{"paper_id":"ca0a4f63-6803-415e-b270-3959a070ef90","body_text":"Submit Manuscript | http://medcraveonline.com\nAbbreviations: PEC, Pre-eclampsia; GDM, Gestational \nDiabetes; LBW, Low birth weight; IUGR, Intra-uterine growth \nrestriction; FGR, fetal growth restriction; PPROM, preterm prelabor \nrupture of membranes; PP, placental previa; PA, placental abruption; \nC/S, cesarean section ; CD, cesarean delivery; SGA, small for \ngestational age; PPH, post-partum hemorrhage; ART, assisted \nreproductive technology; IVF, in-vitro fertilization; IVF/ICSI, in-\nvitro fertilization/intracytoplasmic sperm injection; IVF-ET, in-\nvitro fertilization-embryo transfer; TVUS, transvaginal ultrasound; \nGnRHa, GnRH agonist; GnRH-R, gonadotropin releasing hormone \nreceptor; AMH, anti-Mullerian hormone; CPR, cumulative pregnancy \nrate; HTN, hypertension; PTB, preterm birth \nIntroduction\nAdenomyosis is classically characterized by the presence of \nboth endometrial glands and stroma within the myometrium. This \ncondition, though less commonly discussed than its counterpart, \nendometriosis, has gained increasing attention in recent years \ndue to its potential implications for women’s reproductive health. \nAdenomyosis can produce the following symptoms: abnormal uterine \nbleeding, dyspareunia, dysmenorrhea, or infertility; however, about \n1/3 of women are asymptomatic. 1 The pathogenicity of adenomyosis \nremains deeply divided with the following hypotheses: molecular \nchanges in the endometrium contribute to the migration and survival \nof ectopic endometrial implants versus constant tissue injury and \nrepair on the endometrial-myometrial interface through prior uterine \nsurgery, previous cesarean-sections, and multiple pregnancies. 2 Yet \nanother theory posits that the spread of endometrial tissue through \nboth lymphatic pathways and displaced bone marrow cells could \ncontribute to adenomyosis. Despite the many theories, definitive \npathogenesis of this clinical condition continues to remain unclear. \nWhile the impact of adenomyosis on menstrual and pelvic pain \nsymptoms has been extensively explored, its association with \nobstetrical outcomes remains an area of ongoing investigation. \nPregnancy and childbirth are complex processes that require precise \ncoordination between maternal and fetal factors. Any underlying \nuterine condition, such as adenomyosis, has the potential to \ninfluence these outcomes, making it crucial to gain a comprehensive \nunderstanding of its effects on obstetric health. It is important to \nrecognize that while adenomyosis may have notable effects on \nobstetrical outcomes, managing the condition during pregnancy \nrequires a delicate balance between the well-being of the mother and \nthe developing fetus. As such, a multidisciplinary approach involving \nobstetricians, gynecologists, and maternal-fetal medicine specialists \nis necessary to provide optimal care for women with adenomyosis \nthroughout their pregnancy journey.\nThis literature review aims to provide a thorough analysis of \nexisting literature regarding the impact of adenomyosis on obstetrical \noutcomes. By critically examining relevant studies and data, we seek to \nshed light on potential associations between adenomyosis and various \naspects of pregnancy. Further, it provides detailed explanations as \nto the specific reasons of obstetrical outcomes from physical uterine \ndistortion to creation of an inflammatory environment destructive for \nPregnancy & Child Birth. 2023;9(4):114‒119. 114\n©2023 Vasa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nUnraveling the impact of adenomyosis on obstetrical \noutcomes: a comprehensive review\nVolume 9 Issue 4 - 2023\nRanjitha Vasa,1,2 Ozgul Muneyyirci-Delale1 \n1Department of Obstetrics and Gynecology, SUNY Downstate \nHealth Science University, United States of America \n2Department of Obstetrics and Gynecology, Kings County \nHospital Center, NYC Health and Hospitals, United States of \nAmerica\nCorrespondence: Ranjitha Vasa, SUNY Downstate Health \nScience University, 450 Clarkson Avenue Department of \nObstetrics and Gynecology, Box 24, Brooklyn, NY 11203, \nUnited States of America, T el 732-371-5331, \nEmail \nReceived: July 25, 2023 | Published: August 7, 2023\nAbstract\nObjective: Adenomyosis’ impact on obstetrical outcomes is investigated with detailed \ndiscussion of plausible pathogenesis. Discussion of management strategies to improve \noutcomes included.