The role of hysteroscopy in the diagnosis and treatment of Adenomyosis Keith Isaacson, MD Associate Professor Ob/Gyn Harvard Medical School Adenomyosis • Endometrial glands and stroma present with uterine musculature • Can be focal or diffuse • Incidence 20-30% at time of hysterectomy Etiology Theories • Invagination of basalis endometrium – Loss of tissue cohesion – Tissue trauma  injury endometrial lining – Aberrant immune phenomenon • Stimulation of migratory tissue – High expression of estrogen receptor • De Novo synthesis of ectopic endometrium within the myometrium Bergon. Pathology and physiology of adenomyosis. Best Pract & Research Clin Obstet & Gyn. Ferenczy. Pathophysiology of adenomyosis. Human Reproduction Update 1998 Etiology Theories • Lymphatic Spread • Stem cell theory – Endometrial regeneration after bone marrow transplant Du H, Taylor H. Stem Cell and female reproduction. Reprod Sci 2009 Sasson I, Taylor. Stem Cells and the Pathogenesis of Endometriosis. Ann. N.Y Acad Sci 2008 Pathophysiology • Is Adenomyosis the same as endometriosis? • What leads to the clinical presentation? – Menorrhagia – Dysmenorrhea – Infertility? Descriptive pathophysiology • Biological properties – Extrauterine sites • induction of apoptosis vs. constant proliferation – Reduction in Bcl-2 gene expression • Different hormonal effects: rare secretory phase – Progesterone resistance – Growth factors and cytokines • BFgf, VEGF, macrophages Matsumoto. Apoptosis and Ki-67 expression in adenomyotic lesions and in the corresponding eutopic endometrium. Obstet Gynecol 1999 Ota. Is adenomyosis an immune disease? Hum Repro Update. 1998 Propst. Adenomyosis demonstrates increased expression of the basic fibroblast growth factor receptor/ligand system compared with autologous endometrium. Menopause 2001 Diagnosis HISTOLOGICIAL HYSTEROSCOPY RADIOLOGICAL IMAGING Histological Diagnosis • • • • Ectopic endometrial tissue in myometrium Smooth muscle cell hyperplasia Posterior wall Circumscribed nodular aggregates – 2% endometrial polyps Azzi R. Adenomyosis: current perspectives. Obstet Gynecol Clin. N. Am. 1989 Histological Criteria • One low power field • Foci deeper than 25% of myometrial thickness • Glandular extension >1-3mm – 2.5mm used in most studies Incidence 5-70% due to classification Bazot M, et al. Ultrasound compared with MRI for the diagnosis of adenomyosis: correlation with histopathology. Human Reproduction 2001: 16 (11) p 2427-2433 Histological Diagnosis • Hysterectomy • Biopsy – 5mm loop electrode with hysteroscopy – Cutting needles at time of laparoscopy – Ultrasound guidance biopsy McCausland A. Hysteroscopic myometrial biopsy: Its use in diagnosing adenomyosis and its clinical applications. Am J Obstet Gynecol 1992 Popp L. Myometrial biopsy in the diagnosis of adenomyosis uteri. Am J Obstet Gynecol. 1993 Hysteroscopy • • • • Irregular endometrium with superficial openings Irregular subendometrium Altered vascularity Intramural cystic hemorrhagic lesion Molinas C. Office Hysteroscopy and adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006 Fernandez C. Adenomyosis visualized during hysteroscopy. J Minim Invasive Gynecol 2007 Hysteroscopy Blood filled cystic lesions Molinas CR and Campo R Intramural endometriomas Fernandez C and Fernandez E Hysteroscopic biopsy • McCausland A 1992 – 90 patients with menorragia – 50 normal cavities • 33 (66% with adenomyosis >1 mm) Hysteroscopic biopsy • Campo hysteroscope – under development Hysteroscopic therapy for adenomyosis McCausland A and McCausland V 1996 Endometrial ablation/resection • Rollerball electrode – <2mm successful procedures with or without progesterone therapy – >2mm  hysterectomy • Global ablation – 1.5 increased risk of failure McCausland A, McCausland V. Depth of endometrial penetration in adenomyosis helps determine outcome of rollerball ablation. Am J Obstet Gynecol 1996 Wood C. Surgical and medical treatment of adenomyosis. Human Reproduction Update 1998 El Nashar S, Prediction of treatment outcomes after global endometrial ablation. Obstet Gynecol 2009