{"paper_id":"d8f57030-2e01-4262-8771-debb374138e1","body_text":"* Corresponding author: Farideh Mogharab \n E-mail: Email: faridehmogharabgyn@gmail.com  \n© 2023 by SPC (Sami Publishing Company)  \n \n \nCase Study \nUterine Adenomyosis Relationship with Gravidity, Parity, and \nAbortion in Women with a History of Infertility: A Case -Control \nRetrospective Study \nAthar Rasekhjahromi 1 , Tanaz Torabi 2, Farideh Mogharab 3,*, Mahshid Albo rzi3 , \nNavid Kalani4   \n1Obstetrician and Gynecologist, women's Health and diseases research center, Jahrom University of medical sciences, \nJahrom, Iran \n2Student Research Committee, Jahrom University of medical sciences, Jahrom, Iran \n3Obstetrician and Gynecologist, women's Health and diseases research center, Jahrom University of medical sciences, \nJahrom, Iran \n4Research Center for Non.Communicable Diseases, Jahrom University of Medical Sciences, Jahrom, I ran \n \nA R T I C L E     I N F O  \nA B S T R A C T \nArticle history \nReceive: 2022-03-23 \nReceived in revised: 2022-04-29 \nAccepted: 2022-06-01 \nManuscript ID: JMCS-2205-1515 \nChecked for Plagiarism: Yes \nLanguage Editor:  \nDr. Fatimah Ramezani  \nEditor who approved publication: \nDr. Yasser Fakri Mustafa \nDOI:10.26655/JMCHEMSCI.2023.1.1 \n Introduction: Adenomyosis is reported to be increasingly diagnosed in young \nwomen and affects 20 to 35% of women of reproductive age. This study aimed \nto evaluate the relationship betwe en the types of uterine adenomyosis and \ninfertility, abortion results in adenomyotic and non -adenomyotic women with \na history of infertility. \nMethods: In this case-control study, 50 infertile women of reproductive age of \n18-40 years old in the Gynecology C linic in Jahrom city were included in the \nstudy. Among the participants, infertile women were respectively selected in \ncase of having an adenomyosis diagnosis, and the control group was selected \nfrom women without adenomyosis (25 subjects per group). Study  groups \nwere compared for the primary outcomes of the gravida/para/abortus (GPA) \nsystem.  \nResults: Distribution of the different age, BMI, and residency area categories \nwere similar in the case and control groups (P>0.05). The frequency of the \nsecondary or primary infertility does not differ between adenomyotic or non -\nadenomyotic women with a history of infertility (P=0.039). The frequency of \nvarious gravida, parity, live or dead children, and abortion did not \nsignificantly differ among the study groups (P> 0.05). Infertility -related \nsymptoms and coexisting diseases were not significantly different among the \nstudy groups (P>0.05). \nConclusion: The results of the present study revealed similar frequencies of \nsecondary infertility, abortion, and pregnancy outcom es in adenomyotic and \nnon-adenomyotic women with a history of infertility. \nK E Y W O R D S \nAdenomyosis \nInfertility \nAbortion \npregnancy outcome \n \n \n \nG R A P H I C A L   A B S T R A C T \n \nJournal of Medicinal and Chemical Sciences 6 (2023) 1-8 \n \n \nJournal homepage: http://www.jmchemsci.com/ \n \n \n \n \n \n\n Rasekhjahromi A., et al. / J. Med. Chem. Sci. 2023, 6(1), 1-8 \n2 | P a g e  \n \nIntroduction \nAdenomyosis is defined as an endometrial \ninvasion of t he uterine myometrium resulting in \nuterine enlargement, the formation of \nadenomyotic tumors, heavy menstrual and \nintermenstrual bleeding, and recurrent pain. It is \na benign disease of the uterus in which the \nstroma and ectopic networks of the endometrial \nglands are present inside the myometrium. This \ninvasion induces hypertrophy (enlargement) and \nhyperplasia (increased) of the uterine muscle and \nenlarges the uterus diffusely [1]. Adenomyosis is \nincreasingly diagnosed in young women, affecting \n20-35% of wome n of reproductive age [2]. It is \nassociated with uterine enlargement, pelvic pain, \nexcessive vaginal bleeding, and decreased quality \nof life [3]. However, adenomyosis cannot be \neasily diagnosed among asymptomatic young \nwomen. However, adenomyosis is recent ly \ndiagnosed with better imaging techniques with \nthe increasing frequency of women at an older \nage referring to infertility clinic. The prevalence \nof pregnancy-related adenomyosis complications \nis rising in older pregnant women and \npregnancies resulting fr om assisted reproductive \ntechnologies [4].  