Female pelvic MRI for infertility: Radiological findings in a cohort of patients referred by a fertility specialist.

Female pelvic MRI for infertility: Radiological findings in a cohort of patients referred by a fertility specialist. Poster No.: C-0684 Congress: ECR 2016 Type: Scientific Exhibit Authors: S. Saha, S. J. Knox ; Adelaide, SA/AU, Adelaide/AU Keywords: Outcomes, Diagnostic procedure, MR, Genital / Reproductive system female DOI: 10.1594/ecr2016/C-0684 1 2 1 2 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 22

Aims and objectives 9% couples globally experience infertility [1]. Many go on to receive some form of Assisted Reproductive Technology (ART) which accounted for 3.6% births in Australia in 2012 [2]. A number of female pelvic conditions implicated in infertility may also influence treatment options and outcomes. These include uterine leiomyomas, adenomyosis, congenital abnormalities of uterine structure and endometriosis. MRI has been demonstrated to have high diagnostic accuracy for such pathology. There are no consensus guidelines for the use of this imaging modality in female infertility [3]. In our clinical practice. Pelvic MRI is a frequently requested investigation in female patients for the investigation of infertility, including in patients who have undergone unsuccessful IVF treatment. We aimed to assess detail the range and frequency of imaging findings on pelvic MRI in a cohort of patients referred by a fertility specialist. Methods and materials Retrospective review of MRI pelvis examinations undertaken for evaluation of infertility at a private radiology practice between January 2015 and July 2015. Imaging technique Scans acquired on a 1.5T magnet using a pelvic phased array surface coil. Imaging was performed during late luteal phase. Patients were routinely fasted and asked to void and evacuate bowels prior to the scan. Hyoscine butyl bromide administered to reduce intestinal peristalsis. Page 2 of 22

Fig. 1 on page 3 details the fertility MRI protocol. Sagittal T2 images are acquired early and again at the end of the scan to facilitate distinction between structural uterine pathology and uterine contraction. Image interpretation Images were evaluated using a structured approach to each pelvic organ, describing anatomical findings and recording the presence or absence of pathology implicated in infertility using diagnostic criteria defined in current literature, summarised in Fig. 2 on page 3 Images for this section: Fig. 1: Fertility MRI Sequence Parameters. Page 3 of 22

Fig. 2: Infertility MRI: Structured approach to pelvic organ assessment Page 4 of 22

Results A total of 205 pelvic MRI scans to evaluate the female reproductive organs were undertaken in female patient of reproductive age (<50) between January and July 2015. 157 cases (77%) were for the clinical indication of infertility. Patient characteristics are summaries in Table 1 on page 13 70 patients (44.6%) patients had primary infertility. There was a history of IVF failure in 34 patients (27.1%). Imaging findings Imaging findings associated with clinically relevant pathology were present in 127 cases (81%). In 77 patients (49%), there were 2 or more findings involving either different disease processes or more than 1 pelvic organ. In 30 patients (19%), no pelvic abnormality was reported. Fig. 3 on page 14 summarises the range and frequency of imaging findings. Adenomyosis A direct or indirect imaging finding with high specificity for adenomyosis was identified in 65 patients (41.4%). Submucosal microcysts (direct finding[6]) n=47 Fig. 4 on page 15 JZ thickening (indirect finding [6]) > 12mm n=19 Fig. 5 on page 15 Both findings present n=10 Focal adenomyoma n=3 Fig. 6 on page 17 Page 5 of 22

Fig. 4: Submucosal microcysts - direct sign of adenomyosis. (a) Sagittal T2-weighted MR, (b) T2 axial reconstruction through short axis of the uterus show multiple high T2 signal microcysts (arrows) within the junctional zone. References: Benson Radiology, Adelaide, Australia 2015. Page 6 of 22

