{"paper_id":"f9be7291-de5d-4a11-960e-288212c038f8","body_text":"www.ogscience.org270\nThe timing of adenomyosis diagnosis and its impact on \npregnancy outcomes: a national population-based study\nYoung Mi Jung, MD\n1\n, Wonyoung Wi, BS\n1\n, Hwa Seon Koo, MD, PhD\n2\n, Seung-Hyuk Shim, MD, PhD\n3\n,  \nSoo-Young Oh, MD, PhD\n4\n, Seung Mi Lee, MD, PhD\n5\n, Jin Hoon Chung, MD, PhD\n6\n, SiHyun Cho, MD, PhD\n7\n,  \nHyunjin Cho, MD, PhD\n8\n, Min-Jeong Oh, MD, PhD\n1\n, Geum Joon Cho, MD, PhD\n1\n, Hye-Sung Won, MD, PhD\n9\n1\nDepartment of Obstetrics and Gynecology, Korea University Guro Hospital, \n2\nBest of ME Fertility Clinic, Department of Obstetrics and Gynecology, \n3\nResearch Institute of Medical Science, Konkuk University School of Medicine, \n4\nSamsung Medical Center, Sungkyunkwan University School of Medi-\ncine, \n5\nSeoul National University College of Medicine, \n6\nDivision of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Asan Medical \nCenter, University of Ulsan College of Medicine, Department of Obstetrics and Gynecology, \n7\nGangnam Severance Hospital, Yonsei University College \nof Medicine, Seoul, \n8\nHaeundae Paik Hospital, Inje University, Busan, \n9\nAsan Medical Center, University of Ulsan College of Medicine, Seoul, Korea\nOriginal Article\nObstet Gynecol Sci 2024;67(3):270-278\nhttps://doi.org/10.5468/ogs.23273\neISSN 2287-8580Received: 2023.11.20.   Revised: 2024.01.23.   Accepted: 2024.02.07.\nCorresponding author: Geum Joon Cho, MD, PhD\nDepartment of Obstetrics and Gynecology, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea\nE-mail: md_cho@hanmail.net\nhttps://orcid.org/0000-0001-6761-0944\nCorresponding author: Hye-Sung Won, MD, PhD\nDepartment of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-\ngu, Seoul 05505, Korea\nE-mail: hswon@amc.seoul.kr\nhttps://orcid.org/0000-0003-0611-2401\nMin-Jeong Oh and Geum Joon Cho have been an Editorial Board of Obstetrics & Gynecology Science; however, they are not involved in the peer reviewer selection, evaluation, or \ndecision process of this article. Otherwise, no other potential conflicts of interest relevant to this article were reported.\nArticles published in Obstet Gynecol Sci are open-access, distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/\nlicenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.\nCopyright © 2024 Korean Society of Obstetrics and Gynecology \n\n\nwww.ogscience.org 271\n Young Mi Jung, et al. Adenomyosis on pregnancy outcomes\nIntroduction\nAdenomyosis is a complex gynecological condition character-\nized by the presence of endometrial epithelial and stromal \ncells within the myometrium. Its prevalence is estimated to \nbe between 20% and 35% [1,2]. This condition exhibits a \nwide range of anatomical and clinical variations, including \ndifferences in uterine size and symptoms, which can range \nfrom severe dysmenorrhea and heavy menstrual bleeding to \nbeing completely asymptomatic [3].\nAdenomyosis can significantly impact pregnancy outcomes. \nWomen with adenomyosis can face challenges in achieving \npregnancy and have an increased risk of miscarriage. Ad\n-\nditionally, adenomyosis has been associated with a higher \nlikelihood of preterm birth, preeclampsia, and delivery of a \nsmall-for-gestational-age baby, as well as an elevated rate \nof delivery by cesarean section [4-6]. While the impact of \nadenomyosis on pregnancy can vary among individuals, it \nunderscores the importance of comprehensive prenatal care \nand close collaboration between patients and healthcare \nproviders to optimize maternal and fetal well-being.