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Objective: To determine if ovarian responsiveness to gonadotropin stimulation differs by race/ethnicity and whether this predicts live birth rates (LBRs) in non-White patients undergoing in vitro fertilization (IVF)., Design: Retrospective cohort study., Setting: Academic infertility center., Patient(s): White, Asian, Black, and Hispanic patients undergoing ovarian stimulation for IVF., Intervention(s): Self-reported race and ethnicity., Main Outcome Measure(s): The primary outcome was ovarian sensitivity index (OSI), defined as (the number of oocytes retrieved ÷ total gonadotropin dose) × 1,000 as a measure of ovarian responsiveness, adjusting for age, body mass index, infertility diagnosis, and cycle number. Secondary outcomes included live birth and clinical pregnancy after first retrievals, adjusting for age, infertility diagnosis, and history of fibroids, as well as miscarriage rate per clinical pregnancy, adjusting for age, body mass index, infertility diagnosis, duration of infertility, history of fibroids, and use of preimplantation genetic testing for aneuploidy., Result(s): The primary analysis of OSI included 3,360 (70.2%) retrievals from White patients, 704 (14.7%) retrievals from Asian patients, 553 (11.6%) retrievals from Black patients, and 168 (3.5%) retrievals from Hispanic patients. Black and Hispanic patients had higher OSIs than White patients after accounting for those with multiple retrievals and adjusting for confounders (6.08 in Black and 6.27 in Hispanic, compared with 5.25 in White). There was no difference in OSI between Asian and White patients. The pregnancy outcomes analyses included 2,299 retrievals. Despite greater ovarian responsiveness, Black and Hispanic patients had lower LBRs compared with White patients, although these differences were not statistically significant after adjusting for confounders (adjusted odds ratio, 0.83; 95% confidence interval [CI], 0.63-1.09, for Black; adjusted odds ratio, 0.93; 95% CI, 0.61-1.43, for Hispanic). Ovarian sensitivity index was modestly predictive of live birth in White and Asian patients but not in Black (area under the curve, 0.51; 95% CI, 0.38-0.64) and Hispanic (area under the curve, 0.50; 95% CI, 0.37-0.63) patients., Conclusion(s): Black and Hispanic patients have higher ovarian responsiveness to stimulation during IVF but do not experience a consequent increase in LBR. Factors beyond differences in responsiveness to ovarian stimulation need to be explored to address the racial/ethnic disparity established in prior literature., Competing Interests: Declaration of interests I.T.L has nothing to disclose. D.S.B. has nothing to disclose. N.K. has nothing to disclose. S.S. reports funding from National Institutes of Health and AbbVie and consulting fees for participation on Ferring Oocyte Cryopreservation Advisory Board and is Co-Chair of the Society for Assisted Reproductive Technology Committee, outside the submitted work. M.M. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess comparative rates of further uterine-preserving procedures (UPP) or hysterectomy reintervention, after myomectomy or uterine artery embolisation (UAE)., Design: Population-based, retrospective cohort study., Setting: England., Population: Women who underwent myomectomy or UAE between 2010 and 2015 under the NHS., Methods: Data was abstracted from NHS Health Episode Statistics datasets. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional-hazards regression., Main Outcomes Measures: 30-day readmission, UPP and hysterectomy reintervention rates., Results: 9443 and 6224 women underwent elective myomectomy or UAE, respectively. After 118 136 total person-years of follow-up, the rate of hysterectomy was 8.34 and 20.98 per 1000 patient years for myomectomy or UAE, respectively. There was a 2.4-fold increased risk of undergoing hysterectomy after UAE when compared with myomectomy in adjusted models (HR 2.38 [95% CI 2.10-2.66]) [adjusted for age, ethnicity, multiple deprivation index, geographical region and comorbidities]. The HR for undergoing a UPP reintervention was 1.44 (95% CI 1.29-1.60) in favour of myomectomy. The rate of hysterectomy was increased 22% following UAE compared with laparoscopic myomectomy (0.97-1.52). Age may influence reintervention rates, and there was variation in hysterectomy risk when stratified by geographical region., Conclusions: After a median of 7 years of follow-up, there is a 2.4-fold increased rate of hysterectomy and 44% increased risk of UPPs as reintervention after UAE, relative to myomectomy. These findings will aid pre-procedure counselling for women with fibroids. Future work should investigate the effect of other outcome modifiers, such as fertility intentions and fibroid anatomical characteristics., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Purpose: Uterine myomas are the most common gynecological disease. In these cases, a myomectomy is performed traditionally laparotomically. However, alternatives have been widely used, including laparoscopic, endoscopic, and robotic surgery. During these techniques, diffuse parenchymatous bleeding remains one of the main intraoperative and postoperative complications and sometimes requires unplanned hysterectomies. Recently, hemostatic agents and sealants have been used to prevent excessive blood loss during surgical repair., Methods: We propose a prospective case-control study on the use of a sealing hemostat patch (HEMOPATCH ® ) on uterine sutures in laparotomic myomectomy. In the period between July 2016 and April 2017, 46 patients with symptomatic uterine fibromatosis underwent surgery. They were divided into two groups of 23 patients, with different treatments in the hemostatic phase of oozing bleeding. HEMOPATCH ® is applied in group A, and spray electrocoagulation is applied in group B., Results: In group A, we achieve faster hemostasis (p < 0.05), than in group B. We report a significantly lower C-reactive protein value on the second and third days after surgery for group A compared to group B., Conclusions: HEMOPATCH ® , during laparotomic myomectomy, is a valid alternative solution for obtaining rapid hemostasis and consequently intraoperative and postoperative bleeding. Furthermore, we suggest that a lower inflammatory peritoneal state is probably correlated with the barrier effect of the patch on the suture., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Leiomyomas (LMs) are the most frequent uterine benign tumors, representing the leading cause of hysterectomy indications worldwide. They are highly associated with women's reproductive complications, and endocrine disruptors may influence their etiology. In this sense, air pollution represents a relevant hormonal disruptor that acts on key signaling pathways, resulting in tumor development and infertility. Our goal was to evaluate submucosal LM samples from patients living in the metropolitan and Sao Paulo city regions, focusing on genes involved in tumor development and infertility features. Twenty-four patients were selected based on their region of residence and clinical information availability. Several genes were differentially expressed between women living in metropolitan areas and Sao Paulo city. Significant associations were observed between BCL-2 , DVL1 , FGFR3 , and WNT5b downregulation and contraceptive use in the samples from women living in Sao Paulo city. ESR1 and HHAT downregulation was associated with ethnicity. WNT5b and GREM were associated with LM treatment and related pathologies, respectively. In the samples from women living in other cities of the metropolitan region, abortion occurrence was associated with BMP4 upregulation. Although further studies may be necessary, our results showed that air pollution exposure influences the expression of genes related to LM development and female reproductive features.

