{"paper_id":"11de4f20-d100-4c4a-bd7c-c58135fc79b0","body_text":"Abstract\n!\nIntroduction: Adenomyosis can cause defective\ndeep placentation. Preeclampsia is known to be\nassociated with abnormal placentation. The aim\nof this study was to compare the presence of ad-\nenomyosis on magnetic resonance imaging in pa-\ntients with and without history of preeclampsia\nin order to investigate the possible role of adeno-\nmyosis in the pathogenesis of preeclampsia.\nMaterials and Methods: This prospective, ran-\ndomized study consisted of patients with (n = 35)\nand without (n = 34) history of preeclampsia. Di-\nrect (submucosal microcysts, adenomyoma and\ncystic adenomyoma) and indirect (maximal\nthickness of junctional zone, ratio of maximal\nthickness of junctional zone to myometrial thick-\nness, junctional zone differential, focal thickening\nof junctional zone, globally enlarged uterus and\nnon-uniform junctional zone contours) signs of\nadenomyosis were assessed by pelvic magnetic\nresonance imaging.\nResults: The prevalence of adenomyosis was\nfound to be more common in patients with preec-\nlampsia und fetal growth restriction compared to\npatients without fetal growth restriction (94.4 vs.\n64.7 %; p = 0.041), respectively. There was a strong\nassociation between maximal thickness of junc-\ntional zone (9 vs. 13 mm, p = 0.005), ratio of max-\nimal thickness of junctional zone to myometrial\nthickness (0.42 vs. 0.66, p = 0.001) and junctional\nzone differential (3 vs. 5 mm, p = 0.02) and late-\nonset preeclampsia.\nConclusions: Presence of adenomyoma is more\ncommon in patients with preeclampsia compli-\ncated with fetal growth restriction. Indirect signs\nof adenomyosis detected on pelvic magnetic reso-\nnance imaging might have a role in the patho-\ngenesis of late-onset preeclampsia.\nZusammenfassung\n!\nEinleitung: Die Adenomyose kann zu Einnis-\ntungsstörungen der Plazenta führen. Es ist be-\nkannt, dass die Präeklampsie auf einer abnormen\nPlazentation beruht. Das Ziel dieser Studie be-\nstand darin, die Adenomyose in Patientinnen mit\nund ohne Vorgeschichte der Präeklampsie mittels\nbildgebender Verfahren zu vergleichen, um die\netwaige Rolle der Adenomyose bei der Pathoge-\nnese von Präeklampsie zu evaluieren.\nMaterial und Methoden: Es wurden Patientinnen\nmit (n = 35) oder ohne (n = 34) Vorgeschichte der\nPräeklampsie in diese prospektive, randomisierte\nStudie aufgenommen. Bei allen Patientinnen wur-\nde eine Magnetresonanztomografie des Beckens\ndurchgeführt, zur Beurteilung der direkten (sub-\nmuköse Mikrozysten, Adenomyome und zysti-\nsche Adenomyome) und indirekten (maximale\nDicke der Übergangszone, Verhältnis zwischen\nder maximalen Dicke der Übergangszone und\nder Dicke des Myometriums, Differenzial der\nÜbergangszone, fokale Verbreiterung der Über-\ngangszone, diffus vergrößerter Uterus und irre-\nguläre Kontur der Übergangszone) Anzeichen\nder Adenomyose.\nErgebnisse: Die Adenomyose kam häufiger bei\nPatientinnen mit Präeklampsie und fetaler\nWachstumsretardierung vor, verglichen mit Pa-\ntientinnen ohne fetale Wachstumsretardierung\n(94,4 vs. 64,7 %; p = 0,041). Es bestand eine enge\nVerbindung zwischen der maximalen Dicke der\nÜbergangszone (9 vs. 13 mm, p = 0,005), dem Ver-\nhältnis zwischen der maximalen Dicke der\nÜbergangszone und der Dicke des Myometriums\n(0,42 vs. 0,66, p = 0,001), dem Differenzial der\nÜbergangszone (3 vs. 5 mm, p = 0,02) und der spät\neinsetzenden Präeklampsie.