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Fig. 5: Diffuse adenomyosis. Sagittal T2-weighted MR images show diffuse thickening of the low T2 junctional zone. Anterior and posterior JZ measure >12mm (normal <8mm). References: Benson Radiology, Adelaide, Australia 2015. Fig. 6: Focal adenomyoma. (a) Sagittal T2-weighted MR, (b) T2 axial reconstruction through short axis of the uterus show mass like low T2 signal extending from JZ to outer myometrium. The presence of T2 hyperintense cysts aids differentiation from a leiomyoma. Submucosal cysts are also present in the anterior JZ. References: Benson Radiology, Adelaide, Australia 2015. Endometriosis At least 1 imaging manifestation of endometriosis was identified in 61 patients (38.9%). Uterosacral ligament thickening n=36 Ovarian endometrioma n=35 Fig. 7 on page 17 Other indicators of regional anatomical distortion (retroflexed uterus, medialisation ovaries, tethering of adjacent viscera, peritoneal inclusion cyst, posterior cul-de-sac obliteration) n=27 Fig. 8 on page 18 Low T2 signal fibrotic plaque n=9 Fig. 8 on page 18 High T1/T2 signal haemorrhagic deposits n=4 Bowel serosal involvement/invasion n=4 Fig. 8 on page 18 Bladder serosal involvement/invasion n=1 Page 8 of 22

Haematosalpinx n=3 Fig. 7: Ovarian endometrioma. (a) Axial T1-weighted MR, (b) Axial T1 VIBE Dixon, (c) Axial T2 weighted Axial reconstruction show a 21mm endometrioma in the left ovary (arrows). T1 hyperintensity persists on fat-saturated images (b), there is typical T2 "shading" (c). References: Benson Radiology, Adelaide, Australia. 2015. Fig. 8: Endometriosis. Fibrotic plaque posterior cul-de-sac, regional anatomic distortion, tethering and rectal involvement. (a) Sagittal T2-weighted MR shows low T2 signal fibrotic plaque at the torus uterinus (arrow). (b) Axial reconstructed T2 images show medialisation of both ovaries (O). (c) Low T2 signal fibrotic plaque measuring 19mm with transmural involvement upper rectum (arrows) and tethering of rectum (R) to cervix (C). References: Benson Radiology, Adelaide, Australia 2015. Uterine leiomyoma Page 9 of 22

Leiomyoma were identified in 62 patients (39.5%) and were multiple in 42 patients. The majority were intramural. Clinically relevant submucosal fibroids (FIGO 0, 1, 2) were present in 11 cases (7%). Fig. 9 on page 18 Fig. 9: Submucosal leiomyomas. Sagittal T2-weighted MR images (a, b) and Axial reconstruction through the short axis of the uterus. (a) FIGO 1 (submucosal <50% intramural) 10mm leiomyoma posterior uterine corpus. (b) FIGO 2 (submucosal >50% intramural) 21mm leiomyoma anterior uterine corpus. Mild high T2 signal suggests early degeneration. (c) Arrows show submucosal leiomyomas. Further mural leiomyomas in the right anterior uterine corpus. References: Benson Radiology, Adelaide, Australia 2015. Müllerian Duct Anomalies (MDA) The uterus appeared normal in 109 patient. 42 had arcuate morphology which is considered a normal variant [11]. MDA potentially relevant to fertility were present in 6 patients (3.8%). Septate n = 3 Fig. 10 on page 18 Unicornuate n = 2 Uterus didelphys n = 1 Page 10 of 22

Fig. 10: Septate uterus. T2 Coronal reconstruction through long axis of the uterus shows a septum measuring 34mm dividing the uterine cavity (b). The uterus has a flat external contour, intercornual distance measures <4cm (b) and acute intercornual angle <75 degrees (c). The thickness of the septum and intermediate T2 signal suggest muscular rather than fibrous composition. References: Benson Radiology, Adelaide, Australia 2015. Endocavitary lesions Endocavitary lesions were described in 10 patients. Endometrial polyp n = 9 Fig. 11 on page 19 Uterine synechiae n = 1 Page 11 of 22

