{"paper_id":"d957b699-7aa5-46bb-b09f-f652512bd995","body_text":"Open Access, Volume 7 \nWomen with endometriosis, deep endometriosis and/or \nadenomyosis who undergo art: The challenges faced and \na narrative review of therapeutic strategies for successful \noutcomes\nReview Article\nwww.jcimcr.org\nJournal of\nClinical Images and Medical Case Reports\nReceived: Jan 06, 2026\nAccepted: Jan 26, 2026\nPublished: Feb 02, 2026\nArchived: www.jcimcr.org\nCopyright: © Kaya C (2026).\nDOI: www.doi.org/10.52768/2766-7820/3936\n*Corresponding Author: Cemil Kaya\nDepartment of Obstetrics and Gynecology, Private \nClinic, Çankaya, Ankara, Turkey. \nTel: +00905325248248;\nEmail:kayacemil000@yahoo.com\nISSN 2766-7820\nIntroduction\nEndometriosis\nEndometriosis is a common, chronic, systemic inflamma -\ntory condition characterized by debilitating pain, and issues \nwith infertility. Current theories of endometriosis pathogen -\nesis include retrograde menstruation, recurrent tissue injury \nand repair, endometrial stem cell recruitment, müllerian rest \ninduction, coelomic metaplasia, lymphatic or hematogenous \nspread, genetic or epigenetic changes, and microbiome al -\nteration. Endometriosis-associated infertility include distorted \npelvic anatomy, cytokine-influenced sperm DNA damage and \nAbstract\nEndometriosis and adenomyosis are different clinical conditions \nwith similar pathophsiology. Both conditions involve increased local \nestrogen, decreased progesterone receptor, and increased progesterone \nresistance in the lesions. Adenomyosis, which frequently coexists with \nendometriosis, can impair implantation and increase miscarriage rates. \nIn both conditions, Asisted Repructive Technologies (ART) is a relevant \ntreatment. Endometriosis and adenomyosis patient groups undergoing \nART are patient groups that require special attention and a specialized \nfield of study. In cases where endometriosis and adenomyosis coexist, \nadenomyosis has a greater impact on increased miscarriage and \ndecreased birth rates. In patients with advanced endometriosis who \nhave experienced recurrent miscarriage or implantation failure, and \nin elderly patients, pre-treatment adenomyosis screening may be \nbeneficial. Magnetic resonance imaging and transvaginal ultrasound are \nvery effective in diagnosing endometriosis and adenomyosis. Fertility \nrates are worse in both focal and diffuse adenomyosis associated with \nJZ involvement. Recent scientific evidence indicates that satisfactory \na live birth can be achieved with a cumulative freeze-all policy in \nendometirosis and adenomyosis. Thus, cumulative live birth rates over \nseveral cycles would provide a more accurate estimate of the impact \nof endometriosis and adenomyosis on ART outcomes. Non-surgical \npalliative treatments in adenomyosis are yielding promising results. \nDeep İnfiltrative Endometriosis (DIE) present in up to 20% of women \nwith pelvic endometriosis, is a severe form characterized. Optimal \nmanagement of DIE is still a matter of debate. Based on physiology and \ncurrent evidence, this article discusses the outcomes of surgery and \nART in endometriosis, adenomyosis, and DIE.\nKeywords: Endometriosis; Adenomyosis; Surgery; IVF; Pregnancy.\n\n\nwww.jcimcr.org                Page 2\nCitation: Kaya C. Women with endometriosis, deep endometriosis and/or adenomyosis who undergo art: The challenges \nfaced and a narrative review of therapeutic strategies for successful outcomes. J Clin Images Med Case Rep. 2026; 7(2): 3936.\ndysmotility, microbiome alteration, diminished ovarian reserve, \nand dysregulated ovulation, fertilization, and embryo implanta-\ntion. While its prevalence is 10-15% in the general population, \nit can reach 50% in the infertile population. Sexual dysfunction \ndue to superficial or deep dyspareunia in patients with endo -\nmetriosis should also be included at this point. The risk of se -\nvere endometriosis is six times higher in first-degree relatives \nof affected women compared to unaffected individuals [1]. Orr \net al [2]. found that KRAS (Kirsten Rat Sarcoma Viral Oncogene \nHomolog) mutations correlate with more severe anatomical \nmanifestations of endometriosis. \nThree different types of endometrioses have been identi -\nfied; Ovarian Endometrioma (OMA), Superficial Peritoneal \nEndometriosis (SUP), and Deep İnfilrative Endometriosis (DIE) \n[3]. For diagnosis, the gold standard for diagnosing pelvic endo-\nmetriosis is laparoscopic biopsy with histological confirmation. \nTransvaginal Sonography (TVUSG) the cornerstone imaging \ntechnique for the evaluation and diagnosis of endometriosis.\nMagnetic Resonance İmaging (MRI) is highly accurate for diag -\nnosis of deep infiltrating endometrisosis. The severity of en -\ndometriosis is typically assessed with the help of classification \nsystems such as the Revised American Society for Reproductive \nMedicine (RASRM) score and the ENZIAN system. The ENZIAN \nsystem evaluates lesion size, localization, and depth of infiltra -\ntion. Unfortunately the value of all staging system including rAS-\nRM is limited. It is poorly predictive of chances of spontaneous \nor induced pregnancy and has little correlation with the severity \nof the symptoms presented by the patients [4]. This narrative \nreview examines treatment options, surgical and IVF outcomes \nin endometriosis, adenomyosis, and deep infiltrative endome -\ntriosis.\nSearch strategy\nA literature search was performed using PubMed in the \nEnglish language until september 2025. A narrative review was \ndone. The following combinations of search terms were used: \n“Endometriosis and IVF”, “Adenomyosis and IVF”, “Deep endo-\nmetriosis and IVF ”, “Endometriosis and surgery and IVF”, “Ad-\nenomyosis and frozen embryo transfer ”, “Adenomyosis and \nIVF stimulation”, “Endometriosis and frozen embryo transfer”, \n“Endometriosis and obstetric outcomes”, “Adenomyosis and \nperinatal outcomes”. The references of each cited source were \nassessed to so as not to exclude any other sources relevant to \nthis review. The primary focus was to evaluate the most recent \nliterature on the role of IVF/ICSI and surgery in patients with en-\ndometriosis and/or adenomyosis and the risks that may be an -\nticipated in pregnancy. Articles were chosen for inclusion if they \nwere: [1], retrospective or prospective studies or meta-analyses \ninvolving women with endometriosis and/or adenomyosis of \nreproductive age women and involved IVF-ICSI and/or embryo \ntransfer [2], systematic reviews. Excluded studies [1], were case \nreports, case series, abstracts, expert opinion articles [2], did \nnot involve patients with endometriosis and/or adenomyosis \n[3], did not involvepatients undergoing IVF-ICSI.\nMedical treatment\nAll currently available medical treatments-using GnRH-a, oral \ncontraceptives, or progestins-have no proven effect on natural \nfertility. Medical treatment can reduce the size of lesions and al-\nleviate pain. Suppressive hormonal therapies can be considered \nafter endometriosis surgery to prevent endometriosis associ -\nated symptoms and disease recurrence whilst awaiting ART [5]. \nAccording to ESHRE 2022, hormonal suppression treatments \nare not recommended to improve natural fertility in women \nwith endometriosis [6].\nIn endometriosis ART\nAccording to the 2002 ESHRE guidelines, ART (IUI, IVF/ICSI) \nis recommended for endometriosis-related infertility [6]. Con -\ntrolled Ovarian Hyperstimulation (COH) + IUI is recommended \nas a first-line treatment for ASRM 1-2 patients under 35 years of \nage with normal sperm parameters, normal tubal patency, and \ngood ovarian reserve. IVF/ICSI may be useful in bypassing some \nof the negative effects of endometriosis such as inflammatory \nconditions prevailing in the pelvic cavity. IVF/ICSI is necessary in \n10 to 25% of women with endometriosis [6,7]. Main indications \nfor ART remain tubal impairment, male factor, low endometrio-\nsis fertility index, and failure of other treatments.