Women with endometriosis, deep endometriosis and/or adenomyosis who undergo art: The challenges faced and a narrative review of therapeutic strategies for successful outcomes

Endometriosis Endometriosis is a common, chronic, systemic inflamma - tory condition characterized by debilitating pain, and issues with infertility. Current theories of endometriosis pathogen - esis include retrograde menstruation, recurrent tissue injury and repair, endometrial stem cell recruitment, müllerian rest induction, coelomic metaplasia, lymphatic or hematogenous spread, genetic or epigenetic changes, and microbiome al - teration. Endometriosis-associated infertility include distorted pelvic anatomy, cytokine-influenced sperm DNA damage and

Endometriosis and adenomyosis are different clinical conditions with similar pathophsiology. Both conditions involve increased local estrogen, decreased progesterone receptor, and increased progesterone resistance in the lesions. Adenomyosis, which frequently coexists with endometriosis, can impair implantation and increase miscarriage rates. In both conditions, Asisted Repructive Technologies (ART) is a relevant treatment. Endometriosis and adenomyosis patient groups undergoing ART are patient groups that require special attention and a specialized field of study. In cases where endometriosis and adenomyosis coexist, adenomyosis has a greater impact on increased miscarriage and decreased birth rates. In patients with advanced endometriosis who have experienced recurrent miscarriage or implantation failure, and in elderly patients, pre-treatment adenomyosis screening may be beneficial. Magnetic resonance imaging and transvaginal ultrasound are very effective in diagnosing endometriosis and adenomyosis. Fertility rates are worse in both focal and diffuse adenomyosis associated with JZ involvement. Recent scientific evidence indicates that satisfactory a live birth can be achieved with a cumulative freeze-all policy in endometirosis and adenomyosis. Thus, cumulative live birth rates over several cycles would provide a more accurate estimate of the impact of endometriosis and adenomyosis on ART outcomes. Non-surgical palliative treatments in adenomyosis are yielding promising results. Deep İnfiltrative Endometriosis (DIE) present in up to 20% of women with pelvic endometriosis, is a severe form characterized. Optimal management of DIE is still a matter of debate. Based on physiology and current evidence, this article discusses the outcomes of surgery and ART in endometriosis, adenomyosis, and DIE.

Endometriosis; Adenomyosis; Surgery; IVF; Pregnancy. www.jcimcr.org Page 2 Citation: Kaya C. Women with endometriosis, deep endometriosis and/or adenomyosis who undergo art: The challenges faced and a narrative review of therapeutic strategies for successful outcomes. J Clin Images Med Case Rep. 2026; 7(2): 3936. dysmotility, microbiome alteration, diminished ovarian reserve, and dysregulated ovulation, fertilization, and embryo implanta- tion. While its prevalence is 10-15% in the general population, it can reach 50% in the infertile population. Sexual dysfunction due to superficial or deep dyspareunia in patients with endo - metriosis should also be included at this point. The risk of se - vere endometriosis is six times higher in first-degree relatives of affected women compared to unaffected individuals [1]. Orr et al [2]. found that KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) mutations correlate with more severe anatomical manifestations of endometriosis. Three different types of endometrioses have been identi - fied; Ovarian Endometrioma (OMA), Superficial Peritoneal Endometriosis (SUP), and Deep İnfilrative Endometriosis (DIE) [3]. For diagnosis, the gold standard for diagnosing pelvic endo- metriosis is laparoscopic biopsy with histological confirmation. Transvaginal Sonography (TVUSG) the cornerstone imaging technique for the evaluation and diagnosis of endometriosis. Magnetic Resonance İmaging (MRI) is highly accurate for diag - nosis of deep infiltrating endometrisosis. The severity of en - dometriosis is typically assessed with the help of classification systems such as the Revised American Society for Reproductive Medicine (RASRM) score and the ENZIAN system. The ENZIAN system evaluates lesion size, localization, and depth of infiltra - tion. Unfortunately the value of all staging system including rAS- RM is limited. It is poorly predictive of chances of spontaneous or induced pregnancy and has little correlation with the severity of the symptoms presented by the patients [4]. This narrative review examines treatment options, surgical and IVF outcomes in endometriosis, adenomyosis, and deep infiltrative endome - triosis. Search strategy A literature search was performed using PubMed in the English language until september 2025. A narrative review was done. The following combinations of search terms were used: “Endometriosis and IVF”, “Adenomyosis and IVF”, “Deep endo- metriosis and IVF ”, “Endometriosis and surgery and IVF”, “Ad- enomyosis and frozen embryo transfer ”, “Adenomyosis and IVF stimulation”, “Endometriosis and frozen embryo transfer”, “Endometriosis and obstetric outcomes”, “Adenomyosis and perinatal outcomes”. The references of each cited source were assessed to so as not to exclude any other sources relevant to this review. The primary focus was to evaluate the most recent literature on the role of IVF/ICSI and surgery in patients with en- dometriosis and/or adenomyosis and the risks that may be an - ticipated in pregnancy. Articles were chosen for inclusion if they were: [1], retrospective or prospective studies or meta-analyses involving women with endometriosis and/or adenomyosis of reproductive age women and involved IVF-ICSI and/or embryo transfer [2], systematic reviews. Excluded studies [1], were case reports, case series, abstracts, expert opinion articles [2], did not involve patients with endometriosis and/or adenomyosis [3], did not involvepatients undergoing IVF-ICSI. Medical treatment All currently available medical treatments-using GnRH-a, oral contraceptives, or progestins-have no proven effect on natural fertility. Medical treatment can reduce the size of lesions and al- leviate pain. Suppressive hormonal therapies can be considered after endometriosis surgery to prevent endometriosis associ - ated symptoms and disease recurrence whilst awaiting ART [5]. According to ESHRE 2022, hormonal suppression treatments are not recommended to improve natural fertility in women with endometriosis [6]. In endometriosis ART According to the 2002 ESHRE guidelines, ART (IUI, IVF/ICSI) is recommended for endometriosis-related infertility [6]. Con - trolled Ovarian Hyperstimulation (COH) + IUI is recommended as a first-line treatment for ASRM 1-2 patients under 35 years of age with normal sperm parameters, normal tubal patency, and good ovarian reserve. IVF/ICSI may be useful in bypassing some of the negative effects of endometriosis such as inflammatory conditions prevailing in the pelvic cavity. IVF/ICSI is necessary in 10 to 25% of women with endometriosis [6,7]. Main indications for ART remain tubal impairment, male factor, low endometrio- sis fertility index, and failure of other treatments. A systematic review by Kuan et al. [8], which reported no significant differences in Clinical Pregnancy (CPR) or Live Birth Rates (LBR) between the long GnRH agonist and GnRH antago - nist protocols. A meta analysıs by Han Y et al. [9] demonstrated that the Frozen Embryo Transfer (FET) strategy yielded higher CPR (OR: 1.2), LBR (OR: 1.3), and implantation rates (OR: 1.2) compared to the fresh ET strategy. A recent Cochrane review concluded that the benefit of ultralong GnRH therapy (mini - mum 3 months) versus