\nHowever, assessing the severity of symptoms or interpret\n-\ning ultrasound results involves subjectivity, which presents \nchallenges for conducting research. Moreover, existing \nresearch on the effects of adenomyosis has several limita\n-\ntions that warrant consideration. The diagnostic criteria for \nadenomyosis vary among studies, using methods such as \ntransvaginal ultrasound or magnetic resonance imaging, and \noften fail to distinguish between grades of the condition. \nAdjustments for potential confounders are often limited, and \nsome outcomes are based on small sample sizes, leading to \npotential type II errors. Therefore, the objective of this study \nwas to investigate the impact of the timing of adenomyosis \ndiagnosis on pregnancy outcomes.\nMaterials and methods\n1. Data\nThis study utilized a combined dataset from two primary \nsources: the Korea National Health Insurance (KNHI) claims \ndatabase and the National Health Screening Program for \nInfants and Children (NHSP-IC). The KNHI program covers \napproximately 97% of the Korean population. The database \nprovides information on beneficiaries including demographic, \nsocioeconomic, diagnostic, procedural, and prescription data. \nObjective\nAdenomyosis impacts pregnancy outcomes, although there is a lack of consensus regarding the actual effects. It is \nlikely, however, that the severity of adenomyosis or ultrasound findings or timing of diagnosis can have different \neffects on adverse pregnancy outcomes (APOs). \nMethods\nIn this study, we aimed to investigate the impact of the timing of adenomyosis diagnosis on pregnancy outcomes. Sin-\ngleton pregnant women who delivered between 2017 and 2022 were analyzed based on the timing of adenomyosis \ndiagnosis, using a national database. The final cohort was classified into three groups: 1) group 1, without adenomyo\n-\nsis; 2) group 2, those diagnosed with adenomyosis before pregnancy; and 3) group 3, those diagnosed with adeno-\nmyosis during pregnancy.\nResults\nA total of 1,226,475 cases were ultimately included in this study. Women with a diagnosis of adenomyosis had a sig-\nnificantly higher risk of APOs including hypertensive disorder during pregnancy (HDP), gestational diabetes mellitus \n(GDM), postpartum hemorrhage, placental abruption, preterm birth, and delivery of a small-for-gestational-age in\n-\nfant even after adjusting for covariates. In particular, concerning HDP, the risk was highest in group 3 (group 2: adjust-\ned odds ratio [aOR], 1.15 vs. group 3: aOR, 1.36). However, the highest GDM risk was in group 2 (GDM; group 2: aOR, \n1.24 vs. group 3: aOR, 1.04). \nConclusion\nThe increased risk of APO differed depending on the timing of adenomyosis diagnosis. Therefore, efforts for more \ncareful monitoring and prevention of APOs may be necessary when such women become pregnant.\nKeywords: Adenomyosis; Preeclampsia; Gestational diabetes; Preterm birth; Pregnancy outcome\n\nwww.ogscience.org272\nVol. 67, No. 3, 2024\nWith this dataset, the impact of the timing of adenomyosis \ndiagnosis on pregnancy outcomes was evaluated. The study’s \nprotocol received approval from the Institutional Review \nBoard of the Korea University Guro Hospital (2023GR0532).\n2. Study design\nThis retrospective analysis encompassed a nationwide popu -\nlation of women who gave birth to singleton babies between \n2017 and 2022. The final cohort was classified into three \ngroups: 1) group 1, those without adenomyosis; 2) group 2, \nthose diagnosed with adenomyosis before pregnancy; and \n3) group 3, those diagnosed with adenomyosis during preg\n-\nnancy (Fig. 1).