\nSchlussfolgerung: Die Adenomyose kommt häu-\nfiger bei Patientinnen mit Präeklampsie und feta-\nler Wachstumsretardierung vor. Indirekte An-\nzeichen der Adenomyose, die bei einer Magnet-\nThe Role of Adenomyosis in the Pathogenesis\nof Preeclampsia\nDie Rolle der Adenomyose in der Pathogenese der Präeklampsie\nAuthors P. S. Hasdemir 1, M. Farasat 2, C. Aydin 1,B .C .O z y u r t3, T. Guvenal 1, G. Pekindil 2\nAffiliations 1 Department of Obstetrics and Gynecology, Celal Bayar University Medical School, Manisa, Turkey\n2 Department of Radiology, Celal Bayar University Medical School, Manisa, Turkey\n3 Department of Public Health, Celal Bayar University Medical School, Manisa, Turkey\nKey words\nl\" adenomyosis\nl\" fetal growth restriction\nl\" magnetic resonance imaging\nl\" preeclampsia\nl\" junctional zone\nSchlüsselwörter\nl\" Adenomyose\nl\" fetale Wachstums-\nretardierung\nl\n\" Magnetresonanztomografie\nl\" Präeklampsie\nl\" Übergangszone\nreceived 25. 1. 2016\nrevised 7. 3. 2016\naccepted 20. 4. 2016\nBibliography\nDOI http://dx.doi.org/\n10.1055/s-0042-107080\nGeburtsh Frauenheilk 2016; 76:\n882–887 © Georg Thieme\nVerlag KG Stuttgart · New York ·\nISSN 0016‑5751\nCorrespondence\nPinar Solmaz Hasdemir, MD\nCelal Bayar University\nSchool of Medicine\nDepartment of Obstetrics\n& Gynecology\nUncobozköy Street\n45000, Manisa\nTurkey\nsolmazyildiz@yahoo.com\n882\nHasdemir PS et al. The Role of … Geburtsh Frauenheilk 2016; 76: 882 –887\nGebFra Science\n\n\nIntroduction\n!\nAdenomyosis is a benign invasion of endometrial glands and\nstroma into the myometrium surrounded by a hypertrophic and\nhyperplastic myometrial tissue and represents a spectrum of le-\nsions, ranging from increased thickness of the junctional zone\n(JZ) to overt adenomyosis and adenomyomas [1, 2]. The use of\nmodern imaging techniques, especially magnetic resonance\nimaging (MRI), enables its identification as diffuse or focal thick-\nening of the myometrial JZ and less common forms of adenomyo-\nsis such as adenomyoma, adenomyomatous polyps, and cystic\nadenomyoma have also been described [3].\nDuring pregnancy, trophoblast invasion to the endometrium and\nthe myometrial JZ causes decidualization and unique vascular\nchanges [4]. Defective deep placentation was reported to be asso-\nciated with a spectrum of obstetrical complications such as late\nmiscarriage, preterm labour, fetal growth restriction (FGR) and\npreeclampsia [5].\nPreeclampsia is defined as new hypertension and substantial\nproteinuria at or after 20 weeks of gestation [6]. Although the\ncause of preeclampsia remains largely unknown, the leading hy-\npotheses strongly rely on disturbed placental function in early\npregnancy [7]. Failure of placentation, particularly the physiolog-\nical transformation of spiral arteries, leads to a stressed, unper-\nfused placenta. Most probably because of the similar patho-\ngenesis, preeclampsia could be seen together with FGR, stillbirth,\nplacental abruption and preterm labor [8].\nTo the best of our knowledge, there is no prior clinical study in-\nvestigating the relationship between adenomyosis and preec-\nlampsia. The aim of this study was to compare the presence of ad-\nenomyosis on magnetic resonance imaging in patients with and\nwithout history of preeclampsia in order to investigate the possi-\nble role of adenomyosis in the pathogenesis of preeclampsia.\nMaterial and Methods\n!\nThis study was a prospective, randomized study conducted at an\nObstetrics and Gynecology Clinic of a University Hospital in Tur-\nkey, between January and July 2015.\nA total of 69 women were included in the study. All patients\n(n = 76) with diagnosis of preeclampsia who were delivered at\nour obstetrics clinic during study period were called by phone\nand asked for enrollment in the study. Among this group, a total\nof 35 patients agreed with MRI examination and were enrolled.\nThe control group consisted of 34 patients having presented with\nnon-gynecologic complaint with a history of at least one preg-\nnancy without preeclampsia and without any history of infertili-\nty, endometriosis and/or leiomyoma, uterine surgery except pri-\nor low transverse incision cesarean section and history of hydat-\niform mole. The control group was randomized based on age,\ngravidity and parity numbers by computer.