Fig. 11: Endometrial polyp. (a) Sagittal T2-weighted images, (b) T2 reconstructed axial images through short axis of the uterus show a 9mm, mildly T2 hypointense within the endometrium (short arrows) which appears to have an attachment to the anterior wall (long arrows), consistent with a polyp. References: Benson Radiology, Adelaide, Australia 2015. Hydrosalpinx A dilated fallopian tube was identified in 10 cases, all were unilateral. 7 cases were reported as hydrosalpinx (high T2, low T1 signal intensity). There were 3 cases of haematosalpinx (high T2, high T1 signal intensity) which were associated with other imaging manifestations of endometriosis. Fig. 12 on page 20 Page 12 of 22

Fig. 12: Hydrosalpinx. (a) Axial T2-weighted images (b) Axial T1-weighted images show a thick walled, tubular high T2 signal intensity structure (arrows) surrounding the right ovary which contains a large follicle (O). There is corresponding low T1 signal, consistent with simple fluid rather than blood products. References: Benson Radiology, Adelaide, Australia 2015. Ovarian morphology Polycystic ovarian morphology was reported in 20 patients (12.7%) based on presence of #/= 12 follicles measuring 2-9mm [8]. Hyper stimulated ovaries were identified in 2 patients. Images for this section: Page 13 of 22

Table 1: Infertility cohort patient characteristics. Fig. 3: Infertility cohort: Clinically relevant imaging findings. Page 14 of 22

Fig. 4: Submucosal microcysts - direct sign of adenomyosis. (a) Sagittal T2-weighted MR, (b) T2 axial reconstruction through short axis of the uterus show multiple high T2 signal microcysts (arrows) within the junctional zone. Page 15 of 22

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Fig. 5: Diffuse adenomyosis. Sagittal T2-weighted MR images show diffuse thickening of the low T2 junctional zone. Anterior and posterior JZ measure >12mm (normal <8mm). Fig. 6: Focal adenomyoma. (a) Sagittal T2-weighted MR, (b) T2 axial reconstruction through short axis of the uterus show mass like low T2 signal extending from JZ to outer myometrium. The presence of T2 hyperintense cysts aids differentiation from a leiomyoma. Submucosal cysts are also present in the anterior JZ. Fig. 7: Ovarian endometrioma. (a) Axial T1-weighted MR, (b) Axial T1 VIBE Dixon, (c) Axial T2 weighted Axial reconstruction show a 21mm endometrioma in the left ovary (arrows). T1 hyperintensity persists on fat-saturated images (b), there is typical T2 "shading" (c). Page 17 of 22

Benson Radiology, Adelaide, Australia. 2015. Fig. 8: Endometriosis. Fibrotic plaque posterior cul-de-sac, regional anatomic distortion, tethering and rectal involvement. (a) Sagittal T2-weighted MR shows low T2 signal fibrotic plaque at the torus uterinus (arrow). (b) Axial reconstructed T2 images show medialisation of both ovaries (O). (c) Low T2 signal fibrotic plaque measuring 19mm with transmural involvement upper rectum (arrows) and tethering of rectum (R) to cervix (C). Fig. 9: Submucosal leiomyomas. Sagittal T2-weighted MR images (a, b) and Axial reconstruction through the short axis of the uterus. (a) FIGO 1 (submucosal <50% intramural) 10mm leiomyoma posterior uterine corpus. (b) FIGO 2 (submucosal >50% intramural) 21mm leiomyoma anterior uterine corpus. Mild high T2 signal suggests early degeneration. (c) Arrows show submucosal leiomyomas. Further mural leiomyomas in the right anterior uterine corpus. Page 18 of 22