Objective: To investigate the outcome of total laparoscopic hysterectomy (TLH) and postoperative pain characteristics and compare the pain severity after TLH for adenomyosis or uterine fibroids., Methods: This prospective observational study collected 101 patients received TLH for adenomyosis (AD group) including 41 patients were injected goserelin (3.6 mg) 28 days before TLH, while other adenomyosis patients received TLH without preoperative treatment, and 113 patients received TLH for uterine fibroids (UF group). Pain scores were evaluated at different time sites from operation day to postoperative 72 h using the numeric rating scale. Clinical data were collected from clinical record., Results: Operative time and anaesthetic time were longer in the AD group than those in the UF group (66.88 ± 8.65 vs. 64.46 ± 7.21, p  = 0.04; 83.95 ± 10.05 vs. 79.77 ± 6.88, p  < 0.01), severe endometriosis was quite more common in AD group (23.76% vs. 2.65%, p  < 0.01). Postoperative usage of Flurbiprofen in AD group were more than that of UF group (15.48 ± 38.00 vs. 4.79 ± 18.16, p  = 0.02). Total pains and abdominal visceral pains of AD group were more severe compared with UF group in motion and rest pattern at several time sites, while incision pain and shoulder pain were similar. The total postoperative pains after goserelin preoperative treatment in AD group were less than that without goserelin preoperative treatment ( p  < 0.05). The levels of serum NPY, PGE2 and NGF after laparoscopic hysterectomy of adenomyosis reduced with GnRH agonist pretreatment., Conclusions: Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids. While patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

Background: Uterine leiomyoma (UL) is the most common benign tumor of the reproductive period and become a major health problem. The present umbrella review assessed the environmental risk factors associated with UL based on meta-analyses studies., Materials and Methods: We searched three Major databases until February 2022. The meta-analyses that had focused on evaluating the environmental risk factors associated with the UL were included. The summary effect estimates, 95% CI, heterogeneity I², 95% prediction interval, small-study effects, excess significance biases, and sensitive analysis were applied. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) for assessing the quality of the meta-analyses., Result: The risk factor of chronic psychological stress (OR 1.24, 95% CI: 1.15, 1.34) and obesity (OR 1.19, 95% CI: 1.09, 1.29) was graded as suggestive evidence (class III). The current alcohol intake (OR 1.33, 95% CI: 1.01, 1.76) was graded as the risk factor with weak evidence (class IV). Current oral contraceptive (OCP) use (RR 0.43, 95% CI: 0.25, 0.73) (class IV), and former smokers (OR 0.93, 95% CI: 0.88, 0.99) (class IV) were as the protective factors., Conclusion: The current alcohol intake, chronic psychological stress, and obesity were risk factors for the UL, but current OCP use and former smokers were the protective factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objectives: The goal of this study was to examine the safety, feasibility, and effectiveness of the use of a microsurgical temporary vascular clip system to facilitate the laparoscopic enucleation of very large intramural uterine fibroids., Methods: In this retrospective study, the surgical outcomes of 26 patients who underwent laparoscopic myomectomy with temporary uterine vessel clipping for very large (the largest measured diameter ≥ 9 cm) symptomatic intramural uterine fibroids in two tertiary referral hospitals between September 2017 and March 2020 were examined. Titan-made vascular clips (YASARGIL ® Aneurysm Clip System) were used to temporarily occlude the bilateral uterine arteries and utero-ovarian vessels. Main outcomes included operating time, blood loss, number of leiomyomas and weight, conversion rate, intra- and postoperative complication rates, and length of hospital stay., Results: Twenty six patients were included. Dominant intramural uterine fibroid diameters were 9-22 cm. The general characteristics of the patients were similar. The mean surgery duration and intraoperative blood loss were 175.3 ± 32.7 (range 120-250) min and 241.1 ± 103 (range 100-450) ml, respectively. The median postoperative drop in hemoglobin was 0.89 ± 0.75 g/dL. No patient required blood transfusion. No procedure was converted to laparotomy. No major intra- or postoperative complication occurred., Conclusions: Laparoscopic myomectomy for very large intramural uterine fibroids can be performed safely and effectively, with less intraoperative blood loss, using vascular clips for temporary clamping of the bilateral uterine vessels., (© 2022. The Author(s).)

Study Objective: To assess rates of and factors associated with complications and reoperation after myomectomy., Design: Population-based cohort study., Setting: All non-Veterans Affairs facilities in the state of California from January 1, 2005, to December 31, 2018., Participants: Women undergoing abdominal or laparoscopic myomectomy for myoma disease were identified from the Office of Statewide Health Planning and Development datasets using appropriate International Classification of Diseases, Ninth and Tenth Revision and Current Procedural Terminology codes., Interventions: Demographics, surgery facility type, facility surgical volume, and surgical approach were identified. Primary outcomes included complications occurring within 60 days of surgery and reoperations for myomas. Patients were followed up for over an average of 7.3 years. Univariate and multivariable associations were explored between the above factors and rates of complications and reoperation. All odds ratios (ORs) are adjusted ORs., Measurements and Main Results: Of the 66 012 patients undergoing myomectomy, 5265 had at least one complication (8.0%). Advanced age, black, Asian race, MediCal and Medicare payor status, academic facility, and medical comorbidities were associated with increased odds of a complication. Minimally invasive myomectomy (MIM) was associated with decreased complications compared with abdominal myomectomy (AM) (OR, 0.29; 95% confidence interval [CI], 0.25-0.33; p <.001). Overall, 17 377 patients (26.3%) underwent reoperation. Medicare and MediCal payor status and medical comorbidities were associated with increased odds of a repeat surgery. Reoperation rates were higher in the MIM group over the entire study period (OR, 2.33; 95% CI, 1.95-2.79; p <.001). However, the odds of reoperation after MIM decreased each year (OR, 0.93; 95% CI 0.92-0.95; p <.001), with the odds of reoperation after AM surpassing MIM in 2015., Conclusion: This study identifies outcome disparities in the surgical management of myomas and describes important differences in the rates of complications and reoperations, which can be used to counsel patients on surgical approach. These findings suggest that MIM can be considered a lasting and safe approach in properly selected patients., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

According to recent studies and observations in clinical practice, uterine fibroids increase the risk of preterm birth. There are several theories on the pathogenesis of preterm birth in the presence of fibroids. One theory proclaims that fibroid necrosis leads to preterm birth, though pathophysiological mechanisms have not been described. Necrotic tissue secretes specific cytokines and proteins and we suggest these to be comparable to the inflammatory response leading to spontaneous preterm birth. We hypothesize that fibroid necrosis could induce preterm parturition through a similar inflammatory response. This new hypothesis generates novel perspectives for future research and the development of preventative strategies for preterm birth. Moreover, we emphasize the importance of the recognition of fibroids and especially fibroid necrosis by clinicians during pregnancy.

Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids. This paper comprehensively summarizes the recent research advances on uterine fibroids, focusing on risk factors, development origin, pathogenetic mechanisms, and treatment options. Additionally, we describe the current treatment interventions for uterine fibroids. Finally, future perspectives on uterine fibroids studies are summarized. Deeper mechanistic insights into tumor etiology and the complexity of uterine fibroids can contribute to the progress of newer targeted therapies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

A retrospective study was conducted on patients subjected to laparoscopic myomectomy at our institution from January 2017 to December 2018 to identify predictive factors of blood loss. Two multiple regression models were run to predict intraoperative blood loss and haemoglobin drop. Predictors of an increased intraoperative blood loss and haemoglobin drop were the presence of three-four fibroids at ultrasound (+47 ml, p  = .01; +0.58 g/dl, p  = .05) and increased operative time ( r  = 0.57, p  = .01; r  = 0.01, p  < .01), while predictors of a reduced intraoperative blood loss and haemoglobin drop were epinephrine injection (-50 ml, p  < .01; -0.42 g/dl, p  < .01), FIGO7 (-87 ml, p  < .01; -0.85, p  = .01), and FIGO6 (-35 ml, p  < .01; -0.44, p  = .02) fibroids at the ultrasound. Preoperative ultrasound evaluation is crucial in identifying patients at higher risk for blood loss, which could benefit from optimising haemoglobin values. The injection of diluted epinephrine could be proposed in selected high-risk patients. In the clinical practice, a tailored approach based on fibroids' ultrasonographic characteristics should be implemented to optimise preoperative Hb values and evaluate the use of diluted epinephrine in selected cases, reducing blood loss and the potential related complications.Impact statement What is already known on this subject? Laparoscopic myomectomy is the conservative surgical treatment of choice for symptomatic uterine fibroids. Still, it could represent a challenging procedure even for an experienced surgeon, with the risk of excessive blood loss, need of transfusions, prolonged operative time, and prolonged hospital stay. The knowledge of the predictive factors of blood loss is essential for patient preparation and surgical planning to reduce intraoperative and postoperative complications. What do the results of this study add? The results of the present study focus on the importance of presurgical evaluation to identify predictive factors of intraoperative blood loss and Hb drop such as the number of fibroids and the FIGO classification (at preoperative ultrasound), as well as intraoperative factors like operative time and the intramyometrial injection of diluted epinephrine. What are the implications of these findings for clinical practice and/or further research? A tailored approach based on the ultrasonographic characteristics of fibroids should be implemented to optimise preoperative haemoblobin levels.