\nAll study subjects underwent pelvic MRI examination at least\n6 months after their pregnancy during out of their menstrual\nphase [9, 10]. The primary outcome was the presence of adeno-\nmyosis. The secondary outcomes were early or late onset of pre-\neclampsia, FGR and preeclampsia-related complications (abrupt-\nio placenta, HELLP syndrome and eclampsia) in the presence of\nadenomyosis.\nFull medical histories were obtained. Preeclampsia was defined\nas hypertension with a systolic blood pressure of 140 mmHg or\nhigher or a diastolic blood pressure of 90 mmHg or higher occur-\nring after 20 weeks of gestation in a woman with previously nor-\nmal blood pressure and proteinuria of at least 300 mg/24 hour\nurine collection [6]. Proteinuria in spot urine sample instead of\n24 hour urine collection was used for diagnostic purposes in pa-\ntients having undergone emergency delivery. The onsets of pre-\neclampsia were considered as early (< 34 gestational weeks) or\nlate (≥ 34 gestational weeks). FGR was defined as at least 2 weeks\nof retardation in ultrasonographic measures of the fetus com-\npared to expected gestational week. All clinical assessments of\nthe participants were performed by the same investigator (PSH),\nand all MRI evaluations were assessed by the same experienced\nradiologist (MF). The radiologist was blind for the study groups.\nMRI assessment\nMRI was performed with 1.5-Tesla scanners (Signa, General Elec-\ntric Medical Systems). We acquired 7-mm slices with 1-mm spac-\ning in the sagittal, coronal, and axial planes relative to the orien-\ntation of the uterine cavity, using T2-weighted fast (turbo) spin\necho sequences (TR/TEef, 3500 –4000 ms/100 ms, echo train\nlength 17) in all three planes. Surface coils (phase array pelvic\ncoils) were used for data acquisition and examinations were\ncompleted within 30 minutes in each case.\nPreviously described MRI criteria for the diagnosis of adenomyo-\nsis were used [9, 11]. Both direct and indirect signs of adenomyo-\nsis on MRI were measured. Submucosal microcysts, adenomyo-\nma and cystic adenomyoma were considered as direct signs.\nMaximum thickness of JZ ( ≥ 12 mm), JZ differential (the highest\nvalue calculated as JZ\nmax minus JZ min measured in both anterior\nand posterior walls in the sagittal slices) (> 5 mm), the ratio of\nJZ\nmax thickness to myometrial thickness from the same plane\n(> 40 %), focal thickenning of JZ, globally enlarged uterus and\nnon-uniform JZ contours were considered as indirect signs of ad-\nenomyosis. Presence of adenomyosis was defined as presence of\nat least one direct and/or indirect signs on MRI ( l\n\" Fig. 1).\nEthical consent\nThe research protocol was approved by the institutional review\nboard (no. 20478486-22) on January 14th, 2015. Informed con-\nsent was obtained from each participant.\nStatistical analysis\nStatistical analysis was performed with IBM SPSS Statistics 21.0\n(SPSS Inc., Chicago, IL). The Shapiro –Wilk test was used to calcu-\nlate whether the numeric variables were normally distributed.\nFor normally distributed variables, numeric data were analyzed\nwith the Student ʼs t test and cross-tables and Pearson χ\n2 analysis\nwere employed in the evaluation of the categorical data. The\nMann–Whitney U test was used for abnormally distributed vari-\nables. Fisherʼs exact test was used in data with small sample size\nwith an expected frequency of 5 % or less. P-value < 0.05 was con-\nsidered as statistically significant.\nresonanztomografie des Beckens festgestellt werden, könnten\neine Rolle bei der Pathogenese von spät einsetzender Präeklamp-\nsie spielen.