\n3. Pregnancy and neonatal outcomes\nMaternal health conditions were ascertained by querying the \nInternational Classification of Diseases 10th Revision (ICD-10) \ndiagnosis codes. A diagnosis of maternal adenomyosis, both \nbefore and after pregnancy, was established when patients \nhad been diagnosed with adenomyosis (ICD-10 code N80). \nAdenomyosis during pregnancy was confirmed through the \nidentification of an ICD-10 code for the time during preg\n-\nnancy, as there were no pre-pregnancy ICD-10 codes indicat-\ning its presence. Data on pregnancy outcomes were extract -\ned using ICD-10 codes, which included information on the \nmode of delivery, underlying diseases, hypertensive disorder \nduring pregnancy (HDP), gestational diabetes mellitus (GDM), \npostpartum hemorrhage (PPH), placental abruption, and pla\n-\ncenta previa. Data on neonatal outcomes, including preterm \nbirth and birth weight were extracted from the NHSP-IC \ndatabase. Preterm birth was defined as having a gestational \nage <37 weeks, small for gestational age (SGA) was defined \nas a birthweight below the 10th percentile for the gestation\n-\nal age, and large for gestational age (LGA) was defined as a \nbirthweight over the 90th percentile for the gestational age. \n4. Statistical analysis\nThe continuous variables are presented as means and the \nstandard deviation, and group comparisons were conducted \nusing either Student’s t-test or the analysis of variance model \nfor multiple groups. The categorical variables are presented \nas counts and percentages, and group comparisons were \nperformed using the chi-square test. To assess the adverse \npregnancy outcomes, a regression model was employed to \ncalculate odds ratios (ORs) and their corresponding 95% \nconfidence intervals. The statistical analyses were carried \nout using the SAS software version 9.4 for Windows (SAS \nInc., Cary, NC, USA), and statistical significance was set at a \n \nP-value <0.05.\nResults\n1. Study population\nAmong the 1,316,597 women who delivered between 2017 \nand 2022, after excluding multiple pregnancies and miss\n-\nFig. 1. Flowchart of the study population.\nDeliveries between 2017-2022 (n=1,316,597)\nFinal study cohort (n=1,226,475)\nWomen without adenomyosis \n(n=1,210,178)\nWomen who diagnosed as adenomyosis \nbefore pregnancy (n=10,356)\nWomen who diagnosed as adenomyosis \nduring pregnancy (n=5,941)\nExclusion\n· Multifetal pregnancy (n=65,923)\n· Patients who have missing value (n=24,199)\n\nwww.ogscience.org 273\n Young Mi Jung, et al. Adenomyosis on pregnancy outcomes\ning data, a total of 1,226,475 women were included in the \nfinal analysis. Of these, 1,210,178 women had no diagnosis \nof adenomyosis (group 1), while 10,356 women were diag -\nnosed with adenomyosis before pregnancy (group 2), and \n5,941 women were diagnosed with adenomyosis during \npregnancy (group 3) (Fig. 1). In Supplementary Table 1, the \nnumber of cases diagnosed with adenomyosis is presented \nannually.  \nTable 1 shows the baseline characteristics of the study pop-\nulation. The pregnant women with adenomyosis were older \nand more likely to be nulliparity than the pregnant women \nwith no diagnosis of adenomyosis. The women in groups 2 \nand 3 had higher prevalence of hypertension before preg -\nnancy and a history of overt diabetes compared with those in \ngroup 1, but there was no statistically significant difference \nbetween group 2 and group 3 (hypertension before preg\n-\nnancy, 0.89% in group 1; 1.89% in group 2; and 1.57% in \ngroup 3, P<0.0001; overt diabetes mellitus, 1.76% in group \n1; 3.34% in group 2; 2.54% in group 3, P<0.0001).\n2. Pregnancy and neonatal outcomes\nTable 2 presents the pregnancy and neonatal outcomes of \nthe three groups. The pregnant women with adenomyosis \nhad an increased risk of adverse pregnancy outcomes includ\n-\ning HDP , GDM, cesarean section, PPH, placenta previa, pla -\ncental abruption, preterm delivery, SGA, and LGA compared \nwith those in group 1. For groups 2 and 3, the occurrence \nof GDM and preterm labor was higher in group 2 compared \nwith group 3.