Background: Obesity is observationally associated with altered risk of many female reproductive conditions. These include polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, and pregnancy-related disorders. However, the roles and mechanisms of obesity in the aetiology of reproductive disorders remain unclear. Thus, we aimed to estimate observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive disorders., Methods and Findings: Logistic regression, generalised additive models, and Mendelian randomisation (MR) (2-sample, non-linear, and multivariable) were applied to obesity and reproductive disease data on up to 257,193 women of European ancestry in UK Biobank and publicly available genome-wide association studies (GWASs). Body mass index (BMI), waist-to-hip ratio (WHR), and WHR adjusted for BMI were observationally (odds ratios [ORs] = 1.02-1.87 per 1-SD increase in obesity trait) and genetically (ORs = 1.06-2.09) associated with uterine fibroids (UF), PCOS, heavy menstrual bleeding (HMB), and pre-eclampsia. Genetically predicted visceral adipose tissue (VAT) mass was associated with the development of HMB (OR [95% CI] per 1-kg increase in predicted VAT mass = 1.32 [1.06-1.64], P = 0.0130), PCOS (OR [95% CI] = 1.15 [1.08-1.23], P = 3.24 × 10-05), and pre-eclampsia (OR [95% CI] = 3.08 [1.98-4.79], P = 6.65 × 10-07). Increased waist circumference posed a higher genetic risk (ORs = 1.16-1.93) for the development of these disorders and UF than did increased hip circumference (ORs = 1.06-1.10). Leptin, fasting insulin, and insulin resistance each mediated between 20% and 50% of the total genetically predicted association of obesity with pre-eclampsia. Reproductive conditions clustered based on shared genetic components of their aetiological relationships with obesity. This study was limited in power by the low prevalence of female reproductive conditions among women in the UK Biobank, with little information on pre-diagnostic anthropometric traits, and by the susceptibility of MR estimates to genetic pleiotropy., Conclusions: We found that common indices of overall and central obesity were associated with increased risks of reproductive disorders to heterogenous extents in a systematic, large-scale genetics-based analysis of the aetiological relationships between obesity and female reproductive conditions. Our results suggest the utility of exploring the mechanisms mediating the causal associations of overweight and obesity with gynaecological health to identify targets for disease prevention and treatment., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: C.M.B. reports grants from Bayer AG, AbbVie Inc, Volition Rx, MDNA Life Sciences, Roche Diagnostics Inc., and consultancy for Myovant. He is a member of the independent data monitoring board at ObsEva; I.G. reports grants from Bayer AG; K.T.Z. reports grants from Bayer AG, AbbVie Inc, Volition Rx, MDNA Life Sciences, Roche Diagnostics Inc, and non-financial scientific collaboration with Population Diagnostics Ltd, outside the submitted work; M.V.H. has consulted for Boehringer Ingelheim, and in adherence to the University of Oxford’s Clinical Trial Service Unit & Epidemiological Studies Unit (CSTU) staff policy, did not accept personal honoraria or other payments from pharmaceutical companies; C.M.L. reports grants from Bayer AG and Novo Nordisk and has a partner who works at Vertex; no other relationships or activities that could appear to have influenced the submitted work. All disclosed competing interests are outside the submitted work.

Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found., (© 2021. The Author(s).)

Uterine leiomyoma (LM) is the most common tumor in women. Via its receptor (PGR) expressed in differentiated LM cells, progesterone stimulates paracrine signaling that induces proliferation of PGR-deficient LM stem cells (LSCs). Antiprogestins shrink LM but tumors regrow after treatment cessation possibly due to persisting LSCs. Using sorted primary LM cell populations, we found that the PGR gene locus and its target cistrome are hypermethylated in LSCs, inhibiting the expression of genes critical for progesterone-induced LSC differentiation. PGR knockdown shifted the transcriptome of total LM cells toward LSCs and increased global DNA methylation by regulating TET methylcytosine dioxygenases. DNA methylation inhibitor 5'-Aza activated PGR signaling, stimulated LSC differentiation, and synergized with antiprogestin to reduce tumor size in vivo. Taken together, targeting the feedback loop between DNA methylation and progesterone signaling may accelerate the depletion of LSCs through rapid differentiation and sensitize LM to antiprogestin therapy, thus preventing tumor regrowth., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Uterine leiomyomas represent the most common benign gynecologic tumor. These hormone-dependent smooth-muscle formations occur with an estimated prevalence of ~70% among women of reproductive age and cause symptoms including pain, abnormal uterine bleeding, infertility, and recurrent abortion. Despite the prevalence and public health impact of uterine leiomyomas, available treatments remain limited. Among the potential causes of leiomyomas, early hormonal exposure during periods of development may result in developmental reprogramming via epigenetic changes that persist in adulthood, leading to disease onset or progression. Recent developments in unbiased high-throughput sequencing technology enable powerful approaches to detect driver mutations, yielding new insights into the genomic instability of leiomyomas. Current data also suggest that each leiomyoma originates from the clonal expansion of a single transformed somatic stem cell of the myometrium. In this review, we propose an integrated cellular and molecular view of the origins of leiomyomas, as well as paradigm-shifting studies that will lead to better understanding and the future development of non-surgical treatments for these highly frequent tumors.

Uterine fibroids (UFs) are benign tumors originating from smooth muscle cells and are considered a common pathology that affects numerous women which is a notable socio-economic problem. Several UF risk factors have been identified including black race, obesity, and vitamin D deficiency. Vitamin D is steroid compound with pleiotropic effects on the human body. Vitamin D deficiency is a major public health concern worldwide. Several studies have shown that the majority of UF patients experienced hypovitaminosis D. In addition, sufficient vitamin D serum levels are associated with the reduced risk of UFs. In this review, we present available data highlighting the importance of measuring vitamin D serum levels in women with UFs and women at a high risk for UF development. We proposed a preliminary clinical instruction of 25-hydroxyvitamin D measurements and vitamin D supplementation for clinicians who are involved in the treatment of patients with UFs. Achieving sufficient serum levels of vitamin D might be of interest in patients with UFs. Screening, supplementation, treatment guidelines, and public health strategies for vitamin D deficiency in women with UFs as well as women at a high risk of UF development might be of potential importance as well., (© 2020. The Author(s).)

