{"paper_id":"b0e77f01-792a-4666-b6a8-20d5126c31c0","body_text":"UNCORRECTED\nPROOF\nCase Report\nCongenital Imperforate Hymen with Hydrocolpos and\nHydronephrosis associated with Severe Hydramnios and\nIncrease of Maternal Ovarian Steroidogenic Enzymes\nEmmanouil Karteris 1, Helen Foster 1, Maria Karamouti 2, and Anastasia Goumenou 1,2Q2\n1Centre for Cell Chromosome Biology, Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, UK;\n2University of Crete, Division of Medicine, Department of Obstetrics and Gynecology, Heraklion, Crete, Greece\nAbstract. Study Objective: To study a clinical features of\npatient presented with severe hydramnios, associated with\nhydronephrosis, that was antenatally diagnosed and has\nbeen successfully treated immediately after birth. At a mo-\nlecular level, we investigated the gene expression of key\nsteroidogenic enzymes from the maternal ovary.\nDesign: Ultrasound scan, MRI, semi-quantitative RT-PCR\nSetting: The patient was admitted to the University Hos-\npital, University of Crete, Medical School, Greece, where\nall clinical data has been obtained. Gene expression studies\ntook place at Biosciences, Brunel University, UK.\nResults: Semi-quantitative RT-PCR analyses revealed\nthat there is upregulation of key steroidogenic genes in\nthe maternal ovary, including steroidogenic acute regula-\ntory protein, and the cytochrome P450 heme-containing\nproteins CYP11A, CYP17 and CYP19. From a clinical per-\nspective, the prenatal ultrasound scan and MRI findings\nshowed a multicystic pelvic mass, bilateral hydronephrosis\nand prior to delivery severe polyhydramnios.\nConclusion: This clinical case is the only one that we\nhave found in the current literature where congenital imper-\nforate hymen accompanied with hematocolpos is associated\nwith renal obstruction in combination with polyhydramnios\nand increase in maternal steroidogenic enzymes.\nKey Words. Ovarian steroidogenic enzymes—Hyd\nrocolpos—Polyhydramnios\nIntroduction\nCongenital imperforate hymen is the most frequent\ncongenital malformation of the female genital track,\nwhere mucus and blood from endometrial sloughing\naccumulate in the vagina.\n1 When presented in adults,\nthere is a distension of the vaginal canal that can lead\nto cervical dilation and formation of a hematometra\nand hematosalpinx. Symptoms in adults include cy-\nclic and abdominal pain, amenorrhea, and difficulty\nwith urination.\n2 Retrograde menstruation, i.e., back-\nward menstruation into the peritoneal cavity, can lead\nto the onset of endometriosis.\nEndometriosis is a clinical and pathological entity\nthat is characterized by the presence of tissue that re-\nsembles functioning endometrial glands and stroma\noutside the uterine cavity. Symptoms include infertil-\nity and chronic pelvic pain.\n3 It has been hypothesized\nthat vaginal secretions accumulate in response to cir-\nculating maternal estrogens.\n4 Interestingly, recent\nclinical and laboratory studies support the concept\nthat endometriosis is an estrogen-dependent condi-\ntion. Indeed, high estradiol concentrations have been\nidentified as a requisite for proliferation of endometri-\notic lesions, and inducement of a hypoestrogenic state\nis a current therapeutic approach.