\nA systematic review by Kuan et al. [8], which reported no \nsignificant differences in Clinical Pregnancy (CPR) or Live Birth \nRates (LBR) between the long GnRH agonist and GnRH antago -\nnist protocols. A meta analysıs by Han Y et al. [9] demonstrated \nthat the Frozen Embryo Transfer (FET) strategy yielded higher \nCPR (OR: 1.2), LBR (OR: 1.3), and implantation rates (OR: 1.2) \ncompared to the fresh ET strategy. A recent Cochrane review \nconcluded that the benefit of ultralong GnRH therapy (mini -\nmum 3 months) versus no pre-treatment prior to IVF or ICSI is \nuncertain with regards to CPR, miscarriage, and LBR [10,11]. A \nstudy by Eıssa Khalifa et al. [12], reported that a comparable ef-\nfect of dienogest to the ultra-long protocol particularly impact \non the LBR in endometriosis patients with undergoing IVF [6]. \nOocyte/embryo effect\nHuman Fertilization and Embryology Authority (HFEA) re -\nported no significant difference in LBR in either fresh or FET \ncycles [13]. Euploidy and aneuploidy rates in women with en -\ndometriosis compared to age-matched controls, have reported \nequivalent euploidy rates between groups [14]. Endometriosis \ndoes not have a negative impact on oocytes’ morphology in \nIVF-ICSI cycle [15]. The presence of OMA could decrease the \noocyte yield in patients endometriosis having IVF/ICSI, it does \nnot appear to have an adverse impact on oocyte quality [16]. \nNo differences in the percentage of meiotic abnormalities in in \nvitro matured oocytes from endometriosis or control patients \nafter COS [17]. A recent meta-analysis of 22 studies found that \nendometriosis does not affect embryo morphology, with com -\nparable high-quality embryo rates, cleavage rates [18]. Endo -\nmetriosis per se does not seem to impact oocyte quality and \nLBR were similar between endometriosis patients and controls \nwhen euploid blastocysts were transferred in an HRT-FET cycle \n[19]. This results suggest minimal or no impact of oocyte quality \nin patients with endometriosis.\nFertilization/implantation\nFertilization rates were lower for ASRM stage I-II compared \nto severe endometriosis or tubal factor infertility [20]. Harb \net al. [21], demonstrated that a 7% reduction in fertilization \nand CPR in both mild endometriosis and moderate/severe \n\nwww.jcimcr.org                Page 3\nendometriosis. A recent meta-analysis confirmed that ASRM \nstage I-II endometriosis specifically impairs fertilization (OR \n0.77, CI: 0.63-0.93) and earlier implantation processes (OR \n0.76, CI: 0.62-0.93), whereas more severe endometriosis \nimpacts negatively on all reproduction stages [22]. Another \na retrospective study on 503 IVF cycles found no significant \ndifference in fertilization rates using IVF in women with \nendometriosis compared to women with infertility due to other \ncauses [23]. A meta analyses by Mappa I et al. [24], of eight \nstudies (study group: 4153 out of 5661; control group: 43,979 \nout of 62,972), revealed that no difference in fertilization rates \nwas found. This results suggest fertilization rate seems to be \ncompromised in case of milder endometriosis presentations. \nIn a meta-analysis by Harb et al. [21] reported that 11%-17% \nreduction in implantation ASRM stage III/IVF. Qu et al.’s meta-\nanalysis [22], compared with the control group, the implantation \nrate (p=0.04) was significantly lower in women with endome -\ntriosis but no difference in reproductive outcomes. The effec -\ntiveness of endometrial scratching prior to IVF has shown that \nthere was no significant difference LBR in women with endome-\ntriosis compared to controls [25]. The endometrial receptivity \nanalysis tool found no significant difference in the expression of \n238 genes related to endometrial receptivity between women \nwith and without endometriosis [26]. Bishop et al. [19], evalu -\nated the implantation trend in three populations undergoing \neuploid FET after IVF/ICSI treatments for different indications, \nincluding endometriosis, male factor, and preimplantation ge -\nnetic testing for monosomic disorders. No difference including \nLBR, were found across the groups. In another study, regarding \nthe role of endometrial receptivity in endometriosis-associated \ninfertility, CPR and LBR in FET cycles of euploid embryos did not \ndiffer between patients with endometriosis having IVF/ICSI and \ncontrols [27]. \nClinic pregnancy/ live birth rate\nIn terms of positive IVF/ICSI results, a meta analyses by Map-\npa I et al. [24], in endometriosis patients undergoing IVF/ICSI, \ndoes not significantly impact LBR and CPR, when compared to \nother causes of infertility. HFEA reported no significant differ -\nence in LBR in either fresh or FET cycles in patients with endo -\nmetriosis undergoing IVF [13]. Norwegian retrospective study, \nindicate comparable LBR (66.0% vs. 66.7%), while the 2022 \nSART report showed no significant differences in IVF/ICSI out -\ncome between endometriosis patients compared to control \ngroups [28,29]. \nIn terms of negative IVF/ICSI results, a 12% reduction in LBR \nafter IVF/ICSI was observed by Horton et al. [30] only in pa -\ntients with stage III-IV endometriosis. In compatible with this \nresults, Liao et al. [31], demonstrated a significant reduction in \nLBR for endometriosis patients with undergoing IVF/ICSI treat -\nment compared to normal IVF. A metanalysis by Paffoni A et \nal. [32], (137 182 from SART and 24 900 from HFEA) in which \nanalyzed 7212 oocyte donation cycles showed that a statisti -\ncally significant lower LBR was identified in women with endo -\nmetriosis (OR, 0.89; 95% CI:, 0.81-0.97). Harb et al. [21], carried \nout a meta-analysis of 27 observational studies in women with \nASRM stage I/II and III/IV in patients endometriosis having IVF/\nICSI. In this study, while resulted in a 7% decrease in fertilization \nand CPR across ASRM all stages. ASRM stages III-IV showed a \n14% decrease in LBR (RR: 0.79; 95% CI: 0.69-0.91) along with \nlower implantation rates (RR=0.86, 95% CI: 0.68-1.08). A meta-\nanalysis by Hamdan et al. [33] in which included 17 studies for \na total of n=17,593 IVF cycles, showed a significant decrease in \nLBR (30%) and CPR (40%) in women with ASRM III-IV endome -\ntriosis (OR=0.78, 95% CI: 0.65-0.95). In this meta-analysis, in the \nsubgroup of patients with ASRM stage I/II endometriosis had \ncomparable LBR following IVF compared to patients without \nendometriosis. Rossi et al. [34], meta-analysis found that pa -\ntients with stage I/II endometriosis undergoing IVF had a similar \nCPR to controls. Morcel K et al. [35], demostrated in patients \nwith endometriosis undergoing IVF ASRM stage III/IV had sig -\nnificantly lower cumulative CPR. These results were consistent \nwith Harb et al.’s meta-analysis, which found significantly lower \nimplantation rates and LBR in women with ASRM stage III/IV \nendometriosis but not in women with ASRM stage I/II endome-\ntriosis (Table 1). As a results, overall, LBR is approximately the \nsame as for other causes infertility [13,24,28,29].\nIn SUP/Surgery vs ART\nAccording to ESHRE 2022, routine surgery before ART for \nASRM stage I/II endometriosis is not recommended, as there \nis no proven benefit for LBR. A recent meta-analysis identified \nthat CPR significantly increased following operative laparoscopy \nfor endometriosis compared with placebo (odds ratio (OR) 1.63; \n95% CI: 1.13 to 2.35) [36]. Hodgson et al.’s [37] meta-analysis re-\nvealed that surgical treatment increased CPR in endometriosis \npatients. Only one meta-analysis, Jin’s meta-analysis of 4 trials \non SUP identified laparoscopic surgery to increase LBR (RR=1.52, \n95%, CI: 1.26-1.84, p<0.01 )and pregnancy rates (RR=1.44, 95% \nCI: 1.24-1.68, p<0.01) [38]. The absolute benefit is modest with \na number of women needed to be treated of 12 to achieve one \nadditional pregnancy. There is only a single and retrospective \ncohort study thus far that compared the outcomes in women \nproceeding with IVF/ICSI who underwent complete surgical \nexcision of disease (n=399) versus diagnostic laparoscopy only \n(n=262) for SUP . Overall, 399 women SUP were surgically treat-\ned and all visible endometriosis was completely removed prior \nto IVF/ICSI while the 262 women included in the control group \nunderwent only a diagnostic laparoscopy. In this study, cases \ndemonstrated a significant higher CPR and LBR (OR 1.47; 95% \nCI: 1.01 to 2.13) [39]. Operative laparoscopy is currently an op-\ntion for endometriosis-associated infertility in ASRM stage (I/II) \nwhen is performed for other indications such as pain. \nIn OMA/Surgery vs ART results\nSeveral meta-analyses have concluded that ovarian cystec -\ntomy for in women undergoing OMA IVF/ICSI does not improve \nCPR or LBR [16,33]. Alseshre et al. [40], found that the quan -\ntity and quality of the embryos produced were similar between \nwomen with endometrioma and controls. Ovarian cystectomy \nprior to IVF/ICSI treatment can lead to a higher rates of cycle \ncancellation due to poor ovarian response. A reduction in the \nresponse to COH can be detected only for endometriomas larg-\ner than 4 cm. Surgical treatment of endometriomas does not \nenhance the outcomes of IVF/ICSI. The surgical excision of en -\ndometriomas can lead to a significant decline in Anti-Müllerian \nHormone levels,specially noted for bilateral endometriomas or \nwhen endometriomas exceed 5 cm in size [41]. This decline can \nbe attributed to the removal of normal ovarian tissue, thermal \ndamage during surgery, and subsequent inflammation. Meta-\nanalyses examining the impact of OMA on IVF/ICSI outcomes \nhave shown a significant reduction in the number of mature oo-\ncytes retrieved in women with OMA versus controls. But no dif-\nference in the gonadotropin dose and duration, the total num -\nber of embryos, high-quality embryos, CPR, and LBR between \nwomen with and without OMA [42]. A meta-analysis focusing \non OMA reported recurrence rates of 4%, 14%, 17%, and 27% at \n\nwww.jcimcr.org                Page 4\n3, 6, 12, and 24 months, respectively, after surgery [43]. \nDIE /Surgery results vs ART\nDIE is a severe form characterized by the infiltration of fi -\nbrous and muscular tissues beneath the peritoneum (>5 mm). \nDIE is affects between 3.8% and 37% of all patients with endo -\nmetriosis [44]. DE diagnosis was based on strict İmaging Criteria \n(MRI) and histological confirmation of the disease for women \nwith a previous history of surgery for endometriosis [45]. Thera-\npeutic options include primarily surgical management and ART. \nDIE is often associated with external focal adenomyosis but is \nnot associated with miscarriage.