\nMethods of study:  Terms utilized include ‘adenomyosis’, ‘fertility’, ‘ pregnancy’, \n‘obstetrical outcomes’, ‘preeclampsia, ‘fetal growth restriction’, ‘preterm labor’, ‘preterm \nprelabor rupture of membranes, ‘in vitro fertilization, ‘prelabor rupture of membranes’, \n‘ultrasound’, ‘small for gestational age’, ‘cesarean section’ Inclusion criteria are English, \nbetween January 1990-January 2023, randomized controlled trials, case controls, cohorts, \ncase series, case reports, systematic reviews, and meta-analyses. Exclusion criteria are \nstudies/articles completed prior to 1990, non-relevant, and non-English.\nResults: Limited literature exists evaluating the relationship between adenomyosis impact \non obstetrical outcomes. However, amongst available literature there exists statistically \nsignificant relationship between adenomyosis and adverse obstetrical, neonatal outcomes \nsuch as: ectopic pregnancy, placental abruption, pre-eclampsia (PEC), gestational \ndiabetes (GDM), low birth weight (LBW), intra-uterine growth restriction (IUGR), and \npreterm prelabor rupture of membranes (PPROM). Proposed physiologic mechanisms \ninclude disordered anatomic, functional, and immunological environment in the uterus. \nProposed management strategies to improve obstetrical outcomes include removal of focal \nadenomyotic lesions and pre-treatment with GnRH agonists before conception.\nConclusion: Adenomyosis has a multifactorial impact on obstetrical outcomes; treatment \nmodalities do exist to improve the chances of conception and retaining a pregnancy. \nHowever, more research is required to not only further substantiate treatment modalities \nrelationship to improve pregnancy; but also to clarify adenomyosis impact on infertility.\nKeywords: adenomyosis, obstetrical outcomes, maternal morbidity, pregnancy, adverse \nobstetrical outcomes\nInternational Journal of Pregnancy & Child Birth\nReview Article\n Open Access\n\n\nUnraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review\n115\nCopyright:\n©2023 Vasa et al.\nCitation: Vasa R, Muneyyirci-Delale O. Unraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review. Pregnancy & Child Birth. \n2023;9(4):114‒119. DOI: 10.15406/ipcb.2023.09.00288\npregnancy, amongst others. Discussion of management strategies to \nimprove pregnancy outcomes including both non-invasive and surgical \nmethods are detailed in this article. Understanding these connections \ncan empower healthcare providers to offer more personalized and \neffective care to women with adenomyosis during their reproductive \njourney.\nMaterials and Methods\nThis is a literature review that was conducted utilizing the \nPubMed, Cochrane, Embase, and Google Scholar databases. Terms \nutilized include ‘adenomyosis’, ‘fertility’, ‘ pregnancy’, ‘obstetrical \noutcomes’, ‘preeclampsia, ‘fetal growth restriction’, ‘preterm labor’, \n‘preterm prelabor rupture of membranes, ‘in vitro fertilization, \n‘prelabor rupture of membranes’, ‘ultrasound’, ‘small for gestational \nage’, ‘cesarean section’ Inclusion criteria are English, between \nJanuary 1990-January 2023, randomized controlled trials, case \ncontrols, cohorts, case series, case reports, systematic reviews, and \nmeta-analyses. Exclusion criteria are studies/articles completed prior \nto 1990, non-relevant, and non-English. Additionally, the reference \nsection of salient articles was utilized and included as well in the final \nliterature review (Figure 1).\nFigure 1 Flowchart of the literature screening and selection.\nResults\nLiterature focusing on adenomyosis’ impact on both neonatal and \nobstetrical outcomes is growing; however, limited data exists (Table \n1). Huang’s recent meta-analysis found no statistically significant \ndifferences between both pregnant women with and without \nadenomyosis for the following outcomes: rates of ectopic pregnancy, \nplacental abruption, pre-eclampsia (PEC), gestational diabetes \n(GDM), low birth weight (LBW), and intra-uterine growth restriction \n(IUGR).3 However, meta-analyses conducted by both Nirgianakis \net al., 3 and Razavi et al., 5 found adenomyosis during pregnancy \ndirectly linked to poor neonatal and obstetrical outcomes such as \npreterm delivery, preterm prelabor rupture of membranes (PPROM), \nspontaneous abortion, fetal malpresentation, PEC, cesarean section \n(C/S), fetal malpresentation, small for gestational age (SGA), LBW, \nand post-partum hemorrhage (PPH). 