no pre-treatment prior to IVF or ICSI is uncertain with regards to CPR, miscarriage, and LBR [10,11]. A study by Eıssa Khalifa et al. [12], reported that a comparable ef- fect of dienogest to the ultra-long protocol particularly impact on the LBR in endometriosis patients with undergoing IVF [6]. Oocyte/embryo effect Human Fertilization and Embryology Authority (HFEA) re - ported no significant difference in LBR in either fresh or FET cycles [13]. Euploidy and aneuploidy rates in women with en - dometriosis compared to age-matched controls, have reported equivalent euploidy rates between groups [14]. Endometriosis does not have a negative impact on oocytes’ morphology in IVF-ICSI cycle [15]. The presence of OMA could decrease the oocyte yield in patients endometriosis having IVF/ICSI, it does not appear to have an adverse impact on oocyte quality [16]. No differences in the percentage of meiotic abnormalities in in vitro matured oocytes from endometriosis or control patients after COS [17]. A recent meta-analysis of 22 studies found that endometriosis does not affect embryo morphology, with com - parable high-quality embryo rates, cleavage rates [18]. Endo - metriosis per se does not seem to impact oocyte quality and LBR were similar between endometriosis patients and controls when euploid blastocysts were transferred in an HRT-FET cycle [19]. This results suggest minimal or no impact of oocyte quality in patients with endometriosis. Fertilization/implantation Fertilization rates were lower for ASRM stage I-II compared to severe endometriosis or tubal factor infertility [20]. Harb et al. [21], demonstrated that a 7% reduction in fertilization and CPR in both mild endometriosis and moderate/severe www.jcimcr.org Page 3 endometriosis. A recent meta-analysis confirmed that ASRM stage I-II endometriosis specifically impairs fertilization (OR 0.77, CI: 0.63-0.93) and earlier implantation processes (OR 0.76, CI: 0.62-0.93), whereas more severe endometriosis impacts negatively on all reproduction stages [22]. Another a retrospective study on 503 IVF cycles found no significant difference in fertilization rates using IVF in women with endometriosis compared to women with infertility due to other causes [23]. A meta analyses by Mappa I et al. [24], of eight studies (study group: 4153 out of 5661; control group: 43,979 out of 62,972), revealed that no difference in fertilization rates was found. This results suggest fertilization rate seems to be compromised in case of milder endometriosis presentations. In a meta-analysis by Harb et al. [21] reported that 11%-17% reduction in implantation ASRM stage III/IVF. Qu et al.’s meta- analysis [22], compared with the control group, the implantation rate (p=0.04) was significantly lower in women with endome - triosis but no difference in reproductive outcomes. The effec - tiveness of endometrial scratching prior to IVF has shown that there was no significant difference LBR in women with endome- triosis compared to controls [25]. The endometrial receptivity analysis tool found no significant difference in the expression of 238 genes related to endometrial receptivity between women with and without endometriosis [26]. Bishop et al. [19], evalu - ated the implantation trend in three populations undergoing euploid FET after IVF/ICSI treatments for different indications, including endometriosis, male factor, and preimplantation ge - netic testing for monosomic disorders. No difference including LBR, were found across the groups. In another study, regarding the role of endometrial receptivity in endometriosis-associated infertility, CPR and LBR in FET cycles of euploid embryos did not differ between patients with endometriosis having IVF/ICSI and controls [27]. Clinic pregnancy/ live birth rate In terms of positive IVF/ICSI results, a meta analyses by Map- pa I et al. [24], in endometriosis patients undergoing IVF/ICSI, does not significantly impact LBR and CPR, when compared to other causes of infertility. HFEA reported no significant differ - ence in LBR in either fresh or FET cycles in patients with endo - metriosis undergoing IVF [13]. Norwegian retrospective study, indicate comparable LBR (66.0% vs. 66.7%), while the 2022 SART report showed no significant differences in IVF/ICSI out - come between endometriosis patients compared to control groups [28,29]. In terms of negative IVF/ICSI results, a 12% reduction in LBR after IVF/ICSI was observed by Horton et al. [30] only in pa - tients with stage III-IV endometriosis. In compatible with this results, Liao et al. [31], demonstrated a significant reduction in LBR for endometriosis patients with undergoing IVF/ICSI treat - ment compared to normal IVF. A metanalysis by Paffoni A et al. [32], (137 182 from SART and 24 900 from HFEA) in which analyzed 7212 oocyte donation cycles showed that a statisti - cally significant lower LBR was identified in women with endo - metriosis (OR, 0.89; 95% CI:, 0.81-0.97). Harb et al. [21], carried out a meta-analysis of 27 observational studies in women with ASRM stage I/II and III/IV in patients endometriosis having IVF/ ICSI. In this study, while resulted in a 7% decrease in fertilization and CPR across ASRM all stages. ASRM stages III-IV showed a 14% decrease in LBR (RR: 0.79; 95% CI: 0.69-0.91) along with lower implantation rates (RR=0.86, 95% CI: 0.68-1.08). A meta- analysis by Hamdan et al. [33] in which included 17 studies for a total of n=17,593 IVF cycles, showed a significant decrease in LBR (30%) and CPR (40%) in women with ASRM III-IV endome - triosis (OR=0.78, 95% CI: 0.65-0.95). In this meta-analysis, in the subgroup of patients with ASRM stage I/II endometriosis had comparable LBR following IVF compared to patients without endometriosis. Rossi et al. [34], meta-analysis found that pa - tients with stage I/II endometriosis undergoing IVF had a similar CPR to controls. Morcel K et al. [35], demostrated in patients with endometriosis undergoing IVF ASRM stage III/IV had sig - nificantly lower cumulative CPR. These results were consistent with Harb et al.’s meta-analysis, which found significantly lower implantation rates and LBR in women with ASRM stage III/IV endometriosis but not in women with ASRM stage I/II endome- triosis (Table 1). As a results, overall, LBR is approximately the same as for other causes infertility [13,24,28,29]. In SUP/Surgery vs ART According to ESHRE 2022, routine surgery before ART for ASRM stage I/II endometriosis is not recommended, as there is no proven benefit for LBR. A recent meta-analysis identified that CPR significantly increased following operative laparoscopy for endometriosis compared with placebo (odds ratio (OR) 1.63; 95% CI: 1.13 to 2.35) [36]. Hodgson et al.’s [37] meta-analysis re- vealed that surgical treatment increased CPR in endometriosis patients. Only one meta-analysis, Jin’s meta-analysis of 4 trials on SUP identified laparoscopic surgery to increase LBR (RR=1.52, 95%, CI: 1.26-1.84, p<0.01 )and pregnancy rates (RR=1.44, 95% CI: 1.24-1.68, p<0.01) [38]. The absolute benefit is modest with a number of women needed to be treated of 12 to achieve one additional pregnancy. There is only a single and retrospective cohort study thus far that compared the outcomes in women proceeding with IVF/ICSI who underwent complete surgical excision of disease (n=399) versus diagnostic laparoscopy only (n=262) for SUP . Overall, 399 women SUP were surgically treat- ed and all visible endometriosis was completely removed prior to IVF/ICSI while the 262 women included in the control group underwent only a diagnostic laparoscopy. In this study, cases demonstrated a significant higher CPR and LBR (OR 1.47; 95% CI: 1.01 to 2.13) [39]. Operative laparoscopy is currently an op- tion for endometriosis-associated