was collected from endometriosis patients undergoing surgery and the levels of NGF and VEGFR1 regulators (VEGFA, VEGFB, PLGF, and sVEGFR1) were quantified by ELISA. VEGFR1 regulator concentrations were used to calculate VEGFR1 occupancy. We used genetic depletion, neutralizing antibodies, and pharmacological approaches to specifically block neurotrophic ligands (NGF or BDNF) or receptors (VEGFR1, TRKs) in a murine model of endometriosis-associated pain. Endometriosis-associated pain was measured using von Frey filaments, quantification of spontaneous abdominal pain-related behavior, and thermal discomfort. Disease parameters were evaluated by lesion size and prevalence. To evaluate potential toxicity, we measured the effect of entrectinib dose and schedule on body weight, liver and kidney function, and bone structure (via micro-CT). RESULTS: We found that entrectinib (pan-Trk inhibitor) or anti-NGF treatments reduced evoked pain, spontaneous pain, and thermal discomfort. In contrast, even though calculated receptor occupancy revealed that VEGFR1 agonist levels are sufficient to support signaling, blocking VEGFR1 via antibody or tamoxifen-induced knockout did not reduce pain or lesion size in mice. Targeting BDNF-TrkB with an anti-BDNF antibody also proved ineffective. Notably, changing dosing schedule to once weekly eliminated entrectinib-induced bone-loss without decreasing efficacy against pain. CONCLUSIONS: This suggests NGF-TrkA signaling, but not BDNF-TrkB or VEGF-VEGFR1, mediates endometriosis-associated pain. Moreover, entrectinib blocks endometriosis-associated pain and reduces lesion sizes. Our results also indicated that entrectinib-like molecules are promising candidates for endometriosis treatment.

Amniocytes can serve a dual function as a source of iPS cells and feeder layers.

Clinical barriers to stem-cell therapy include the need for efficient derivation of histocompatible stem cells and the zoonotic risk inherent to human stem-cell xenoculture on mouse feeder cells. We describe a system for efficiently deriving induced pluripotent stem (iPS) cells from human and mouse amniocytes, and for maintaining the pluripotency of these iPS cells on mitotically inactivated feeder layers prepared from the same amniocytes. Both cellular components of this system are thus autologous to a single donor. Moreover, the use of human feeder cells reduces the risk of zoonosis. Generation of iPS cells using retroviral vectors from short- or long-term cultured human and mouse amniocytes using four factors, or two factors in mouse, occurs in 5-7 days with 0.5% efficiency. This efficiency is greater than that reported for mouse and human fibroblasts using similar viral infection approaches, and does not appear to result from selective reprogramming of Oct4(+) or c-Kit(+) amniocyte subpopulations. Derivation of amniocyte-derived iPS (AdiPS) cell colonies, which express pluripotency markers and exhibit appropriate microarray expression and DNA methylation properties, was facilitated by live immunostaining. AdiPS cells also generate embryoid bodies in vitro and teratomas in vivo. Furthermore, mouse and human amniocytes can serve as feeder layers for iPS cells and for mouse and human embryonic stem (ES) cells. Thus, human amniocytes provide an efficient source of autologous iPS cells and, as feeder cells, can also maintain iPS and ES cell pluripotency without the safety concerns associated with xenoculture.

Exhaustion of racing sperm in nature-mimicking microfluidic channels during sorting.

Fertilization is central to the survival and propagation of a species, however, the precise mechanisms that regulate the sperm's journey to the egg are not well understood. In nature, the sperm has to swim through the cervical mucus, akin to a microfluidic channel. Inspired by this, a simple, cost-effective microfluidic channel is designed on the same scale. The experimental results are supported by a computational model incorporating the exhaustion time of sperm.

Vitrification and levitation of a liquid droplet on liquid nitrogen.