Study Question: To what extent are ambient concentrations of particulate matter <2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3) associated with risk of self-reported physician-diagnosed uterine leiomyomata (UL)?, Summary Answer: In this large prospective cohort study of Black women, ambient concentrations of O3, but not PM2.5 or NO2, were associated with increased risk of UL., What Is Known Already: UL are benign tumors of the myometrium that are the leading cause of gynecologic inpatient care among reproductive-aged women. Black women are clinically diagnosed at two to three times the rate of white women and tend to exhibit earlier onset and more severe disease. Two epidemiologic studies have found positive associations between air pollution exposure and UL risk, but neither included large numbers of Black women., Study Design, Size, Duration: We conducted a prospective cohort study of 21 998 premenopausal Black women residing in 56 US metropolitan areas from 1997 to 2011., Participants/material, Setting, Methods: Women reported incident UL diagnosis and method of confirmation (i.e. ultrasound, surgery) on biennial follow-up questionnaires. We modeled annual residential concentrations of PM2.5, NO2 and O3 throughout the study period. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for a one-interquartile range (IQR) increase in air pollutant concentrations, adjusting for confounders and co-pollutants., Main Results and the Role of Chance: During 196 685 person-years of follow-up, 6238 participants (28.4%) reported physician-diagnosed UL confirmed by ultrasound or surgery. Although concentrations of PM2.5 and NO2 were not appreciably associated with UL (HRs for a one-IQR increase: 1.01 (95% CI: 0.93, 1.10) and 1.05 (95% CI: 0.95, 1.16), respectively), O3 concentrations were associated with increased UL risk (HR for a one-IQR increase: 1.19, 95% CI: 1.07, 1.32). The association was stronger among women age <35 years (HR: 1.26, 95% CI: 0.98, 1.62) and parous women (HR: 1.28, 95% CI: 1.11, 1.48)., Limitations, Reasons for Caution: Our measurement of air pollution is subject to misclassification, as monitoring data are not equally spatially distributed and we did not account for time-activity patterns. Our outcome measure was based on self-report of a physician diagnosis, likely resulting in under-ascertainment of UL. Although we controlled for several individual- and neighborhood-level confounding variables, residual confounding remains a possibility., Wider Implications of the Findings: Inequitable burden of air pollution exposure has important implications for racial health disparities, and may be related to disparities in UL. Our results emphasize the need for additional research focused on environmental causes of UL., Study Funding/competing Interest(s): This research was funded by the National Cancer Institute (U01-CAA164974) and the National Institute of Environmental Health Sciences (R01-ES019573). L.A.W. is a fibroid consultant for AbbVie, Inc. and accepts in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com and Kindara.com for primary data collection in Pregnancy Study Online (PRESTO). M.J. declares consultancy fees from the Health Effects Institute (as a member of the review committee). The remaining authors declare they have no actual or potential competing financial interests., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the relationship between vitamin D deficiency and the risk of asymptomatic uterine fibroids (UFs)., Design: Cross-sectional study., Setting: University hospital., Patient(s): The present analysis recruited 133 asymptomatic patients with UFs and 80 normal control subjects from October 2017 to June 2020. Age matching created 61 pairs., Intervention(s): Medical history, transvaginal or transabdominal genital ultrasound scan, blood sampling, and measurement of vitamin D concentrations., Main Outcome Measure(s): Evaluation of the impact of vitamin D level on the risk of newly diagnosed asymptomatic UFs in premenopausal Han Chinese women., Result(s): Vitamin D levels of UF-positive patients were lower than those of healthy control subjects in unmatched samples (12.1 ng/mL vs. 16.8 ng/mL) and in matched samples (11.4 vs. 17.5 ng/mL). Younger patients (≤40 years) had a lower vitamin D level than older subjects in healthy control group (15.1 ng/mL vs. 19.0 ng/mL). We did not observe any age-vitamin D interactive effect in unmatched samples. Multivariate logistic regression revealed that asymptomatic patients presented a lower level of vitamin D than did normal groups in both unmatched and matched sample. In addition, the optimal threshold vitamin D level for having asymptomatic UFs was 14.34 ng/mL., Conclusion(s): Vitamin D deficiency may be associated with increased risk of asymptomatic UFs in premenopausal Han Chinese women., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Uterine myomas or fibroids are the most common benign female tumors of the reproductive organs, associated with significant morbidity and quality of life impairment. Several epidemiological risk factors for their occurrence have been identified so far, including nutrition and dietary habits. In this investigation, authors reviewed, as a narrative review, the data about diet and uterine myoma development in order to homogenize the current data. A PubMed search was conducted for the years 1990-2020, using a combination of keywords of interest for the selected topic. The authors searched the databases, selecting the randomized clinical studies, the observational studies, and the basic (experimental), clinical, and epidemiological researches. Once they collected the articles, they analyzed them according to the number of citations of each article, starting from the most cited to the least cited articles. Subsequently, authors collected the data of each article and inserted them in the various research paragraphs, summarizing the data collected. In this way, they crossed the available data regarding the association between nutrition habits and dietary components and myoma onset and growth. Many nutrients and dietary habits are associated with myoma development risk. These factors include low intakes of fruit, vegetables, and vitamin D, as well as pollutants in food. Despite the available data on the influence of some foods on the development of fibroids, further research is mandatory to understand all the nutrition risk factors which contribute to myoma growth and how exactly these risk factors influence myoma pathogenesis.

Uterine leiomyomata (UL) are associated with severe reproductive morbidity and are the primary indication for hysterectomy in the United States. A recent prospective cohort study of Black women reported positive associations between intakes of marine-sourced ω-3 fatty acids and UL risk. We examined whether intakes of dietary fat were associated with UL incidence in a 5-year prospective study of premenopausal Black women living in Detroit who underwent serial ultrasound. At baseline (2010-2012) and 20, 40, and 60 months of follow-up, participants underwent transvaginal ultrasound. Among 1,171 UL-free women at baseline, incident UL were detected in 277 women. Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of dietary fat and UL incidence. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and trans-fat were not appreciably associated with UL incidence. Intake of the marine ω-3 polyunsaturated fatty acid, docosahexaenoic acid, was associated with 49% higher UL incidence (quartile 4 vs. 1: hazard ratio = 1.49, 95% confidence interval: 1.04, 2.14; P for trend = 0.01). Intakes of total marine ω-3 polyunsaturated fatty acids were similarly associated with elevated UL incidence (hazard ratio = 1.35, 95% confidence interval: 0.94, 1.93; P for trend = 0.03). It remains unclear whether the fatty acids or persistent environmental pollutants drive the association., (© Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Electromechanical power morcellation is a widely used technique to extract uterine fibroids during laparoscopic hysterectomy. Although the complication rate of morcellators is low, ectopic leiomyoma can appear several years after their use. Patients and methods: We present a case of an ectopic leiomyoma and a literature review of power morcellation-induced complications and ectopic leiomyoma. Results: A 49-year-old female presented with epigastric pain 12 years after laparoscopic subtotal hysterectomy with morcellation of the specimen. Radiological examinations revealed an epigastric mass of 45 mm that was laparoscopically removed. Histological examination confirmed the diagnosis of an ectopic leiomyoma. Complications of power morcellation are rarely reported and include perioperative injuries to bowel, vascular and urinary tract, spreading of ectopic leiomyoma and occult malignancy. Conclusions: Ectopic leiomyoma are a late and rare complication of a laparoscopic hysterectomy with power morcellation of the uterus.

A cross sectional study was done at Era's Lucknow Medical College & Hospital, Lucknowwith the objective to evaluate 25-hydroxyVitaminD3 level in women with and without uterine fibroid. Ninety subjects (45 cases and 45 controls) were enrolled. Cases were those having at least 1 uterine fibroid ≥10 mm detected on ultrasonography, while controls were those not having any uterine pathology. Estimation of Serum 25-hydroxyvitaminD3 Level was done. The mean ± SD concentration of 25-hydroxyvitaminD3 was Significantly lower in cases compared with controls (15.10 ± 6.09 vs 26.09 ± 7.90 respectively, p < 0.001).The number of women with 25-hydroxyvitaminD3 deficiency in cases and controls was 9(20%) and 3(6.67%) respectively (p < 0.001). Uterine fibroid size increased proportionately with decrease in 25-hydroxyvitaminD3 levels, (p = 0.014). We concluded that VitaminD3 deficiency is significantly associated with the occurrence of Uterine fibroids. Further studies need to be conducted in order to evaluate the therapeutic benefits VitaminD3 supplementation in the patients of Uterine fibroid.Impact Statement what is already known on this subject? Vitamin D is believed to regulate cell proliferation and differentiation, inhibit angiogenesis and stimulate apoptosis. Now a days hypovitaminosis D is believed to be a major risk factor in the development of uterine fibroids. There are several ideas about the use of vitamin D in uterine fibroid prevention or as a long term treatment but ongoing clinical trials in the area remain scarce. what do the results of this study add? Our study showed that 25-hydroxivitamin d3 deficiency is significantly associated with uterine fibroid.Lower levels of 25-hydroxivitamin d3were found to have aninverse relationship with increased size of fibroid uterus. what are the implications of these findings for clinical practice and / or further reasearch? Vitamin D seems to be a promising, safe and low-cost agent for the prevention and treatment of uterine fibroids. However, further studies with larger sample size are needed to confirm our findings.