\n5\nTo the best of our knowledge, hydrocolpos (cystic\ndilatation of the vagina) as an isolated prenatal finding\nhas only been reported twice previously.\n6,7 V aginal\nobstruction may be characterized by the sole presence\nof an imperforate hymen, a transverse vaginal septum,\nor by the presence of a urogenital sinus or cloacal\nmalformation.\n8 Imperforate hymen is the result of\nthe failure of canalization of the vaginal plate, 1 which\nis formed in part of the Mu ¨llerian ducts and from the\nurogenital sinus. 8 A rare condition of congenital im-\nperforate hymen has been presented in which obstruc-\ntion of the vagina was associated with accumulation\nof uterovaginal secretions produced under circulating\nmaternal estrogen stimulation, and the development\nof a hydrometrocolpos. Large hematocolpos may lead\nAddress correspondence to: Emmanouil Karteris, PhD, Centre for\nCell Chromosome Biology, Biosciences, School of Health Sci-\nences and Social Care, Brunel University, Uxbridge, UB8 3PH,\nUK; E-mail: Emmanouil.karteris@brunel.ac.uk\n/C2112009 North American Society for Pediatric and Adolescent Gynecology\nPublished by Elsevier Inc.\n1083-3188/09/$36.00\ndoi:10.1016/j.jpag.2009.10.002\nJ Pediatr Adolesc Gynecol (2009) -:-\nARTICLE IN PRESS\n1\n2\n3\n4\n5\n6\n7\n8\n9\n10\n11\n12\n13\n14\n15\n16\n17\n18\n19\n20\n21\n22\n23\n24\n25\n26\n27\n28\n29\n30\n31\n32\n33\n34\n35\n36\n37\n38\n39\n40\n41\n42\n43\n44\n45\n46\n47\n48\n49\n50\n51\n52\n53\n54\n55\n56\n57\n58\n59\n60\n61\n62\n63\n64\n65\n66\n67\n68\n69\n70\n71\n72\n73\n74\n75\n76\n77\n78\n79\n80\n81\n82\n83\n84\n85\n86\n87\n88\n89\n90\n91\n92\n93\n94\n95\n96\n97\n98\n99\n100\n101\n102\n103\n104\n105\n106\n107\n108\n109\n110\n111\n112\n113\n114\n115\n116\n117\n118\n119\n120\n121\n122\n123\n124\n125\n126\n127\n128\n129\n130\n131\n132\n133\n134\nPEDADO1098_proof /C138 09–11–2009 23:14:21\n\nUNCORRECTED\nPROOF\nto secondary oligoamniosis, due to renal obstruction\nand deteriorating renal function. Interestingly, an\nadult case of hematocolpos was a consequence of\nradiotherapy for cervix carcinoma.\n9 Moreover, in a re-\ncent study of a 15-year-old girl with imperforate\nhymen with hematocolpometra, the serum tumor\nmarker CA125 was elevated.\n10\nThis particular clinical case is the only that we have\nfound in the current literature in which congenital\nimperforate hymen accompanied with hydrocolpos is\nassociated with renal obstruction in combination with\npolyhydramnios and increase in key steroidogenic\ncomponents of the maternal ovary.\nMethods\nOvarian Samples\nThe sample used in this clinical case was obtained\nduring cesarean section surgery, due to the presence\nof a cyst. Therefore, apart from the cyst, an ovarian\nbiopsy was also obtained from surface to clarify the\nnature of the cyst. The ovarian biopsy was taken with\nscissors and there was no significant bleeding. All\ncontrol women were age matched, undergoing cesar-\nean section, and there was a presence of ovarian cysts.\nFor this study, maternal informed consent was ob-\ntained after the procedure was fully explained. All\nprocedures followed were in accordance with the eth-\nical standards of the responsible institutional commit-\ntee on human experimentation. Ovarian samples\n(n 5 4; 1 from the clinical case and 3 pooled controls)\nwere placed in RNAlater /C210(Sigma Aldrich, UK) until\nfurther use.