\n883\nHasdemir PS et al. The Role of … Geburtsh Frauenheilk 2016; 76: 882 –887\nOriginal Article\n\n\nThirty-three patients in each group had a power of 0.80 with the\neffect size of d = 0.70 and α = 0.05 based on sample size calcula-\ntions.\nResults\n!\nDescription of the sample\nStudy population consisted of 69 patients (median age 29 years\nold, range 17–41). Baseline demographic and clinical characteris-\ntics in patients with and without preeclampsia were similar ex-\ncept for the older gestational age at delivery in control group\nmost likely due to larger proportion of uncomplicated pregnan-\ncies (l\n\" Table 1).\nMean age, number of gravidity and parity rates of patients with\nand without FGR were similar (28.77 ± 5.52 vs. 28.84 ± 5.42,\np = 0.772; 2 ± 1.37 vs. 2.21 ± 1.49, p = 0.646; 1.55 ± 0.85 vs.\n1.57 ± 0.94, p = 0.983), respectively. Mean age, number of gravid-\nity and parity rates of patients with early and late onset preec-\nlampsia were similar (26.27 ± 4.31 vs. 29.76 ± 6.75, p = 0.068;\n1.77 ± 1.16 vs. 2.29 ± 1.86, p = 0.562; 1.27 ± 0.75 vs. 1.70 ± 0.92,\np = 0.105), respectively.\nIn patients with preeclampsia, the rate of HELLP syndrome,\nabruptio placenta and eclampsia were 45.7, 14.3 and 8.6 %, re-\nspectively.\nComparison of adenomyosis and preeclampsia,\nits related complications and FGR\nAdenomyosis was present in 85.5 % of the study population. The\nprevalence of adenomyosis was not different between patients\nwith and without preeclampsia (88.6 vs. 82.4 %, p = 0.513), re-\nspectively (l\n\" Table 2 ). The JZ differential tended to be higher in\npatients with preeclampsia compared to control subjects\n(4.14 ± 2.54 vs. 3.11 ± 1.96; p = 0.066), respectively ( l\n\" Table 2).\nThere was no relationship between the presence of adenomyosis\nand preeclampsia-related complications including abruptio\nplacenta (p = 0.477), HELLP syndrome (p = 1.000) and eclampsia\n(p = 0.313). Presence of adenomyosis were compared in patients\nwith preeclampsia with or without FGR and only the presence of\nadenomyoma was more common in patients with FGR compared\nto patients without FGR (94.4 vs. 64.7 %; p = 0.041), respectively\n(l\n\" Table 3). There was no correlation between FGR and early/late\nonset preeclampsia; 9 out of of 18 patients with FGR (50 %) had\npregnancy complicated with early-onset preeclampsia while 9\nout of 18 patients with FGR were complicated with late-onset\npreeclampsia (p = 0.862).\nSubgroup analysis based on the early or late onset\nof preeclampsia\nDiagnostic signs (direct and indirect) of adenomyosis were com-\npared in patients with early and late onset preeclampsia. There\nwas a strong association between three indirect signs of adeno-\nmyosis and late-onset preeclampsia; JZ\nmax/myometrial thickness,\nJZ differential and JZ max were found to be significantly higher in\npatients with late-onset preeclampsia than in patients with\nearly-onset preeclampsia [0.42 (0.21 –0.72) vs. 0.66 (0.36 –0.83),\np = 0.001; 3 (1 –6) vs. 5 (2 –13), p = 0.020; 9 (4 –15) vs. 13 (7 –19),\np = 0.005], respectively (l\n\" Table 4).\nDiscussion\n!\nMRI is currently an important technique with high diagnostic\nvalue for the diagnosis of adenomyosis [12]. Histopathologic\nevaluation of uterus has been the gold standard diagnostic meth-\nod for adenomyosis until Hricak et al. described the normal zonal\nanatomy as a distinct low signal on T2-weighted sequences sep-\nerating endometrium in high signal intensity from outer myome-\ntrium in intermediate signal on MRI in 1983 [13].\nAdenomyosis is not a uniform disease. It rather represents a spec-\ntrum of lesions, ranging from disruption of the JZ architecture\nwith little or no endometrial invasion to overt diffuse adenomyo-\nsis and focal adenomyomas [4]. JZ is the inner\n11⁄33 part of myome-\ntrium and found to be different than outer myometrium by its\nembryonic origin and functions [4, 14]. Although the distinct my-\nometrial zonal anatomy on MRI disappears in pregnancy, disrup-\ntion of the JZ prior to conception may have profound repercus-\nsion on deep placentation and subsequent pregnancy outcome.