Although uterine leiomyomas are the most common benign uterine tumors in women, there is no effective therapy that can also preserve the uterus and maintain fertility. The work aimed to work was to discover a potential natural agent that has pharmacological activities on uterine leiomyomas with fewer adverse effects. We chose Rhus verniciflua Stokes (RVS) as a candidate after primary cytotoxicity testing, and analyzed the RVS components that showed pharmacological activity. Leiomyoma cells and myometrium cells were cultured from uterine tissues obtained from patients, and were treated with RVS at varying concentrations. RVS was cytotoxic in both leiomyoma and myometrium cells; however, the effects were more prominent in the leiomyoma cells. Among the bioactive components of RVS, fisetin showed significant pharmacological effects on leiomyoma cells. Fisetin showed excellent leiomyoma cell cytotoxicity and induced apoptotic cell death with cell cycle arrest. The apoptotic cell death appeared to involve not one specific pathway but multichannel pathways (intrinsic, extrinsic, MARK, and p53-mediated pathways), and autophagy. The multichannel apoptosis pathways were activated with a low concentration of fisetin (20 ) and were more vigorously activated at high concentrations (>IC 50 ). This is the first demonstration to show the pharmacological activities of fisetin on leiomyoma cells. These findings suggest that fisetin may be used for the prevention and treatment of uterine leiomyomas. Since fisetin can be obtained from plants, it may be a safe and effective alternative treatment for uterine leiomyomas.

Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. Their prevalence usually is estimated at 30-40%, but may reach up to 70-80% in predisposed groups of women. UFs may cause various clinical issues which might constitute the major reason of the overall deterioration of the quality of life. The mechanisms leading to UFs formation and growth still remain poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is thought to be a starting point of all pathways leading to UF formation. Micro-ribonucleic acids (miRNAs) are non-coding single-stranded RNAs about 22 nucleotides in length, that regulate gene expression. One of recent advances in this field is the comprehension of the role of miRNAs in tumorigenesis. Alterations in the levels of miRNAs are related to the formation and growth of several tumors which show a distinct miRNA signature. The aim of this review is to summarize the current data about the role of miRNAs in the pathophysiology of UFs. We also discuss future directions in the miRNA research area with an emphasis on novel diagnostic opportunities or patient-tailored therapies. In our opinion data concerning the regulation of miRNA and its gene targets in the UFs are still insufficient in comparison with gynecological malignancies. The potential translational use of miRNA and derived technologies in the clinical care is at the early phase and needs far more evidence. However, it is one of the main areas of interest for the future as the use of miRNAs in the diagnostics and treatment of UFs is a new and exciting opportunity.

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To determine whether or not the risk of recurrence of uterine leiomyoma (UL) was different between laparoscopic myomectomy (LM) and open myomectomy (OM)., Methods: This study combined a multicenter cohort study with a meta-analysis. The cohort study included women aged 18-44 years with 1-3 leiomyomas who underwent LM or OM for UL at one of three teaching hospitals. The meta-analysis included trials comparing recurrence rates of UL between OM and LM., Results: A total of 396 patients (LM: n = 83; OM: n = 313) were recruited in the cohort study. For women aged 18-44 years with 1-3 leiomyomas, surgical approach (LM vs. OM) was not an independent risk factor of UL recurrence (31.3% vs. 34.2%, P = 0.571), and the reoperation rate of UL was similar between the LM and OM (2.4% vs. 4.2%, P = 0.726). A total of 2566 patients were meta-analyzed. The recurrence of UL was similar between LM and OM when the patients had ≤ 5 leiomyomas (OR 1.10; 95% CI 0.76-1.61; P = 0.610; I 2  = 0%), while the recurrence rate in LM group was higher when the patients had > 5 leiomyomas (OR 1.50; 95% CI 1.14-1.97; P = 0.004; I 2  = 38%)., Conclusion: From the meta-analysis, the recurrence rate of UL was similar between LM and OM when the patients had ≤ 5 leiomyomas, while the recurrence of LM was higher when the number of leiomyomas was > 5. The cohort study partially supported this conclusion and it further proved the reoperation rate of UL was also similar among women aged 18-44 years with ≤ 3 leiomyomas. Therefore, OM should be considered for patients with > 3 or 5 leiomyomas if myomectomy has already been chosen.

Background: Uterine fibroids (UFs) are the most common benign tumors of the uterus with an unknown etiology, affecting many women of reproductive age. We aimed to evaluate the association between UFs and anthropometric features, subcutaneous and preperitoneal fat thickness and lipid profile., Methods: This is a case-control study conducted on 212 women who were available in the Al-Zahra specialized referral hospital from March 2018 to March 2019. Study variables including weight, height, waist and hip circumference were measured for all individuals. For patients with UFs, the size, number and location of fibroids were recorded. Also, subcutaneous and preperitoneal fat thicknesses were measured. Finally, the data were analyzed using the SPSS software ver.16.0., Results: The most common complaint was abnormal uterine bleeding (AUB) in both groups. Most of the patients had a body mass index (BMI) of 25-30. There were significant differences between the two groups in terms of age (P = 0.0001) and waist circumference (P = 0.011). Cholesterol levels were much higher in the case group. Only age and low-density lipoprotein-cholesterol (LDL-C) levels in the case group were positively related to developing UFs, such that with advancing aging and increasing levels of LDL-C, the likelihood of experiencing UFs rose by 10% and 1.1%, respectively. Also, there were no significant differences between the two groups regarding in either preperitoneal fat thickness (PFT) or subcutaneous fat thickness (SFT)., Conclusion: Our findings suggest that with aging and higher levels of LDL-C, the likelihood of developing UFs rises., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: Uterine leiomyoma (UL) can be considered as the most common benign gynecological tumors of the smooth muscle cells in the myometrium. They are likely to be associated with infertility and recurrent abortion as well as obstructed labor and post-partum hemorrhage. Moreover, altered vascular-related genes can be linked to developing leiomyoma. Polymorphisms of the angiotensin-converting enzyme (ACE) gene are associated with some vascular diseases. The present study was carried out to investigate the association of ACE I/D and AGTR1 A1166C gene polymorphisms and the risk of uterine leiomyoma in a sample of Iranian population. Methods: The study was carried out on a total of 413 women divided into 202 patients with diagnosed uterine leiomyomas and a control group of 211. Genotyping was performed using the PCR or PCR-RFLP methods. Results: The ID and DD genotypes of ACE I/D polymorphism were associated with 2 and 2.9 fold higher risk of UL compared to II genotype (OR, 2 [95% CI, 1.3 to 3.2]; P = 0.004 and OR, 2.9 [95% CI, 1.6 to 5]; P = 0.0002). The frequencies of ACE D alleles were 53.7% in women with UL and 40.3% in controls, which were observed to be statistically different (P < 0.0001). The alleles and genotypes of AGTR1 A1166C polymorphism were not different between UL and control women (P=0.9). Conclusion: The ACE ID and DD genotypes were associated with a higher risk of UL. No relationship was found between AGTR1 A1166C polymorphism and UL.