\nA retrospective cohort study, 222 DIE endometriosis patients \nunderwent a total of 440 ART cycles (fresh and FET). One hun -\ndred fifty-five women (69.8%) had a prior history of surgery for \nendometriosis. The CLBR was 26% after four IVF/ICSI cycles in \nthe “previous history of surgery for endometriosis” group, while \nit reached 51.3% after four cycles (p<0.001) in patients who had \nnot previously undergone surgery for endometriosis. A previous \nhistory of surgery for endometriosis (p=0.001) and a past sur -\ngery for endometrioma (p=0.005) were established as indepen-\ndent factors associated with lower pregnancy rates. This results \nsuggest that for DIE patients, a previous history of surgery may \nbe associated with negative IVF-ICSI outcomes [46]. \nA meta-analysis by Liang et al. [47], that show pregnancy \nrate per patient (OR: 1.47), pregnancy rate per cycle (OR: 1.16), \nand LBR (OR:1.66) were comparable in DIE patients, treated \nwith surgery or IVF-ICSI as a first line of treatment. When both \ncomplete and incomplete surgical DIE excision procedures were \ntaken into account, surgery was associated with a significant en-\nhancement in the pregnancy rate per patient (OR, 1.63; 95% CI:, \n1.11 to 2.40). A meta analyses by Casals G et al. [48], compare \nreproductive outcomes in patients who underwent surgery \nfor DIE before IVF with those in patients who underwent IVF \nwithout a previous surgery for DIE. In this meta-anaylysis, pa -\ntients who underwent DIE surgery before IVF, pregnancy rate \nper patient was 1.84, and LBR per patient was 2.22 times more \nlikely for operated patients than for nonoperated ones. In con-\ntrast to Casal G et al. Daniilidis A et al. [49], showed that there \nis no evidence to suggest the surgical removal of DIE prior to \nIVF-ICSI in patients with endometriosis to improve reproduc -\ntive outcomes. Another meta-analysis by Bourdon et al. [50], \ncompared ongoing pregnancy rates and LBR in patients who \nunderwent endometriosis surgery before ART in comparison \nwith patients who underwent first-line IVF/ICSI. After the exclu-\nsion of the studies with high risk bias, the LBR per cycle was \nsignificantly reduced in the case of surgical treatmet before IVF/\nICSI. These results were consistent with those of Danilidis et al. \nMore recently, a metaanalysıs by Liao L et al. [31] demonstrated \nthat underwent prior surgical treatment for endometriosis, no \nimprovement was observed in CPR (OR: 0.79), and LBR were \nfurther reduced (OR: 0.67).\nAdenomyosis/Definition, diagnosis, clinical manifestations\nAdenomyosis (AD) is presenting in two main forms: diffuse \nadenomyosis of the inner myometrium, and focal adenomyosis \nof the outer myometrium. The diffuse type of adenomyosis is \nmore common than the focal type, and the disease develops \nmore often in the posterior. Diffuse adenomyosis frequently \noccurs in older age, while focal adenomyosis is more common \nin younger individuals and is more frequently associated \nwith endometriosis. Internal adenomyosis is more commonly \nassociated with uterine fibroids, whereas external adenomyosis \nis more often linked to endometriosis [51]. Two predominant \ntheories have been proposed to explain its origin: one suggests \nthat it results from the invagination of the endometrial basalis \ninto the myometrium, while de novo development as a \nconsequence of metaplasia of embryonic Müllerian remnants \n[52]. There is increasing evidence concerning the role of KRAS \nand PIK3CA mutations in the pathogenesis of adenomyosis \n[2,53].\nDiagnosis of adenomyosis is made via TVUSG or MRI. MRI \nbetter predicts adenomyosis while performed in the secretory \nphase of the menstrual cycle. A histopathological diagnosis is \nobviously not required to treat qualified patients for infertility. \nAD is strongly suspected when the JZ measures at least 12 mm \nin thickness on MR images. JZ thickness can vary depending on \nmenstrual cycle and hormone therapy. When measured against \nhistopathology TVS had a sensitivity of 72%-82% and a specific-\nity of 81%-85%, whereas MRI had a sensitivity and specificity \nof 77% and 89%, respectively. According to MUSA (Morpho -\nlogical Uterus Sonographic Assessment) criteria, a diagnosis \nof adenomyosis was made if at least one of the direct features \n(myometrial cysts, hyperechogenic islands, or subendometrial \nlines or buds) was identified. Recent studies have shown that \nnulligravid young women can also suffer from adenomyosis, \nsuggesting that the disorder may develop earlier in reproduc -\ntive life than previously thought. Clinical manifestations are \nreported by 65% of the women with adenomyosis. However, \none third of patients are asymptomatic [53,54]. Adenomyosis \nis present in approximately 24.4% of young infertile women in \nIVF-ICSI cycles. Its prevalence was respectively 38.2% and 34.7% \nin cases of recurrent pregnancy loss and previous ART failure. \nAdenomyosis contributes to infertility through including in -\ncreased junctional zone thickness, utero tubal disperistaltism, \nbiochemical, functional, and epigenetic changes in both eutopic \nand ectopic endometrium. Microtraumas also in the endo-myo-\nmetrial junction that may develop into AD. Possible the other \nmechanisms, anatomical distortion of the uterine cavity, altered \nsex steroid hormone pathways, increased inflammatory mark -\ners and oxidative stress, the reduced expression of implanta -\ntion markers, a lack of expression of adhesion molecules, and \naltered function of the gene for embryonic development. The \nextension and type of adenomyosis appear to be important \nfactors that affect fertility. The common association of adeno -\nmyosis with endometriosis may be another cause. Leiomyomas \ncoexists 35% to 55% in patients with adenomyosis [54,55]. Hov-\newer, the relationship between adenomyosis and infertility has \nnot yet been fully established.\nIn adenomyosis ART\nIn adenomyosis IVF outcomes are mixed, although negative \nin numerous studies and meta-analyses. Younes & Tulandi [56], \nconfirmed in meta-analysis a 41% decrease in live pregnancy \nrates and an increased risk of miscarriage in women with ad -\nenomyosis. In the meta-analysis by A 55% reduction in LBR after \nIVF/ICSI was reported by Horton et al. [30], whereas Nirgianakis \net al. [57], did not find a difference between cases and controls \nin patients with ademoyosis. Nirgianakis’s study presented data \nsupporting that the type of adenomyosis (focal or diffuse) does \nnot significantly affect the reproductive outcome of patients. \nMore recently, Bourdon et al. [58], 285 women with adeno -\nmyosis were matched with 285 controls. The cumulative LBR \nwas significantly lower in the adenomyosis group compared to \n\nwww.jcimcr.org                Page 5\ncontrols (41.4% versus 51.9%; OR=0.65, 95% CI: [0.47-0.91]; \nP=0.012). Similarly, the CPR was reduced in the adenomyosis \ngroup (53.3% versus 63.9%; P=0.011). In contrast to these find-\nings, a prospective IVF cohort study explored the reproductive \noutcomes of a total of 99 adenomyosis patients and 549 non-\nadenomyosis patients undergoing preimplantation genetic test-\ning for aneuploidies and subsequent FET. As for the CPR, LBR \nand miscarriage rates, no difference was seen between the ad-\nenomyosis and non-adenomyosis groups [59].\nIn Mavrelos et al. [60], demonstrated that mild forms of ad -\nenomyosis have limited impact while more severely affected \nwomen have poorer outcomes. In terms of miscarriage, in a \nmeta-analysis by Vercellini et al. [61], the miscarriage rate was \nmore prevalent (RR=2.1 (95% CI: 1.20-3.75) in women with \nadenomyosis vs control (32% vs 14%). A systematic review by \nHorton et al. (30) which seven comparative observational stud-\nies that involved IVF/ICSI cycles, there was an increase in mis -\ncarriages (OR=3.49, CI: 1.41-8.65, P=0.007; n=6). In patients \nwith adenomyosis undergoing ART in oocyte donation, normal \nimplantation rates and higher miscarriage rates have been re -\nported [62,63]. Furthermore, women with adenomyosis have \nan increased risk of miscarriage, even using euploid embryos \n[64] (Table 2).