Fig. 10: Septate uterus. T2 Coronal reconstruction through long axis of the uterus shows a septum measuring 34mm dividing the uterine cavity (b). The uterus has a flat external contour, intercornual distance measures <4cm (b) and acute intercornual angle <75 degrees (c). The thickness of the septum and intermediate T2 signal suggest muscular rather than fibrous composition. Fig. 11: Endometrial polyp. (a) Sagittal T2-weighted images, (b) T2 reconstructed axial images through short axis of the uterus show a 9mm, mildly T2 hypointense within the endometrium (short arrows) which appears to have an attachment to the anterior wall (long arrows), consistent with a polyp. Page 19 of 22

Fig. 12: Hydrosalpinx. (a) Axial T2-weighted images (b) Axial T1-weighted images show a thick walled, tubular high T2 signal intensity structure (arrows) surrounding the right ovary which contains a large follicle (O). There is corresponding low T1 signal, consistent with simple fluid rather than blood products. Page 20 of 22

Conclusion MRI has an increasing role in the work up of infertility patients, enabling high diagnostic accuracy for clinically important pathology. In our cohort of patients referred by a fertility specialist, adenomyosis and endometriosis were the most frequent finding on MRI. Leiomyomas were identified in a similar proportion of patients, however, submucosal fibroids which are implicated in subfertility were found at a much lower frequency. The frequency of multiple organ involvement, either by the same disease process or a distinct pathology approached half of the cohort. Excellent soft tissue contrast resolution, multiplanar imaging and unlimited scope for post acquisition image manipulation are ideally suited for such complex cases. Identification of pelvic pathology which is amenable to surgical or medical intervention as recommended in current practice guidelines [12-14], could potentially avoid the financial and emotional stress associated with repeated ART cycles. Personal information Dr S. Saha is a final year RANZCR trainee based in Adelaide, South Australia. References 1. 2. 3. 4. Boivin J, Bunting L, Collins JA et al. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Human Reproduction. 2007; 22: 1506-12. Macaldowie A, Wang YA, Chambers GA et al. Assisted reproductive technology in Australia and New Zealand 2010. Assisted reproductive technology series no. 16 Cat. no. PER 55. Canberra: AIHW. Practice Committee of the American Society for Reproductive Medicine. Diagnostic Evaluation of the Infertile Female: A Committee Opinion. Fertil Steril 2015; 103(6): 44-50. Mueller GC, Hussain HK, Smith YR et al. Müllerian Duct Anomalies: Comparison of MRI Diagnosis and Clinical Diagnosis. AJR 2007; 189: 1294-1302. Page 21 of 22

5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Munro MG, Critchley HO, Broder MS et al. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Obst Gyn 2011; 113: 3-13. Bazot M, Cortez A, Darai E et al. Ultrasonography compared with magnetic resonance imaging for the diagnosis of adenomyosis: correlation with histopathology. Hum Reprod 2001; 16: 2427-2433. Novellas S, Chassang M, Delotte J et al. MRI characteristics of the uterine junctional zone: From normal to the diagnosis of adenomyosis. AJR 2011; 196: 1206-13. Rotterdam ESHRE/ASRM - Sponsored PCOS Concensus Workshop Group. Revised 2003 concencus on diagnostic criteria and long term health risks related to polycystic ovary syndrome. Marcal L, Nothalft MA, Coelho F et al. Deep pelvic endometriosis: MR imaging. Abdom Imaging 2010; 35:7-8-715. Kataoka ML, Togashi K, Yamaokoa T et al. Posterior cul-de-sac obliteration associated with endometriosis: MR imaging Evaluation. Steinkeler JA, Woodfield CA, Lazarus E et al. Female infertility: A systematic approach to radiologic imaging and diagnosis. Radiographics. 2009; 29: 1353-70. Koch J, Rowan K, Rombauts L et al. Endometriosis and infertility - a consensus statement from ACCEPT. ANZJOG 2012; 52:513-22. Consensus statement of RANZCOG and ACCEPT group. Fibroids in infertility. March 2011. Dunselman, GA, Vermeulen N, Becker C et al. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014; 29(3): 400-412. Page 22 of 22