Adenomyosis can vary \nconsiderably regarding the extent and location of \nthe invasion in the uterus; therefore, there are no \nindependent pathological features for the \ndefinitive diagnosis of adenomyosis through non -\ninvasive imaging. However, non -invasive imaging \nmodalities, such as transvaginal ultrasound \n(TVUS) and magnetic resonance imaging (MRI) \ncan be used to strictly diagnose adenomyosis to \nguide treatment options and monitor response to \ntreatment [5 -6]. During  pregnancy, trophoblast \ninvasion of the endometrium, and myometrial \njunction causes significant decidualization and \nmarked vascular changes [7]. The junction \nthickening and disruption in women with \nadenomyosis may be associated with placental \ninsufficiency and pregnancy outcome \ncomplications. Additionally, the type of \nadenomyosis is considered an important factor in \ndeciding on the shape and function of the \nendometrium and placenta. Adenomyosis can be \ndivided into two categories. 1) Focal \nadenomyosis is sometimes considered isolated in \nwhich the endometrial area is hypertrophic and \ndeformed and is surrounded by the myometrium \n(usually located within the myometrium), 2) \nDiffuse adenomyosis is the most prevalent and \nwidespread form of the disease characterized  by \nendometrial mucosal foci (glands and stroma) \nwhich are dispersed throughout the uterine \nmuscle [8]. The recent reports indicate that \npregnant women with adenomyosis are at risk \nfor abortion, preterm delivery, early rupture of \nmembranes, spontaneous ute rine rupture during \nlabor, and postpartum hemorrhage [9]. \nNevertheless, the mechanism by which \nadenomyosis affects fertility remains \ncontroversial.  Adenomyosis can affect uterine \ncontractions, sperm transport in the uterine \ncavity, and embryo implantation , ultimately \nreducing fertility [10 -11]; it also reduces sperm \nfunction due to high levels of nitric oxide in the \nuterine cavity [12]. However, the potential \ninfluence of adenomyosis on pregnancy outcomes \nis still unclear, because these cases have been \naddressed in few studies. This study aimed to \ndetermine the relationship between the type of \nuterine adenomyosis and pregnancy outcomes, \nabortion, and infertility in women with \nadenomyosis. \nMaterials and Methods  \nIn this case-control study, all women with history \nof infertility in reproductive age (18 -40 years) in \nJahrom, who referred to the women’s clinic in \n2020-2021 to receive medical services, were \nincluded in the study.  Women with and without \nof adenomyosis were selected as the case and \ncontrol groups (n  = 25 per group). Research \napproval (with the code of ethics \nIR.JUMS.REC.2020.148) was received from the \nVice-Chancellor for Research at Jahrom \nUniversity of Medical Sciences.  \nInclusion criteria were age between 18 and 40 \nyears, history of infertility, no rmal primary \npregnancy (without using assisted reproductive \ntechnique such as IVF), women diagnosed with \nadenomyosis (case group), women without \nadenomyosis (control group), no history of \nradiotherapy, various cancers, autoimmune and \nchronic diseases (such  as hypertension, diabetes \nmellitus, polycystic ovary syndrome, etc.), no \n\n Rasekhjahromi A., et al. / J. Med. Chem. Sci. 2023, 6(1), 1-8 \n3 | P a g e  \n \nlong-term drug use, medical and surgical \nabortions, and no abortion with any \nchromosomal abnormality. Exclusion criteria \nwere incomplete information, anatomical \nabnormalities in the female