\nRNA Isolation and cDNA Synthesis\nEach sample was lysed in 600 ml of RNA lysis buffer\nusing the TissueLyser (Qiagen, UK). Total RNA was\nextracted from these specimens using an RNA extrac-\ntion kit (Sigma, UK), according to manufacturer’s in-\nstructions. RNA concentration was determined by\nspectrophotometric analysis (NanoDrop, Thermo Sci-\nentific, UK). RNA (200ng) was reverse-transcribed into\ncDNA using 5 IU/ ml RNase H reverse transcriptase\n(Invitrogen, UK).\nSemiquantitative RT-PCR\nPCR amplification was carried out using Taq poly-\nmerase (Invitrogen). The primers used for this\nstudy were: steroidogenic acute regulatory protein\n(StAR, 181 bp): 5’-CGTGACTTTGTGAGCG-3’ and\n5’-GCCACGTAAGTTTGGT-3’; CYP11A (202 bp):\n5’-AGAGTTGAAA TCCAACA CC-3’ and 5’-TGGG\nACAGACGACTGA-3’; CYP17 (205 bp): 5’-GTGA\nCCGTAA CCGTCT-3’ and 5’- A TGAACTGA TCC\nGGCT-3’; HSD3B2 (298 bp): 5’-CCA TACCCGTA-\nCAGCA-3’and 5’-A T TGACCTCGGACACT-3’;\nCYP19 (242 bp) 5’-CAGAGGCCAAGAGTTTGA\nGG-3’ and 5’-ACACTAGCAGGTGGGTTTGG-3’;\nb-actin (216 bp): 5’-AAGAGAGGCA TCCTCACC\nCT-3’ and 5’-TACA TGGCTGG GGTGTTGAA-3’.\nAfter an initial denaturation step of 94\n/C14C for 4 min,\n28 cycles were performed consisting of an initial de-\nnaturing step at 94\n/C14C for 30s, followed by extension\nat 60 /C14C for 30 s and elongation at 72 /C14C for 1 min.\nDensitometric analysis of resulted PCR products re-\nsolved on a 2% agarose gel were quantified using\nthe AlphaEase FC software.\nResults\nMolecular Findings—Changes in the Gene\nExpression of Steroidogenic Components in the\nMaternal Ovary\nAs mentioned previously, it has been hypothesized\nthat vaginal secretions accumulate in response to cir-\nculating maternal estrogens.\n4 In this study we also\nsought to investigate this hypothesis by assessing\nthe gene expression of key steroidogenic enzymes\nfrom the maternal ovary compared to age-matched\npooled controls. Semi-quantitative RT-PCR revealed\nsignificant upregulation of the following genes when\ncompared to an age-matched normal ovary: StAR\nby 1.55, CYP11A by 1.67, CYP17 by 7.1 and\nCYP19 by 5.2 fold ( Fig 1 ). The most profound in-\ncrease was that of CYP17 and CYP19 when compared\nto the normal ovary, whereas the levels of 3 bHSD2 re-\nmained unaltered (data not shown). This is the first\nstudy that we have found to describe a fetus with\nhydrocolpos exhibiting changes in the expression of\nmaternal steroidogenic enzymes at the ovarian level.\nClinical Findings—Identification of Cystic Mass\nand Hydronephrosis Using Ultrasound Scan and\nSurgical Procedures\nAn abdominal cystic mass with maximum diameter\n43.5 /C229.4 mm was discovered on a prenatal sono-\ngram in a female fetus at 29 weeks gestation in\na 32-year-old woman para 1, gravida 3. Fetal biome-\ntry was within the normal range for gestational age.