3–23 There has been conflicting \ninformation about cesarean section rate as previous studies have not \ntaken into account different aspects of patient care that would result in \nthis mode of delivery such as: prior obstetrical history, socioeconomic \nstatus, socio-culture demographics, and structural factors. \nInterestingly, small for gestational age (SGA) neonate with a \nweight of <2500g and <1500g is significantly increased for patients \nwith adenomyosis as directly evidenced by Yamaguchi; however, there \nhave been studies that merely showed only an increased risk without \nany associated significance.3,16 Hypertensive disorders of pregnancy, \nparticularly preeclampsia, were another commonly assessed outcome \nin the current literature as evidenced by Porpora et al.,20 and the studies \nmentioned above.20 Though multiple studies endorse a significantly \nincreased risk of preeclampsia with adenomyosis, one study showed \nno statistically significant increased risk.8,13 Interestingly, Shinohara et \nal.,21 provided evidence that individuals with diffuse adenomyosis had \nsignificantly increased risk of poor obstetrical outcomes mentioned \nabove; however, it is merely the only study that states that individuals \nwith focal adenomyosis did not have statistically different outcomes \ncompared to those without any adenomyosis.21 \nT able 1 Impact of adenomyosis on obstetrical outcomes\nAuthor Year Study design Intervention Result References\nDommisse & \nTiltman 1992 Prospective \nDescriptive Study\nPlacental bed biopsies were obtained at \ncaesarean section in patients with placental \nabruption \nVascular malformations in the setting of placental \nabruption was seen. 12\nJuang, et al. 2007 Case Control\nTypes of adverse obstetric outcomes \ninvestigated in pregnant patients with and \nwithout adenomyosis\nGravid women with adenomyosis were associated \nwith significantly increased risk of PTB12 and \nPPROM.13\n19\nCostello, et al. 2011 Retrospective \nCohort Study\nIVF/ICSI27 outcome in women with and without \nadenomyosis. \nThere was no difference in live birth rate per \npatient between the two groups. 24\nY oum, et al. 2011\nRetrospective \nCase Control \nStudy\nPatients undergoing IVF-ET1 were divided into \ngroups based on myometrial thickness and \noutcomes were observed.\nMyometrial thickening greater than 2.50 cm exerts \nadverse effects on IVF-ET28 outcomes (decreased \nimplantation CPR,2 increased spontaneous \nabortion rates, and with significantly lower live \nbirth rates). Mild myometrial thickening (2.00–\n2.49 cm) is associated with adverse outcomes of \nIVF-ET.28 \n25\nThalluri, et al. 2012 Retrospective \ncohort study\nA single IVF-ICSI27 cycle in patients with and \nwithout adenomyosis. \nAdenomyosis group had a statistically significant \ndecreased CPR29 of 23.6% compared with 44.6% in \nthe non-adenomyosis group. \n26\nBallester, et al. 2012 Prospective \nlongitudinal study\nCPR29 in patients with and without adenomyosis \nundergoing IVF-ICSI27\nCPR29 for patient with adenomyosis was 19% and \nwithout adenomyosis was 82.4% (p=0.01). Patient \nover 35 years and anti-Mullerian hormone serum \nlevel under 2ng/ml associated with a decreased \nCPR.29\n27\n\nUnraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review\n116\nCopyright:\n©2023 Vasa et al.\nCitation: Vasa R, Muneyyirci-Delale O. Unraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review. Pregnancy & Child Birth. \n2023;9(4):114‒119. DOI: 10.15406/ipcb.2023.09.00288\nAuthor Year Study design Intervention Result References\nMochimaru A, \net al. 2015 Retrospective \nCase Control\nTypes of adverse obstetric outcomes \ninvestigated in pregnant patients with and \nwithout adenomyosis\nAdenomyosis subjects were associated with PTB,12 \nPPROM,13 SGA,3 and CD4 as compared with the \ncontrol group. PPH5 reported to be increased risk \nin those with adenomyosis.