\n3. Risk of adverse pregnancy outcomes\nTable 3 summarizes the ORs of the presence of adenomyosis \nbefore pregnancy for adverse pregnancy outcomes such as \nHDP , GDM, cesarean section, PPH, placenta previa, placental \nabruption, preterm delivery, SGA, and LGA compared with \nthose with no adenomyosis or adenomyosis diagnosed dur\n-\ning pregnancy after adjustment for confounding variables. \nIn group 3, HDP , the risks of cesarean section, PPH, pla -\ncenta previa, placental abruption, and SGA were the highest. \nHDP and the risk of cesarean section exhibited a statistically \nsignificant difference between groups 2 and 3. In group 2, \nthe risks of GDM and preterm delivery were the highest. In\n-\nterestingly, for GDM, the risk was found to decrease in group \n3 compared to group 2, and for preterm delivery, there was \nno statistically significant difference between the two groups.\nTable 1. Baseline characteristics of the study population\nGroup 1 (n=1,210,178) Group 2 (n=10,356) Group 3 (n=5,941) P-value\na)\nP-value\nb)\nP-value\nc)\nP-value\nd)\nAge (yr) 32.94±4.2 35.05±4.03 34.83±4.25 <0.0001 <0.0001 <0.0001 0.0051\nNulliparity 675,514 (55.82) 6,918 (66.8) 3,556 (59.86) <0.0001 <0.0001 <0.0001 <0.0001\nChronic hypertension 10,814 (0.89) 196 (1.89) 93 (1.57) <0.0001 <0.0001 <0.0001 0.1277\nOvert diabetes mellitus 21,262 (1.76) 346 (3.34) 151 (2.54) <0.0001 <0.0001 <0.0001 0.0043\nMyoma before pregnancy 90,476 (7.48) 3,804 (36.73) 1.205 (20.28) <0.0001 <0.0001 <0.0001 <0.0001\nValues are presented as mean±standard deviation or number (%).\na)\nP-value of comparison among the three groups.\nb)\nP-value of comparison between groups 1 and 2.\nc)\nP-value of comparison between groups 1 and 3.\nd)\nP-value of comparison between groups 2 and 3.\n\nwww.ogscience.org274\nVol. 67, No. 3, 2024\nTable 2. Pregnancy outcomes and neonatal outcomes according to the timing of adenomyosis diagnosis\nGroup 1 (n=1,210,178) Group 2 (n=10,356) Group 3 (n=5,941) P-value\na)\nP-value\nb)\nP-value\nc)\nP-value\nd)\nPregnancy outcomes\nHDP 56,877 (4.7) 642 (6.2) 404 (6.8) <0.0001 <0.0001 <0.0001 0.1319\nGDM 124,352 (10.28) 1,586 (15.31) 750 (12.62) <0.0001 <0.0001 <0.0001 <0.0001\nCesarean section 605,010 (49.99) 6,549 (63.24) 3,752 (63.15) <0.0001 <0.0001 <0.0001 0.9144\nPPH 146,814 (12.13) 1,375 (13.28) 793 (13.35) <0.0001 0.0004 0.0042 0.8984\nPlacenta previa 370,46 (3.06) 584 (5.64) 356 (5.99) <0.0001 <0.0001 <0.0001 0.3522\nPlacental abruption 5,142 (0.42) 76 (0.73) 44 (0.74) <0.0001 <0.0001 0.0002 0.9614\nNeonatal outcomes\nBirthweight 3.22±0.45 3.12±0.51 3.13±0.5 <0.0001 <0.0001 <0.0001 0.643\nPreterm delivery 35,429 (2.93) 696 (6.72) 351 (5.91) <0.0001 <0.0001 <0.0001 0.0417\nSGA 153,109 (12.65) 1,588 (15.33) 945 (15.91) <0.0001 <0.0001 <0.0001 0.3318\nLGA 92,159 (7.62) 696 (6.72) 469 (7.89) 0.0021 0.0006 0.4187 0.0051\nValues are presented as mean±standard deviation or numbe (%).\nHDP , hypertensive disorder during pregnancy; GDM, gestational diabetes mellitus; PPH, postpartum hemorrhage; SGA, small for gestational age; LGA, small for gestational age. \na)\nP-value of comparison among the three groups.\nb)\nP-value of comparison between groups 1 and 2.\nc)\nP-value of comparison between groups 1 and 3.\nd)\nP-value of comparison between groups 2 and 3.