infertility in ASRM stage (I/II) when is performed for other indications such as pain. In OMA/Surgery vs ART results Several meta-analyses have concluded that ovarian cystec - tomy for in women undergoing OMA IVF/ICSI does not improve CPR or LBR [16,33]. Alseshre et al. [40], found that the quan - tity and quality of the embryos produced were similar between women with endometrioma and controls. Ovarian cystectomy prior to IVF/ICSI treatment can lead to a higher rates of cycle cancellation due to poor ovarian response. A reduction in the response to COH can be detected only for endometriomas larg- er than 4 cm. Surgical treatment of endometriomas does not enhance the outcomes of IVF/ICSI. The surgical excision of en - dometriomas can lead to a significant decline in Anti-Müllerian Hormone levels,specially noted for bilateral endometriomas or when endometriomas exceed 5 cm in size [41]. This decline can be attributed to the removal of normal ovarian tissue, thermal damage during surgery, and subsequent inflammation. Meta- analyses examining the impact of OMA on IVF/ICSI outcomes have shown a significant reduction in the number of mature oo- cytes retrieved in women with OMA versus controls. But no dif- ference in the gonadotropin dose and duration, the total num - ber of embryos, high-quality embryos, CPR, and LBR between women with and without OMA [42]. A meta-analysis focusing on OMA reported recurrence rates of 4%, 14%, 17%, and 27% at www.jcimcr.org Page 4 3, 6, 12, and 24 months, respectively, after surgery [43]. DIE /Surgery results vs ART DIE is a severe form characterized by the infiltration of fi - brous and muscular tissues beneath the peritoneum (>5 mm). DIE is affects between 3.8% and 37% of all patients with endo - metriosis [44]. DE diagnosis was based on strict İmaging Criteria (MRI) and histological confirmation of the disease for women with a previous history of surgery for endometriosis [45]. Thera- peutic options include primarily surgical management and ART. DIE is often associated with external focal adenomyosis but is not associated with miscarriage. A retrospective cohort study, 222 DIE endometriosis patients underwent a total of 440 ART cycles (fresh and FET). One hun - dred fifty-five women (69.8%) had a prior history of surgery for endometriosis. The CLBR was 26% after four IVF/ICSI cycles in the “previous history of surgery for endometriosis” group, while it reached 51.3% after four cycles (p<0.001) in patients who had not previously undergone surgery for endometriosis. A previous history of surgery for endometriosis (p=0.001) and a past sur - gery for endometrioma (p=0.005) were established as indepen- dent factors associated with lower pregnancy rates. This results suggest that for DIE patients, a previous history of surgery may be associated with negative IVF-ICSI outcomes [46]. A meta-analysis by Liang et al. [47], that show pregnancy rate per patient (OR: 1.47), pregnancy rate per cycle (OR: 1.16), and LBR (OR:1.66) were comparable in DIE patients, treated with surgery or IVF-ICSI as a first line of treatment. When both complete and incomplete surgical DIE excision procedures were taken into account, surgery was associated with a significant en- hancement in the pregnancy rate per patient (OR, 1.63; 95% CI:, 1.11 to 2.40). A meta analyses by Casals G et al. [48], compare reproductive outcomes in patients who underwent surgery for DIE before IVF with those in patients who underwent IVF without a previous surgery for DIE. In this meta-anaylysis, pa - tients who underwent DIE surgery before IVF, pregnancy rate per patient was 1.84, and LBR per patient was 2.22 times more likely for operated patients than for nonoperated ones. In con- trast to Casal G et al. Daniilidis A et al. [49], showed that there is no evidence to suggest the surgical removal of DIE prior to IVF-ICSI in patients with endometriosis to improve reproduc - tive outcomes. Another meta-analysis by Bourdon et al. [50], compared ongoing pregnancy rates and LBR in patients who underwent endometriosis surgery before ART in comparison with patients who underwent first-line IVF/ICSI. After the exclu- sion of the studies with high risk bias, the LBR per cycle was significantly reduced in the case of surgical treatmet before IVF/ ICSI. These results were consistent with those of Danilidis et al. More recently, a metaanalysıs by Liao L et al. [31] demonstrated that underwent prior surgical treatment for endometriosis, no improvement was observed in CPR (OR: 0.79), and LBR were further reduced (OR: 0.67). Adenomyosis/Definition, diagnosis, clinical manifestations Adenomyosis (AD) is presenting in two main forms: diffuse adenomyosis of the inner myometrium, and focal adenomyosis of the outer myometrium. The diffuse type of adenomyosis is more common than the focal type, and the disease develops more often in the posterior. Diffuse adenomyosis frequently occurs in older age, while focal adenomyosis is more common in younger individuals and is more frequently associated with endometriosis. Internal adenomyosis is more commonly associated with uterine fibroids, whereas external adenomyosis is more often linked to endometriosis [51]. Two predominant theories have been proposed to explain its origin: one suggests that it results from the invagination of the endometrial basalis into the myometrium, while de novo development as a consequence of metaplasia of embryonic Müllerian remnants [52]. There is increasing evidence concerning the role of KRAS and PIK3CA mutations in the pathogenesis of adenomyosis [2,53]. Diagnosis of adenomyosis is made via TVUSG or MRI. MRI better predicts adenomyosis while performed in the secretory phase of the menstrual cycle. A histopathological diagnosis is obviously not required to treat qualified patients for infertility. AD is strongly suspected when the JZ measures at least 12 mm in thickness on MR images. JZ thickness can vary depending on menstrual cycle and hormone therapy. When measured against histopathology TVS had a sensitivity of 72%-82% and a specific- ity of 81%-85%, whereas MRI had a sensitivity and specificity of 77% and 89%, respectively. According to MUSA (Morpho - logical Uterus Sonographic Assessment) criteria, a diagnosis of adenomyosis was made if at least one of the direct features (myometrial cysts, hyperechogenic islands, or subendometrial lines or buds) was identified. Recent studies have shown that nulligravid young women can also suffer from adenomyosis, suggesting that the disorder may develop earlier in reproduc - tive life than previously thought. Clinical manifestations are reported by 65% of the women with adenomyosis. However, one third of patients are asymptomatic [53,54]. Adenomyosis is present in approximately 24.4% of young infertile women in IVF-ICSI cycles. Its prevalence was respectively 38.2% and 34.7% in cases of recurrent pregnancy loss and previous ART failure. Adenomyosis contributes to infertility through including in - creased junctional zone thickness, utero tubal disperistaltism, biochemical, functional, and epigenetic changes in both eutopic and ectopic endometrium. Microtraumas also in the endo-myo- metrial junction that may develop into AD. Possible the other mechanisms, anatomical distortion of the uterine cavity, altered sex steroid hormone pathways, increased inflammatory mark - ers and oxidative stress, the reduced expression of implanta - tion markers, a lack of expression of adhesion molecules, and altered function of the gene for embryonic development. The extension and type of adenomyosis appear to be important factors that affect fertility. The common association of adeno - myosis with endometriosis may be another cause. Leiomyomas coexists 35% to 55% in patients with adenomyosis [54,55]. Hov- ewer, the relationship between adenomyosis and infertility has not yet been fully established. In adenomyosis ART In adenomyosis IVF outcomes are mixed, although negative in numerous studies and meta-analyses. Younes & Tulandi [56], confirmed in meta-analysis a 41% decrease in live pregnancy rates and an increased risk of miscarriage in women with ad - enomyosis. In the meta-analysis by A 55% reduction in LBR after IVF/ICSI was reported by Horton et al. [30], whereas Nirgianakis et al. [57], did not find a difference between cases and controls in patients with ademoyosis. Nirgianakis’s study presented data supporting that the type of adenomyosis (focal or diffuse) does not significantly affect the reproductive outcome of patients. More recently, Bourdon et al. [58], 285 women with adeno - myosis were matched with 285 controls. The cumulative LBR was significantly lower in the adenomyosis group compared to www.jcimcr.org Page 5 controls (41.4% versus 51.9%; OR=0.65, 95% CI: [0.47-0.91]; P=0.012). Similarly, the CPR was reduced in the adenomyosis group (53.3% versus 63.9%; P=0.011). In contrast to these find- ings, a prospective IVF cohort study explored the reproductive outcomes of a total of 99 adenomyosis patients and 549 non- adenomyosis patients undergoing preimplantation genetic test- ing for aneuploidies and subsequent FET. As for the CPR, LBR and miscarriage rates, no difference was seen between the ad- enomyosis and non-adenomyosis groups [59]. In Mavrelos et al. [60], demonstrated that mild forms of ad - enomyosis have limited impact while more severely affected women have poorer outcomes. In terms of miscarriage, in a meta-analysis by Vercellini et al. [61], the miscarriage rate was more prevalent (RR=2.1 (95% CI: 1.20-3.75) in women with adenomyosis vs control (32% vs 14%). A systematic review by Horton et al. (30) which seven comparative observational stud- ies that involved IVF/ICSI cycles, there was an increase in mis - carriages (OR=3.49, CI: 1.41-8.65, P=0.007; n=6). In patients with adenomyosis undergoing ART in oocyte donation, normal implantation rates and higher miscarriage rates have been re - ported [62,63]. Furthermore, women with adenomyosis have an increased risk of miscarriage, even using euploid embryos [64] (Table 2). Phenotypic aspects of IVF outcomes in adenomyosis, a ret - rospective multicenter study revealed that a higher LBR per transfer was described in diffuse adenomyosis compared to focal adenomyosis: 47/166 (28.3%) versus 9/62 (15%), respec - tively (OR=2.32, 95% CI: 1.03-5.78, p=0.034) [53]. Hovewer, a meta-analysis, by Wang at. [65], revealed that LBR were low - er (OR=0.57; 95% CI: 0.34-0.96) and miscarriage rates were higher(OR=2.48, 95% CI: 1.28-4.82) in patients with in cases of diffuse and symptomatic adenomyosis than focal adenomyosis. A meta analysıs by Han Y et al. [9] in women with adenomy- osis, pregnancy outcomes were comparable between the FET and fresh ET groups. FET are best performed in E2 and proges - terone replacement cycle. Bordoun M et al. [66], showed that the FET ET group was associated with significantly higher cumu- lative LBRs (OR=1.80; 95% CI: 1.02-3.16). A meta-analysis by Ge Li et al. [67], evaluated the reproductive outcomes of different ovarian stimulation protocols in adenomyosis IVF/ICSI. In fresh ET in women aged ≥35, the CPR was higher (OR=1.33; 95% CI: 1.06-1.66, I2=40%) in the ultra-long and long protocols than in the antagonist and short protocols. The results elucidate that an ultra-long or long protocol might benefit women with ad - enomyosis receiving IVF-ICSI with fresh ET compared to a short protocol. In the FET cycles, there were no statistical differences in the IR, CPR, or LBR of embryos derived from different stimula- tion protocols. GnRH agonist and aromatase inhibitör pretreatment in adenomyosis A meta-analysıs by Gonzales- Comadran M. [68], revealed that there is no evidence GnRHa downregulation before COS or pre-treatment before FET among women with adenomyosis undergoing IVF. Galati G et al. [69], the use of long-term GnRH agonist therapy (minimum 3 months) in patients with adeno - myosis, which enhances the CPR (odds ratio (OR 1.49, 95% CI: 1.15 to 1.92) in IVF-ICSI with fresh ET, while the comparison in women undergoing FET cycles did not reach statistical signifi - cance (OR 1.34 95% CI: 0.70-2.55). Lan et al. [70], revealed that women with diffuse adenomyosis had significantly higher CPR (55.3% vs. 37.9%, P=0.025) and LBRs (43.4% vs. 25.9%, P=0.019) with the ultra-long versus the long GnRH-a protocol. A meta- analysis by Steinmann M, et al. [71], current evidence does not demonstrate the superiority of GnRHa pretreatment plus HRT over HRT alone in women with adenomyosis prior to FET. The increased aromatase activity in adenomyotic tissue has led to the use of Aromatase İnhibitors (AI) in symptomat - ic women with adenomyosis undergoing IVF. In a randomized trial, Badawi AM et al. [72], found GnRH agonists and aroma - tase inhibitors to be equally effective in reducing adenomyo - sis. Sharma et al. [73], reported in a randomized controlled trial that the use of low-dose letrozole could be an effective option for women with symptomatic adenomyosis awaiting IVF. Hov - ewer, there is lack of research comparing different IVF protocols among women with adenomyosis undergoing pre-treatment with AI prior to ovarian stimulation. Endometriosis/adenomyosis coexisting Both conditions involve increased local estrogen, decreased progesterone receptor, and increased progesterone resistance in the lesions. Adenomyosis, which frequently coexists with en- dometriosis, can impair implantation, affect uterine function, and increase miscarriage rates. Adenomyosis associated with DIE is external in 96% of cases, while intrinsic adenomyosis is present in 15%. OMA and DIE were more commonly associated to extrinsic AM. Focal adenomyosis is observed in up to 66% of cases in women with deep infiltrating endometriosis [51,53,74]. A meta-analysis by Wang et al. [65], revealed that concur - rent adenomyosis in endometriosis is associated with a signifi - cantly lower LBR (OR=0.44; 95% CI: 0.26-0.75, grade: low) than endometriosis alone. Sharma et al. [75], were the first to retro- spectively examine pregnancy outcomes in cases of endome - triosis accompanied by adenomyosis and endometriosis alone, using the tubal factor as a control group. It divided 973 women into the endometriosis-only cohort (n=355), the endometriosis with adenomyosis cohort (n=88), the adenomyosis-only cohort (n=64) and the control cohort (n=466). In this study, LBR were found to be low and miscarriage rates were high in the group with adenomyosis and endometriosis or in the group with ad - enomyosis alone. Higher local TNF-α level was found to correlate with active lesions of endometriosis and adenomyosis. For endometriosis and adenomyosis women, peri-implantation treatment with TNF-α inhibitör (Adalimumab) significantly increased CPR in FET cycles [76]. Rees CO, et al. [77], showed that only the com- bined adenomyosis and endometriosis group showed a signifi - cantly reduced ongoing pregnancy (p=0.001, OR 0.302 (95% CI: (0.167-0.608)) and LBR (OR= 03.39 95% CI: 0.168-LBR 0.644, p=0.001) compared to matched male subfertility controls. Alson S et al. [78], showed that after stratifying the results per treat - ment cycle, the LBR after the first treatment for women with endometriosis and/or adenomyosis was 30.7% (RR 0.69 (95% CI: 0.57-0.84), P<0.001), after the second 28.6% (RR 0.72 (95% CI: 0.54-0.96), P=0.023), and after the third treatment 26.2% (RR 0.83 (95% CI: 0.54-1.28), P=0.183). The LBR was 45.1% in the first cycle, 41.4% in the second, and 32.3% in the third cycle. Based on this evidence, presence