Khan, Zaraq

Objective: To describe reported outcomes of nonsurgical radiologic interventions for abdominal wall endometriosis in comparison with surgery where available. Data sources: A systematic search of Ovid Medline, Embase, PubMed, and Cochrane Controlled Register of Trials was performed from inception to January 2019 with no language restrictions. Study eligibility criteria: Studies were included if they evaluated a nonsurgical intervention in women with symptomatic abdominal wall endometriosis with both comparative and noncomparative study designs. Study appraisal and synthesis methods: Titles and abstracts were reviewed for relevance, and full-text articles were obtained and evaluated for inclusion, all in duplicate. Meta-analysis was performed when possible using a fixed effects model. Results: Of the 114 records reviewed, 16 full-text articles were assessed and 7 were included in analysis. The standard mean difference between pre- and post-intervention pain scores was similar between ultrasound-guided high-intensity focused ultrasound (USgHIFU) (−3.00; 95% confidence interval −3.34, −2.66) and cryoablation (−3.93; 95% confidence interval −5.73, −2.12). The mean percent decrease in lesion size following intervention was similar between USgHIFU (−61.38%; 95% confidence interval −78.64%, −44.11%), and cryoablation (−88.16%; 95% confidence interval −83.90%, −55.06%). When compared with surgical excision, mean length of stay was 2.78 days less in the nonsurgical intervention group (95% confidence interval −3.78, −1.79). Conclusions: Both USgHIFU and cryoablation are effective at reducing pain scores and lesion size in abdominal wall endometriosis. Mean length of stay was significantly less following a nonsurgical radiologic intervention for abdominal wall endometriosis compared with surgery. More studies are needed comparing complication and recurrence rates between nonsurgical radiologic interventions for abdominal wall endometriosis and surgery.

Abstract Objective: The aim of this research was to study the long-term risk of de novo mental health conditions in women who underwent hysterectomy with bilateral ovarian conservation compared with age-matched referent women. Methods: Using the Rochester Epidemiology Project records-linkage system, we identified a historical cohort of 2,094 women who underwent hysterectomy with ovarian conservation for benign indications at age ≥18 years and with an index date between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman residing in the same county who had not undergone hysterectomy or any oophorectomy before the index date. These two cohorts were followed historically to identify de novo mental health conditions. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) using Cox proportional hazards models adjusted for 20 preexisting chronic conditions and other potential confounders. We also calculated absolute risk increases (ARIs) and reductions (ARRs) at 30 years of follow-up. Results: Over a median follow-up of 21.9 years, women who underwent hysterectomy at any age experienced increased risks of de novo depression (adjusted HR 1.26; 95% CI, 1.12-1.41; ARI 6.6%) and anxiety (adjusted HR 1.22; 95% CI, 1.08-1.38; ARI 4.7%). The association for depression increased significantly with younger age at hysterectomy, but did not vary significantly by indication. Interactions were not significant for anxiety. Conclusions: Hysterectomy, even with ovarian conservation, is associated with an increased long-term risk of de novo depression and anxiety, especially when performed in women who are younger. Video Summary: http://links.lww.com/MENO/A465.

INTRODUCTION: The incidence of ovarian hyperstimulation syndrome (OHSS) after assisted reproduction is approximately 3%. The outcomes of pregnancy in immediate versus delayed pregnancy has not been previously studied. METHODS: A retrospective cohort study was conducted using the Rochester Epidemiology Project Database. Residents of Olmsted County and the surrounding 9 counties with OHSS were identified between 1995 and 2017. Patients were included if they had a pregnancy lasting ≥20 weeks gestation after the diagnosis of OHSS. Background data and pregnancy outcomes were collected. Data were then analyzed using a combination of t-test and Chi squared test. Women with OHSS and same cycle pregnancy were compared to those with subsequent cycle pregnancy. RESULTS: 85 women with OHSS were analyzed, 47 with same-cycle pregnancies and 38 with subsequent cycle pregnancies. Background data did not differ between the two groups for infertility cause, body mass index, gestational age, parity, or number of embryos transferred. OHSS treatment modalities (paracentesis, thoracentesis, hospitalization and medical treatment) did not differ between groups. Patients with same-cycle pregnancies had neonates delivered at 35.6 weeks compared to 38.3 weeks with delayed pregnancies (p=0.0006). Patients with same cycle pregnancies also had lower birth weights compared to patients with delayed pregnancies (3201 g v 2628 g, p=0.003). Incidence of hypertensive disorders, diabetes, placental abruption, thromboembolism, intrauterine fetal death, intrauterine growth restriction, and 1 and 5 minute Apgar scores did not differ between the two groups. CONCLUSION: The data gives new insight into the risk of same-cycle pregnancies in patients with OHSS. Larger studies are needed to confirm the data.