\n\nwww.ogscience.org 275\n Young Mi Jung, et al. Adenomyosis on pregnancy outcomes\nTable 3. Multivariate analyses for pregnancy and neonatal outcomes\nOdds ratio (95% CI) P-value\na)\nOdds ratio (95% CI) P-value\na)\nHDP\nNo adenomyosis (Reference) 　 0.870 (0.802-0.944) 0.0008\nAdenomyosis before pregnancy 1.149 (1.059-1.246) 0.0008 (Reference) 　\nAdenomyosis during pregnancy 1.356 (1.224-1.502) <0.0001 1.180 (1.037-1.344) 0.0123\nGDM\nNo adenomyosis (Reference) 　 0.807 (0.764-0.853) <0.0001\nAdenomyosis before pregnancy 1.239 (1.172-1.309) <0.0001 (Reference) 　\nAdenomyosis during pregnancy 1.039 (0.961-1.124) 0.331 0.839 (0.763-0.923) 0.0003\nCesarean section\nNo adenomyosis (Reference) 0.786 (0.754-0.819) <0.0001\nAdenomyosis before pregnancy 1.273 (1.221-1.326) <0.0001 (Reference)\nAdenomyosis during pregnancy 1.434 (1.359-1.514) <0.0001 1.127 (1.053-1.206) 0.0005\nPPH\nNo adenomyosis (Reference) 0.913 (0.862-0.966) 0.0018\nAdenomyosis before pregnancy 1.096 (1.035-1.161) 0.0018 (Reference)\nAdenomyosis during pregnancy 1.114 (1.033-1.201) 0.0049 1.016 (0.925-1.116) 0.7357\nPlacenta previa\nNo adenomyosis (Reference) 0.667 (0.613-0.727) <0.0001\nAdenomyosis before pregnancy 1.498 (1.376-1.632) <0.0001 (Reference)\nAdenomyosis during pregnancy 1.700 (1.526-1.894) <0.0001 1.135 (0.990-1.300) 0.0696\nPlacental abruption\nNo adenomyosis (Reference) 0.662 (0.526-0.833) 0.0004\nAdenomyosis before pregnancy 1.510 (1.200-1.899) 0.0004 (Reference)\nAdenomyosis during pregnancy 1.603 (1.189-2.160) 0.0019 1.135 (0.731-1.542) 0.7528\nPreterm delivery\nNo adenomyosis (Reference) 0.508 (0.469-0.550) <0.0001\nAdenomyosis before pregnancy 1.968 (1.818-2.131) <0.0001 (Reference)\nAdenomyosis during pregnancy 1.823 (1.634-2.034) <0.0001 0.926 (0.811-1.059) 0.2627\nSGA\nNo adenomyosis (Reference) 0.819 (0.776-0.865) <0.0001\nAdenomyosis before pregnancy 1.220 (1.156-1.288) <0.0001 (Reference)\nAdenomyosis during pregnancy 1.293 (1.206-1.387) <0.0001 1.060 (0.970-1.157) 0.1961\nLGA\nNo adenomyosis (Reference) 1.189 (1.100-1.285) <0.0001\nAdenomyosis before pregnancy 0.841 (0.778-0.909) <0.0001 (Reference)\nAdenomyosis during pregnancy 1.004 (0.913-1.104) 0.9342 1.194 (1.056-1.349) 0.0045\nCI, confidence interval; HDP , hypertensive disorder during pregnancy; GDM, gestational diabetes mellitus; PPH, postpartum hemorrhage; SGA, \nsmall for gestational age; LGA, small for gestational age. \na)\nAdjusted for age, parity, hypertension before pregnancy, overt diabetes, pregnancy-associated hypertension, gestational diabetes, and myoma \nbefore pregnancy.\n\nwww.ogscience.org276\nVol. 67, No. 3, 2024\nDiscussion\nThe main findings of this study were 1) women with a diag -\nnosis of adenomyosis had significantly higher risk of adverse \npregnancy outcomes; 2) HPD, the risks of cesarean section, \nPPH, placenta previa, placental abruption, and SGA were all \nhighest in cases with diagnosed adenomyosis during preg -\nnancy, and HDP and cesarean section exhibited a statistically \nsignificant difference between groups 2 and 3; and 3) con\n-\nversely, the risks of GDM and preterm delivery were highest \nrisk in the group diagnosed with adenomyosis before preg\n-\nnancy. However, only GDM exhibited a statistically significant \ndifference between groups 2 and 3.\nPrevious research has shown an increased risk of adverse \npregnancy outcomes in women with adenomyosis. These \noutcomes include a higher likelihood of preterm delivery, \nfetal malpresentation, postpartum hemorrhage, preeclamp\n-\nsia, low birth weight, and having a small-for-gestational-age \nnewborn [3,5,7]. Additionally, women with adenomyosis \nhave been found to have an elevated risk of miscarriage and \na reduced chance of achieving a live birth [8,9]. While the \nseverity and timing of adenomyosis diagnosis can influence \nthe extent of these adverse outcomes, the collective evidence \nunderscores the importance of close monitoring and tailored \ncare for pregnant individuals with adenomyosis to optimize \npregnancy outcomes. \nThe impact of adenomyosis on pregnancy outcomes can \nvary depending on the region and extent of adenomyotic in\n-\nvolvement. Women with diffuse or extensive forms of adeno-\nmyosis have been reported to have a higher risk of