The vitrification of a liquid occurs when ice crystal formation is prevented in the cryogenic environment through ultrarapid cooling. In general, vitrification entails a large temperature difference between the liquid and its surrounding medium. In our droplet vitrification experiments, we observed that such vitrification events are accompanied by a Leidenfrost phenomenon, which impedes the heat transfer to cool the liquid, when the liquid droplet comes into direct contact with liquid nitrogen. This is distinct from the more generally observed Leidenfrost phenomenon that occurs when a liquid droplet is self-vaporized on a hot plate. In the case of rapid cooling, the phase transition from liquid to vitrified solid (i.e., vitrification) and the levitation of droplets on liquid nitrogen (i.e., Leidenfrost phenomenon) take place simultaneously. Here, we investigate these two simultaneous physical events by using a theoretical model containing three dimensionless parameters (i.e., Stefan, Biot, and Fourier numbers). We explain theoretically and observe experimentally a threshold droplet radius during the vitrification of a cryoprotectant droplet in the presence of the Leidenfrost effect.

Fertility restoration in mice with chemotherapy induced ovarian failure using differentiated iPSCs.

BACKGROUND: Treatment options for premature ovarian insufficiency (POI) are limited to hormone replacement and donor oocytes. A novel induced pluripotent stem cell (iPSC) transplant paradigm in a mouse model has potential translational applications for management of POI. METHODS: Mouse ovarian granulosa cell derived-iPSCS were labelled with green fluorescent protein (GFP) reporter and differentiated in vitro into oocytes. Differentiated cells were assayed for estradiol and progesterone secretion by enzyme-linked immunosorbent assays. After Fluorescence-Activated Cell Sorting (FACS) for the cell surface marker anti-Mullerian hormone receptor (AMHR2), enriched populations of differentiated cells were surgically transplanted into ovaries of mice that had POI secondary to gonadotoxic pre-treatment with alkylating agents. A total of 100 mice were used in these studies in five separate experiments with 56 animals receiving orthotopic ovarian injections of either FACS sorted or unsorted differentiated iPSCSs and the remaining animals receiving sham injections of PBS diluent. Following transplantation surgery, mice were stimulated with gonadotropins inducing oocyte development and underwent oocyte retrieval. Nine transplanted mice were cross bred with wild-type mice to assess fertility. Lineage tracing of resultant oocytes, F1 (30 pups), and F2 (42 pups) litters was interrogated by GFP expression and validation by short tandem repeat (STR) lineage tracing. FINDINGS: [1] iPSCs differentiate into functional oocytes and steroidogenic ovarian cells which [2] express an ovarian (GJA1) and germ cell (ZP1) markers. [3] Endocrine function and fertility were restored in mice pretreated with gonadotoxic alkylating agents via orthotopic transplantation of differentiated iPSCS, thus generating viable, fertile mouse pups. INTERPRETATION: iPSC-derived ovarian tissue can reverse endocrine and reproductive sequelae of POI. FUNDING: Center for Infertility and Reproductive Surgery Research Award, Siezen Foundation award (RMA). Reproductive Scientist Development Program, Marriott Foundation, Saltonstall Foundation, Brigham Ovarian Cancer Research Fund (K.E).

A Comparative Analysis of Health-Related Quality of Life 1 Year Following Myomectomy or Uterine Artery Embolization: Findings from the COMPARE-UF Registry.

Objective: To compare 12-month post-treatment health-related quality of life (HR-QoL) and symptom severity (SS) changes among patients with symptomatic uterine fibroids (SUF) not seeking fertility and undergo a hysterectomy, abdominal myomectomy (AM), or uterine artery embolization (UAE). Materials and Methods: The Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF) Registry is a multi-institutional prospective observational cohort study of patients treated for SUF. A subset of 1465 women 31-45 years of age, who underwent either hysterectomy (n = 741), AM (n = 446), or UAE (n = 155) were included in this analysis. Demographics, fibroid history, and symptoms were obtained by baseline questionnaires and at 1 year post-treatment. Results were stratified by all treatments and propensity score weighting to adjust for differences in baseline characteristics. Results: Women undergoing UAE reported the lowest baseline HR-QoL and highest SS scores (mean = 40.6 [standard deviation (SD) = 23.8]; 62.3 [SD = 24.2]) followed by hysterectomy (44.3 [24.3]; 59.8 [SD = 24.1]). At 12 months, women who underwent a hysterectomy experienced the largest change in both HR-QoL (48.7 [26.2]) and SS (51.9 [25.6]) followed by other uterine-sparing treatments. Propensity score weighting revealed all treatments produced substantial improvement, with hysterectomy patients reporting the highest HR-QoL score (92.0 [17.8]) compared with myomectomy (86.7 [17.2]) and UAE (82.6 [21.5]) (p < 0.0001). Similarly, hysterectomy patients reported the lowest SS scores (8.2 [15.1]) compared with myomectomy (16.5 [15.1]) and UAE (19.6 [17.5]) (p < 0.0001). Conclusion: All procedures showed improvement in HR-QoL and reduction in SS score at 12 months, hysterectomy showing maximum improvement. Of importance, at 12 months, patients who underwent either a myomectomy or UAE reported comparable symptom relief and HR-QoL. Clinicaltrials.Gov Identifier: NCT02260752.