Despite the major negative impact uterine fibroids (UFs) have on female reproductive health, little is known about early events that initiate development of these tumors. Somatic fibroid-causing mutations in mediator complex subunit 12 (MED12), the most frequent genetic alterations in UFs (up to 85% of tumors), are implicated in transforming normal myometrial stem cells (MSCs) into tumor-forming cells, though the underlying mechanism(s) leading to these mutations remains unknown. It is well accepted that defective DNA repair increases the risk of acquiring tumor-driving mutations, though defects in DNA repair have not been explored in UF tumorigenesis. In the Eker rat UF model, a germline mutation in the Tsc2 tumor suppressor gene predisposes to UFs, which arise due to "second hits" in the normal allele of this gene. Risk for developing these tumors is significantly increased by early-life exposure to endocrine-disrupting chemicals (EDCs), suggesting increased UF penetrance is modulated by early drivers for these tumors. We analyzed DNA repair capacity using analyses of related gene and protein expression and DNA repair function in MSCs from adult rats exposed during uterine development to the model EDC diethylstilbestrol. Adult MSCs isolated from developmentally exposed rats demonstrated decreased DNA end-joining ability, higher levels of DNA damage, and impaired ability to repair DNA double-strand breaks relative to MSCs from age-matched, vehicle-exposed rats. These data suggest that early-life developmental EDC exposure alters these MSCs' ability to repair and reverse DNA damage, providing a driver for acquisition of mutations that may promote the development of these tumors in adult life.

Uterine leiomyomas are common and life-altering for many women. Despite a wide range of symptoms, varying characteristics of the uterus and the leiomyomas themselves, and many alternatives, hysterectomy accounts for almost three fourths of all surgical therapy, yet there is increasing evidence for a variety of procedural therapies for symptomatic leiomyomas and a new generation of medical therapies under development. With increasing evidence of long-term risk from hysterectomy and new data regarding leiomyoma biology, individualized medical approaches to leiomyomas are likely in the near future. Key biological attributes that influence this disease process are common driver mutations and the new appreciation of the interaction of smooth muscle cells and fibroblasts. Additionally, the interaction between cell types and steroid hormone responsiveness likely plays a role in pathogenesis that can be leveraged in individualized therapy. However, given the independent clonal nature of leiomyomas within the same uterus, moving in the direction of biopsies for individual leiomyomas to understand the biology is unlikely to be fruitful. Use of advanced imaging will likely continue to evolve not only to accurately predict malignant disease, including sarcomas, but to predict leiomyoma subtypes, response to therapy, or both. We predict the continued evolution of therapy from excisional or interventional therapies to medical therapies and ultimately prediction of at-risk individuals. Ideally, individualized therapies will offer primary prevention for women at high risk of leiomyomas and secondary prevention after initial treatment.

This study aims to retrospectively analyze the potential risk factors for uterine leiomyoma and prospectively examine whether these risk factors can increase the incidence of uterine leiomyoma.Women who attended our outpatient department from January 1, 2010 to December 31, 2010 were enrolled. General demographical characteristics, personal information, and living habits were collected. Univariate and multivariate logistic regression analyses were used to identify the potential risk factors. Follow-up was regularly conducted to complete the prospective analysis.A total of 1273 women were enrolled including 213 uterine leiomyomas (case group) and 1060 nonuterine leiomyoma women (control group). No statistical differences were found on the age, marital status, number and complication of pregnancy, frequent physical exercise, frequent alcohol consumption, and family history of uterine diseases between two groups (all P > .05). Mean body mass index (P = .043), high school education (P = .041), frequent smoking (P = .030), frequent caffeine consumption (P = .019), frequent milk or soybean consumption (P = .025), and frequent oral contraceptive use (P = .034) were statistically correlated with the onset of uterine leiomyoma. Multivariate analysis verified that frequent milk or soybean consumption (7.349 [5.081-9.454]; P = .039] and frequent oral contraceptive use (8.103 [4.486-12.583]; P = .018] were the independent risk factors for uterine leiomyoma.Frequent milk or soybean consumption and frequent oral contraceptive use are associated with a high risk of uterine leiomyoma, and proper education on the prevention of uterine leiomyoma is highly recommended in clinical practice.

Objectives: Uterine myomas (UM) are responsible for significant morbidity and have adverse effects on quality of life in women. Reactive oxygen species (ROS) and antioxidant enzymes (AOE), as well as sex steroids play important roles in the reproductive physiology processes. Thus, we aimed to investigate the role of oxidant-antioxidant status in UM by measuring the AOE activities and lipid peroxidation (LPO) levels. This is the first study assessing these parameters together in UM based on also menopausal status and evaluating possible correlations between AOE activities, LPO markers, tumor biomarkers, female reproductive system hormone levels, comprehensively., Study Design: The study group consisted of patients who have undergone surgical resection with confirmed pathology of uterine myoma (UM, n = 25) and divided into subgroups; premenopausal (UM pre ) and postmenopausal (UM post ). Erythrocyte copper-zinc superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx1) activities were measured along with plasma malondialdehyde (MDA) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) levels in patients with UM. The obtained data were compared to the data of healthy individuals (C, n = 25) and its subgroups; premenopausal (C pre ) and postmenopausal (C post )., Results: All AOE activities were higher (∼40% for Cu,Zn-SOD, p = 0.003; ∼55% for CAT, p = 0.001; ∼15% for GPx1, p = 0.169) and the LPO levels were lower (∼60% for MDA, p = 0.011 and ∼45% for 8-epi-PGF2α, p = 0.055) in patients with UM vs control. Approximately similar alterations were observed in UM pre vs C pre and in UM post vs C post. A significant negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels (r = -0.431, p = 0.005) was reported., Conclusion: Decreased LPO levels might be the consequence of compensator high antioxidant enzyme activities against mild oxidative stress in the circulation of patients with UM. The marked negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels also supported this finding., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To evaluate individual characteristics of women with fibroids in relation to fibroid size and number., Methods: This cross-sectional study involved 2302 women (black and white, age range 18-87) with image- or surgery-confirmed fibroids from the Synthetic Derivative, a database of de-identified demographic and clinical information from patient electronic health records (EHRs) from the Vanderbilt University Medical Center. We performed multivariate regression analyses on the following outcomes: volume of largest fibroid, largest dimension of all fibroids, and number of fibroids (single vs multiple). Candidate risk factors included age at diagnosis, body mass index (BMI), race, type 2 diabetes status, and number of living children (a proxy for parity). We assessed potential effect measure modification by race and both age and BMI using a likelihood ratio test., Results: Black race was strongly associated with having multiple fibroids (adjusted odds ratio [aOR]: 1.83, 95% confidence interval [CI]: 1.49, 2.24) and larger fibroid volume (adjusted beta: 1.77, 95% CI: 1.38, 2.27) and greater largest dimension (adjusted beta: 1.28, 95% CI: 1.18, 1.38). Having multiple fibroids was most strongly associated with ages 43-47 (aOR = 3.37, 95% CI: 2.55, 4.46) compared with the youngest age group (ages 18-36). Having a larger number of living children was associated with having single a fibroid (aOR: 0.88, 95% CI: 0.78, 0.99)., Conclusions: Our findings suggest that different underlying etiologies are involved for women developing single versus multiple fibroids and small versus large fibroids. Studies are needed of the mechanisms by which these characteristics influence fibroid formation and growth., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Uterine fibroids remain a burning issue for modern gynecology and cause suffering to women, significantly worsening their quality of life. This article includes the latest information about etiology, risk factors, pathobiochemical, genetic and immunological features of pathogenesis, clinical findings, early detection of fibroids and sarcoma differential diagnostic criteria by ultrasonography and MRI. Foreign publications form the basis of the given article, as well as domestic ones.