\nPhenotypic aspects of IVF outcomes in adenomyosis, a ret -\nrospective multicenter study revealed that a higher LBR per \ntransfer was described in diffuse adenomyosis compared to \nfocal adenomyosis: 47/166 (28.3%) versus 9/62 (15%), respec -\ntively (OR=2.32, 95% CI: 1.03-5.78, p=0.034) [53]. Hovewer, a \nmeta-analysis, by Wang at. [65], revealed that LBR were low -\ner (OR=0.57; 95% CI: 0.34-0.96) and miscarriage rates were \nhigher(OR=2.48, 95% CI: 1.28-4.82) in patients with in cases of \ndiffuse and symptomatic adenomyosis than focal adenomyosis.\nA meta analysıs by Han Y et al. [9] in women with adenomy-\nosis, pregnancy outcomes were comparable between the FET \nand fresh ET groups. FET are best performed in E2 and proges -\nterone replacement cycle. Bordoun M et al. [66], showed that \nthe FET ET group was associated with significantly higher cumu-\nlative LBRs (OR=1.80; 95% CI: 1.02-3.16). A meta-analysis by Ge \nLi et al. [67], evaluated the reproductive outcomes of different \novarian stimulation protocols in adenomyosis IVF/ICSI. In fresh \nET in women aged ≥35, the CPR was higher (OR=1.33; 95% CI: \n1.06-1.66, I2=40%) in the ultra-long and long protocols than in \nthe antagonist and short protocols. The results elucidate that \nan ultra-long or long protocol might benefit women with ad -\nenomyosis receiving IVF-ICSI with fresh ET compared to a short \nprotocol. In the FET cycles, there were no statistical differences \nin the IR, CPR, or LBR of embryos derived from different stimula-\ntion protocols.\nGnRH agonist and aromatase inhibitör pretreatment in \nadenomyosis\nA meta-analysıs by Gonzales- Comadran M. [68], revealed \nthat there is no evidence GnRHa downregulation before COS \nor pre-treatment before FET among women with adenomyosis \nundergoing IVF. Galati G et al. [69], the use of long-term GnRH \nagonist therapy (minimum 3 months) in patients with adeno -\nmyosis, which enhances the CPR (odds ratio (OR 1.49, 95% CI: \n1.15 to 1.92) in IVF-ICSI with fresh ET, while the comparison in \nwomen undergoing FET cycles did not reach statistical signifi -\ncance (OR 1.34 95% CI: 0.70-2.55). Lan et al. [70], revealed that \nwomen with diffuse adenomyosis had significantly higher CPR \n(55.3% vs. 37.9%, P=0.025) and LBRs (43.4% vs. 25.9%, P=0.019) \nwith the ultra-long versus the long GnRH-a protocol. A meta-\nanalysis by Steinmann M, et al. [71], current evidence does not \ndemonstrate the superiority of GnRHa pretreatment plus HRT \nover HRT alone in women with adenomyosis prior to FET. \nThe increased aromatase activity in adenomyotic tissue \nhas led to the use of Aromatase İnhibitors (AI) in symptomat -\nic women with adenomyosis undergoing IVF. In a randomized \ntrial, Badawi AM et al. [72], found GnRH agonists and aroma -\ntase inhibitors to be equally effective in reducing adenomyo -\nsis. Sharma et al. [73], reported in a randomized controlled trial \nthat the use of low-dose letrozole could be an effective option \nfor women with symptomatic adenomyosis awaiting IVF. Hov -\newer, there is lack of research comparing different IVF protocols \namong women with adenomyosis undergoing pre-treatment \nwith AI prior to ovarian stimulation.\nEndometriosis/adenomyosis coexisting\nBoth conditions involve increased local estrogen, decreased \nprogesterone receptor, and increased progesterone resistance \nin the lesions. Adenomyosis, which frequently coexists with en-\ndometriosis, can impair implantation, affect uterine function, \nand increase miscarriage rates. Adenomyosis associated with \nDIE is external in 96% of cases, while intrinsic adenomyosis is \npresent in 15%. OMA and DIE were more commonly associated \nto extrinsic AM. Focal adenomyosis is observed in up to 66% of \ncases in women with deep infiltrating endometriosis [51,53,74]. \nA meta-analysis by Wang et al. [65], revealed that concur -\nrent adenomyosis in endometriosis is associated with a signifi -\ncantly lower LBR (OR=0.44; 95% CI: 0.26-0.75, grade: low) than \nendometriosis alone. Sharma et al. [75], were the first to retro-\nspectively examine pregnancy outcomes in cases of endome -\ntriosis accompanied by adenomyosis and endometriosis alone, \nusing the tubal factor as a control group. It divided 973 women \ninto the endometriosis-only cohort (n=355), the endometriosis \nwith adenomyosis cohort (n=88), the adenomyosis-only cohort \n(n=64) and the control cohort (n=466). In this study, LBR were \nfound to be low and miscarriage rates were high in the group \nwith adenomyosis and endometriosis or in the group with ad -\nenomyosis alone. \nHigher local TNF-α level was found to correlate with active \nlesions of endometriosis and adenomyosis. For endometriosis \nand adenomyosis women, peri-implantation treatment with \nTNF-α inhibitör (Adalimumab) significantly increased CPR in \nFET cycles [76]. Rees CO, et al. [77], showed that only the com-\nbined adenomyosis and endometriosis group showed a signifi -\ncantly reduced ongoing pregnancy (p=0.001, OR 0.302 (95% CI: \n(0.167-0.608)) and LBR (OR= 03.39 95% CI: 0.168-LBR 0.644, \np=0.001) compared to matched male subfertility controls. Alson \nS et al. [78], showed that after stratifying the results per treat -\nment cycle, the LBR after the first treatment for women with \nendometriosis and/or adenomyosis was 30.7% (RR 0.69 (95% \nCI: 0.57-0.84), P<0.001), after the second 28.6% (RR 0.72 (95% \nCI: 0.54-0.96), P=0.023), and after the third treatment 26.2% \n(RR 0.83 (95% CI: 0.54-1.28), P=0.183). The LBR was 45.1% in \nthe first cycle, 41.4% in the second, and 32.3% in the third cycle. \nBased on this evidence, presence of adenomyosis reduces LBR \nin IVF/ICSI cycles for endometriosis.\nSurgery adenomyosis before ART\nAdenomyomectomy is the most commonly used as minimally \ninvasive approaches in patients with adenomyosis. Non-surgical \nablative techniques are High-Intensity Focused Ultrasound \n\nwww.jcimcr.org                Page 6\n(HIFU) and Radiofrequency Ablation (RFA). More recently a \nmeta-analysis by Liu et al. [79], showed that pregnancy rates \nwere 50.1% (95% CI: 40.0-60.2%) and 52.0% (32.4-71.6%) after \nadenomyomectomy and thermal ablation, respectively. The \ndelivery rates were 39.5% (29.9-49.2%) and 32.5% (26.0-38.9%) \nfor adenomyomectomy and thermal ablation, respectively. The \nspontaneous miscarriage rates were 16.3% (9.7-22.9%) and 27.1% \n(8.1-46.1%) after adenomyomectomy and thermal ablation, \nrespectively. In this study, the pregnancy loss rate (39.5%) and \nmiscarriage rate (27.1%) after thermal ablation were relatively \nhigh compared to those following adenomyomectomy. The high \nmiscarriage in the thermal ablation group was attributed to \npossible endometrial thermal damage. It should be known that \nnone of these data are from randomized trials. Uterine Artery \nEmbolization (UEA) is considered controversial low pregnancy \nrates and high rates of obstetric complications. Endometrial \nreceptivity is also diminished after UEA. A systematic review \nand meta-analysis by Tan et al. [80], revealed that at the adverse \neffects of adenomyomectomy, reported uterine rupture and \npreterm birth rates of 6.8% (3/44) and 4.5% (2/44) in pregnant \npatients with diffuse adenomyosis and 0% (0/35) and 10.9% \n(12/110) in patients with focal adenomyosis. Only one study \nshowed that HIFU achieved better postoperative reproductive \noutcomes (pregnancy rate: 52.0%, delivery rate: 36.0%) \nthan adenomyomectomy (pregnancy rate: 30.2%, delivery \nrate: 27.9%) [81]. In select patients, robotic-assisted surgical \nmanagement of diffuse adenomyosis can be advantageous [82].\nIn endometriosis and perinatal outcomes\nA metaanalysis by Matsuzaki et al. [83], reported a signifi -\ncantly increased risk of placenta previa in women with severe \nendometriosis compared with that in women with non-endo -\nmetriosis group (OR, 5.22; 95% CI: 2.51-10.85). The risk of pla -\ncenta previa in women undergoing IVF was 3 times higher when \ninfertility was associated with endometriosis than when it was \nassociated with other causes (OR, 2.96; 95% CI: 1.25-7.03). In \naddition, women with endometriosis had an increased risk of \nplacenta accreta (adjusted OR, 3.39; 95% CI: 1.96-5.87).