\nTable 1 Baseline demographic and clinical characteristic of the preeclampsia\nand control groups.\nPreeclampsia\ngroup (n = 35)\nControl\ngroup\n(n = 34)\np-value\nAge 27.97 ± 5.81 30.17 ± 4.92 0.094*\nSmoking 12 % 26 % 0.138**\nGravidity 2.02 ± 1.54 2.20 ± 1.14 0.591*\nParity 1.48 ± 0.85 1.76 ± 0.95 0.205*\nAbortion 0.54 ± 1.06 0.47 ± 0.89 0.762*\nGestational age at\ndelivery\n33.75 ± 4.26 36.73 ± 2.95 0.001*\nTime interval (delivery\nto MRI)\n12.25 ± 3.48 13.26 ± 3.06 0.207*\nDM and/or GDM 15 % 3 % 0.197***\nPresence of myoma 17.1 % 5.9 % 0.259***\nPresence of endome-\ntriosis/endometrioma\n2.9 % 8.8 % 0.356***\nDM: diabetes mellitus, GDM: gestational diabetes mellitus, MRI: magnetic resonance\nimaging\n* studentʼs t-test, ** χ\n2 test, *** Fisherʼs exact test\nFig. 1 Pelvic MRI at mid-sagittal plane showing (arrows) increased focal\njunctional zone thickness.\n884\nHasdemir PS et al. The Role of … Geburtsh Frauenheilk 2016; 76: 882 –887\nGebFra Science\n\n\nThickening and disruption of the JZ appearance is strongly asso-\nciated with uterine adenomyosis [4].\nThe placental bed, the area of the uterus underlying the placenta,\nplays a key role in supporting placental function by supplying\noxygenated blood to the intervillous space via the spiral arteries\n[15, 16]. Decidualization initiates some morphologic changes in\nJZ spiral arteries outside the placental bed [17]. Defective deep\nplacentation was reported to be associated with a spectrum of\nobstetrical complications such as late miscarriage, preterm la-\nbour, fetal growth restriction and preeclampsia [5]. Interstitial\ntrophoblast invasion of the JZ appears adequate, although im-\npaired decidualization of the myometrial spiral arteries predis-\nposes for failed intravascular trophoblast invasion in those condi-\ntions [18, 19].\nAlthough the cause of preeclampsia remains largely unknown,\nfailured remodeling of the spiral artery has especially been con-\nsidered as an early defect causing preeclampsia. This abnormal\nplacentation leads to reduced uteroplacental arterial flow and\nepisodes of irregular placental perfusion resulting in oxidative\nstress, subsequent apoptotic and necrotic disruption of syncytial\narchitecture and release of various components from the intervil-\nlous space into the maternal circulation, stimulating production\nof inflammatory cytokines. This leads to systemic maternal dis-\nease as the second stage of preeclampsia [20].\nPreeclampsia consists of many different clinical subtypes like\nearly-onset preeclampsia often complicated by FGR, preeclamp-\nsia accompanied with HELLP syndrome and late-onset preec-\nlampsia. Early and late-onset preeclampsia are defined as preec-\nlampsia that develops before and at or after 34 weeks of gesta-\ntion, respectively. Although the presenting features overlap, they\nare associated with different maternal and fetal outcomes, bio-\nchemical markers, heritability, and clinical features [21]. Early\nonset preeclampsia has a worse prognosis characterized with\nearly birth, perinatal death and/or severe neonatal morbidity.\nTable 2 Comparison of MRI findings based on adenomyosis characteristics in\npreeclampsia and control groups.