reproductive system, \nlack of cooperation, patients with known causes \nof abortion (such as chromosomal aberrations \nand lupus), and patients with known causes of \ninfertility (such as polycystic ovaries and \nendometriosis). Next, all patients underwent \ntransvaginal ultrasound. Those patients who \nwere diagnosed with and without adenomyosis \non ultrasound were assigned to the case and \ncontrol groups, respectively. The writte consent \nforms were obtained from the participants who \nwere sampled by observing all  ethical issues and \nassuring the confidentiality of their information. \nFirst, a history was obtained from the patients. \nThen, questionnaires for demographic \ninformation(age, BMI, and location) and clinical \ndata (pregnancy status and type of contraception, \nhistory of infertility, oligomenorrhea, hair loss, \nacne, hypertrichosis, obesity, diabetes, thyroid \ndisease, hypertension, sterility, parity, number of \ndeliveries, number of live births, number of \nstillbirths, number of abortions, history of \ndepression, cr amping pain, heavy bleeding, \nbloating and swelling, behavior change, breast \nresizing, history of headache, PMS problems, \npainful intercourse, bleeding during intercourse, \ndecreased libido, itching and inflammation, \ndischarge, and history of ovarian lazines s) were \ncompleted by the researchers. All women in both \ngroups were matched in terms of age, week of \npregnancy, abortion week, history of infertility, \nand multiple pregnancies in both groups. The \npatients’ information was collected and recorded \nto examine the relationships between abortion, \ninfertility, and fertility results from adenomyosis. \nData were analyzed by descriptive (mean, \npercentage, and standard deviation) and \ninferential (Fisher’s and Chi -square) statistical \ntests using SPSS software (version 2 1) at a \nsignificant level of P <0.05 in all tests.  \nResults and Discussions \nFifty women referred to Jahrom Women’s Clinic \nwere participated in the study and assigned to \nthe groups of women without adenomyosis (25 \nsubjects) and those with adenomyosis (25 \nsubjects). The results of statistical analyses \nrevealed that the distribution of the different age, \nBMI, and residency area categories were similar \nin the case and control groups (P>0.05) (Table 1). \nTable 1: Frequency of demographic variables in groups of women without adenomyosis infertility and women \nwith adenomyosis and infertility \n With adenomyosis Without adenomyosis P-value* Frequency Percentage Frequency Percentage \nAge \n15-20 1 4.0 2 8.0 0.6092 \n21-25 2 8.0 5 20.0 0.4174 \n26-30 9 36.0 10 40.0 1 \n31-35 8 32.0 2 8.0 0.0738 \n36-40 5 20.0 6 24.0 1 \nBMI \nNormal 11 44.0 18 72.0 0.0845 \nOverweight 11 44.0 7 28.0 0.3772 \nObesity 3 12.0 0 0.0 0.2347 \nResidency area City 18 72.0 14 56.0 0.5427 \nRural 7 28.0 11 44.0 0.3772 \n*Fisher exact test \n \nThe frequ ency of infertility -related symptoms \nand co -existing diseases were not significantly \ndifferent incidences among the study groups \n(P>0.05). \nFrequency of different gravidities, parities, \nnumber of the live children of the mother, dead \nchildren, and abortion did not differ among the \ngroups (P>0.05)(Table 3). \n \n \n \n \n\n Rasekhjahromi A., et al. / J. Med. Chem. Sci. 2023, 6(1), 1-8 \n4 | P a g e  \n \nTable 2: Frequency of infertility related symptoms and co-existing diseases in study groups \n With adenomyosis Without adenomyosis P-value Frequency Percentage Frequency Percentage \nOligomenorrhea 2 8.0 7 28.0 0.14 \nHair loss 15 60.0 13 52.0 0.57 \nAcne 6 24.0 4 16.0 0.48 \nHypertrichosis 10 40.0 6 24.0 0.22 \nObesity 2 8.0 0 0.0 0.49 \nDiabetes 1 4.0 0 0.0 0.39 \nThyroid disease 3 12.0 7 29.2 0.99 \nBlood Pressure 1 4.0 1 4.0 0.17 \nInfertility Primary 9 36.0 12 48.0 0.39 Secondary 16 64.0 13 52.0 \n \nTable 3: Frequency of pregnancy status and type of contraception in groups in women without adenomyosis \ninfertility and women with adenomyosis and infertility \n With adenomyosis Without adenomyosis P-value Frequency Percentage Frequency Percentage \nGravida \n0 9 36.0 12 48.0 0.5672 \n1 6 24.0 8 32.0 0.7536 \n2 5 20.0 2 8.0 0.4174 \n3 3 12.0 3 12.0 0.99 \n5 2 8.0 0 0.0 0.4898 \nPara \n0 11 44.0 15 60.0 0.3961 \n1 12 48.0 9 36.0 0.5672 \n2 2 8.0 1 4.0 0.99 \nLive \n0 11 44.0 15 60.0 0.3961 \n1 12 48.0 9 36.0 0.5672 \n2 2 8.0 1 4.0 0.99 \nDead Children 0 24 96.0 25 100.0 0.99 \n1 1 4.0 0 0.0 0.99 \nAbortions \n0 14 56.0 18 72.0 0.3772 \n1 8 32.0 4 16.0 0.3209 \n2 1 4.0 3 12.0 0.487 \n3 1 4.0 0 0.0 0.99 \n4 1 4.0 0 0.0 0.99 \nAs depicted in Table 4, none of the symptoms \nstudied in our study were statistically \nsignificantly distributed among the study groups \n(P>0.05) (Table 4). \n \nTable 4: Frequency of symptoms in groups of women without adenomyosis and women with adenomyosis  \n With adenomyosis Without adenomyosis P-value Frequency Percentage Frequency Percentage \nDepression 2 8.0 1 4.0 0.99 \nCrampy pains 7 28.0 11 44.0 0.24 \nSevere bleeding 1 4.0 5 20.0 0.19 \nBreast change 14 56.0 10 40.0 0.26 \nHeadache 9 36.0 11 44.0 0.56 \nAcne 4 16.0 1 4.0 0.16 \nPMS problems 1 4.0 5 20.0 0.19 \nPainful intercourse 4 16.0 8 32.0 0.18 \nBleeding when \napproaching 1 4.0 2 8.0 0.99 \nDecreased libido 0 0.0 2 8.0 0.49 \nItching and inflammation 6 24.0 7 28.0 0.75 \nSecretion 1 4.0 3 12.0 0.61 \nHistory of PCOS 5 20.0 3 12.0 0.71 \n \n\n Rasekhjahromi A., et al. / J. Med. Chem. Sci. 2023, 6(1), 1-8 \n5 | P a g e  \n \nIn recent years, the frequency of adenomyosis in \npregnancy has been on the rise with the \nincreased number of pregnancies in older women \nand the increasing rates of pregnancies using \nassisted reproductive techniques [13]. Rece nt \nstudies have indicated that adenomyosis can \nadversely affect in vitro fertilization, pregnancy, \nand live birth rates, and has been reported to \nincrease the risk of abortion. Additionally, \nadenomyosis increases the risk of pregnancy \ncomplications, includ ing preterm delivery and \npremature rupture of the amniotic membranes \n[14-15]. However, the potential effect of \nadenomyosis on pregnancy outcomes is still \nunclear, as the association between adenomyosis \nand pregnancy outcomes has been examined in \nfew studies. Therefore, this study focused on the \nrelationship between uterine adenomyosis and \npregnancy outcomes, abortion, and infertility in \nwomen with adenomyosis. The results of the \npresent study showed that the frequency of \nsecondary or primary infertility doe s not differ \nbetween infertile women with adenomyosis or \nnone-adenomyotic ones. Association of infertility \nwith adenomyosis was reported in several \nstudies [16]. Likewise, adenomyosis might affect \nthe outcome of the IVF [17]. In adenomyotic \npatients, ferti lity can be disrupted by various \nmechanisms, including gamete and fetal transfer \nin an abnormal fallopian tube and endometrial \ndysfunction and acceptance [18]. An enlarged \nuterus, anatomical deformity, and adenoma \nwithin the wall can all affect the shape o f the \nuterine cavity, and may also adversely influence \nsperm migration, embryo transfer, and \nimplantation potential [18, 19]. The results of this \nstudy showed that abortion did not occur more \nfrequently in women with adenomyosis than in \nthose without adeno myosis. Furthermore, \nTamura et al . (2017) observed a higher rate of \nabortion in pregnant women with adenomyosis \n(24%), particularly after 12 weeks of gestation \n(9.9%) [20]. In another study, a high rate of \nabortion was reported in pregnant women with \nadenomyosis (31.8%) versus a control group \n(12.5%) [21]. Our results are also similar to a \nstudy where a high rate of abortion was observed \nin adenomyotic pregnant women (32.8%) \ncompared to the control group (16.3%) [22]. In a \nsystematic and meta -analysis study, Huang et al. \n(2020) investigated the relationship