\nThe negative impact of adenomyosis continues to affect \npregnancy outcomes. Including an elevated likelihood of ex -\nperiencing preeclampsia (OR 4.35 to 7.87), preterm delivery \n(OR 2.65-3.09), delivering an infant small-for- gestational-age \n(SGA) (OR 2.86 to 3.90), and postpartum haemorrhage (OR \n2.90) [30,84]. The overexpression Oxytocin Receptor (OTR) in \nadenomyosis-affceted uteri may induce hyperperistaltism and \nmicrotrauma junctional zone. Administering an oxytocin recep-\ntor antagonist during FET may reduce the early miscarriage \nrates in women with adenomyosis [86]. For outcomes of ad -\nverse pregnancy in both conditions, proposed mechanisms in -\nclude increased myometrial prostaglandin production, chronic \ninflammation, altered uterine contractility and defective spiral \nartery remodelling, leading to abnormal placentation. The un -\nderlying mechanism is highly complex and currently under de -\nbate. Two diseases might interact with each other. In term of \nphenotypic outcomes, a meta-analysis Xia et al. [87], revealed \nthat women with diffuse adenomyosis had higher odds of ex -\nperiencing preterm birth (OR1.66, 95% CI: 1.03-2.67, P=0.038) \nand hypertensive disorders of pregnancy (OR 2.23, 95% CI: \n1.323.77; P=0.002).\nDiscussion\nEndometriosis is associated with a reduced number \nof retrieved oocytes and high-quality embryos, but LBR \nis approximately the same as for other causes infertility \n[13,19,21]. Advanced-stage endometriosis or those who have \npreviously undergone surgery for endometriosis maintain \nsimilar implantation and LBR compared to women with \ntubal factor infertility. Recent evidence indicates that the \nendometriosis phenotype does not significantly impact ART \noutcomes [13,14,19,22,24,28,29]. In past studies, the failure to \nexclude cases with adenomyosis associated with endometriosis \nmay have led to LBR. \nHovewer, in women with endometriosis may still face chal -\nlenges during IVF-ICSI cycles. The patient’s age and ovarian re -\nserve, rather than endometriosis itself, appear to be the most \nimportant factors affecting IVF outcomes in women with en -\ndometriosis. The current evidence suggests that high-quality \nembryos are transfer for frozen embryo transfer cycle, do not \nexhibit any marked defect in endometrial receptivity. Such find-\nings suggest that endometrial receptivity is similar regardless of \nthe presence or severity of endometriosis [19]. Transcriptomic \nstudies and results from donation cycles in endometriosis show \nthat receptivity is normal and independent of stage [19,27]. In \nthis case, impaired implantation rates may be related to oocyte \nand embryo quality. An important contributory role of reduced \noocyte yield and quality of embryo on IVF/ICSI success in women \nwith endometriosis [33]. Given that the most important aspect \nof IVF/ICSI success is cumulative pregnancy rates, a reduced \nnumber of retrieved oocytes is becoming increasingly impor -\ntant to consider [20,22,30,33]. However, more comprehensive \nstudies are needed on this subject. In endometriosis, disruption \nof the ovarian microenvironment through multiple mechanisms \nand its effect on granulosa cells can impair oocyte quality. On \nthe other hand, diminished ovarian reserve, advanced mater -\nnal age, DIE and adenomyosis itself are thought to contribute \nto suboptimal IVF-ICSI outcomes in endometriosis. High BMI \nshowed a notable influence, obesity negatively affects LBR [31]. \nDIE is a stronger predictor of poor IVF outcomes, significantly \nreducing pregnancy rates compared to superficial disease (58% \nvs. 83%) [50]. Adenomyosis and chronic endometritis may po -\ntentially compromise endometrial receptivity in endometriosis \n[76]. Dysregulation in the PI3K/AKT and NOTCH signaling path -\nways may further reduce implantation-related transcription \nfactors like FOXO1 and IGFBP1. BMI also negatively affects LBR \n[31]. As a results, although there are conflicting results, accord-\ning to the current meta-analysis results, endometriosis IVF re -\nsults give similar results in terms of LBR rates when compared \nwith the control group. The exclusion of adenomyosis with cur-\nrent TV USG and MRI diagnostic criteria has provided an ad -\nvantage in terms of pure endometriosis IVF results and has led \nto clearer interpretation of the results. Still, despite different \napproaches to the problem of infertility due to endometrio -\nsis, standart treatment protocols before IVF have not yet been \ndefined [21,30,32,33,35]. These findings underline the impor -\ntance of individualized patient management strategies in IVF/\nICSI for women with various types of endometriosis.\nCPR and LBR in FET cycles of euploid embryos did not dif -\nfer between patients with endometriosis and controls [27]. \nFET embryo transfer yielded higher CPR (OR: 1.2) and LBR (OR: \n1.3), and implantation rates (OR: 1.2) compared to the fresh ET \nstrategy [9]. Such findings suggest that endometrial receptivity \nis similar regardless of the presence or severity of endometrio-\nsis. Hovewer, in adenomyosis, FET and fresh embryo transfer \nresults are similar to metanalysis results [9]. Endometriosis and \nadenomyosis group consecutive frozen embryo transfer can be \nencouraged in this patients group, as the cumulative LBR was \n\nwww.jcimcr.org                Page 7\nTable 1: The characteristics of selected studies related to ART outcomes with endometriosis.\nReference Intervention and/or study type Comparable and/or Positive IVF/\nICSI outcomes\nUncertain and/or \nNegative IVF/ICSI \noutcomes\nConclusion and/or \nRecommendations\nKuan 2023 [8] Systematic review/GnRH agonist \nvs antagonist outcomes\nNo significant differences in CPR \nor LBR\nThe latest ESHRE guidance does \nnot recommend ultra-long GnRH \nagonist before IVF/ICSI\nHan 2025 [9]\nSystematic review and meta-\nanalysis/ FET vs Fresh cycle \noutcomes\nThe FET strategy yielded higher \nclinical pregnancy (OR: 1.25; 95% \nCI: 1.11, 1.40), live birth rates \n(OR: 1.31; 95% CI: 1.15, 1.49), and \nimplantation rates (OR: 1.27; 95% \nCI: 1.05, 1.54) compared to the \nfresh ET strategy.\nFET strategy has been associated \nwith more favorable reproductive \noutcomes compared to the \nfresh ET strategy in women with \nendometriosis\nCochrane Review  \n(2019) [11] Ultra-long GnRH agonist\nUncertain with regards \nto CPR, miscarriage, \nand LBR\nNot recommended\nKamath (2022) \n[13]\nHFEA anonymized data from \n1996 to 2016. This comprised \nof a total of 758 donor oocyte \nrecipients, where the recipients \nwere women diagnosed with \nendometriosis, and 12 856 \nautologous IVF cycles where the \nwomen were diagnosed with \nendometriosis as the sole cause \nof infertility.\nThere was no significant difference \nin the LBR in women with \nendometriosis undergoing donor \noocyte recipient fresh embryo \ntransfer cycles compared to women \nundergoing autologous IVF fresh \nembryo transfer cycles (31.6% vs \n31.0%; odds ratio (OR) 1.03, 99.5% \nCI 0.79-1.35). \nEndometriosis does not \ncompromise embryo quality from \nthe perspective of morphology.\nJuneau 2017 [14]\n305 patients with endometriosis \nwho produced 1,880 blastocysts \nand PGS\nAneuploidy rates equivalent to \ntheir age-matched peers in IVF \npopulation who do not have \nendometriosis.\nAneuploidy rates equivalent to \ntheir age-matched peers in IVF \npopulation who do not have \nendometriosis.\nRobin 2021 [15] A total of 596 women treated for \nIVF-ICSI, retrospective study\nNo difference in AOQI and MOMS \nscores was found between \nendometriosis and control women \n(adjusted p = 0.084 and 0.053, \nrespectively).\nEndometriosis does not have \na negative impact on oocytes' \nmorphology in IVF-ICSI.\nBarcelos 2008 \n[17]\nTo evaluate the meiotic \nspindle and the chromosome \ndistribution of in vitro mature \noocytes from stimulated \ncycles of infertile women with \nendometriosis, and with male \nand/or tubal infertility factors\nThere was no significant difference \nin the IVM rates between the two \ngroups evaluated (45.6 and 54.5% \nfor the Endometriosis and Control \nGroups, respectively).\nEndometriosis does not increase \nmeiotic abnormality.\nDongye 2021 [18] A systematic review and meta-\nanalysis (22 studies)\nCompared with the control group, \nwomen with endometriosis had a \nsimilar high-quality embryo rate \n(RR = 1.00; 95% CI, 0.94-1.06), a \ncomparable cleavage rate (RR = \n1.00; 95% CI, 0.97-1.02), and a \nsimilar embryo formation rate (RR = \n1.10; 95% CI, 0.97-1.24). In women \nwith stage III-IV endometriosis, \nthere was no statistically \nsignificantly difference in high-\nquality embryo rate (RR = 1.02; 95% \nCI, 0.94-1.10), cleavage rate (RR = \n1.00; 95% CI, 0.98-1.02)\nEndometriosis does not \ncompromise embryo quality from \nthe perspective of morphology.