\nPreeclampsia\ngroup (n = 35)\nControl\ngroup\n(n = 34)\np-value\nSubmucosal microcyst 0 % 2.9 % 0.490***\nCystic adenomyoma 2.9 % 2.9 % 1.000***\nPresence of\nadenomyoma\n80 % 70.6 % 0.364**\nAdenomyoma max\n(mm)\n5.20 ± 4.22 4.94 ± 4.24 0.800*\nAdenomyoma location % % 0.177**\n\" Anterior 28.6 8.7\n\" Posterior 25 13\n\" Fundal 17.9 39.1\n\" Posterior–fundal 7.1 4.3\n\" Anterior–fundal 7.1 26.1\n\" Anterior–posterior 7.1 4.3\n\" Anterior–posterior–\nfundal\n7.1 4.3\nTotal size of adeno-\nmyoma (mm)\n11.82 ± 12.32 12.12 ± 7.82 0.918*\nFocal JZ (JZmax) (mm) 10.40 ± 3.98 11.32 ± 3.99 0.340*\nLocalization of JZmax % % 0.208**\n\" Anterior 21.7 29.2\n\" Posterior 52.2 16.7\n\" Fundal 8.7 8.3\n\" Fundal–posterior 0 7.2\n\" Fundal–anterior 4.3 8.3\n\" Anterior–posterior 8.7 29.2\n\" Anterior–posterior–\nfundal\n4.3 4.2\nJZmax/myometrium 0.53 ± 1.18 0.55 ± 0.13 0.726*\nJZ differential (mm) 4.14 ± 2.54 3.11 ± 1.96 0.066*\nJZ not-uniform 51.4 % 52.9 % 0.900**\nUterine size (mm) 47.48 ± 7.83 50.33 ± 7.62 0.130*\nAdenomyosis\ndiagnostic criteria\n% % 0.239**\n\" Absent 11.4 17.6\n\" Indirect 34.3 20.6\n\" Direct 11.4 2.9\nPresence of overall\nadenomyosis\n88.6 % 82.4 % 0.513***\n* studentʼs t-test, ** χ2 test, *** Fisherʼs exact test, max: maximal, mm: milimeters\nTable 3 Comparison of MRI findings based on adenomyosis characteristics in\npatients with preeclampsia with and without fetal growth restriction.\nAdenomyosis\ncharacteristics\nFGR (+) (%)\n(n = 18)\n(median\n[min–max])\nFGR (−)( % )\n(n = 17)\n(median\n[min–max])\np-value\nPresence of\nadenomyoma\n94.4 % 64.7 % 0.041**\nAdenomyoma max\n(mm)\n5.5 (0–20) 3 (0 –11) 0.115*\nTotal size of adeno-\nmyoma (mm)\n8( 3–54) 6 (2 –35) 0.273*\nJZmax/myometrium 0.47\n(0.21–0.83)\n0.54\n(0.22–0.83)\n0.175*\nJZ differential (mm) 3 (1 –9) 3 (2 –13) 0.366*\nJZ non-uniform 66.7 % 50 % 0.241***\nFocal JZ (JZmax) (mm) 10 (4 –18) 10 (4 –19) 0.295*\nUterine size (mm) 47.75 (37 –73) 44 (35.5 –61) 0.590*\nFGR: fetal growth restriction, JZ: Junctional Zone, max: maximal, mm: milimeters.\n* Mann-Whitney U test, ** Fisher ʼs exact test, *** χ2 test.\nTable 4 Comparison of MRI findings based on adenomyosis characteristics in\npatients with early and late-onset preeclampsia.\nAdenomyosis\ncharacteristics\n< 34 weeks\n(n = 18)\n(median\n[min–max])\n≥ 34 weeks\n(n = 17)\n(median\n[min–max])\np-value\nPresence of\nadenomyoma\n72.2 % 88.2 % 0.402**\nAdenomyoma max\n(mm)\n4( 0–11) 6 (0 –20) 0.175*\nTotal size of adeno-\nmyoma (mm)\n7( 2–27) 9 (2 –54) 0.262*\nJZmax/myometrium 0.42\n(0.21–0.72)\n0.66\n(0.36–0.83)\n0.001*\nJZ differential (mm) 3 (1 –6) 5 (2 –13) 0.020*\nJZ non-uniform 38.9 % 64.7 % 0.127***\nFocal JZ (JZmax) (mm) 9 (4 –15) 13 (7 –19) 0.005*\nUterine size (mm) 45.25\n(38.5–61)\n49\n(35.5–73)\n0.107*\nJZ: Junctional Zone, max: maximal, mm: milimeters\n* Mann-Whitney U test, ** Fisher ʼs exact test, *** χ2 test\n885\nHasdemir PS et al. The Role of … Geburtsh Frauenheilk 2016; 76: 882 –887\nOriginal Article\n\n\nLisonkova et al. reported that congenital anomalies were more\nstrongly associated with early-onset disease, suggesting the pres-\nence of associated placental abnormalities that affect perfusion.\nIn contrast, a stronger positive association between diabetes mel-\nlitus and late-onset preeclampsia suggests that relative placental\ninsufficiency is more likely to occur in diabetic pregnancies with\na larger fetus. They also observed a strong association between\nearly-onset disease and small-for-gestational age fetuses, likely\nbecause of the profound effects of poor placental perfusion early\nin gestation [22]. We found a relationship between late-onset\npreeclampsia and indirect signs of adenomyosis on MRI suggest-\ning that adenomyosis might be related with a relative placental\ninsufficiency.