\n14\nExacoustos, et al. 2016 Cohort study\nTypes of adverse obstetric outcomes \ninvestigated in pregnant patients with \nadenomyosis\nWhen compared with the control group, women \nwith adenomyosis had a higher risk of pregnancy \ncomplicated by PTB,12 P P,6 PA,7 and HTN.8\n17\nHasdemir, et al. 2016 Prospective \ncohort study\nWomen with diagnosis of pre-eclampsia with \nand without adenomyosis\nThe prevalence of adenomyosis was found to be \nmore common in patients with FGR.9 18\nHashimoto A, \net al. 2018 Retrospective \ncase control\nTypes of adverse obstetric outcomes \ninvestigated in pregnant patients with and \nwithout adenomyosis \nAdenomyosis subjects had significantly increased \nrisk of PEC,10 PTB.12  13\nShin Y, et al. 2018\nRetrospective \ncase control \nstudy\nTypes of adverse obstetric outcomes \ninvestigated in pregnant patients with and \nwithout adenomyosis\nThe adenomyosis group was associated with \nsignificantly higher rates of PTB,12 LBW11 than the \nnon-adenomyosis group. Risks of either outcome \nare significantly higher in pregnant women \nwith adenomyosis who conceived by assisted \nreproductive technologies versus those who \nconceived naturally.\n15\nHarada, et al. 2019 Prospective \nCohort Study\nWomen with endometriosis and adenomyosis \nwere followed for incidence of obstetric \ncomplications\nThe presence of endometriosis and adenomyosis \nsignificantly increased prevalence of obstetrical \ncomplications such as PTB,12 PPROM,13 P P.14\n11\nHashimoto A, \net al. 2018 Retrospective \nCase Control \nTypes of adverse obstetric outcomes \ninvestigated in pregnant patients with and \nwithout adenomyosis\nAdenomyosis subjects were significantly more \nlikely to have a second trimester miscarriage, \nPEC,15 placental malposition, and PTB,12 compared \nto the control group.\n13\nYamaguchi, et al. 2019 Prospective \ncohort study\nTypes of adverse obstetric outcomes \ninvestigated in pregnant patients with \nadenomyosis\nAdenomyosis was a risk factor for PTB,12 LBW \n<2500g,19 LBW <1500g,19 and SGA.16 CD17 \nsignificantly increased in those with adenomyosis.\n16\nPorpora, et al. 2020 Prospective \nCohort Study \nObstetrical outcomes measured in women with \nand without adenomyosis\nA significantly increased relationship was noted \nwith pregnancy-induced hypertension and \npreeclampsia in the presence of adenomyosis. \n20\nShinohara, et al. 2020\nRetrospective \nCase Control \nStudy\nObstetrical outcomes measured in women with \nand without adenomyosis\nThe adenomyosis group had significantly higher \nincidence of PTB,12 hypertensive disorders of \npregnancy, CD,17 and PPH15 risk than the control \ngroup.\n21\n112IVF/ICSI: In-vitro fertilization/Intracytoplasmic sperm injection \nIVF-ET: In vitro fertilization-embryo transfer\n2CPR, cumulative pregnancy rate\n3SGA, small-for-gestational age\n4CD, Cesarean delivery\n5PPH, Postpartum hemorrhage\n6PP , Placenta previa\n7PA, Placental abruption\n8HTN, Hypertension\n9FGR, Fetal growth restriction\n10PEC, preeclampsia\n11LBW, low birth weight\n12PTB, preterm birth\n13PPROM, preterm prelabor rupture of membranes\n14PP , placenta previa\n15PPH, Postpartum hemorrhage\nTable 1 Continued...\n\nUnraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review\n117\nCopyright:\n©2023 Vasa et al.\nCitation: Vasa R, Muneyyirci-Delale O. Unraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review. Pregnancy & Child Birth. \n2023;9(4):114‒119. DOI: 10.15406/ipcb.2023.09.00288\nFurther, adenomyosis has a negative impact on patients undergoing \nassisted reproductive technology (ART). For example, Shin et \nal.,15 provided evidence that pregnant women with adenomyosis \nwho conceived via ART had significantly higher preterm birth rate \nand associated low birth weight neonates. 8,15 Chiang et al., 22 also \nprovided preliminary evidence that patients with a sonographically \ndiffused enlarged uterus without distinct uterine masses had a \nhigher spontaneous abortion rate when undergoing IVF (in-vitro \nfertilization), thus requiring enhanced luteal support prior to \nconception.22 Interestingly, there has been a discrepancy in women \nwith a sonographically diffuse adenomyosis undergoing IVF/\nICSI (in-vitro fertilization/intracytoplasmic sperm injection) with \nGnRH pretreatment for either short-term (3 months) or long-term \n(more than 3 months) with Chiang et al., 22 documenting a higher \nspontaneous rate of miscarriage with both regimens. 