of adenomyosis reduces LBR in IVF/ICSI cycles for endometriosis. Surgery adenomyosis before ART Adenomyomectomy is the most commonly used as minimally invasive approaches in patients with adenomyosis. Non-surgical ablative techniques are High-Intensity Focused Ultrasound www.jcimcr.org Page 6 (HIFU) and Radiofrequency Ablation (RFA). More recently a meta-analysis by Liu et al. [79], showed that pregnancy rates were 50.1% (95% CI: 40.0-60.2%) and 52.0% (32.4-71.6%) after adenomyomectomy and thermal ablation, respectively. The delivery rates were 39.5% (29.9-49.2%) and 32.5% (26.0-38.9%) for adenomyomectomy and thermal ablation, respectively. The spontaneous miscarriage rates were 16.3% (9.7-22.9%) and 27.1% (8.1-46.1%) after adenomyomectomy and thermal ablation, respectively. In this study, the pregnancy loss rate (39.5%) and miscarriage rate (27.1%) after thermal ablation were relatively high compared to those following adenomyomectomy. The high miscarriage in the thermal ablation group was attributed to possible endometrial thermal damage. It should be known that none of these data are from randomized trials. Uterine Artery Embolization (UEA) is considered controversial low pregnancy rates and high rates of obstetric complications. Endometrial receptivity is also diminished after UEA. A systematic review and meta-analysis by Tan et al. [80], revealed that at the adverse effects of adenomyomectomy, reported uterine rupture and preterm birth rates of 6.8% (3/44) and 4.5% (2/44) in pregnant patients with diffuse adenomyosis and 0% (0/35) and 10.9% (12/110) in patients with focal adenomyosis. Only one study showed that HIFU achieved better postoperative reproductive outcomes (pregnancy rate: 52.0%, delivery rate: 36.0%) than adenomyomectomy (pregnancy rate: 30.2%, delivery rate: 27.9%) [81]. In select patients, robotic-assisted surgical management of diffuse adenomyosis can be advantageous [82]. In endometriosis and perinatal outcomes A metaanalysis by Matsuzaki et al. [83], reported a signifi - cantly increased risk of placenta previa in women with severe endometriosis compared with that in women with non-endo - metriosis group (OR, 5.22; 95% CI: 2.51-10.85). The risk of pla - centa previa in women undergoing IVF was 3 times higher when infertility was associated with endometriosis than when it was associated with other causes (OR, 2.96; 95% CI: 1.25-7.03). In addition, women with endometriosis had an increased risk of placenta accreta (adjusted OR, 3.39; 95% CI: 1.96-5.87). The negative impact of adenomyosis continues to affect pregnancy outcomes. Including an elevated likelihood of ex - periencing preeclampsia (OR 4.35 to 7.87), preterm delivery (OR 2.65-3.09), delivering an infant small-for- gestational-age (SGA) (OR 2.86 to 3.90), and postpartum haemorrhage (OR 2.90) [30,84]. The overexpression Oxytocin Receptor (OTR) in adenomyosis-affceted uteri may induce hyperperistaltism and microtrauma junctional zone. Administering an oxytocin recep- tor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis [86]. For outcomes of ad - verse pregnancy in both conditions, proposed mechanisms in - clude increased myometrial prostaglandin production, chronic inflammation, altered uterine contractility and defective spiral artery remodelling, leading to abnormal placentation. The un - derlying mechanism is highly complex and currently under de - bate. Two diseases might interact with each other. In term of phenotypic outcomes, a meta-analysis Xia et al. [87], revealed that women with diffuse adenomyosis had higher odds of ex - periencing preterm birth (OR1.66, 95% CI: 1.03-2.67, P=0.038) and hypertensive disorders of pregnancy (OR 2.23, 95% CI: 1.323.77; P=0.002).

Endometriosis is associated with a reduced number of retrieved oocytes and high-quality embryos, but LBR is approximately the same as for other causes infertility [13,19,21]. Advanced-stage endometriosis or those who have previously undergone surgery for endometriosis maintain similar implantation and LBR compared to women with tubal factor infertility. Recent evidence indicates that the endometriosis phenotype does not significantly impact ART outcomes [13,14,19,22,24,28,29]. In past studies, the failure to exclude cases with adenomyosis associated with endometriosis may have led to LBR. Hovewer, in women with endometriosis may still face chal - lenges during IVF-ICSI cycles. The patient’s age and ovarian re - serve, rather than endometriosis itself, appear to be the most important factors affecting IVF outcomes in women with en - dometriosis. The current evidence suggests that high-quality embryos are transfer for frozen embryo transfer cycle, do not exhibit any marked defect in endometrial receptivity. Such find- ings suggest that endometrial receptivity is similar regardless of the presence or severity of endometriosis [19]. Transcriptomic studies and results from donation cycles in endometriosis show that receptivity is normal and independent of stage [19,27]. In this case, impaired implantation rates may be related to oocyte and embryo quality. An important contributory role of reduced oocyte yield and quality of embryo on IVF/ICSI success in women with endometriosis [33]. Given that the most important aspect of IVF/ICSI success is cumulative pregnancy rates, a reduced number of retrieved oocytes is becoming increasingly impor - tant to consider [20,22,30,33]. However, more comprehensive studies are needed on this subject. In endometriosis, disruption of the ovarian microenvironment through multiple mechanisms and its effect on granulosa cells can impair oocyte quality. On the other hand, diminished ovarian reserve, advanced mater - nal age, DIE and adenomyosis itself are thought to contribute to suboptimal IVF-ICSI outcomes in endometriosis. High BMI showed a notable influence, obesity negatively affects LBR [31]. DIE is a stronger predictor of poor IVF outcomes, significantly reducing pregnancy rates compared to superficial disease (58% vs. 83%) [50]. Adenomyosis and chronic endometritis may po - tentially compromise endometrial receptivity in endometriosis [76]. Dysregulation in the PI3K/AKT and NOTCH signaling path - ways may further reduce implantation-related transcription factors like FOXO1 and IGFBP1. BMI also negatively affects LBR [31]. As a results, although there are conflicting results, accord- ing to the current meta-analysis results, endometriosis IVF re - sults give similar results in terms of LBR rates when compared with the control group. The exclusion of adenomyosis with cur- rent TV USG and MRI diagnostic criteria has provided an ad - vantage in terms of pure endometriosis IVF results and has led to clearer interpretation of the results. Still, despite different approaches to the problem of infertility due to endometrio - sis, standart treatment protocols before IVF have not yet been defined [21,30,32,33,35]. These findings underline the impor - tance of individualized patient management strategies in IVF/ ICSI for women with various types of endometriosis. CPR and LBR in FET cycles of euploid embryos did not dif - fer between patients with endometriosis and controls [27]. FET embryo transfer yielded higher CPR (OR: 1.2) and LBR (OR: 1.3), and implantation rates (OR: 1.2) compared to the fresh ET strategy [9]. Such findings suggest that endometrial receptivity is similar regardless of the presence or severity of endometrio- sis. Hovewer, in adenomyosis, FET and fresh embryo transfer

are similar to metanalysis results [9]. Endometriosis and adenomyosis group consecutive frozen embryo transfer can be encouraged in this patients group, as the cumulative LBR was www.jcimcr.org Page 7 Table 1: The characteristics of selected studies related to ART outcomes with endometriosis.