adverse \npregnancy outcomes, including preterm delivery, postpartum \nhemorrhage, fetal malpresentation, and preeclampsia [6,10]. \nThis suggests that widespread distribution of adenomyotic \nlesions within the uterine wall may lead to greater uterine \ndysfunction and complications during pregnancy [11]. How\n-\never, it is important to note that the specific regional charac-\nteristics and extent of adenomyosis can influence the extent \nof its impact, with diffuse forms generally associated with \nmore pronounced adverse outcomes. \nIn the current study, the individuals diagnosed with ad\n-\nenomyosis before pregnancy had an increased risk of some \nadverse pregnancy outcomes. Typically, those diagnosed with \nadenomyosis before pregnancy might have had more severe \nsymptoms or a broader disease extent, making it easier to \ndiagnose through methods such as ultrasound or magnetic \nresonance imaging. The pathogenic mechanisms underly\n-\ning the impact of adenomyosis on the course of pregnancy \nare multifaceted. Adenomyosis can disrupt the uterine junc\n-\ntional zone (JZ), thereby affecting uterine peristalsis during \nthe luteal phase, which is crucial for successful implantation \n[12]. This abnormal uterine contractility has been associated \nwith conditions such as placenta previa and accreta, as well \nas uterine hyperstimulation, atony, placental retention, and \npostpartum hemorrhage [4,13]. Additionally, adenomyosis \ncan increase intrauterine oxidative stress, thereby leading to \nmaternal endothelial dysfunction, which underlies abnormal \nplacentation. Such oxidative stress can result in hyperplastic \nchanges in the spiral arteries, thereby increasing flow imped\n-\nance in the uterine arteries and contributing to placentation \ndefects [14]. Furthermore, the inflammatory environment as\n-\nsociated with adenomyosis can alter myometrial decidualiza-\ntion and disrupt trophoblastic JZ invasion during pregnancy \n[15]. These complex pathogenic mechanisms shed light on \nhow adenomyosis can adversely affect pregnancy outcomes, \nincluding preeclampsia, preterm delivery, fetal malpresenta\n-\ntion, postpartum hemorrhage, low birth weight, and small-\nfor-gestational-age infants. Understanding these mechanisms \nis key to improving the care and management of pregnant \nindividuals with adenomyosis [16].\nThis study, using a large-scale national dataset, investigated \npregnancy and neonatal outcomes based on the timing of \nadenomyosis diagnosis, providing additional evidence re\n-\ngarding the existing research on disease severity and extent. \nHowever, as a retrospective study, this research has limita\n-\ntions, and there may be constraints associated with defining \nthe disease using ICD codes. Additionally, due to the nature \nof the data, it was not possible to assess the impact of the \nmode of conception, which can influence pregnancy out\n-\ncomes. Furthermore, we could not ascertain the severity of \nadenomyosis, as our analysis was based on diagnostic codes \nand the timing of diagnosis.\nIn conclusion, women with a diagnosis of adenomyosis \nhad a significantly higher risk of adverse pregnancy out\n-\ncomes. The timing of adenomyosis diagnosis had varying \nrisk levels depending on the type of pregnancy and neonatal \noutcomes. Therefore, efforts for more careful monitoring \nand prevention of adverse outcomes may be necessary when \nsuch women become pregnant.\n\nwww.ogscience.org 277\n Young Mi Jung, et al. Adenomyosis on pregnancy outcomes\nConflicts of interest\nNone to declare.\nEthical approval\nThe study’s protocol received approval from the Institu -\ntional Review Board of the Korea University Guro Hospital \n(2023GR0532).\nPatient consent\nPatient consent was waived by the IRB due to the retrospec -\ntive nature of the study.