\nThe patient’s prenatal course, which included amnio-\nparacentesis (because of patient’s family history for\ntrisomy 21 in a maternal aunt) had been uncompli-\ncated and previous ultrasound scan examinations as\nwell as 21 weeks ultrasound scan were reported nor-\nmal. Cytogenetic analysis revealed a normal female\nkaryotype (46 XX), and no chromosomal abnormali-\nties were detected. There was no history of familial\nimperforate hymen. All serial prenatal ultrasound\nscans were performed at a specialist fetal medicine\nunit. On follow-up scans every 5 e10 days, the ap-\npearance of the pelvic cystic mass showed a gradual\nenlargement ( Fig 2 , panels a, b) and mild bilateral\n2 Karteris et al: Congenital Imperforate Hymen\nARTICLE IN PRESS\n135\n136\n137\n138\n139\n140\n141\n142\n143\n144\n145\n146\n147\n148\n149\n150\n151\n152\n153\n154\n155\n156\n157\n158\n159\n160\n161\n162\n163\n164\n165\n166\n167\n168\n169\n170\n171\n172\n173\n174\n175\n176\n177\n178\n179\n180\n181\n182\n183\n184\n185\n186\n187\n188\n189\n190\n191\n192\n193\n194\n195\n196\n197\n198\n199\n200\n201\n202\n203\n204\n205\n206\n207\n208\n209\n210\n211\n212\n213\n214\n215\n216\n217\n218\n219\n220\n221\n222\n223\n224\n225\n226\n227\n228\n229\n230\n231\n232\n233\n234\n235\n236\n237\n238\n239\n240\n241\n242\n243\n244\n245\n246\n247\n248\n249\n250\n251\n252\n253\n254\n255\n256\n257\n258\n259\n260\n261\n262\n263\n264\n265\n266\n267\n268\nPEDADO1098_proof /C138 09–11–2009 23:14:21\n\nUNCORRECTED\nPROOF\nStAR\nCYP11A\nCYP17A\nCYP19A\nββ-actin\n1      2     3\n0\n0.2\n0.4\n0.6\n0.8\n1\n1.2\n1.4\n1.6\n1.8\nNormal\na e r cid l oFs\n0\n0.2\n0.4\n0.6\n0.8\n1\n1.2\n1.4\n1.6\n1.8\n2\na e rc nidloF s\n0\n1\n2\n3\n4\n5\n6\n7\n8\na erc n i d l oF s\n0\n1\n2\n3\n4\n5\n6\na e r c n i d l oFs\n0\n1\n2\n3\ne s a e r c nidloF\nPatient\nNormal Patient\nNormal Patient\nNormal Patient\nNormal Patient\nFig. 1. Changes in the gene expression of steroidogenic components in the maternal ovary. Lane 1: cDNA from normal ovaries;\nLane 2: cDNA from patient; Lane 3: negative control.\nQ13Karteris et al: Congenital Imperforate Hymen\nARTICLE IN PRESS\n269\n270\n271\n272\n273\n274\n275\n276\n277\n278\n279\n280\n281\n282\n283\n284\n285\n286\n287\n288\n289\n290\n291\n292\n293\n294\n295\n296\n297\n298\n299\n300\n301\n302\n303\n304\n305\n306\n307\n308\n309\n310\n311\n312\n313\n314\n315\n316\n317\n318\n319\n320\n321\n322\n323\n324\n325\n326\n327\n328\n329\n330\n331\n332\n333\n334\n335\n336\n337\n338\n339\n340\n341\n342\n343\n344\n345\n346\n347\n348\n349\n350\n351\n352\n353\n354\n355\n356\n357\n358\n359\n360\n361\n362\n363\n364\n365\n366\n367\n368\n369\n370\n371\n372\n373\n374\n375\n376\n377\n378\n379\n380\n381\n382\n383\n384\n385\n386\n387\n388\n389\n390\n391\n392\n393\n394\n395\n396\n397\n398\n399\n400\n401\n402\nPEDADO1098_proof /C138 09–11–2009 23:14:21\n\nUNCORRECTED\nPROOF\nhydronephrosis ( Fig 2 , panel c), but there were no\nchanges in amniotic fluid volume.\nThe patient was admitted to the hospital at 32\nweeks because of premature uterine contractions and\ncorticosteroids were administered to prepare for even-\ntual preterm birth as well as tocolytic therapy intrave-\nnously (IV) to control contractions. At 35 weeks of\ngestation the size of cystic mass increased, measuring\n86 /C275 mm maximum and hydronephorsis worsened.\nUreteronephrosis was noticed while amniotic fluid\nvolume significantly increased (amniotic fluid index\n(AFI) was 25 e27 cm) followed by hydramnios\ndevelopment. The estimated fetal weight was 3150 g.