Intervention and/or study type Comparable and/or Positive IVF/ ICSI outcomes Uncertain and/or Negative IVF/ICSI outcomes

and/or Recommendations Kuan 2023 [8] Systematic review/GnRH agonist vs antagonist outcomes No significant differences in CPR or LBR The latest ESHRE guidance does not recommend ultra-long GnRH agonist before IVF/ICSI Han 2025 [9] Systematic review and meta- analysis/ FET vs Fresh cycle outcomes The FET strategy yielded higher clinical pregnancy (OR: 1.25; 95% CI: 1.11, 1.40), live birth rates (OR: 1.31; 95% CI: 1.15, 1.49), and implantation rates (OR: 1.27; 95% CI: 1.05, 1.54) compared to the fresh ET strategy. FET strategy has been associated with more favorable reproductive outcomes compared to the fresh ET strategy in women with endometriosis Cochrane Review (2019) [11] Ultra-long GnRH agonist Uncertain with regards to CPR, miscarriage, and LBR Not recommended Kamath (2022) [13] HFEA anonymized data from 1996 to 2016. This comprised of a total of 758 donor oocyte recipients, where the recipients were women diagnosed with endometriosis, and 12 856 autologous IVF cycles where the women were diagnosed with endometriosis as the sole cause of infertility. There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles compared to women undergoing autologous IVF fresh embryo transfer cycles (31.6% vs 31.0%; odds ratio (OR) 1.03, 99.5% CI 0.79-1.35). Endometriosis does not compromise embryo quality from the perspective of morphology. Juneau 2017 [14] 305 patients with endometriosis who produced 1,880 blastocysts and PGS Aneuploidy rates equivalent to their age-matched peers in IVF population who do not have endometriosis. Aneuploidy rates equivalent to their age-matched peers in IVF population who do not have endometriosis. Robin 2021 [15] A total of 596 women treated for IVF-ICSI, retrospective study No difference in AOQI and MOMS scores was found between endometriosis and control women (adjusted p = 0.084 and 0.053, respectively). Endometriosis does not have a negative impact on oocytes' morphology in IVF-ICSI. Barcelos 2008 [17] To evaluate the meiotic spindle and the chromosome distribution of in vitro mature oocytes from stimulated cycles of infertile women with endometriosis, and with male and/or tubal infertility factors There was no significant difference in the IVM rates between the two groups evaluated (45.6 and 54.5% for the Endometriosis and Control Groups, respectively). Endometriosis does not increase meiotic abnormality. Dongye 2021 [18] A systematic review and meta- analysis (22 studies) Compared with the control group, women with endometriosis had a similar high-quality embryo rate (RR = 1.00; 95% CI, 0.94-1.06), a comparable cleavage rate (RR = 1.00; 95% CI, 0.97-1.02), and a similar embryo formation rate (RR = 1.10; 95% CI, 0.97-1.24). In women with stage III-IV endometriosis, there was no statistically significantly difference in high- quality embryo rate (RR = 1.02; 95% CI, 0.94-1.10), cleavage rate (RR = 1.00; 95% CI, 0.98-1.02) Endometriosis does not compromise embryo quality from the perspective of morphology. Bishop 2020 [19] Retrospective cohort study Euploid FET-ET cycles, LBR, CPR , no difference endometriosis vs control group LBR are not affected by endometriosis after euploid blastocysts in HRT FET-ET cycles www.jcimcr.org Page 8 Harb 2013 [21] Systematic review and meta- analysis (27 observational study) Fertilisation rates were reduced in stage I/ II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. Endometriosis ASRM III/IV is associated with poor implantation and CPR. Qu 2022 [22] Systematic review and meta- analysis (70 study) Implantation rate (p = 0.04) and the number of oocyte retrieved (p<0.00001) were significantly lower in women with endometriosis All other major reproductive and obstetric outcomes were similar in women with and without endometriosis. Endometriosis have similar reproductive outcomes, but women with endometriosis who conceived after ART are in high risk pregnancy. Mappa 2024 [24] Systematic review and meta- analysis(40 studies/8970 women with endometriosis and 42,946 control) There were no significant differences between the endometriosis and control groups in terms of LBR (OR 1.03, 95% CI 0.75-1.41, p = 0.84), CBR (OR 0.86, 95% CI 0.72-1.02, p = 0.1), or fertilization rate (OR 0.96, 95% CI 0.79-1.15, p = 0.64). Endometriosis was associated with a significantly lower implantation rate (OR 0.85, 95% CI 0.74-0.97, p = 0.02). Endometriosis significantly negatively affects implantation rates in women undergoing IVF, despite the absence of significant differences in LBR, CPR, and fertilization rates. Nienke E van Hoogenhuijze 2023 [25] Meta-analysis(13 RCTs, (12 published, one unpublished) 4112 participants There was no significant difference LBR in women with endometriosis compared to controls Endometrial scratching in clinical practice should be considered with caution Horton 2019 [30] Systematic review and meta- analysis in Endometriosis and adenomyosis (104 study) Milder forms of endometriosis were most likely to affect the fertilization (FR OR 0.77, CI 0.63- 0.93) and earlier implantation processes (implantation rate OR 0.76, CI 0.62-0.93). Increased miscarriage in both adenomyosis and endometriosis (OR 3.40, CI 1.41-8.65 and OR 1.30, CI 1.25-1.35, respectively), Milder forms of endometriosis were most likely to affect the fertilization. Liao 2025 [31] Systematic review and meta- analysis (19 studies) CPR were not significantly different between groups (OR: 1.03) Decreased total oocytes (mean difference [MD]: -2.06),mature oocytes (MD: -2.07) and LBR (OR: 0.87) in endometriosis/ BMI significantly influenced the risk of endometriosis *Higher BMI is associated with an increased risk of endometriosis, which negatively affects IVF outcomes * Surgical treatment before IVF/ ICSI does not appear to enhance IVF success and may further compromise LBR. Hamdan 2015 [33] Systematic review and meta- analysis (36 studies, three were RCTs) a similar LBR [OR] 0.94, 95% [CI] 0.84-1.06, I=35%) a lower CPR (OR 0.78, 95% CI 0.65- 0.94,I=66%), a lower mean number of oocyte (1.98, 95% CI -2.87 I=97%) ASRM III/IV have a lower LBR and CPR Rossi 2016 [34] Systematic review and meta- analysis 813 study) CPR were similar between stage I-II and controls (OR 0.99; 95 % CI 0.63-1.56) CPR lower in stage III-IV than controls (OR 0.45; 95 % CI 0.29-0.70), ASRM III/IV endometriosis had significantly lower cumulative CPR and ongoing pregnancy rates Morcel 2024 [35] Retrospective clinical study ASRM stage III/IV had significantly lower cumulative CPR and ongoing pregnancy rates ASRM III/IV pregnancy rates are decreasing cumulatively. www.jcimcr.org Page 9 Liang 2024 [47] Systematic review and meta- analysis/ART vs Surgery Pregnancy rate per patient (OR, 1.47; 95% CI, 0.59 to 3.63), pregnancy rate per cycle (OR, 1.16; 95% CI, 0.45 to 2.99), and live births per patient (OR, 1.66; 95% CI, 0.56 to 4.91) were comparable in DIE patients First-line surgery and ART can be effective DIE treatments with similar fertility outcomes Casal 2021 [48] Systematic review and meta- analysis (98 studies) (Surgery for DIE before IVF/ICSI) The pregnancy rate per patient was 1.84 (95% confidence interval [CI], 1.28-2.64), the pregnancy rate per cycle was 1.84 (95% CI, 1.26-2.70), and the LBR per patient was 2.22 (95% CI, 1.42-3.46) times more likely for operated patients than for nonoperated ones. A statistically significant benefit for surgery before IVF/ICSI in patients with DIE endometriosis Bourdon 2024 [50] Systematic review and meta- analysis (19 studies) (Surgery for DIE before IVF/ICSI) The LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ ICSI [0.53[0.33, 0.86]; I2 = 30%) The LBR per cycle was significantly reduced in the case of surgical treatmet before IVF/ICSI ART: Assisted reproductive treatment; HFEA: Human Fertilization and Embryology Authority; PGS: Preimplantation genetic screening; AOQI: Average Oocyte Quality Index; MOMS: Metaphase II; MOMS: Oocyte Morphological Scoring System; CPR: Clinical Pregnancy Rate; LBR: Live Birth Rate; FET: Frozen Embryo Transfer; ET: Embryo Transfer; FET: Frozen Embryo Cycles.; DIE: Deep Infiltrative Endometriosis.; IVF: In Vitro Fertilization;ICSI: Intra-Cytoplasmic Sperm Injection. Table 2: The characteristics of selected studies related to ART outcomes with adenomyosis.