\nFunding information\nNot applicable.\nReferences\n  1. Vercellini P , Viganò P , Somigliana E, Daguati R, Abbiati \nA, Fedele L. Adenomyosis: epidemiological factors. Best \nPract Res Clin Obstet Gynaecol 2006;20:465-77.\n  2. Abbott JA. Adenomyosis and abnormal uterine bleed\n-\ning (AUB-A)-pathogenesis, diagnosis, and management. \nBest Pract Res Clin Obstet Gynaecol 2017;40:68-81.\n  3. Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, Spaan\n-\nderman M, Kramer BW, Mueller MD, et al. Fertility, preg-\nnancy and neonatal outcomes of patients with adeno -\nmyosis: a systematic review and meta-analysis. Reprod \nBiomed Online 2021;42:185-206. \n  4. Buggio L, Dridi D, Barbara G. Adenomyosis: impact \n \non fertility and obstetric outcomes. Reprod Sci 2021;28:  \n3081-4. \n  5. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, \nCheong Y. Reproductive, obstetric, and perinatal out\n-\ncomes of women with adenomyosis and endometriosis: \na systematic review and meta-analysis. Hum Reprod Up\n-\ndate 2019;25:592-632. \n  6. Shi J, Wu Y, Li X, Gu Z, Zhang C, Yan H, et al. Effects of \nlocalization of uterine adenomyosis on clinical features \nand pregnancy outcome. Sci Rep 2023;13:14714. \n  7. Razavi M, Maleki-Hajiagha A, Sepidarkish M, Rouhola\n-\nmin S, Almasi-Hashiani A, Rezaeinejad M. Systematic \nreview and meta-analysis of adverse pregnancy out\n-\ncomes after uterine adenomyosis. Int J Gynaecol Obstet \n2019;145:149-57. \n  8. Lalani S, Choudhry AJ, Firth B, Bacal V, Walker M, Wen \nSW, et al. Endometriosis and adverse maternal, fetal \nand neonatal outcomes, a systematic review and meta-\nanalysis. Hum Reprod 2018;33:1854-65. \n  9. Huang Y, Zhao X, Chen Y, Wang J, Zheng W, Cao L. Mis\n-\ncarriage on endometriosis and adenomyosis in women \nby assisted reproductive technology or with spontane\n-\nous conception: a systematic review and meta-analysis. \nBiomed Res Int 2020;2020:4381346. \n10. Sõritsa D, Saare M, Laisk-Podar T, Peters M, Sõritsa A, \nMatt K, et al. Pregnancy rate in endometriosis patients \naccording to the severity of the disease after using a \ncombined approach of laparoscopy, GnRH agonist treat\n-\nment and in vitro fertilization. Gynecol Obstet Invest \n2015;79:34-9. \n11. Rees CO, Rupert IAM, Nederend J, Consten D, Mischi M, \nvan Vliet HAAM, et al. Women with combined adeno\n-\nmyosis and endometriosis on MRI have worse IVF/ICSI \noutcomes compared to adenomyosis and endometriosis \nalone: a matched retrospective cohort study. Eur J Obstet \n \nGynecol Reprod Biol 2022;271:223-34. \n12. Cha J, Sun X, Dey SK. Mechanisms of implantation:  \nstrategies for successful pregnancy. Nat Med 2012;18:  \n1754-67. \n13. Rees CO, van Vliet H, Siebers A, Bulten J, Huppelschoten \nA, Westerhuis M, et al. The ADENO study: ADenomyosis \nand its effect on neonatal and obstetric outcomes: a ret\n-\nrospective population-based study. Am J Obstet Gynecol \n2023;229:49.e1-12. \n14. Khan KN, Fujishita A, Mori T. Pathogenesis of human \nadenomyosis: current understanding and its association \nwith infertility. J Clin Med 2022;11:4057. \n15. Salmeri N, Farina A, Candiani M, Dolci C, Bonavina G, \nPoziello C, et al. Endometriosis and impaired placenta\n-\ntion: a prospective cohort study comparing uterine ar -\nteries Doppler pulsatility index in pregnancies of patients \nwith and without moderate-severe disease. Diagnostics \n(Basel) 2022;12:1024. \n\nwww.ogscience.org278\nVol. 67, No. 3, 2024\n16. Martone S, Centini G, Exacoustos C, Zupi E, Afors K, \nZullo F, et al. Pathophysiologic mechanisms by which \nadenomyosis predisposes to postpartum haemorrhage \nand other obstetric complications. Med Hypotheses \n2020;143:109833.","source_license":"CC0","license_restricted":false}