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      The Impact of Adenomyosis on Women's Fertility

      research-article
      , MD, PhD, DMSci * , , MB, BS , , MD, PhD , , MD § , , MD, PhD , , MD, PhD
      Obstetrical & Gynecological Survey
      Lippincott Williams & Wilkins

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          Abstract

          Until recently, adenomyosis has been associated with multiparity, not impaired fertility. Currently, adenomyosis is diagnosed with increasing frequency in infertile patients since women delay their first pregnancy until their late 30s or early 40s. Although an association between adenomyosis and infertility has not been fully established, based on the available information, recent studies suggested that adenomyosis has a negative impact on female fertility. Several uncontrolled studies with limited data also suggested that treatment of adenomyosis may improve fertility. This article discusses (i) the hypothesis and epidemiology of adenomyosis, (ii) diagnostic techniques, (iii) clinical evidence of correlation between adenomyosis and infertility, (iv) proposed mechanism of infertility in women with adenomyosis, (v) different treatment strategies and reproductive outcomes, and (vi) assisted reproductive technology outcome in women with adenomyosis.

          Target Audience

          Obstetricians and gynecologists, family physicians.

          Learning Objectives

          After completing this activity, the learner should be better able to: Recall the hypothesis and epidemiology of adenomyosis; Evaluate the important findings on improved imaging techniques to diagnose adenomyosis; Understand that the presence of adenomyosis may impair the reproductive outcomes in women with adenomyosis; Explain the proposed mechanism of infertility in women with adenomyosis; Give the most appropriate treatment for better reproductive outcomes in women with adenomyosis; and Advise patients that surgery could be effective in women with adenomyosis with a history of IVF failure although latter finding could be partly attributed to the higher rate of early miscarriage.

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          Most cited references90

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          Adenomyosis: epidemiological factors.

          Epidemiological studies of adenomyosis are difficult to interpret because the diagnostic criteria vary so widely that the disease may be easily over-diagnosed. This would severely hamper any attempt to define incidence and prevalence of the condition and the related risk factors, and would limit the possibility of clarifying to what extent adenomyosis contributes to clinical symptoms. There is a need for stringent and widely accepted diagnostic criteria in order to define not only the presence of adenomyosis but also depth of penetration and degree of spread of foci. Moreover, the evidence available on epidemiological characteristics of women with adenomyosis is greatly biased by the type of population studied, i.e. women undergoing hysterectomy. Therefore, a consensus on non-surgical diagnostic criteria at transvaginal ultrasonography and MRI is indispensable and urgently needed in order to be able to conduct epidemiological studies in women younger than those evaluated until now.
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            The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy.

            Vaginal ultrasonography of uterine peristalsis during the follicular phase of the menstrual cycle demonstrates an increasing frequency and intensity of subendometrial and myometrial peristaltic waves as the follicular phase progresses. During this time the numbers of contraction waves with a fundo-cervical direction decrease considerably in favour of waves of contraction with a cervico-fundal direction. There is evidence that rapid sperm transport through the female genital tract is passive and is provided by these uterine contractions. Using hysterosalpingoscintigraphy, rapid sperm transport was studied by placing technetium-labelled albumin macrospheres of sperm size at the external os of the uterine cervix and following their path through the female genital tract. Ascension of the macrospheres occurred immediately following deposition at the external os of the cervix. As early as 1 min thereafter, the macrospheres had reached the intramural and isthmical part of the tube. Quantitatively, the extent of ascension increased with progression of the follicular phase. While only a few macrospheres entered the uterine cavity and even fewer the tubes during the early follicular phase, the proportion of macrospheres that entered the uterine cavity increased dramatically during the mid-follicular phase despite continuing limited entry into the tube. During the late follicular phase there was considerable ascension of the macrospheres which was directed preferentially into the tube ipsilateral to the dominant follicle. These data indicate that rapid transport of the spermatozoa through the female genital tract is under the endocrine control of the dominant follicle, ensuring the preferential accumulation of spermatozoa at the site of fertilization.
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              Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium.

              To determine whether local estrogen production takes place in endometriotic or adenomyotic tissues, in eutopic endometrium from patients with endometriosis or adenomyosis, and in normal endometrium, tissue specimens were examined by immunohistochemistry, catalytic activity, and mRNA expression for aromatase cytochrome P450 (P450arom). P450arom was immunohistochemically localized in the cytoplasm of glandular cells of endometriotic and adenomyotic tissues, and of eutopic endometrium from patients with the respective diseases, whereas estrogen receptors and progesterone receptors were localized in the nuclei of the glandular cells and stroma. Aromatase activity in the microsomal fraction of adenomyotic tissues was inhibited by the addition of danazol, aromatase inhibitors, and anti-human placental P450arom monoclonal antibody (mAb3-2C2) in a manner similar to such inhibition in other human tissues. Reverse transcription polymerase chain reaction and Southern blot analysis also revealed P450arom mRNA in these tissues. However, neither P450arom protein activity nor mRNA was detected in endometrial specimens obtained from normal menstruating women with cervical carcinoma in situ but without any other gynecological disease. These results suggest that at a local level, endometriotic and adenomyotic tissues produce estrogens, which may be involved in the tissue growth through interacting with the estrogen receptor.
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                Author and article information

                Journal
                Obstet Gynecol Surv
                Obstet Gynecol Surv
                OGX
                Obstetrical & Gynecological Survey
                Lippincott Williams & Wilkins
                0029-7828
                1533-9866
                September 2016
                12 September 2016
                : 71
                : 9
                : 557-568
                Affiliations
                [1]*Professor and †Postgraduate Student, Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Tottori, Japan; ‡Associate Professor, §Training Doctor, and ∥Professor, Department of Obstetrics and Gynecology, Patras University School of Medicine, Patra, Greece; and ¶Associate Professor, Department of Obstetrics and Gynecology, Tottori University, Faculty of Medicine, Tottori, Japan
                Author notes
                Correspondence requests to: Tasuku Harada, MD, PhD, DMSci, Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, 36-1 Nishicho, Yonago, Tottori, 683-8504, Japan. E-mail: tasuku@ 123456med.tottori-u.ac.jp .
                Article
                OGX50116 00020
                10.1097/OGX.0000000000000346
                5049976
                27640610
                9e44b80b-32a8-4c5a-8b38-57f5f5e873f2
                Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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