between \nendometriosis and adenomyosis with abortion in \npregnancies using assisted reproductive \ntechniques. They found that these diseases were \nassociated with abortion and particularly cause \npremature abortion (under 12 weeks); the rate of \nabortion caused by these diseases was lower in \nthe second trimester. Moreover, the abortion rate \nwas higher in pregnant women with \nadenomyosis and endometriosis who used \nassisted reproductive techniques than in those \nwho became pregnant spontaneously. Their \nstudy revealed that the risk of abortion increased \nin women with superficial (SUP) and deep \ninfiltrating endometriosis (DIE), respectively, \nwhile no marked association was found between \nendometrioma (OMI) and abortion.  However, the \nrisk of abortion is not significantly different from \nthe staging of endometriosis, and the differences \nseem to be related to epidemiological areas, but \nthe relationship of adenomyosis subtypes with \nabortion was not studied in their research [ 23]. \nHashimoto et al . (2018) reported that the \nincidence of abortion increased in pregnancies \ncomplicated by adenomyosis in the second \ntrimester [24]. Martinez et al . (2011) examined \nthe effect of adenomyosis on patients receiving \negg donation and reported  an increase in \nabortion in adenomyosis patients who were \nfertilized using embryos obtained from young egg \ndonors [22]. In a meta-analysis study, Younes and \nTulandi (2017) investigated the effects of \nadenomyosis on in vitro fertilization results and \nfound an increase in the rate of abortion in \nwomen with adenomyosis [25].  \nPatients with adenomyosis possess high levels of \ninflammatory substances, including \nprostaglandins, which can potentially cause \nuterine contractions [9]. Uterine contractions \ncaused by ch ronic inflammation and high \nintrauterine pressure due to myometrial stiffness \nmay be the factors causing adenomyosis -\nassociated abortion and cervical disability. \nTakeuchi et al . (2006) reported the prevalence \nrates of diffuse and focal adenomyosis to be \n81.7% and 18.3%, respectively [26]. In another \n\n Rasekhjahromi A., et al. / J. Med. Chem. Sci. 2023, 6(1), 1-8 \n6 | P a g e  \n \nstudy, diffuse adenomyosis was observed in \n58.2% of pregnant women [20]. Diffuse \nadenomyosis seems to be worse than focal or \nlocalized adenomyosis. Moreover, focal \nadenomyosis can be easily removed to increase \nthe pregnancy rate [27, 28]. Diffuse adenomyosis \nis associated with multiple findings, including an \nenlarged uterus, which involves the entire \nmyometrium in the anterior or posterior wall. In \ndiffuse adenomyosis, such cases as \ndecidualization disorder may also be more severe \nthan the focal type. \nConclusion \nThe results of the present study demonstrated no \ndifferences in pregnancy history status among \nthe adenomyotic and non -adenomyotic women \nwith a history of infertility. Therefore, studies \nwith a higher numb er of participants are needed \nto investigate the hypothesis more accurately. \nAcknowledgment \nWe would like to thank the Clinical Research \nDevelopment Unit of Peymanieh Educational and \nResearch and Therapeutic Center of Jahrom \nUniversity of Medical Sciences for providing \nfacilities for this work. \nFunding \nThis research did not receive any specific grant \nfrom fundig agencies in the public, commercial, or \nnot-for-profit sectors. \nAuthors' contributions \nAll authors contributed to data analysis, drafting, \nand revis ing of the paper and agreed to be \nresponsible for all the aspects of this work. \n \nConflict of Interest \nThere are no conflicts of interest in this study. \n \nORCID: \nAthar Rasekhjahromi  \nhttps://www.orcid.org/0000-0003-0322-239X \nMahshid Alborzi  \nhttps://www.orcid.org/0000-0003-4803-6654 \nNavid Kalani \nhttps://www.orcid.org/0000-0003-1900-4215 \n \nReferences \n [1]. 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