\nAlthough the causes of preeclampsia remain one of the great\nmedical mysteries of our time, some promising researches are\nbeing published recently. Fisher et al. reported that cytotropho-\nblasts that are isolated from the placentas of affected pregnancies\nnormalized their gene expression over 48 hours in vitro; this un-\nexpected finding suggests that some aspects of the aberrant dif-\nferentiation of cytotrophoblasts within the uterine wall that is\nobserved in situ may be reversible. This result points to the im-\nportance of environment factors in driving the phenotype. The\nnext challenge is to identify what they are. There are new clues\nto the longstanding mystery of the reason of abnormal\nplacentation in preeclampsia and the added urgency to find the\nanswers, because these pathways could be valuable therapeutic\ntargets for reversing abnormal placental function in patients\n[23]. In light of our study, we speculate that adenomyosis (espe-\ncially defective junctional zone) might be one of these mysterious\nfactors. Thus, careful assessment for defective junctional zone\nduring routine ultrasonographic examinations in pregnancy as a\npredictive factor for late-onset preeclampsia should be made.\nA recent retrospective study investigated the relationship be-\ntween adenomyosis and uterine enlargement and poor preg-\nnancy outcomes on 36 cases with adenomyosis and 144 control\npregnancies. They found that the adenomyosis group had signifi-\ncantly higher rates of preterm delivery, preterm premature rup-\nture of membranes, small-for-gestational age, fetal malpresenta-\ntion and higher cesarean delivery as compared with the control\ngroup. The authors concluded that adenomyosis was associated\nwith a higher preterm delivery rate and more frequent occur-\nrences of FGR and fetal malpresentation. There were no statistical\ndifferences in terms of preeclampsia between groups [24]. Simi-\nlarly, we could not find any relationship between preeclampsia\nand overall frequency of adenomyosis. This was probably due to\nthe fact that neither preeclampsia in itself is not a uniform diease\nnor adenomyosis has only one diagnostic sign [25]. We believe\nthat subgroup analyses in larger group of patients are important\nto make a comment in this point of view.\nYorifuji et al. reported two pregnant cases with non-contrast\nmagnetic resonance angiography technique. Both of the cases\nhad large adenomyomas at the posterior site of the uteruses and\nboth pregnancies resulted in FGR. One of the cases had preec-\nlampsia. They speculated that “vascular steal ” by adenomyosis\nmight be the reason for the FGR in the cases [26]. We also found\na relationship between the presence of adenomyoma on MRI and\nFGR, suggesting that presence of adenomyoma might be related\nwith a poor placental perfusion. We found no relationship be-\ntween signs of adenomyosis on MRI and development of preec-\nlampsia-related complications such as placental abruption and\neclampsia.\nThere are two important results of our study. Firstly, there was no\noverall relationship between preeclampsia and adenomyosis.\nComparison of patients with late and early-onset preeclampsia\nand MRI characteristics showed a significant relationship be-\ntween late-onset preeclampsia and indirect signs of adenomyo-\nsis. Secondly, we found a significant relationship between pres-\nence of adenomyoma and FGR. Thus, not only the mere presence\nof adenomyosis, but also the type and/or size of the adenomyotic\nlesions might have a role in the development of preeclampsia and\nFGR. As a limitation of our study, there was no control group of\nSGA without preeclampsia and numbers of the patients in sub-\ngroups were relatively small.\nConclusion\n!\nPresence of adenomyoma on MRI is more common in cases with\npreeclampsia complicated with FGR and indirect signs of adeno-\nmyosis detected on MRI might play a role in the pathogenesis of\nlate-onset preeclampsia. Further studies with larger groups of\npatients are needed to confirm these findings.\nConflict of Interest\n!\nThe authors declare that they have no competing interests.\nReferences\n1 Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Ob-\nstet Gynaecol 2006; 20: 449 –463\n2 Gordts S, Brosens JJ, Fusi L et al. 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