Anxiety, Depression, and Quality of Life After Procedural Intervention for Uterine Fibroids.

Background: Quality of life (QOL) and psychological health has been reported to be decreased among women with gynecological conditions such as uterine fibroids (UFs). Materials and Methods: Women enrolled in the Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry, receiving procedural therapy for symptomatic UFs, were eligible for this analysis if they completed a series of health-related QOL surveys administered at three time points (baseline, 6-12 weeks postprocedure, and 1 year postprocedure; n = 1486). Ethical approval for this study was obtained at each recruiting site and the coordinating center (NCT02260752, clinicaltrials.gov). Results: More than 26% (n = 393) of women reported moderate anxiety/depression on the baseline anxiety/depression domain of the Euro-QOL 5-dimension instrument. At both the 6-12 weeks and 1-year postprocedural follow-up, there was significant improvement in the UF QOL symptom severity score (p < 0.001, p < 0.001), the total UF symptom QOL score (p < 0.001, p < 0.001), and the Euro-QOL 5-dimension visual analog scale (p < 0.001, p = 0.004) compared with the preprocedural baseline scores. The reporting of anxiety/depression decreased by 66.4% among women who were at baseline, whereas 5.6% of women previously reporting no anxiety/depression reported anxiety/depression at the 1-year follow-up. Conclusion: UF symptoms were more severe among women reporting anxiety/depression at baseline. At the 1-year follow-up, health-related QOL scores improved among all women and the prevalence of anxiety/depression decreased in most, but not all women, whereas severity of anxiety/depression worsened in a small percentage of women (5.6%). Overall, these results suggest that UF treatment improves symptoms of anxiety/depression associated with symptomatic UFs.

Route of myomectomy and fertility: a prospective cohort study.

OBJECTIVE: To assess prospectively the association between the myomectomy route and fertility. DESIGN: Prospective cohort study. SETTING: The Comparing Treatments Options for Uterine Fibroids (COMPARE-UF) Study is a multisite national registry of eight clinic centers across the United States. PATIENT(S): Reproductive-aged women undergoing surgery for symptomatic uterine fibroids. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): We used life-table methods to estimate cumulative probabilities and 95% confidence intervals (CI) of pregnancy and live birth by the myomectomy route during 12, 24, and 36 months of follow-up (2015-2019). We also conducted 12-month interval-based analyses that used logistic regression to estimate odds ratios and 95% CIs for associations of interest. In all analyses, we used propensity score weighting to adjust for differences across surgical routes. RESULT(S): Among 1,095 women who underwent myomectomy (abdominal = 388, hysteroscopic = 273, and laparoscopic = 434), 202 reported pregnancy and 91 reported live birth during 36 months of follow-up. There was little difference in the 12-month probability of pregnancy or live birth by route of myomectomy overall or among women intending pregnancy. In interval-based analyses, adjusted ORs for pregnancy were 1.28 (95% CI, 0.76-2.14) for hysteroscopic myomectomy and 1.19 (95% CI, 0.76-1.85) for laparoscopic myomectomy compared with abdominal myomectomy. Among women intending pregnancy, adjusted ORs were 1.27 (95% CI, 0.72-2.23) for hysteroscopic myomectomy and 1.26 (95% CI, 0.77-2.04) for laparoscopic myomectomy compared with abdominal myomectomy. Associations were slightly stronger but less precise for live birth. CONCLUSION(S): The probability of conception or live birth did not differ appreciably by the myomectomy route among women observed for 36 months postoperatively. CLINICAL TRIALS REGISTRATION NUMBER: (NCT02260752, clinicaltrials.gov).