Intervention and/or study type Comparable and/ or Positive IVF/ICSI outcomes Uncertain and/or Negative IVF/ICSI outcomes Conclusion and/or Recommendations Younes 2017 [56] A meta-analysis a 41% decrease in LBR and an increased risk of miscarriage in women with adenomyosis. Adenomyosis has a detrimental effect on IVF/ICSI reproductive outcomes. Han 2025 [9] Systematic review and meta-analysis/ FET vs Fresh cycle outcomes In adenomyosis, the IVF/ICSI outcomes were comparable between the FET and fresh ET strategies. Comparable pregnancy rates between the two groups (FET vs Fresh cycle) Horton 2019 [30] Systematic review and meta-analysis A 55% reduction in LBR after IVF-ICSI Adenomyosis has a detrimental effect on IVF/ICSI reproductive outcomes. Nirgianakis 2020 [57] Systematic review and meta-analysis A lower CPR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.51-0.94) and higher miscarriage rate (OR 2.17; 95% CI 1.25-3.79) in adenomyosis Adenomyosis has a detrimental effect on IVF/ICSI reproductive outcomes. Mavrelos 2017 [60] A prospective multicentre study A lower clinical pregnancy rate (21/72 [29.2%, 95% CI 18.6-39.6] versus 129/303 [42.6%, 95% CI 37.1-48.2], P = 0.044, relative risk (RR) 0.68 [95% CI 0.47-1.00]). Condition severity expressed as a number of morphological features on ultrasound scan increases the magnitude of the effect. Neal 2020 [59] A prospective cohort study No difference in the rate of CPR, 1.47 (95% CI, 0.85-2.56)), miscarriage (aOR, 1.3 (95% CI, 0.62- 2.72)) or LBR 1.28 (95% CI, 0.78-2.08)) between subjects with and those without adenomyosis. Routine screening for asymptomatic adenomyosis in an unselected infertile patient population undergoing frozen embryo transfer may not be warranted Vercellini 2014 [61] Systematic review and meta-analysis (17 studies) The miscarriage rate was more prevalent (RR 2.1 (95% CI 1.20- 3.75) in women with adenomyosis vs control (32% vs 14%). Adenomyosis has an increased risk of miscarriage Sachs-Guedj 2023 [64] HRT- FET cycle/Euploid ET Adenomyosis decreased CPR (aOR 0.62, 95% CI: 0.39-0.98, p = 0.040) and LBR (aOR 0.46, 95% CI: 0.27-0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98-4.37, p = 0.045) Even with euploid embryo transfer, the low rates are high in adenomyosis www.jcimcr.org Page 10 Bourdon 2023 [66] A single-center observational study. FET-ET was associated with significantly higher odds of LBR compared with fresh ET (odds ratio = 1.80; 95% CI= 1.02- 3.16). FET-ET is an attractive option in adenomyosis regardless of different type HRT: Hormone Replacement Therapy; FET: Frozen Embryo Transfer; ET: Embryo Transfer; CPR: Clinical Pregnancy Rate; LBR: Live Birt Rate; CI: Confidence Interval; IVF: In Vitro Fertilization; ICSI: Intra-Cytoplasmic Sperm Injection. Table 3: The characteristics of selected studies related to ART outcomes with endometriosis coexisting adenomyosis vice versa.

Intervention and/or study type Comparable and/or Positive IVF/ICSI outcomes Uncertain and/or Negative IVF/ICSI outcomes

and/or Recommendations Wang 2023 [65] Systematic review and meta- analysis (cohort studies) Adenomyosis in endometriosis is associated with a significantly LBR (OR = 0.44; 95% CI: 0.26-0.75) than endometriosis alone In the coexistence of endometriosis and adenomyosis, adenomyosis reduces LBR Liu 2025 [76] A retrospective analysis In women with endometriosis and/or adenomyosis, peri- implantation treatment with TNF-α inhibitor increased CPR significantly compared with control group in FET cycles. More extensive studies are needed. Rees 2022 [78] A matched retrospective cohort study the combined adenomyosis and endometriosis group showed a significantly reduced LBR (p = 0.001, OR 0.309 (95% CI: (0.168-0.644)) In the coexistence of endometriosis and adenomyosis, adenomyosis reduces LBR Sharma 2019 [75] Retrospective cohort study LBR were 27.47% in controls; 26.48% in women with only endometriosis; 11.36% in women with endometriosis and adenomyosis; and 12.5% in women with only adenomyosis. In the coexistence of endometriosis and adenomyosis, adenomyosis reduces LBR CPR: Clinical Pregnancy Rate; LBR: Live Birt Rate; CI: Confidence Interval. not reduced in patients with endometriosis and adenomyosis group [78]. LBR are not affected by adenomyosis or endome - triosis after the transfers of euploid blastocysts in HRT cycles [19,59]. Based on these results, the suppressive effect of HRT on ovarian function may positively influence endometrial re - ceptivity. According to ESHRE 2022, routine surgery before ART for ovarian endometrioma and SUP are not recommended. A the latest meta-analysis results underwent prior surgical treatment for endometriosis, no improvement was observed in CPR (OR: 0.79) and LBR were further reduced [OR: 0.67 [0.23, 0.76]; I2 = 39%] [31]. Furthermore, the other study and meta-analysis also, the LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ICSI (OR: 0.53) [31,46]. In line with previus studies, Bourdon et al. [50], found in their meta- analysis that endometriosis surgery before IVF/ICSI significantly reduced LBR [OR=0.53 [0.33, 0.86]; I2 = 30%]. Considering these meta-analysis results, endometriosis surgery before IVF nega - tively affects fertility. On the other hand, the available evidence suggests that both first-line surgery and IVF/ICSI can be effective DIE treatments with similar fertility outcomes [47]. There is no strong evidence from RCTs that operative laparoscopy enhances fertility outcomes in patients with DIE. According to Casal’s [48], meta-analysis results, patients who underwent DIE surgery be - fore IVF, pregnancy rate per patient was 1.84, and LBR per pa - tient was 2.22 times more likely for operated patients than for nonoperated ones. Hovewer, this meta-analysis did not include any RCTs, and therefore all included the other studies have high risk of selection and allocation bias. In DIE, surgery before IVF negatively affects IVF outcomes. A meta-analysis by Bourdon et al. [50], compared LBR in patients who underwent endometrio- sis surgery before ART in comparison with patients who under- went first-line IVF/ICSI. After the exclusion of the studies with high risk bias, the LBR per cycle was significantly reduced in the case of surgical treatmet before IVF/ICSI. Long-term morbidity is high in DIE surgery, with complication rates ranging from 9% to 23% [35]. In cases where pre-IVF adenomyosis is excluded in stage 3-4 cases, it is not yet clear whether surgery should be performed before the first IVF attempt or after unsuccessful IVF attempts. Probably in view of these complications and contro - versial postoperative outcomes, surgery is necessary if there is bowel or urinary obstruction or if severe pain persisting despite medical treatment [6,31,33,40,45,46]. Management decisions should be individualized based on patient choice, age, associ - ated symptoms, and the risk repeat surgery. First-line IVF seems to be a valid choice, in asymptomatic patients. According to meta-analyses, adenomyosis causes significant suppression in IVF/ICSI and pregnancy outcomes [30,56,57,61]. www.jcimcr.org Page 11