\nBishop 2020 [19] Retrospective cohort study\nEuploid FET-ET cycles, LBR, CPR , no \ndifference endometriosis vs control \ngroup\nLBR are not affected by \nendometriosis after euploid \nblastocysts in HRT FET-ET  cycles\n\nwww.jcimcr.org                Page 8\nHarb 2013 [21] Systematic review and meta-\nanalysis (27 observational study)\nFertilisation rates were \nreduced in stage I/\nII of endometriosis \n(relative risk [RR] = \n0.93, 95% confidence \ninterval [95% CI] \n0.87-0.99, P = 0.03). \nThere was a decrease \nin the implantation \nrate (RR = 0.79, 95% CI \n0.67-0.93, P = 0.006) \nand clinical pregnancy \nrate (RR = 0.79, 95% CI \n0.69-0.91, P = 0.0008) \nin women with stage \nIII/IV endometriosis \nundergoing IVF \ntreatment.\nEndometriosis ASRM III/IV is \nassociated with poor implantation \nand CPR.\nQu 2022 [22] Systematic review and meta-\nanalysis (70 study)\nImplantation rate (p = 0.04) \nand the number of oocyte \nretrieved (p<0.00001) were \nsignificantly lower in women with \nendometriosis\nAll other major \nreproductive and \nobstetric outcomes \nwere similar in women \nwith and without \nendometriosis.\nEndometriosis have similar \nreproductive outcomes, but \nwomen with endometriosis who \nconceived after ART are in high \nrisk pregnancy.\nMappa 2024 [24]\nSystematic review and meta-\nanalysis(40 studies/8970 women \nwith endometriosis and 42,946 \ncontrol)\nThere were no significant \ndifferences between the \nendometriosis and control groups \nin terms of LBR (OR 1.03, 95% \nCI 0.75-1.41, p = 0.84), CBR (OR \n0.86, 95% CI 0.72-1.02, p = 0.1), or \nfertilization rate (OR 0.96, 95% CI \n0.79-1.15, p = 0.64). \nEndometriosis was \nassociated with a \nsignificantly lower \nimplantation rate (OR \n0.85, 95% CI 0.74-0.97, \np = 0.02).\nEndometriosis significantly \nnegatively affects implantation \nrates in women undergoing IVF, \ndespite the absence of significant \ndifferences in LBR, CPR, and \nfertilization rates. \nNienke E van \nHoogenhuijze \n2023 [25]\nMeta-analysis(13 RCTs, (12 \npublished, one unpublished) \n4112 participants\nThere was no significant difference \nLBR in women with endometriosis \ncompared to controls\nEndometrial scratching in clinical \npractice should be considered \nwith caution\nHorton  2019 [30]\nSystematic review and meta-\nanalysis in Endometriosis and \nadenomyosis (104 study)\nMilder forms of \nendometriosis were \nmost likely to affect \nthe fertilization (FR \nOR 0.77, CI 0.63-\n0.93) and earlier \nimplantation processes \n(implantation rate OR \n0.76, CI 0.62-0.93). \nIncreased  miscarriage \nin both adenomyosis \nand endometriosis (OR \n3.40, CI 1.41-8.65 and \nOR 1.30, CI 1.25-1.35, \nrespectively),\nMilder forms of endometriosis \nwere most likely to affect the \nfertilization.\nLiao 2025 [31] Systematic review and meta-\nanalysis (19 studies)\n CPR were not significantly different \nbetween groups (OR: 1.03)\nDecreased total \noocytes (mean \ndifference [MD]: \n-2.06),mature \noocytes (MD: -2.07) \nand LBR (OR: 0.87)  \nin endometriosis/ \nBMI significantly \ninfluenced the risk of \nendometriosis\n*Higher BMI is associated with an \nincreased risk of endometriosis, \nwhich negatively affects IVF \noutcomes \n* Surgical treatment before IVF/\nICSI does not appear to enhance \nIVF success and may further \ncompromise LBR.\nHamdan 2015 \n[33]\nSystematic review and meta-\nanalysis (36 studies, three were \nRCTs)\na similar LBR [OR] 0.94, 95% [CI] \n0.84-1.06, I=35%)\na lower CPR (OR \n0.78, 95% CI 0.65-\n0.94,I=66%), a lower \nmean number of \noocyte (1.98, 95% CI \n-2.87 I=97%)\nASRM III/IV have a lower LBR and \nCPR\nRossi 2016 [34] Systematic review and meta-\nanalysis 813 study)\nCPR were similar between stage \nI-II and controls (OR 0.99; 95 % CI \n0.63-1.56) \nCPR lower in stage III-IV \nthan controls (OR 0.45; \n95 % CI 0.29-0.70),\nASRM III/IV endometriosis had \nsignificantly lower cumulative CPR \nand ongoing pregnancy rates\nMorcel 2024 [35] Retrospective clinical study\nASRM stage III/IV had \nsignificantly lower \ncumulative CPR and \nongoing pregnancy \nrates\nASRM III/IV pregnancy rates are \ndecreasing cumulatively.\n\nwww.jcimcr.org                Page 9\nLiang 2024 [47] Systematic review and meta-\nanalysis/ART vs Surgery\nPregnancy rate per patient (OR, \n1.47; 95% CI, 0.59 to 3.63), \npregnancy rate per cycle (OR, 1.16; \n95% CI, 0.45 to 2.99), and live \nbirths per patient (OR, 1.66; 95% CI, \n0.56 to 4.91) were comparable in \nDIE patients\nFirst-line surgery and ART can \nbe effective DIE treatments with \nsimilar fertility outcomes\nCasal 2021 [48]\nSystematic review and meta-\nanalysis (98 studies)\n(Surgery for DIE before IVF/ICSI)\nThe pregnancy rate per patient was \n1.84 (95% confidence interval [CI], \n1.28-2.64), the pregnancy rate per \ncycle was 1.84 (95% CI, 1.26-2.70), \nand the LBR per patient was 2.22 \n(95% CI, 1.42-3.46) times more \nlikely for operated patients than for \nnonoperated ones. \nA statistically significant benefit \nfor surgery before IVF/ICSI in \npatients with DIE endometriosis\nBourdon 2024 \n[50]\nSystematic review and meta-\nanalysis (19 studies)\n(Surgery for DIE before IVF/ICSI)\nThe LBR per cycle was \nsignificantly reduced \nin the case of surgical \ntreatment before IVF/\nICSI [0.53[0.33, 0.86]; \nI2 = 30%)\nThe LBR per cycle was significantly \nreduced in the case of surgical \ntreatmet before IVF/ICSI\nART: Assisted reproductive treatment; HFEA: Human Fertilization and Embryology Authority; PGS: Preimplantation genetic screening; AOQI: \nAverage Oocyte Quality Index; MOMS: Metaphase II; MOMS: Oocyte Morphological Scoring System; CPR: Clinical Pregnancy Rate; LBR: Live \nBirth Rate; FET: Frozen Embryo Transfer; ET: Embryo Transfer; FET: Frozen Embryo  Cycles.; DIE: Deep Infiltrative Endometriosis.; IVF: In Vitro \nFertilization;ICSI: Intra-Cytoplasmic Sperm Injection.\nTable 2: The characteristics of selected studies related to ART outcomes with adenomyosis. \nReferences Intervention and/or \nstudy type\nComparable and/\nor Positive IVF/ICSI \noutcomes\nUncertain and/or Negative IVF/ICSI \noutcomes Conclusion and/or Recommendations\nYounes 2017 \n[56] A meta-analysis\na 41% decrease in LBR and an \nincreased risk of miscarriage in women \nwith adenomyosis.\nAdenomyosis has a detrimental effect \non IVF/ICSI reproductive outcomes.\nHan 2025 [9]\nSystematic review and \nmeta-analysis/ FET vs \nFresh cycle outcomes\nIn adenomyosis, the \nIVF/ICSI outcomes were \ncomparable between \nthe FET and fresh ET \nstrategies.\nComparable pregnancy rates between \nthe two groups (FET vs Fresh cycle)\nHorton  2019 \n[30]\nSystematic review and \nmeta-analysis A 55% reduction in LBR after IVF-ICSI Adenomyosis has a detrimental effect \non IVF/ICSI reproductive outcomes.\nNirgianakis \n2020 [57]\nSystematic review and \nmeta-analysis\nA lower CPR (odds ratio [OR] 0.69; 95% \nconfidence interval [CI] 0.51-0.94) and \nhigher miscarriage rate (OR 2.17; 95% \nCI 1.25-3.79) in adenomyosis\nAdenomyosis has a detrimental effect \non IVF/ICSI reproductive outcomes.\nMavrelos 2017 \n[60]\nA prospective \nmulticentre study\nA lower clinical pregnancy rate (21/72 \n[29.2%, 95% CI 18.6-39.6] versus \n129/303 [42.6%, 95% CI 37.1-48.2], P \n= 0.044, relative risk (RR) 0.68 [95% CI \n0.47-1.00]).\nCondition severity expressed as a \nnumber of morphological features \non ultrasound scan increases the \nmagnitude of the effect.\nNeal 2020 [59] A prospective cohort \nstudy\nNo difference in the rate \nof CPR, 1.47 (95% CI, \n0.85-2.56)), miscarriage \n(aOR, 1.3 (95% CI, 0.62-\n2.72)) or LBR 1.28 (95% \nCI, 0.78-2.08)) between \nsubjects with and those \nwithout adenomyosis.\nRoutine screening for asymptomatic \nadenomyosis in an unselected infertile \npatient population undergoing frozen \nembryo transfer may not be warranted\nVercellini 2014 \n[61]\nSystematic review \nand meta-analysis (17 \nstudies)\nThe miscarriage rate was more \nprevalent (RR 2.1 (95% CI 1.20- 3.75) \nin women with adenomyosis vs control \n(32% vs 14%).   \nAdenomyosis has an increased risk of \nmiscarriage\nSachs-Guedj \n2023 [64]\nHRT- FET cycle/Euploid \nET\nAdenomyosis decreased CPR (aOR \n0.62, 95% CI: 0.39-0.98, p = 0.040) and \nLBR (aOR 0.46, 95% CI: 0.27-0.75, p = \n0.003) and significantly increased the \nmiscarriage rates (aOR 2.13, 95% CI: \n0.98-4.37, p = 0.045)\nEven with euploid embryo transfer, the \nlow rates are high in adenomyosis\n\nwww.jcimcr.org                Page 10\nBourdon 2023 \n[66]\nA single-center \nobservational study.\nFET-ET was associated \nwith significantly higher \nodds of LBR compared \nwith fresh ET (odds ratio \n= 1.80; 95% CI= 1.02-\n3.16).\nFET-ET is an attractive option in \nadenomyosis regardless of different \ntype\nHRT: Hormone Replacement Therapy; FET: Frozen Embryo Transfer; ET: Embryo Transfer; CPR: Clinical Pregnancy Rate; LBR: Live Birt Rate; CI: \nConfidence Interval; IVF: In Vitro Fertilization; ICSI: Intra-Cytoplasmic Sperm Injection.\nTable 3: The characteristics of selected studies related to ART outcomes with endometriosis coexisting adenomyosis vice versa.