Black Women Are More Likely Than White Women to Schedule a Uterine-Sparing Treatment for Leiomyomas.

Background: To evaluate differences in the proportion of uterine fibroid (UF) treatments that are uterine-sparing between Black women and White women and identify factors that could explain disparities. Methods: Women at age 18-54 years who were enrolled from 10 clinical sites in the United States into the Comparing Options for Management: Patient-Centered Results for UFs (COMPARE-UF) treatment registry completed questionnaires before their UF procedure. UF symptoms and quality of life were assessed by questionnaires. Details on UF imaging and treatment (hysterectomy, myomectomy, or uterine artery embolization [UAE]) were collected from each patient's medical record. Random-effects logistic regression was used to assess the association between race and the odds of having a uterine-sparing procedure versus hysterectomy. Subgroup analyses compared each uterine-sparing procedure with hysterectomy. Results: In this cohort of 1141 White women and 1196 Black women, Black women tended to be younger (median 41.0 vs. 42.0 years) and report worse symptoms, pain, and function on every scale compared with White women. Black women were more likely to have had a prior UF treatment compared with White women (22.8% vs. 14.6%). White women had more hysterectomies (43.6% vs. 32.2%) and myomectomies (50.9% vs. 50.2%) versus Black women. Black women had more UAEs (15.1% vs. 4.7%) than White women. After adjusting for clinical site and other variables, Black women had greater odds than White women of having a myomectomy (odds ratio [OR] = 2.41, 95% confidence interval [CI] = 1.63-3.56) or a UAE versus hysterectomy (OR = 4.24, 95% CI = 2.41-7.46). Conclusion: In these participants, Black women were more likely to schedule a uterine-sparing UF treatment and a nonsurgical UF treatment than their White counterparts; this may not be true for all women. Longer comparative effectiveness studies are needed to inform women about the durability of UF treatments. Greater understanding of factors influencing treatment selection is needed as are studies that include women without access to tertiary care centers. Clinical Trial Registration: Clinicaltrials.gov, NCT02260752 (enrollment start: November 2015).

Comparative effectiveness of hysterectomy versus myomectomy on one-year health-related quality of life in women with uterine fibroids.

OBJECTIVE: To compare long-term health-related quality of life (HRQOL) 1 year after hysterectomy or myomectomy for treatment of uterine fibroids (UFs) and to determine whether route of procedure, race, or age affected improvements in HRQOL. DESIGN: Prospective cohort study. SETTING: Eight clinical sites throughout the United States. PATIENT(S): A total of 1,113 premenopausal women with UFs who underwent hysterectomy or myomectomy as part of Comparing Options for Management: Patient-Centered Results for Uterine Fibroids. INTERVENTION(S): None. MAIN OUTCOME MEASURE (S): Self-reported HRQOL measures including Uterine Fibroid Symptom Quality of Life, the European QOL 5 Dimension Health Questionnaire, and the visual analog scale at baseline and 1-year after hysterectomy or myomectomy. RESULT (S): Hysterectomy patients were older with a longer history of symptomatic UF compared with myomectomy patients. There were no differences in baseline HRQOL. After adjustment for baseline differences between groups, compared with myomectomy, patients' HRQOL (95% confidence interval [CI], 5.4, 17.2) and symptom severity (95% CI, -16.3, -8.8) were significantly improved with hysterectomy. When stratified across race/ethnicity and age, hysterectomy had higher HRQOL scores compared with myomectomy. There was little difference in HRQOL (95% CI, 0.1 [-9.5, 9.6]) or symptom severity (95% CI, -3.4 [-10, 3.2]) between abdominal hysterectomy and abdominal myomectomy. CONCLUSION (S): HRQOL improved in all women 1 year after hysterectomy or myomectomy. Hysterectomy patients reported higher HRQOL summary scores compared with myomectomy patients. When stratified by route, minimally invasive hysterectomy had better HRQOL scores than minimally invasive myomectomy. There was little difference in scores with abdominal approaches.

Short-Term Health-Related Quality of Life After Hysterectomy Compared With Myomectomy for Symptomatic Leiomyomas.

