Marsh, Erica E.

Background With improvements in in vitro culture techniques, there has been a steady shift in practice to transfer in vitro fertilisation (IVF) embryos at the blastocyst-stage to increase pregnancy rates per embryo transfer (ET) and reduce the risk of multiple pregnancy. In patients with fewer embryos (≤5 zygotes), fresh cleavage-stage ET is still commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst-stage in vitro. However, evidence for improved outcomes with cleavage-stage embryo transfer in this subgroup of patients is lacking. We will compare blastocyst-stage to cleavage-stage ET with regard to cumulative live birth rates (CLBR) per oocyte retrieval and other patient-centred cycle outcomes in patients with ≤5 zygotes. Methods and analysis Multicentre, randomised pragmatic comparative effectiveness trial with superiority design comparing blastocyst-stage to cleavage-stage ET in patients with ≤5 zygotes. This trial will enrol and randomise 1126 women aged 18–44 undergoing IVF to either fresh cleavage-stage or blastocyst-stage ET at eleven IVF centres. Surplus embryos will be vitrified at the blastocyst-stage. The primary outcome is the CLBR per oocyte retrieval. Secondary outcomes include: multiple pregnancy, pregnancy loss <20 weeks and cycle cancellation. Exploratory outcomes include: live birth per fresh ET, ectopic pregnancy, time to pregnancy, stillbirth, preterm birth, financial burden, patient distress and facilitators and barriers for patient involvement and implementation. All primary analyses will be conducted according to the intent-to-treat principle. We also will report per-protocol analyses as a sensitivity analysis. A multidisciplinary stakeholder team, including a 5-patient stakeholder panel, will participate in study design, conduct and oversight. Ethics and dissemination The Institutional Review Board at Beth Israel Deaconess Medical Center (BIDMC) provides central regulatory oversight. Results will inform timing of embryo transfer in patients with ≤5 zygotes and will be disseminated through academic publications, meeting presentations and communications to advocacy groups and patient participants. Trial registration number NCT06746129 .

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.

INTRODUCTION: Iron-deficiency anemia is common in women with uterine fibroid (UF)-related heavy menstrual bleeding. Severe anemia is defined as hemoglobin (Hb) levels <10g/dL. The effect of linzagolix, an oral GnRH antagonist, on UF-related severe anemia was assessed in two Phase 3 trials. METHODS: PRIMROSE 1 and 2 are randomized, double-blind, placebo-controlled Phase 3 trials investigating the efficacy and safety of linzagolix 100 mg and 200 mg once daily, with or without hormonal add-back therapy (ABT) in the treatment of UF. Subjects were considered responders if an increase of ≥2g/dL from baseline was achieved. Patients with severe anemia were given iron supplements until they reached the Hb levels >12g/dL. RESULTS: In PRIMROSE 1, of 165 subjects with severe anemia, 57.9%, 61.5%, 82.1% and 65.2% of patients were responders at 24 weeks, in the respective treatment groups (100 mg, 100 mg+ABT, 200 mg and 200 mg+ABT), compared to 50% in the placebo group. In PRIMROSE 2, of 93 patients with severe anemia, 62.5%, 75%, 60% and 73.7%, respectively, were responders, compared to 46.2% for placebo. Given the small sample sizes, statistical significance was not reached. Improvements were maintained at week 52: in PRIMROSE 1, 69.2%, 62.5%, 81.3% and 75% of patients were responders in the respective treatment groups, compared to 40% in placebo, in PRIMROSE 2, 66.7%, 100%, 80%, 87% were responders, respectively. CONCLUSION: High and low doses of linzagolix improved Hb levels in patients with UF suffering from severe anemia.

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.

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).

Background: Most women will experience uterine fibroids by the age of 50, yet few data exist describing the overall patient experience with fibroids. The objective of this population-based survey was to characterize symptom burden, patient awareness, and treatment decision-making for fibroids, including a comparison among women of varying backgrounds. Materials and Methods: Women (≥18 years) were recruited via email from GfK KnowledgePanel ® , a representative panel of US households, or identified with opt-in consumer panels. The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QOL) questionnaire and Aberdeen Menorrhagia Severity Scale (AMSS) were included. Results: Eligible women were grouped into three cohorts: “at-risk” (symptoms suggestive of fibroids without clinical diagnosis, n = 300), “diagnosed” ( n = 871), and fibroid-related “hysterectomy” ( n = 272). Cohort and intracohort race/ethnicity and income analyses revealed differences in symptom burden, awareness/perception, and treatment history. Based on UFS-QOL scores, at-risk women reported significantly greater symptom severity and decreased health-related QOL versus diagnosed women; Hispanic women reported greater symptom severity versus white and black women. At-risk women also reported heavy menstrual bleeding and significant impact on work productivity. Among diagnosed women, 71% used pharmacologic therapy for symptom relief, and 30% underwent surgical or procedural treatment. Initial discussions with healthcare providers significantly impacted treatment outcomes; the hysterectomy cohort was most likely to first discuss hysterectomy. Conclusions: Women with fibroids or symptoms suggestive of fibroids experience significant distress that reduces QOL, particularly racial minorities and women in lower income brackets. Survey results suggest that many women are likely undiagnosed, underscoring the need for improved awareness and education.