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      Uterine fibroid management: from the present to the future

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          Abstract

          Uterine fibroids (also known as leiomyomas or myomas) are the most common form of benign uterine tumors. Clinical presentations include abnormal bleeding, pelvic masses, pelvic pain, infertility, bulk symptoms and obstetric complications.

          Almost a third of women with leiomyomas will request treatment due to symptoms. Current management strategies mainly involve surgical interventions, but the choice of treatment is guided by patient's age and desire to preserve fertility or avoid ‘radical’ surgery such as hysterectomy. The management of uterine fibroids also depends on the number, size and location of the fibroids. Other surgical and non-surgical approaches include myomectomy by hysteroscopy, myomectomy by laparotomy or laparoscopy, uterine artery embolization and interventions performed under radiologic or ultrasound guidance to induce thermal ablation of the uterine fibroids.

          There are only a few randomized trials comparing various therapies for fibroids. Further investigations are required as there is a lack of concrete evidence of effectiveness and areas of uncertainty surrounding correct management according to symptoms. The economic impact of uterine fibroid management is significant and it is imperative that new treatments be developed to provide alternatives to surgical intervention.

          There is growing evidence of the crucial role of progesterone pathways in the pathophysiology of uterine fibroids due to the use of selective progesterone receptor modulators (SPRMs) such as ulipristal acetate (UPA). The efficacy of long-term intermittent use of UPA was recently demonstrated by randomized controlled studies.

          The need for alternatives to surgical intervention is very real, especially for women seeking to preserve their fertility. These options now exist, with SPRMs which are proven to treat fibroid symptoms effectively. Gynecologists now have new tools in their armamentarium, opening up novel strategies for the management of uterine fibroids.

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          Most cited references203

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          Uterine fibroids.

          E Stewart (2001)
          Uterine leiomyomas (fibroids or myomas), benign tumours of the human uterus, are the single most common indication for hysterectomy. They are clinically apparent in up to 25% of women and cause significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pressure or pain, and, in rare cases, reproductive dysfunction. Thus, both the economic cost and the effect on quality of life are substantial. Surgery has been the mainstay of fibroid treatment, and various minimally invasive procedures have been developed in addition to hysterectomy and abdominal myomectomy. Formation of new leiomyomas after these conservative therapies remains a substantial problem. Although medications that manipulate concentrations of steroid hormones are effective, side-effects limit long-term use. A better approach may be manipulation of the steroid-hormone environment with specific hormone antagonists. There has been little evidence-based evaluation of therapy. New research into the basic biology of these neoplasms may add new treatment options for the future as the role of growth factors and genetic mutations in these tumours are better understood.
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            MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas.

            Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and that can cause considerable morbidity. To study the genetic basis of this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing and identified tumor-specific mutations in the mediator complex subunit 12 (MED12) gene in 10. Through analysis of 207 additional tumors, we determined that MED12 is altered in 70% (159 of 225) of tumors from a total of 80 patients. The Mediator complex is a 26-subunit transcriptional regulator that bridges DNA regulatory sequences to the RNA polymerase II initiation complex. All mutations resided in exon 2, suggesting that aberrant function of this region of MED12 contributes to tumorigenesis.
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              Assessment of menstrual blood loss using a pictorial chart.

              Objective menstrual blood loss measurements (in ml) were compared with the score obtained from a pictorial blood loss assessment chart (PBAC) which took into account the degree to which each item of sanitary protection was soiled with blood as well as the total number of pads or tampons used. Twenty eight women used the chart during 55 menstrual cycles and a single observer assessed 122 cycle collections in a similar manner. A pictorial chart score of 100 or more, when used as a diagnostic test for menorrhagia, was found to have a specificity and sensitivity of greater than 80%. Demonstration of the relation between self assessed pictorial chart scores and the objective measurement of blood loss enables us to provide a simple, cheap and reasonably accurate method of assessing blood loss before embarking upon treatment.
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                Author and article information

                Journal
                Hum Reprod Update
                Hum. Reprod. Update
                humupd
                Human Reproduction Update
                Oxford University Press
                1355-4786
                1460-2369
                November 2016
                20 October 2016
                20 October 2016
                : 22
                : 6
                : 665-686
                Affiliations
                [1 ] Professor EM, Catholic University of Louvain , Director, Société de Recherche pour l'Infertilité (SRI), 143 Avenue Grandchamp, B-1150 Brussels, Belgium
                [2 ] Gynecology Department, Cliniques Universitaires St-Luc , Avenue Hippocrate 10, 1200 Brussels, Belgium; Pôle de Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Avenue Mounier 52, bte B1.52.02, 1200 Brussels, Belgium
                Author notes
                [* ]Correspondence address. E-mail: jacques.donnez@ 123456gmail.com
                Article
                dmw023
                10.1093/humupd/dmw023
                5853598
                27466209
                55e49c9a-8a2b-4013-ab88-03a0085add1e
                © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

                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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited

                History
                : 02 February 2016
                : 12 May 2016
                : 27 May 2016
                Categories
                Grand Theme Review
                Custom metadata
                November/December 2016

                Human biology
                uterine fibroids,leiomyomas,selective progesterone receptor modulators,ulipristal acetate,surgery,medical therapy,myomectomy

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