OBJECTIVE: To compare short-term health-related quality of life (HRQOL) 6-12 weeks after hysterectomy or myomectomy for the treatment of symptomatic leiomyomas. METHODS: We conducted a prospective comparative effectiveness analysis of data. In an existing multisite registry, we compared 6-12-week postsurgical HRQOL using the disease-specific Uterine Fibroid Symptom Quality of Life and the generic EuroQoL 5-Dimension Health Questionnaire, in women from the ages of 18-54 years with documented leiomyomas undergoing hysterectomy or myomectomy. Propensity score weighting was used to adjust for confounding, and analyses were also stratified by route of surgery. RESULTS: A total of 1,295 patients (727 with hysterectomy and 568 with myomectomy) enrolled from registry initiation in November 2015 until June 2018 met inclusion criteria. At baseline, leiomyoma-specific HRQOL (44.0±25.4 and 50.2±25.3, P<.01), symptom severity (60.7±23.6 and 51.7±24.6, P<.01), and generic HRQOL (69.3±20.4 and. 73.4±18.9, P<.01) were significantly different between the hysterectomy compared with myomectomy groups, respectively. Differences were eliminated by propensity adjustment. Substantial improvement in HRQOL measures were seen in both groups at 6-12 weeks, with the mean propensity-adjusted symptom severity score 4 points lower in hysterectomy patients (mean difference -4.6; 95% CI -7.0 to -2.3), compared with myomectomy patients. Hysterectomy patients had better scores on the concern and self-consciousness subscales compared with myomectomy patients. When stratified by surgical route, these two subscale findings were similar between minimally invasive hysterectomy and minimally invasive myomectomy. Symptom severity scores did not differ after abdominal myomectomy compared with abdominal hysterectomy, but subscale scores on activity and energy/mood were higher with myomectomy. CONCLUSION: Both hysterectomy and myomectomy were associated with substantial improvement in HRQOL at short-term follow-up, with small but statistically significant differences in symptom severity and certain subscales. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02260752.

Implementation of the uterine fibroids Option Grid patient decision aids across five organizational settings: a randomized stepped-wedge study protocol.

BACKGROUND: Uterine fibroids are non-cancerous overgrowths of the smooth muscle in the uterus. As they grow, some cause problems such as heavy menstrual bleeding, pelvic pain, discomfort during sexual intercourse, and rarely pregnancy complications or difficulty becoming pregnant. Multiple treatment options are available. The lack of comparative evidence demonstrating superiority of any one treatment means that choosing the best option is sensitive to individual preferences. Women with fibroids wish to consider treatment trade-offs. Tools known as patient decision aids (PDAs) are effective in increasing patient engagement in the decision-making process. However, the implementation of PDAs in routine care remains challenging. Our aim is to use a multi-component implementation strategy to implement the uterine fibroids Option Grid™ PDAs at five organizational settings in the USA. METHODS: We will conduct a randomized stepped-wedge implementation study where five sites will be randomized to implement the uterine fibroid Option Grid PDA in practice at different time points. Implementation will be guided by the Consolidated Framework for Implementation Research (CFIR) and Normalization Process Theory (NPT). There will be a 6-month pre-implementation phase, a 2-month initiation phase where participating clinicians will receive training and be introduced to the Option Grid PDAs (available in text, picture, or online formats), and a 6-month active implementation phase where clinicians will be expected to use the PDAs with patients who are assigned female sex at birth, are at least 18 years of age, speak fluent English or Spanish, and have new or recurrent symptoms of uterine fibroids. We will exclude postmenopausal patients. Our primary outcome measure is the number of eligible patients who receive the Option Grid PDAs. We will use logistic and linear regression analyses to compare binary and continuous quantitative outcome measures (including survey scores and Option Grid use) between the pre- and active implementation phases while adjusting for patient and clinician characteristics. DISCUSSION: This study may help identify the factors that impact the implementation and sustained use of a PDA in clinic workflow from various stakeholder perspectives while helping patients with uterine fibroids make treatment decisions that align with their preferences. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03985449. Registered 13 July 2019, https://clinicaltrials.gov/ct2/show/NCT03985449.