\nDue to premature contractions and a history of pre-\nvious cesarean section, the patient underwent an\nemergency cesarean section and a female neonate\nweighting 3250 g, at 35 weeks of pregnancy, with Ap-\ngar scores of 8 and 9 after 1 and 5 minutes, respec-\ntively, was delivered. The neonate was admitted to\nthe neonatal intensive care unit for ventilatory support\nand further investigations. Physical examination\nshowed soft but distended mass above the umbilicus\nabdomen measuring 8 /C27 cm.\nBladder catheterization was performed with\ndifficulty and clear urine was expressed. Renal func-\ntion tests were normal at birth, with a creatinine of\n0.7 mmol/L, and urea at 24 mmol/L. Abdominal ultra-\nsound examination showed a cystic mass posterior to\nthe bladder, bilateral hydronephrosis (1.3 cm) and\nhydroureter. MRI revealed an abdominal cystic mass\nwith maximal diameter 90 /C270 mm, which was felt\nto be a hydrometrocolpos due to an imperforate\nhymen.\nAdditional investigation of the urinary system dem-\nonstrated normal kidneys, renal calyces, ureter, and\na small bladder displaced to the anterior abdominal wall\ndue to the mass effect of the hydrocolpos. Neither reflux\nnor ureteroceles were observed. The patient was re-\nferred to pediatric surgery. Consent was obtained from\nthe baby’s parents, and a hymenectomy was performed\nwhere approximately 200 mL of clear serous and\nmucoid fluid was drained ( Figs 3 and 4 ).\nDiscussion\nCongenital imperforate hymen is the most frequent\nobstructive anomaly of the female genital tract. This\ngenerally occurs sporadically, with a reported\nweb 4C=FPO\nFig. 2. Panel a: Longitudinal view of the large cystic ab-\ndominal mass with gravity dependent echoes, extending\nup to the diaphragm at 33 /C65 weeks gestation. Panel b:\nTransverse view at 33 /C65 weeks gestation reveals a large\ncystic abdominal mass. Panel c: Sagittal view of bilateral\nhydronephrosis, at 33 /C65 weeks gestation\nweb 4C=FPO\nFig. 3. A view of surgical hymenotomy performed by pedi-\natric surgeons.\n4 Karteris et al: Congenital Imperforate Hymen\nARTICLE IN PRESS\n403\n404\n405\n406\n407\n408\n409\n410\n411\n412\n413\n414\n415\n416\n417\n418\n419\n420\n421\n422\n423\n424\n425\n426\n427\n428\n429\n430\n431\n432\n433\n434\n435\n436\n437\n438\n439\n440\n441\n442\n443\n444\n445\n446\n447\n448\n449\n450\n451\n452\n453\n454\n455\n456\n457\n458\n459\n460\n461\n462\n463\n464\n465\n466\n467\n468\n469\n470\n471\n472\n473\n474\n475\n476\n477\n478\n479\n480\n481\n482\n483\n484\n485\n486\n487\n488\n489\n490\n491\n492\n493\n494\n495\n496\n497\n498\n499\n500\n501\n502\n503\n504\n505\n506\n507\n508\n509\n510\n511\n512\n513\n514\n515\n516\n517\n518\n519\n520\n521\n522\n523\n524\n525\n526\n527\n528\n529\n530\n531\n532\n533\n534\n535\n536\nPEDADO1098_proof /C138 09–11–2009 23:14:21\n\nUNCORRECTED\nPROOF\nincidence at term 11 of 0.014e1% and gives rise to hy-\ndrometrocolpos in less than 1/16000 female births. 12\nFailure of this membrane to rupture results in congen-\nital imperforate hymen, which in combination with\naccumulation of uterovaginal secretions, (produced\nas a consequence of intrauterine stimulation of cervi-\ncal mucous glands by maternal estrogen hormones),\nmay lead to the development of an internal\nQ3 hydrome-\ntrocolpos.13 This can be presented as a pelvic mass in\ncombination or not with urinary track obstruction and\noligohydramnios.