\nReferences Intervention and/or study \ntype\nComparable and/or Positive \nIVF/ICSI outcomes\nUncertain and/or Negative \nIVF/ICSI outcomes\nConclusion and/or \nRecommendations\nWang 2023 [65] Systematic review and meta-\nanalysis (cohort studies)\nAdenomyosis in \nendometriosis is associated \nwith a significantly LBR (OR = \n0.44; 95% CI: 0.26-0.75) than \nendometriosis alone\nIn the coexistence of \nendometriosis and \nadenomyosis, adenomyosis \nreduces LBR\nLiu 2025 [76] A retrospective analysis \nIn women with endometriosis \nand/or adenomyosis, peri-\nimplantation treatment with \nTNF-α inhibitor increased CPR \nsignificantly compared with \ncontrol group in FET cycles. \nMore extensive studies are \nneeded.\nRees 2022 [78] A matched retrospective \ncohort study\nthe combined adenomyosis \nand endometriosis group \nshowed a significantly \nreduced LBR (p = 0.001, OR \n0.309 (95% CI: (0.168-0.644))\nIn the coexistence of \nendometriosis and \nadenomyosis, adenomyosis \nreduces LBR\nSharma 2019 [75] Retrospective cohort study\nLBR were 27.47% in controls; \n26.48% in women with only \nendometriosis; 11.36% in \nwomen with endometriosis \nand adenomyosis; and \n12.5% in women with only \nadenomyosis.\nIn the coexistence of \nendometriosis and \nadenomyosis, adenomyosis \nreduces LBR\nCPR: Clinical Pregnancy Rate; LBR: Live Birt Rate; CI: Confidence Interval.\nnot reduced in patients with endometriosis and adenomyosis \ngroup [78]. LBR are not affected by adenomyosis or endome -\ntriosis after the transfers of euploid blastocysts in HRT cycles \n[19,59]. Based on these results, the suppressive effect of HRT \non ovarian function may positively influence endometrial re -\nceptivity.\nAccording to ESHRE 2022, routine surgery before ART for \novarian endometrioma and SUP are not recommended. A the \nlatest meta-analysis results underwent prior surgical treatment \nfor endometriosis, no improvement was observed in CPR (OR: \n0.79) and LBR were further reduced [OR: 0.67 [0.23, 0.76]; I2 \n= 39%] [31]. Furthermore, the other study and meta-analysis \nalso, the LBR per cycle was significantly reduced in the case of \nsurgical treatment before IVF/ICSI (OR: 0.53) [31,46]. In line \nwith previus studies, Bourdon et al. [50], found in their meta-\nanalysis that endometriosis surgery before IVF/ICSI significantly \nreduced LBR [OR=0.53 [0.33, 0.86]; I2 = 30%]. Considering these \nmeta-analysis results, endometriosis surgery before IVF nega -\ntively affects fertility. On the other hand, the available evidence \nsuggests that both first-line surgery and IVF/ICSI can be effective \nDIE treatments with similar fertility outcomes [47]. There is no \nstrong evidence from RCTs that operative laparoscopy enhances \nfertility outcomes in patients with DIE. According to Casal’s [48], \nmeta-analysis results, patients who underwent DIE surgery be -\nfore IVF, pregnancy rate per patient was 1.84, and LBR per pa -\ntient was 2.22 times more likely for operated patients than for \nnonoperated ones. Hovewer, this meta-analysis did not include \nany RCTs, and therefore all included the other studies have high \nrisk of selection and allocation bias. In DIE, surgery before IVF \nnegatively affects IVF outcomes. A meta-analysis by Bourdon et \nal. [50], compared LBR in patients who underwent endometrio-\nsis surgery before ART in comparison with patients who under-\nwent first-line IVF/ICSI. After the exclusion of the studies with \nhigh risk bias, the LBR per cycle was significantly reduced in the \ncase of surgical treatmet before IVF/ICSI. Long-term morbidity \nis high in DIE surgery, with complication rates ranging from 9% \nto 23% [35]. In cases where pre-IVF adenomyosis is excluded \nin stage 3-4 cases, it is not yet clear whether surgery should be \nperformed before the first IVF attempt or after unsuccessful IVF \nattempts. Probably in view of these complications and contro -\nversial postoperative outcomes, surgery is necessary if there is \nbowel or urinary obstruction or if severe pain persisting despite \nmedical treatment [6,31,33,40,45,46]. Management decisions \nshould be individualized based on patient choice, age, associ -\nated symptoms, and the risk repeat surgery. First-line IVF seems \nto be a valid choice, in asymptomatic patients. \nAccording to meta-analyses, adenomyosis causes significant \nsuppression in IVF/ICSI and pregnancy outcomes [30,56,57,61]. \n\nwww.jcimcr.org                Page 11\nReferences Intervention and/or \nstudy type\nComparable and/\nor Positive IVF/ICSI \noutcomes\nUncertain and/or \nNegative IVF/ICSI \noutcomes\nJunctional Zon İnvolvoment Conclusion and/or \nRecommendations\nTrinchant 2025 \n[53]\nMulticenter and \nretrospective cohort \nstudy\nA higher LBR per \ntransfer was described \nin diffuse adenomyosis \ncompared to focal \nadenomyosis: 47/166 \n(28.3%) versus 9/62 \n(15%), respectively (OR \n= 2.32, 95% CI: 1.03-\n5.78, p = 0.034). \nNA\nDiffuse adenomyosis \nprovides a higher \nLBR\nWang 2023 [65] A systematic review and \nmeta-analysis\nDiffuse and \nsymptomatic \nadenomyosis, lower \nLBR (OR = 0.57; \n95% CI: 0.34-0.96) \nand miscarriage \n(OR = 2.48, 95% CI: \n1.28-4.82)\nNA\nOn USG Diffuse \nand symptomatic \nadenomyosis \nreduces LBR\nBourdon 2023 \n[66]\nA single-center \nobservational study \n(FET vs Fresh cycle)\nLBR (86 (44.1%) vs. 34 \n(30.6%), respectively), \nwere significantly \nhigher in the freeze-all \ngroup compared with \nthe fresh ET group.\nNA\n The adenomyosis \nphenotype \n(internal diffuse \nadenomyosis, \nexternal focal \nadenomyosis, and \nadenomyoma) was \nnot significantly \ndifferent between \nthe two groups.\nSharma 2025 [91] A prospective cohort \nstudy  \nDiffuse \nadenomyosis \nhave a lower \nLBR (20.65% vs. \n29.95%; OR: 0.61, \n95% CI: 0.41-0.89, \np = 0.011) than \nwomen without \nadenomyosis. \nDiffuse adenomyotic lesions \naffecting the JZ exhibited \nsignificantly lower LBR (16.42% \nvs. 25.75%; OR: 0.57, 95% CI: \n0.34-0.94, p = 0.029) \nIn diffuse \nadenomyosis \nshowing JZ \ninvolvement, live \nbirth rates are much \nlower.\nExacoustos 2020 \n[92]\nA multicenter, \nobservational, \nprospective study.\nHigher percentage of infertility \nand miscarriage in focal \nadenomyosis of both the outer \nmyometrium and the JZ\nIn focal adenomyosis \nshowing JZ \ninvolvement, \nmiscarriae are \nincreased\nCozzolino 2024 \n[85]\nA prospective \nobservational cohort \nstudy.\nDiffuse adenomyosis in the JZ \nincreased the relative risk of \nmiscarriage two-fold (RR, 2.29; \n95% CI, 1.22-4.30).\nIn diffuse \nadenomyosis \nshowing JZ \ninvolvement, \nmiscarriae are \nincreased\nXia 2025 [87]\nA systematic review and \nmeta-analysis (involving \n390 women with diffuse \nadenomyosis and 233 \nwomen with focal \nadenomyosis)\nDiffuse \nadenomyosis \nhad higher odds \nof experiencing \npreterm \nbirth(OR1.66, \n95% CI1.03-2.67, \nP = 0.038) and \nhypertensive \ndisorders of \npregnancy (OR \n2.23, 95% CI 1.32-\n3.77; P = 0.002).\nNA\nDiffuse adenomyosis \nwas significantly \nassociated with an \nincreased risk of \nadverse pregnancy \noutcomes\nTable 4: IVF/ICSI outcomes related to phenotype and junctional zone involvement in adenomyosis.\nNA: Not Assessed; CBR: Clinical Pregnancy Rate; LBR: Live Birth Rate; JZ: Junctional Zone; CI: Confidince Inreval; FET: Frozen Embryo Cycle. \n\nwww.jcimcr.org                Page 12\nWansg et al.’s [65], meta-analysis showed that particularly \nsymptomatic and diffuse adenomyosis adversely affected IVF/\nICSI outcomes. Regardless of phenotypic differentiation, fertil -\nity is impaired, especially in adenomyosis involving junctional \nzone involvement [85]. In a study of euploid embryo transfer \nin adenomyosis, CPR, miscarraige, and LBR were similar to the \ncontrol group [59]. However, in this study, while most patients \nexhibited only one MUSA criterion, 17 patients exhibited two \ncharacteristics. The Age-Adjusted Relative Risk (ARR) for with at \nleast one MUSA criteria 0.58 (95% CI: 0.45-0.75) in adenomyo -\nsis. CPR decreased from 42.7% in women with no adenomyosis \nto 13.0% in those with four and seven ultrasound diagnostic \nfeatures of adenomyosis [60]. This situation must be taken into \naccount when evaluating these results. \nThe phenotypic effect of adenomyosis on IVF/ICSI outcomes \nis mixed. While some studies have found a correlation with LBR \n[53,65], other studies have found no such correlation [78]. The \nanswer remains unclear for which type of adenomyosis has the \nworst fertility outcome. According to current findings, pheno -\ntypes associated with JZ involvement are more severely affect-\ned [65,91,92]. The studies in patients with adenomyosis having \nIVF/ICSI involve heterogenity in participant age, whether or not \nto administer GnRH treatment before IVF, duration of infertility, \nand different stimulation protocols. Phenotypic differences in \nadenomyosis, heterogenity in diagnostic criteri coexisting en -\ndometriosis and leiyomyoas are factors that affect IVF success. \nWhether adenomyosis is symptomatic or not, the use of direct \nor indirect diagnostic criteria in diagnosis, and the results ob -\ntained from the number of criteria are all factors involved. Most \nof the studies the diagnostic criteria used are heterogeneous \nand sometimes not well defined, especially for adenomyosis, \nbecause some studies used TVUSG, some MRI, and others both. \nMost studies have not demonstrated a correlation between \neach characteristic used in the diagnosis of adenomyosis and \nthe study results.