Risk factors, both modifiable and non-modifiable, are associated with the development of fibroids. These include age, race, endogenous and exogenous hormonal factors, obesity, uterine infection, and lifestyle (diet, caffeine and alcohol consumption, physical activity, stress, and smoking). Some of the epidemiological data were conflicting; consequently, further studies are needed to better understand the factors that influence fibroid prevalence., (Copyright © 2017. Published by Elsevier Ltd.)

Uterine telocytes are interstitial cells characterized by a very long cytoplasmic prolongations, which form a 3D network, functionally integrating a wide variety of different cells. Leiomyomas (uterine fibroids) are benign tumors, which pose a huge threat concerning various health problems in women affected by this condition. The exact cause of leiomyomas development is, however, still largely unknown. Therefore, in an attempt to clarify their etiology, we performed an immunohistochemical characterization of telocytes in leiomyomas as well as in normal myometrium. Tissue samples of intramural leiomyomas from 26 women (age 46.26 ± 11.07) were immunohistochemically stained for the expression of c-kit (CD117) antigen, one of the markers of telocytes. C-kit (CD117) antigen is useful for a routine immunohistochemical identification of uterine telocytes in histological sections of myometrium. In normal, healthy myometrium the c-kit positive telocytes occupy approximately 2.2% of the area of a tissue slide, contrasting with no detectable c-kit positive cells within leiomyomas. As telocytes are thought to be key players in the regulation of tissue homoeostasis, our data suggest that uterine telocyte loss may have important implications in the pathogenesis of leiomyomas. In addition, we supposed to summarize three hypotheses on the association of the cells telocytes loss within the myometrium and formation of leiomyomas. These hypotheses include the loss of telocytes' functions as "sex hormone sensors" and regulators of smooth muscle cells cycle; the role of telocytes as progenitor cells for the development of leiomyomas; and the hypothesis of decreased angiogenesis after telocytes' loss with subsequent hypoxia (as a key factor for leiomyomas development)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Uterine fibroids (UFs) are the most common neoplasm affecting women that can cause significant morbidity and may adversely impact fertility., Objectives: To examine UF epidemiology and to evaluate the relative strengths of putative risk factors., Search Strategy: MEDLINE and Embase were searched for studies published in English between January 1995 and April 2015., Selection Criteria: Publications reporting relevant data from registries and other observational studies with over 1000 patients and single-centre studies with over 100 patients were selected., Data Collection and Analysis: Data on UF incidence, prevalence and associated risk factors were extracted from 60 publications., Main Results: Wide ranges were reported in both UF incidence (217-3745 cases per 100 000 women-years) and prevalence (4.5-68.6%), depending on study populations and diagnostic methods. Black race was the only factor that was recurrently reported to increase UF risk, by two-threefold compared with white race. Eleven other factors affected UF risk to a magnitude similar to or greater than race. Age, premenopausal state, hypertension, family history, time since last birth, and food additive and soybean milk consumption increased UF risk; use of oral contraceptives or the injectable contraceptive depot medroxyprogesterone acetate, smoking in women with low body mass index and parity reduced UF risk., Conclusions: We identified 12 risk factors that play an important role in UF epidemiology. The UF risk factor with the strongest evidence is black race. High-quality prospective observational data are needed to improve our understanding of UF epidemiology, and thus its aetiology and optimal management., Tweetable Abstract: Uterine fibroids occur in about 70% of women. Black race and 11 other factors affect uterine fibroid risk., (© 2017 IPAS. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Uterine fibroids are the most common neoplasm of the genital tract in reproductive women. Obesity holds a role as risk factor for uterine fibroids, through hormonal and inflammatory mechanisms. Visceral fat is a hormonally active tissue, so an increase in visceral fat may be considered as a risk factor, through the increased production of inflammatory mediators. The aim of the study was, therefore, to evaluate the association between the presence of uterine fibroids and fat tissue distribution, and to assess the efficacy of both anthropometric and instrumental indicators, in particular the sonographic measurement of preperitoneal fat thickness (PFT) and subcutaneous fat thickness (SFT). Study group consisted of childbearing-age women with at least one uterine fibroid with a diameter ≥10 mm (n = 71), all the childbearing-age women who access to the outpatient service of our institution in the same period, without evidence of uterine fibroids, constituted the control group (n = 145). A significantly difference in BMI (p = 0.0034), PFT (p < 0.0001), and SFT (p = 0.0003) emerged. At the multivariate analysis, only PFT showed an independent significant association with the presence of uterine fibroids (p < 0.0001). The ROC curve analysis identified a cut-off value of 6.7 mm of PFT as discriminator for the presence of uterine fibroids.

Uterine leiomyomas have drawn much attention since being described more than 200 years ago. These common benign uterine tumors often present with prolonged menstrual bleeding, pelvic pressure, and reproductive disorders and pose a true financial burden on health care systems all over the world. Over the past few decades, surgical treatment of uterine leiomyomas has received most of the focus compared with other treatment options. Choosing the appropriate surgical technique depends on many factors such as uterine leiomyoma location, patient's age, interest in future fertility, concomitant comorbidities, and the patient's preference. Pharmacologic treatments such as gonadotropin-releasing hormone agonists and antagonists have been used for the treatment of symptomatic uterine leiomyomas with only partial success. Myriad side effects and limited clinical results have rendered them less popular and have exposed a true need for new effective medical treatments. Recently, treatment with selective progesterone receptor modulators has shown promising results with shrinkage of uterine leiomyomas and a prolonged clinical effect. Selective progesterone receptor modulators provide hope for women with this challenging condition and are a promising new option in the armamentarium of medical treatments for uterine leiomyomas.

Background: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease., Objective: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution., Method: We examined the clinical manifestations and immunological workup of these patients. Their DNA was also screened for causative mutation. Post transplantation, clinical and immunological data for the transplanted patient was also collected., Results: All patients had a severe course of the disease with rarely reported severe complications in HIES. One patient died with lymphoma while another died with progressive multifocal leukoencephalopathy (PML) due to a slow virus. All our patients had two novel mutations in the DOCK8 gene. One of these mutations was a novel pathogenic mutation and explains the severity of the disease (homozygous splice site mutation at position 5 after the end of exon 45), while the other mutation was mostly non-pathogenic. Hematopoietic stem cell transplantation (HSCT) was performed in the youngest patient with excellent engraftment and full reversibility of the clinical manifestations., Conclusion: We report 3 patients from a consanguineous family diagnosed with AR-HIES due to a novel pathogenic mutation in DOCK8 gene leading to fatal outcome in 2 patients and complete resolution of the clinical and immunological features in the third patient by HSCT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Uterine fibroids, also known as uterine leiomyoma (UL), are monoclonal tumors of the smooth muscle tissue layer (myometrium) of the uterus. Although ULs are considered benign, uterine fibroids are the source of major quality-of-life issues for approximately 25% of all women, who suffer from clinically significant symptoms of UL. Despite the prevalence of UL, there is no treatment option for UL which is long term, cost-effective, and leaves fertility intact. The lack of understanding about the etiology of UL contributes to the scarcity of medical therapies available. Studies have identified an important role for sex steroid hormones in the pathogenesis of UL, and have driven the use of hormonal treatment for fibroids, with mixed results. Dysregulation of cell signaling pathways, miRNA expression, and cytogenetic abnormalities have also been implicated in UL etiology. Recent discoveries on the etiology of UL and the development of relevant genetically modified rodent models of UL have started to revitalize UL research. This review outlines the major characteristics of fibroids; major contributors to UL etiology, including steroid hormones; and available preclinical animal models for UL., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Uterine fibroids, or leiomyoma, are the most common benign tumors in women of reproductive age. In this work, the effect of silencing the mediator complex subunit 12 (Med12) gene in human uterine fibroid cells was evaluated. The role of Med12 in the modulation of Wnt/β-catenin and cell proliferation-associated signaling was evaluated in human uterine fibroid cells. Med12 was silenced in the immortalized human uterine fibroid cell line (HuLM) using a lentivirus-based Med12 gene-specific RNA interference strategy. HuLM cells were infected with lentiviruses carrying Med12-specific short hairpin RNA (shRNA) sequences or a nonfunctional shRNA scrambled control with green fluorescence protein. Stable cells that expressed low levels of Med12 protein were characterized. Wnt/β-catenin signaling, sex steroid receptor signaling, cell cycle-associated, and fibrosis-associated proteins were measured. Med12 knockdown cells showed significantly (P < 0.05) reduced levels of Wnt4 and β-catenin proteins as well as cell proliferation, as compared with scrambled control cells. Med12 knockdown cells also showed reduced levels of cell cycle-associated cyclin D1, Cdk1, and Cdk2 proteins as well as reduced activation of p-extracellular signal-regulated kinase, p-protein kinase B, and transforming growth factor (TGF)-β signaling pathways as compared with scrambled control cells. Moreover, TGF-β-regulated fibrosis-related proteins such as fibronectin, collagen type 1, and plasminogen activator inhibitor-1 were significantly (P < 0.05) reduced in Med12 knockdown cells as compared with scrambled control cells. Together, these results suggest that Med12 plays a key role in the regulation of HuLM cell proliferation through the modulation of Wnt/β-catenin, cell cycle-associated, and fibrosis-associated protein expression., (Copyright © 2017 by the Endocrine Society.)