\nIn this clinical case the cystic mass presented for the\nfirst time during the 3rd trimester (29 weeks of gesta-\ntion), having hypoechoic content with a maximum\ndiameter of 43.5 /C229.4 mm. At 35 weeks the cystic\nmass had a maximum diameter of 86 /C275 mm causing\nbilateral urinary obstruction and hydronephrosis. What\nis interesting and unique in our case is the fact that\nalthough there was a lack of a normal urinary outlet,\noligohydramnios was not found. On the contrary, an\nevident increase of the amniotic fluid volume (AFI,\n25e27 cm) was observed. Cianciosi et al suggested\nthe following mechanisms for accompanied hydram-\nnios in abdominal cystic masses: (a) the compression\nof the adjacent bowel by the expanding cyst causing\na hypoperistaltic intestine, or reduction of the absorp-\ntive capacity of the stomach and bowel by modifying\nthe gastrointestinal vascularization, and (b) the depres-\nsion\nQ4or an incorrect swallowing process, as suggested\nby tongue protrusion, reducing the fluid removal from\nthe amniotic cavity.\n14\nThe differential diagnosis of imperforate hymen is\nfrom labial adhesions, vaginal atresia, vaginal agene-\nsis, and transverse vaginal septum. However, the ab-\ndominal mass has to be diagnosed differentially\nfrom distental urinary bladder, ovarian tumors and\nneoplasms, mesenteric cysts, anterior meningoceles,\nreduplication of sigmoid and sacral tumors. Prenatal\nultrasonographic diagnosis of hydrocolpos has only\nbeen reported in three cases,\n7,15,16 none of which\nhad hydramnios detected.\nAs mentioned previously, it has been hypothesized\nthat vaginal secretions accumulate in response to\ncirculating maternal estrogens.\n4 Therefore, based on\nour observations from the gene expression studies, it\nis attractive to speculate that, in this particular clinical\ncase of hydrocolpos, the overall steroidogenic activity\nin the maternal ovary would have been enhanced. In-\ndeed, when compared to control patients, the largest\nincrease in gene expression was that of CYP17 and\nCYP19. CYP17 is expressed in all classic steroido-\ngenic organs and in the human ovary it is selectively\nweb 4C=FPO\nFig. 4. View of tubing for drainage of retained secretions\ntrough vagina.web 4C=FPO\nFig. 5. Diagrammatic\nQ5\nrepresentation of steroid hormone biosynthesis steps in the human ovary. In red Q6are the key components\nthat have been upregulated in the maternal ovary of the fetus with hydrocolpos.\n5Karteris et al: Congenital Imperforate Hymen\nARTICLE IN PRESS\n537\n538\n539\n540\n541\n542\n543\n544\n545\n546\n547\n548\n549\n550\n551\n552\n553\n554\n555\n556\n557\n558\n559\n560\n561\n562\n563\n564\n565\n566\n567\n568\n569\n570\n571\n572\n573\n574\n575\n576\n577\n578\n579\n580\n581\n582\n583\n584\n585\n586\n587\n588\n589\n590\n591\n592\n593\n594\n595\n596\n597\n598\n599\n600\n601\n602\n603\n604\n605\n606\n607\n608\n609\n610\n611\n612\n613\n614\n615\n616\n617\n618\n619\n620\n621\n622\n623\n624\n625\n626\n627\n628\n629\n630\n631\n632\n633\n634\n635\n636\n637\n638\n639\n640\n641\n642\n643\n644\n645\n646\n647\n648\n649\n650\n651\n652\n653\n654\n655\n656\n657\n658\n659\n660\n661\n662\n663\n664\n665\n666\n667\n668\n669\n670\nPEDADO1098_proof /C138 09–11–2009 23:14:22\n\nUNCORRECTED\nPROOF\nexpressed in thecal cells. 