\nAlson et al. [78], found that women with endometriosis and \nadenomyosis had a 15% lower cumulative chance of achiev -\ning an LBR after three consecutive IVF/ICSI cycles compared to \nwomen without these conditions. The lower LBR in the com -\nbined adenomyosis and endometriosis women can be attrib -\nuted to more severe adenomyosis in these women. Hovewer, \ndespite a lower CLBR over three IVF/ICSI cycles, women with \nendometriosis and/or adenomyosis still have a reasonable \nchance of achieving LBR with consecutive treatments [78]. \nIn this study, there was no difference in adenomyosis phe -\nnotypes between the groups that became pregnant and those \nthat did not. Hovewer, most studies did not distinguish between \nthe subtypes of endometriosis and adenomyosis. In studies, the \nexclusion of adenomyosis with current TV USG and MRI diag -\nnostic strict criteria has provided an advantage in terms of pure \nendometriosis IVF/ICSI results and has led to clearer interpreta-\ntion of the results.\nIn adenomyosis, miscarriage rates occur independently of \nthe embryo’s genetics. In oocyst donation cycles, implantation \nrates were found to be normal, but miscarriage rates were high \n[63]. Even with euploid embryo transfer, the low rates are high \nin adenomyosis [64]. The endometrial gene expression profile \nof women with adenomyosis does not differ with the gene ex -\npression pattern of the controls [21]. Based on these results, \nit is thought that miscarriages occurring in adenomyosis are \nrelated to molecular mechanisms other than those related to \nimplantation window gene alterations. AD a high JZ thickness \n(>10 mm) is considered to be independent faktör for implan -\ntation failure [62,63]. Cozzolino M et al. [85], reported that a \nthreefold higher relative risk of miscarriage when particularly \ndiffuse adenomyosis involved in contact with the JZ. The reduc-\ntion in implantation and miscarriage may be dependent on the \ntype and extent of disease [70]. While it is not clear how each \ntype of adenomyosis affects fertility, hovewer, fertility rates are \nworse in both focal and diffuse adenomyosis associated with \nJZ involvement. The Age-Adjusted Relative Risk (ARR) for LBR \nwas maximally reduced (OR: 0.29, 95% CI: 0.11-0.74) in women \nwith involvement of the JZ [60]. According to recent studies, the \npredominantly diffuse phenotype reduces LBR and leads to pre-\nterm birth, while JZ involvement negatively affects fertility in \nboth focal and diffuse phenotypes [91,92], (Table 4). \nIn adenomyosis, determining the embryo transfer day based \non transcriptomic analysis or increasing luteal support proges -\nterone dose did not affect pregnancy outcomes in cases of pro-\ngesterone resistance in FET cycles [88]. These results support \nthe theory of progesterone resistance in adenomyosis. In com-\npatible with this results, Alsbjerg et al. [89], reported that preg-\nnancy outcomes were optimized with a luteal progesterone \nlevel of 37.1 ng/mL in endometriosis patients having HRT-FET \ncycle. Hovewer, Bourdon et al. [90], there was no significant dif-\nference in the mean progesterone level on the day of HRT-FET \nbetween those with endometriosis and/or adenomyosis those \nwithout (13.6±4.3 ng/mL vs 13.2±4.4 ng/mL, respectively; \nP=0.302). Researchers have suggested that the effect of proges-\nterone resistance in FET cycles may be minimal. Hovewer, these \nresults make optimal luteal progesterone levels for pregnancy \noutcomes controversial in relation to progesterone resistance \nin endometriosis and/or adenomyosis patients undergoing HRT-\nFET cycles. \nConsidering the latest meta-analysis results, pregnancy rates \nafter surgery in adenomyosis are promising [79]. Meta-analyses \nhave shown favourable results after uterus-sparing surgeries, \nwith a range of pregnancy rates (38.5-49.1%) depending on the \nextent of adenomyosis. Postoperative GnRH agonist therapy has \nbeen shown to improve outcomes, however, results have been \ninconsistent. IVF/ICSI in conjunction with surgery showed im -\nproved outcomes in one meta-analysis, while it showed compa-\nrable outcomes to natural conception after surgery in another \n[79]. Perhaps with a greater advantage among younger patients \nwith focal adenomyosis [80]. Pregnancy rates after HIFU are \npromising. Surgery may increase the risk of rupture and not ef-\nfective as a fertility treatment for women over the age 40 years.\nBased on curent evidence, surgery should only be considered \nfor symptomatic women with repeated IVF/ICSI failure after the \ntransfer of high quality embryos [51,52,55].\nA meta-analysis by Ge Li et al. [67], showed that the ultra-long \nGnRH-a protocol may positively influence fresh ET outcomes in \nwomen with adenomyosis by possibly correcting implantation \ndefects. There is another study that previously supported these \nresults [70]. However, Ge’s meta-analysis, lacked randomiza -\ntion, did not phenotypically determined adenomyosis before \nIVF/ICSI, and while CPR were high and miscarriage rates similar \nin fresh cycles, this was not reflected in LBR. The latest ESHRE \nguidance does not recommend ultra-long GnRH agonist before \nIVF [6].\nIn terms of pregnancy outcomes, pregnancy complications \nare increased in both endometriosis and adenomyosis. DIE has \n\nwww.jcimcr.org                Page 13\nbeen identified as a risk factor plasenta previa and for spon -\ntaneous hemoperitoneum during gestation. Specific conditions \nthat may arise for both situations should be considered during \npregnancy monitoring. As early diagnosis and careful monitor -\ning can help prevent or reduce the risk of complications for both \nthe mother and the fetus. \nConclusion\nLBR after IVF/ICSI is comparable in women with and with -\nout endometriosis. Laparoscopy routine is not recommended \nexcept in symptomatic cases before IVF/ICSI. DIE and adeno -\nmyosis itself are thought to contribute to suboptimal IVF-ICSI \noutcomes in endometriosis. Surgical treatment of DIE before \nIVF/ICSI is controversial. \nThe phenotypic effect of adenomyosis on IVF/ICSI outcomes \nis mixed. The answer remains unclear for which type of ad -\nenomyosis has the worst fertility outcome. Disturbance in the \nuterine junctional zone have been implicated as potential con -\ntributers to AD associated miscarriage. Junctional zone involve-\nment impairs fertility regardless of phenotypic characteristics. \nParticularly symptomatic and diffuse adenomyosis adversely af-\nfected IVF/ICSI outcomes. Women with the most severe forms \nof adenomyosis have a trend toward worse outcomes. \nIn endometriosis and adenomyosis, the presence of adeno -\nmyosis reduces LBR. While both conditions may independently \nimpair IVF/ICSI success, the percentages of women with both \ndiseases remain a matter of debate. Based on current evidence, \nadenomyosis has a more prominent negative impact on LBR \nand miscarriage rates. The exclusion of adenomyosis with cur -\nrent TV USG and MRI diagnostic criteria has provided an advan-\ntage in terms of pure endometriosis IVF results. Surgical pallia -\ntive treatments in adenomyosis are yielding promising results. \nPregnancy complications are increased in both endometriosis \nand adenomyosis.\nDeclarations\nEthics committee: Support not used. Due to the review, no \nethics committee approval was received. \nCredit authorship contribution statement:  CK: \nConceptualization, Data curation, Formal analysis, Investigation, \nMethodology, Validation, Writing - original draft.\nFunding statement: The author received no external funding \nor assistance for this study.\nConflict of interest statement for all authors:  The author \nhas no conflict to declare. \nAttestation statements: Data regarding any of the subjects \nin the study has not been previously published unless specified. \nData will be made available to the editors of the journal pre and/\nor post publication for review or query upon request. Artificial \nintelligence and artificial intelligence-supported technologies \nwere not used.\nData sharing statement:  All the data is shared in the \nmanuscript.\nReferences\n1. Carey ET, Wong JMK, Khan Z. Comprehensive Revire of \nEndometriosis Care. 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