Objective: To evaluate the influence of 25-hydroxyvitamin D and transforming growth factor β3 (TGF-β3) serum concentrations, weight, and family history on the risk of developing uterine fibroids., Design: Retrospective cohort study., Setting: University hospital., Patient(s): A total of 188 women, including patients admitted for uterine fibroid surgery (n = 105) as the study group and healthy women of similar age (n = 83) as controls., Intervention(s): Medical history and completion of specially designed questionnaire, transvaginal or transabdominal genital ultrasound scan, blood sampling, and measurement of vitamin D and TGF-β3 serum concentrations., Main Outcome Measure(s): Evaluation of the impact of family history, vitamin D, and TGF-β3 serum concentrations on the risk of developing uterine fibroids., Result(s): Mean 25-hydroxyvitamin D serum concentrations were 21.9 ± 8.9 ng/mL and 26.7 ± 11.9 ng/mL in patients with uterine fibroids and controls, respectively. The difference was statistically significant. The TGF-β3 serum concentrations in the fibroid-positive group ranged from 1.20 to 436.15 pg/mL (half the patients had concentrations >16.25 pg/mL). Concentrations in the control group ranged from 0.96 to 49.08 pg/mL (half the women had concentrations of >11.80 pg/mL). The differences were statistically significant. Higher body mass index (BMI) and positive family history were also found to be among the risk factors for uterine fibroids., Conclusion(s): Our study confirmed higher BMI, positive family history, and lower vitamin D and higher TGF-β3 serum concentrations as risk factors for uterine fibroids., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effect of vitamin D supplementation in women with hypovitaminosis D and "small burden" uterine fibroids.This study focused on 208 women diagnosed with uterine fibroids and concomitant hypovitaminosis D, from January to December 2014. One hundred eight women of the initial study population were diagnosed with "small burden" uterine fibroids. Among them, those who underwent a proper vitamin D supplementation constituted the "study group" (n = 53), while women who spontaneously refused the therapy or did not perform it properly, constituted the "control group" (n = 55). The characteristics of uterine fibroids, the fibroid-related symptoms, and the vitamin D serum levels were evaluated 12 months after the initial diagnosis.In women with uterine fibroids, a negative correlation emerged between the baseline 25-hydroxy-cholecalciferol (25-OH-D3) concentration and both the volume of the largest fibroid (r = -0.18, P = 0.01) and the total volume of fibroids (r = -0.19, P = 0.01). No correlation was found between the baseline 25-OH-D3 levels and the number of fibroids per patient (r = -0.10, P = 0.16). In women of the "study group," a significant increase in the 25-OH-D3 serum level was observed after 12 months of supplementation, and a lower rate of surgical or medical treatment due to the "progression to extensive disease" was reported (13.2% vs 30.9%, P = 0.05).Supplementation therapy with 25-OH-D3 restores normal vitamin D serum levels in women with "small burden" fibroids. In these women, vitamin D supplementation seems to reduce the progression to an extensive disease, and thus the need of conventional surgical or medical therapy., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Background: Iatrogenic parasitic myomas (PMs), caused by intra-corporeal power morcellation during laparoscopy is gradually increasing. However, the pathogenesis and medical treatment of PMs remain largely unelucidated., Methods: Laparoscopically-induced PM xenografted mouse model was conducted by xenografting human uterine myoma fragments into the abdominal cavity of SCID mice and hormonal manipulation was performed using this mouse model to demonstrate the role of oestrogen in the development of implanted PMs. Immunohistochemistry of oestrogen receptor α (ERα), progesterone receptor (PR), vimentin, vascular endothelial growth factor (VEGF), microvessel density (MVD) and Ki-67 index was performed and compared., Results: In the patient with PMs, ERα, PR, angiogenesis and proliferative property expression were upregulated in PM lesions compared to uterine myomas. In the laparoscopically-induced PM mouse model, implanted myomas had more steroid receptor expressions, angiogenesis and proliferative property compared with pre-xenografted or non-implanted myoma. Depletion of oestrogen in the ovariectomized (OVX) mice decreased laparoscopically-induced PM implantations. In comparison, the implantations of PMs were increased with additional E2 supplement. Hormonal manipulation in the PM mouse model, including AI, GnRHa and SERM groups, were compared and AI significantly decreased the implantations, steroid receptor, angiogenesis, cell density, and proliferative index of PMs compared with control group. Furthermore, GnRHa significantly decreased VEGF and MVD expressions compared with control group., Conclusions: These data highlight the crucial role of oestrogen in the development of laparoscopically-induced PMs and suggest that hormone manipulation may be a potential therapeutic agent., Trial Registration: This protocol was approved by the Human and Animal Institutional Review Board of Taipei Veterans General Hospital ( VGHIRB No 2014-10-002C on Nov. 17 th , 2014; IACUC 2014-119 on Aug. 22 nd , 2014).

Uterine leiomyoma (UL) is a monoclonal tumor which arises from uninhibited proliferation of a single myometrial cell; therefore, the imbalance in cell cycle regulation could be a key event in its development. In the present study, we aimed to assess the association of p21 gene polymorphisms and UL. Genomic DNA was extracted from blood samples of 154 women with UL and 197 age-, BMI-, and ethnically matched controls. p21 C98A (rs1801270) and C70T (rs1059234) polymorphism genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The CA genotype of p21 C98A polymorphism was significantly higher in UL women (28 %) compared to the controls (18 %), and the UL risk was 1.8-fold greater in women with CA genotype compared to CC genotype before and after adjusting for age, BMI, and ethnicity (OR, 1.8 [95 % CI, 1.1 to 3]; P = 0.02). There was no association between the AA genotype of p21 C98A polymorphism and UL. Moreover, the frequency of p21 98A allele was significantly higher in the UL women compared to controls (17 vs. 12 %, p = 0.04). The p21 C70T polymorphism did not correlate with UL before and after adjusting for age, BMI, and ethnicity. There was no difference in haplotype frequency of p21 C70T and C98A polymorphisms between UL patients and the controls. CA genotype of p21 C98A polymorphism may be a risk factor for UL susceptibility; however, p21 C70T polymorphism did not associate with UL.