17 CYP19, on the other hand,\nhas a far wider distribution and in the human ovary is\nprimarily expressed in the corpus luteum. This is of\nparticular importance to this case because CYP19\ncatalyzes reactions leading to estrogen biosynthesis.\nDepending on its expression, CYP19 (P450arom)\ncatalyzes the conversion of the C19 androgens, an-\ndrostenedione and testosterone, to the C18 estrogens,\nestrone and estradiol, respectively.\n17\nIt is well known that steroids such as maternal\nestrogens as well as progesterone rise exponentially\nduring the later stages in pregnancy. What is interesting\nin this clinical case is that the control ovarian samples\nwere also taken from age-matched women, undergoing\ncesarean section. As a result, it is the possible dysregu-\nlation of the maternal steroidogenic pathway in this\nclinical case that might contribute to the upregulation\nof certain enzymes. In addition, with regard to a link be-\ntween types of circulating estrogens and polyhydram-\nnios, very little is known. However, a study by Phocas\net al showed that there was a discrepancy in the estrogen\nlevels regarding their increase. This was due to the type\npolyhydramnios, the pregnancy outcome, and the\ncondition of fetus at birth.\n18\nIn conclusion, this is a novel clinical case where there\nis clear evidence of a maternal steroidogenic over-drive\nassociated with fetal hydrocolpos, thus potentially link-\ning maternal ovarian steroidal stimulation with this\npathophysiological condition.\nUncited Figure\nFig 5\nReferences\n1. Messina M, Severi FM, Bocchi C, et al: V oluminous perinatal\npelvic mass: a case of congenital hydrometrocolpos. J Matern\nFetal Neonatal Med 2004; 15:135\n2. Bakos O, Berglund L: Imperforate hymen and ruptured\nhematosalpinx: a case report with a review of the literature.\nJ Adolesc Health 1999; 24:226\n3. Kobayashi H, Yamada Y , Kanayama S, et al: The role of\niron in the pathogenesis of endometriosis. Gynecol\nEndocrinol 2009; 25:39\n4. 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Payne AH, Hales DB: Overview of steroidogenic enzymes\nin the pathway from cholesterol to active steroid hormones.\nEndocr Rev 2004; 25:947\n18. Phocas I, Salamalekis E, Sarandakou A, et al: Hormonal and\nbiochemical parameters in polyhydramnios. Eur J Obstet\nGynecol Reprod Biol 1987; 25:277\n6 Karteris et al: Congenital Imperforate Hymen\nARTICLE IN PRESS\n671\n672\n673\n674\n675\n676\n677\n678\n679\n680\n681\n682\n683\n684\n685\n686\n687\n688\n689\n690\n691\n692\n693\n694\n695\n696\n697\n698\n699\n700\n701\n702\n703\n704\n705\n706\n707\n708\n709\n710\n711\n712\n713\n714\n715\n716\n717\n718\n719\n720\n721\n722\n723\n724\n725\n726\n727\n728\n729\n730\n731\n732\n733\n734\n735\n736\n737\n738\n739\n740\n741\n742\n743\n744\n745\n746\n747\n748\n749\n750\n751\n752\n753\n754\n755\n756\n757\n758\n759\n760\n761\n762\n763\n764\n765\n766\n767\n768\n769\n770\n771\n772\n773\n774\n775\n776\n777\n778\n779\n780\n781\n782\n783\n784\n785\n786\n787\n788\n789\n790\n791\n792\n793\n794\n795\n796\n797\n798\n799\n800\n801\n802\n803\n804\nPEDADO1098_proof /C138 09–11–2009 23:14:22","source_license":"CC0","license_restricted":false}