24 However, \nMijatovic et al.’s most recent retrospective study showed no adverse \noutcomes with women who were treated with the same regimen. 22,23 \nYoum et al., 25 provided evidence that women undergoing IVF-ET \n(in-vitro fertilization-embryo transfer) with a myometrial thickness \nof 2.50cm on transvaginal ultrasound (TVUS), led to a significant \ndecrease in successful implantation, clinical pregnancy, live birth \nrate, and increased abortion rate. 25 The findings of Youm et al., 25 \nwere corroborated by Thalluri et al., 26 who additionally corrected for \nincreased maternal age and duration of infertility.26\nIt was previously demonstrated that women with adenomyosis \nwho conceived using ART were at an increased risk of obstetrical \ncomplications, such as placenta previa and placenta abruption. 10 A \nrecent review article states that not a negligible risk of placenta \nprevia and placenta accreta exists in those who become pregnant with \nadenomyosis.11 In patients with endometriosis, Exacoustos et al.,17 has \nprovided evidence that a higher risk of placenta previa and placental \nabruption exists.17 Pregnant women with adenomyosis had a high risk \nof placental abruption and fetal growth restriction compared to those \nwithout.18 Furthermore, a statistically significant higher frequency of \nplacenta previa cases have been reported in those with adenomyosis, \nas the uterine environment is greatly altered in these patients.10,13\nPlacental pathologies in those with adenomyosis have been \nexamined. A single case report described a 52-year-old woman \nwith adenomyosis who had a live twin delivery after taking GnRH \nagonist (GnRHa) therapy. This medication decreased uterine size and \nJZ thickness; however, her delivery was complicated by expansive \naccretas of both placentas requiring cesarean hysterectomy. Pathology \nof both placentas demonstrated no decidualized endometrium. Previous \nmolecular studies have offered evidence that genetic variance in the \nexpression of the gonadotropin releasing hormone receptor (GnRH-R) \ncould explain the expansive lack of decidualized endometrium after \nGnRHa therapy. However, further studies are needed to determine if \nGnRHa therapy contributes to placental abnormalities (Table 1).9 \nProposed physiologic mechanisms for adverse \nobstetrical outcomes \nThrough disordered anatomic, functional, and immunological \nmechanisms in the uteri of adenomyotic patients, there is an increased \nrisk of abnormal placentation. 10 Rationale for placental abruption in \npatients is due to increased incidence of PPROM in adenomyotic \npatients. Blood flow to the adenomyotic lesions is increased, \ndecreasing blood flow to the placenta, thus decreasing its size. As \na result, there is an increase risk placental membranes can rupture \npreterm, compounding the risk for placental abruption. 10 Further, in \nadenomyotic affected women, alterations of the JZ leads to vascular \nresistance, contributing to insufficient deep placental placentation and \nfailure of spinal artery remodeling. In fact, the altered remodeling of \nthe placental vasculature can lead to placental abruption and PEC. 5,12 \nIt has been proposed that the underlying physiology leading to the \nobstetrical outcomes listed above is the increased inflammatory \nenvironment in the uterus due to elevated levels of inflammatory \nfactors such as prostaglandin E2, cyclooxygenase 2, and interleukin \n8.5 These inflammatory markers are thought to trigger endometrial \nvasoconstriction and stimulation of cervical ripening which serves \nas the basis for PEC, preterm birth, and PPROM. Because of the \nfunctional and structural changes of the uterus over time, uterine \nfunction is inherently impaired, increasing risk of a multitude of \nadverse obstetrical outcomes.  \nLastly, AMH serum (anti-Mullerian hormone) levels are a lead \npredictor of cumulative pregnancy rate (CPR). In patients with \nadenomyosis and even endometriosis numerous studies have found \nlow AMH levels. Poor ovarian reserve is defined as under 2ng/ml \nwhile others define the cutoff of 1 or 0.6 ng/ml. There is a higher CPR \nwhen patients have an AMH serum elevation above 2ng/ml, while no \nbenefit was observed after two ICS-IVF (intra-cytoplasmic-in vitro \nfertilization) cycles with an AMH below this level.27 \nProposed management strategies to improve \nobstetrical outcomes\nRemoval of ectopic endometrial lesions in patients led to \nimprovement in both spontaneous and IVF pregnancy rates, as \nevidenced by Stepniewska et al.,28 Though the study examined patients \nwith endometriosis, it should be attempted to be translated in patients \nwith focal adenomyosis where removal of lesions is more feasible. 28 \nAnother study by de Ziegler has provided adequate evidence that \nremoval of focal adenomyotic/endometriotic implants should be an \noption in patients less than 38 years, with documented good ovarian \nreserve, and no other indications compromising natural conception \nsuch as tubal or semen abnormalities. Interestingly, Costello et al., 24 \nprovided evidence that ultrasound diagnosed adenomyosis did not \nsignificantly affect outcomes in women undergoing IVF/ICSI with \nno documented differences in clinical outcomes. 24 Ballester et al., 27 \nmeasured the cumulative pregnancy rate (CPR) for patients undergoing \nIVF/ICSI cycles; however, the CPR in patients with adenomyosis \nwas significantly decreased compared to those without. 29 Barri et \nal.,30 showed that the combination of both ICSI-IVF and endoscopic \nsurgery led to a significant higher CPR in patients younger than 35 \nthan individual intervention alone. Surgery should be considered after \nfailure of two ICSI–IVF cycles for patients younger than 35 years with \npoor ovarian reserve before opting for an oocyte donation program.30 \nAlternatively Berlanda et al. states that women receiving GnRHa \npre-treatment reported an improved CPR with a reduced miscarriage \nrate.10 As expected, an increased live birth rate was observed after \nsurgical management, which was mentioned previously. 10 There is a \nmultitude of contradictory studies described in this section, and more \ntime needs to be invested into research on the impact that adenomyosis \nnot only has on fertility but also farther along during pregnancy and \npost-partum.\nDiscussion\nAdenomyosis is a disease that has not been well researched in \npre-menopausal women who desire fertility, as it has traditionally \nbeen determined upon pathological evaluation of the uterus post-\nhysterectomy. Traditional signs and symptoms of adenomyosis \nare characterized by abnormal uterine bleeding, pelvic pain, and \ndysmenorrhea; however, many women may remain asymptomatic. \nThe relationship between adenomyosis and adverse obstetrical \n\nUnraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review\n118\nCopyright:\n©2023 Vasa et al.\nCitation: Vasa R, Muneyyirci-Delale O. Unraveling the impact of adenomyosis on obstetrical outcomes: a comprehensive review. Pregnancy & Child Birth. \n2023;9(4):114‒119. DOI: 10.15406/ipcb.2023.09.00288\noutcomes is an understudied facet. This literature review consolidates \nand clarifies specific mechanisms by which adenomyosis leads to \nadverse obstetrical outcomes in the pre-menopausal population. \nFurther, recent advances in management strategies for pregnancy \nmaintenance in the adenomyotic population are stated. Based on \nextensive literature review sufficient evidence that adenomyosis \ncontributes to increased risk of ectopic pregnancy, placental abruption, \nPEC, GDM, LBW, IUGR, PTD, PPROM, spontaneous abortion, fetal \nmalpresentation, C/S, fetal malpresentation, SGA, LBW, and PPH. \nIn fact, the path by which pregnancy was attained also plays a role \nin adverse obstetrical and neonatal outcomes. For those women with \nadenomyosis conceiving through ART, this patient had significantly \nhigher rate of PTD and LBW neonates. Likewise, this patients also had \nincreased risk of placenta previa and placental abruption. Plausible \nexplanations for the adverse obstetrical outcomes listed above include \ndisordered anatomic, function, and immunological environment of the \nuterus. At this time, two management strategies have yielded positive \nresults for improved obstetrical outcomes: GnRHa pre-treatment \nbefore conception and removal of adenomyotic lesions.