AbstractIntroductionAdenomyosis is a benign uterine disease where endometrial glands and stroma are found within the myometrium surrounded by an area of hypertrophic myometrium. Symptomatology includes heavy menstrual bleeding and pelvic pain. The pathogenesis of adenomyosis is not known; however, animal models have shown increased uterine concentration of prolactin as a risk factor. Prolactin acts as a smooth muscle cell mitogen. If prolactin is central to adenomyosis pathogenesis, reducing uterine prolactin could be a possible medical treatment option. In this pilot study, we aim to evaluate the effect of bromocriptine, a prolactin inhibitor, on menstrual bleeding and pain in women with adenomyosis.Material and methods23 women with diffuse adenomyosis were enrolled from a university hospital in Sweden and a tertiary care center in the USA. Nineteen patients completed 6 months of treatment with vaginal bromocriptine at a dose of 5 mg daily. Participants completed validated measures at baseline, 3 and 6 months of treatment, and at 9 months (3 months after cessation of bromocriptine). Validated measures utilized included Pictorial Blood Loss Assessment Chart (PBLAC), Aberdeen Menorrhagia Clinical Outcomes Questionnaire (AMCOQ), Visual Analog Scale for pain (VAS), McGill Pain Questionnaire (MPQ), Endometriosis Health Profile (EHP‐30), Female Sexual Function Index (FSFI) and the Fibroid Symptom Quality of Life (UFS‐QOL) symptom severity and health‐related quality of life (HRQL) subscores. Scores were compared between baseline and 9 months using the Wilcoxon signed rank test.ResultsMean age of participants was 44.8 years. About 77.8% reported PBLAC scores >250 and 68.4% reported moderate to severe pain at baseline. Compared with baseline, women had lower 9‐month scores (median [interquartile range] for all) on PBLAC (baseline 349 [292‐645] vs 9‐month 233 [149‐515], P = 0.003), VAS (5.0 [4‐8.3] vs 2.5 [0‐4.5], P < 0.001), EHP Core Pain (15.9 [9.1‐50.0] vs 3.4 [2.3‐34.1], P = 0.029), EHP Core Self‐image (41.7 [16.7‐58.3] vs 25 [0‐5], P = 0.048) and Symptom Severity Score (60 [44‐72] vs 44 [25‐56], P < 0.001) and higher HRQL scores (57 [37‐63] vs 72 [51‐85], P < 0.001) following bromocriptine treatment. Other EHP core parameters and FSFI were not significantly different.ConclusionsSignificant improvement in menstrual bleeding, pain and quality of life after vaginal bromocriptine treatment suggests a novel therapeutic agent for adenomyosis.

Abstract Objective: The aim of the study was to determine the long-term risk of cardiovascular disease and metabolic conditions in women undergoing hysterectomy with bilateral ovarian conservation compared with age-matched referent women. Methods: Using the Rochester Epidemiology Project records-linkage system, we identified 2,094 women who underwent hysterectomy with ovarian conservation for benign indications between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman residing in the same county who had not undergone prior hysterectomy or any oophorectomy. These two cohorts were followed historically to identify de novo cardiovascular or metabolic diagnoses. We estimated hazard ratios (HRs) and 95% CIs using Cox proportional hazards models adjusted for 20 preexisting chronic conditions and other potential confounders. We also calculated absolute risk increases and reductions from Kaplan–Meier estimates. Results: Over a median follow-up of 21.9 years, women who underwent hysterectomy experienced increased risks of de novo hyperlipidemia (HR 1.14; 95% CI, 1.05-1.25), hypertension (HR 1.13; 95% CI, 1.03-1.25), obesity (HR 1.18; 95% CI, 1.04-1.35), cardiac arrhythmias (HR 1.17; 95% CI, 1.05-1.32), and coronary artery disease (HR 1.33; 95% CI, 1.12-1.58). Women who underwent hysterectomy at age ≤35 years had a 4.6-fold increased risk of congestive heart failure and a 2.5-fold increased risk of coronary artery disease. Conclusions: Even with ovarian conservation, hysterectomy is associated with an increased long-term risk of cardiovascular and metabolic conditions, especially in women who undergo hysterectomy at age ≤35 years. If these associations are causal, alternatives to hysterectomy should be considered to treat benign gynecologic conditions.

AbstractEndocrine regulation of uterine biology is critical for embryo receptivity and human reproduction. Uterine endometrium depends on extrinsic sex steroid input and hence likely has mechanisms that enable adaptation to hormonal variation. Emerging evidence suggests that sex steroid bioavailability in the endometrium is determined by adjusting their metabolic rate and fate via regulation of cytochrome (CYP) p450 enzymes. The CYP enzymes are targeted by ubiquitously expressed Sp/Krüppel-like (Sp/KLF) transcription factors. Specifically, KLF11 is highly expressed in reproductive tissues, regulates an array of endocrine/metabolic pathways via epigenetic histone-based mechanisms and, when aberrantly expressed, is associated with diabetes and reproductive tract diseases, such as leiomyoma and endometriosis. Using KLF11 as a model to investigate epigenetic regulation of endometrial first-pass metabolism, we evaluated the expression of a comprehensive array of metabolic enzymes in Ishikawa cells. KLF11 repressed most endometrial CYP enzymes. To characterize KLF11-recruited epigenetic regulatory mechanisms, we focused on the estrogen-metabolizing enzyme CYP3A4. KLF11 expression declined in secretory phase endometrial epithelium associated with increased CYP3A4 expression. Additionally, KLF11 bound to CYP3A4 promoter GC elements and thereby repressed promoter, message, protein as well as enzymatic function. This repression was epigenetically mediated, because KLF11 colocalized with and recruited the corepressor SIN3A/histone deacetylase resulting in selective deacetylation of the CYP3A4 promoter. Repression was reversed by a mutation in KLF11 that abrogated cofactor recruitment and binding. This repression was also pharmacologically reversible with an histone deacetylase inhibitor. Pharmacological alteration of endometrial metabolism could have long-term translational implications on human reproduction and uterine disease.