\nEssentially, the large gaps in the literature when it comes to the \nrelationship between poor obstetrical outcomes and adenomyosis is a \ngreat field of opportunity for further exploration. The main limitation \nof this article is that research identifying the aforementioned \nrelationship between adenomyosis and adverse obstetrical outcomes \nis not as thorough as it should be, and major gaps exist when it comes \nto extensive management strategies to allow for a safe pregnancy. \nStrengths of this article is the expansive timeline by which articles \nwere evaluated and use of relevant resources to provide explanations \nas to the rationales behind observed impact of adenomyosis. This \narticle clearly lists proposed mechanisms by which adenomyosis \nimpacts obstetrical outcomes cohesively; further, relevant outcomes \nto research are listed in table format. Shortcomings of this review \ninclude the overall abysmal amount of research being done to \ninvestigate the relationship between adenomyosis and obstetrical \noutcomes. Over the designated timeline, about 30 papers were \nincluded after exclusion criteria is accounted for. Further, there needs \nto be more baseline research done concerning the pathogenesis and \ntreatment management strategies to improve our outcomes of interest \nin women with infertility. Ultimately, more research is required to not \nonly further substantiate either approaches listed prior to aid those \nwomen struggling with infertility given an adenomyotic uterus, but \nalso elucidate adverse obstetrical outcomes. \nConclusion\nAs expected adenomyosis does have significant adverse obstetrical \noutcomes. Adverse obstetrical outcomes described previously have \nbeen linked to the altered uterine environment which contribute to \nabnormal placentation that places expectant mothers at risk for \nhypertensive disorders of pregnancy, placental pathologies, and poor \npreterm outcomes (both PPROM and FGR). Specifically, adenomyotic \nlesions consume an increased amount of blood decreasing placental \nblood flow. This decreases the placental size and increases risk of \nearly rupture and ultimately both PPROM and placental abruption. \nFurther, alterations of the JZ leads to vascular resistance, contributing \nto insufficient deep placental placentation and failure of spinal artery \nremodeling. In fact, the altered remodeling of the placental vasculature \nleads to placental abruption and PEC. It has also been proposed that \nthe underlying physiology leading to adverse obstetrical outcomes \nlisted above is the increased concentration of inflammatory markers. \nThese markers are thought to trigger endometrial vasoconstriction \nand stimulation of cervical ripening which serves as the basis for \nPEC, preterm birth, and PPROM. Thus, adverse obstetrical outcomes \nobserved in women impacted by adenomyosis are multifactorial.\nWomen with adenomyosis have baseline lower AMH levels, \nindicative of low ovarian reserve. Therefore, in women with \nadenomyosis undergoing ART there is a significantly higher preterm \nbirth rate and higher spontaneous abortion rate. There is conflicting \ndata about the use of GnRH pretreatment for either short (less than \n3 months) or long term (more than 3 months) for women undergoing \nIVF in order to achieve pregnancy. However, for those with focal \nadenomyosis removal of the lesions has led to more successful natural \nconception. Management strategies to improve obstetrical outcomes \nin this population continue to remain quite sparse; however GnRHa \npretreatment before conception in combination with surgical removal \nof focal adenomyotic lesions have provided promising results. \nAcknowledgements\nWe would like to thank the State University of New York (SUNY) \nDownstate Health Sciences University for granting us access to the \ndatabases of interest. \nConflicts of interest\nNone to disclose.\nReferences\n1. Vannuccini S, Tosti C, Carmona F, et al. Pathogenesis of \nadenomyosis: an update on molecular mechanisms. Reprod Biomed \nOnline. 2017;35(5):592–601.\n2. García–Solares J, Donnez J, Donnez O, et al. Pathogenesis of \nuterine adenomyosis: invagination or metaplasia?. Fertil Steril.  \n2018;109(3):371–379.\n3. Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, et al. Fertility, \npregnancy and neonatal outcomes of patients with adenomyosis: \na systematic review and meta–analysis. 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