Intervention and/or study type Comparable and/ or Positive IVF/ICSI outcomes Uncertain and/or Negative IVF/ICSI outcomes Junctional Zon İnvolvoment Conclusion and/or Recommendations Trinchant 2025 [53] Multicenter and retrospective cohort study A higher LBR per transfer was described in diffuse adenomyosis compared to focal adenomyosis: 47/166 (28.3%) versus 9/62 (15%), respectively (OR = 2.32, 95% CI: 1.03- 5.78, p = 0.034). NA Diffuse adenomyosis provides a higher LBR Wang 2023 [65] A systematic review and meta-analysis Diffuse and symptomatic adenomyosis, lower LBR (OR = 0.57; 95% CI: 0.34-0.96) and miscarriage (OR = 2.48, 95% CI: 1.28-4.82) NA On USG Diffuse and symptomatic adenomyosis reduces LBR Bourdon 2023 [66] A single-center observational study (FET vs Fresh cycle) LBR (86 (44.1%) vs. 34 (30.6%), respectively), were significantly higher in the freeze-all group compared with the fresh ET group. NA The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. Sharma 2025 [91] A prospective cohort study Diffuse adenomyosis have a lower LBR (20.65% vs. 29.95%; OR: 0.61, 95% CI: 0.41-0.89, p = 0.011) than women without adenomyosis. Diffuse adenomyotic lesions affecting the JZ exhibited significantly lower LBR (16.42% vs. 25.75%; OR: 0.57, 95% CI: 0.34-0.94, p = 0.029) In diffuse adenomyosis showing JZ involvement, live birth rates are much lower. Exacoustos 2020 [92] A multicenter, observational, prospective study. Higher percentage of infertility and miscarriage in focal adenomyosis of both the outer myometrium and the JZ In focal adenomyosis showing JZ involvement, miscarriae are increased Cozzolino 2024 [85] A prospective observational cohort study. Diffuse adenomyosis in the JZ increased the relative risk of miscarriage two-fold (RR, 2.29; 95% CI, 1.22-4.30). In diffuse adenomyosis showing JZ involvement, miscarriae are increased Xia 2025 [87] A systematic review and meta-analysis (involving 390 women with diffuse adenomyosis and 233 women with focal adenomyosis) Diffuse adenomyosis had higher odds of experiencing preterm birth(OR1.66, 95% CI1.03-2.67, P = 0.038) and hypertensive disorders of pregnancy (OR 2.23, 95% CI 1.32- 3.77; P = 0.002). NA Diffuse adenomyosis was significantly associated with an increased risk of adverse pregnancy outcomes Table 4: IVF/ICSI outcomes related to phenotype and junctional zone involvement in adenomyosis. NA: Not Assessed; CBR: Clinical Pregnancy Rate; LBR: Live Birth Rate; JZ: Junctional Zone; CI: Confidince Inreval; FET: Frozen Embryo Cycle. www.jcimcr.org Page 12 Wansg et al.’s [65], meta-analysis showed that particularly symptomatic and diffuse adenomyosis adversely affected IVF/ ICSI outcomes. Regardless of phenotypic differentiation, fertil - ity is impaired, especially in adenomyosis involving junctional zone involvement [85]. In a study of euploid embryo transfer in adenomyosis, CPR, miscarraige, and LBR were similar to the control group [59]. However, in this study, while most patients exhibited only one MUSA criterion, 17 patients exhibited two characteristics. The Age-Adjusted Relative Risk (ARR) for with at least one MUSA criteria 0.58 (95% CI: 0.45-0.75) in adenomyo - sis. CPR decreased from 42.7% in women with no adenomyosis to 13.0% in those with four and seven ultrasound diagnostic features of adenomyosis [60]. This situation must be taken into account when evaluating these results. The phenotypic effect of adenomyosis on IVF/ICSI outcomes is mixed. While some studies have found a correlation with LBR [53,65], other studies have found no such correlation [78]. The answer remains unclear for which type of adenomyosis has the worst fertility outcome. According to current findings, pheno - types associated with JZ involvement are more severely affect- ed [65,91,92]. The studies in patients with adenomyosis having IVF/ICSI involve heterogenity in participant age, whether or not to administer GnRH treatment before IVF, duration of infertility, and different stimulation protocols. Phenotypic differences in adenomyosis, heterogenity in diagnostic criteri coexisting en - dometriosis and leiyomyoas are factors that affect IVF success. Whether adenomyosis is symptomatic or not, the use of direct or indirect diagnostic criteria in diagnosis, and the results ob - tained from the number of criteria are all factors involved. Most of the studies the diagnostic criteria used are heterogeneous and sometimes not well defined, especially for adenomyosis, because some studies used TVUSG, some MRI, and others both. Most studies have not demonstrated a correlation between each characteristic used in the diagnosis of adenomyosis and the study results. Alson et al. [78], found that women with endometriosis and adenomyosis had a 15% lower cumulative chance of achiev - ing an LBR after three consecutive IVF/ICSI cycles compared to women without these conditions. The lower LBR in the com - bined adenomyosis and endometriosis women can be attrib - uted to more severe adenomyosis in these women. Hovewer, despite a lower CLBR over three IVF/ICSI cycles, women with endometriosis and/or adenomyosis still have a reasonable chance of achieving LBR with consecutive treatments [78]. In this study, there was no difference in adenomyosis phe - notypes between the groups that became pregnant and those that did not. Hovewer, most studies did not distinguish between the subtypes of endometriosis and adenomyosis. In studies, the exclusion of adenomyosis with current TV USG and MRI diag - nostic strict criteria has provided an advantage in terms of pure endometriosis IVF/ICSI results and has led to clearer interpreta- tion of the results. In adenomyosis, miscarriage rates occur independently of the embryo’s genetics. In oocyst donation cycles, implantation rates were found to be normal, but miscarriage rates were high [63]. Even with euploid embryo transfer, the low rates are high in adenomyosis [64]. The endometrial gene expression profile of women with adenomyosis does not differ with the gene ex - pression pattern of the controls [21]. Based on these results, it is thought that miscarriages occurring in adenomyosis are related to molecular mechanisms other than those related to implantation window gene alterations. AD a high JZ thickness (>10 mm) is considered to be independent faktör for implan - tation failure [62,63]. Cozzolino M et al. [85], reported that a threefold higher relative risk of miscarriage when particularly diffuse adenomyosis involved in contact with the JZ. The reduc- tion in implantation and miscarriage may be dependent on the type and extent of disease [70]. While it is not clear how each type of adenomyosis affects fertility, hovewer, fertility rates are worse in both focal and diffuse adenomyosis associated with JZ involvement. The Age-Adjusted Relative Risk (ARR) for LBR was maximally reduced (OR: 0.29, 95% CI: 0.11-0.74) in women with involvement of the JZ [60]. According to recent studies, the predominantly diffuse phenotype reduces LBR and leads to pre- term birth, while JZ involvement negatively affects fertility in both focal and diffuse phenotypes [91,92], (Table 4). In adenomyosis, determining the embryo transfer day based on transcriptomic analysis or increasing luteal support proges - terone dose did not affect pregnancy outcomes in cases of pro- gesterone resistance in FET cycles [88]. These results support the theory of progesterone resistance in adenomyosis. In com- patible with this results, Alsbjerg et al. [89], reported that preg- nancy outcomes were optimized with a luteal progesterone level of 37.1 ng/mL in endometriosis patients having HRT-FET cycle. Hovewer, Bourdon et al. [90], there was no significant dif- ference in the mean progesterone level on the day of HRT-FET between those with endometriosis and/or adenomyosis those without (13.6±4.3 ng/mL vs 13.2±4.4 ng/mL, respectively; P=0.302). Researchers have suggested that the effect of proges- terone resistance in FET cycles may be minimal. Hovewer, these

make optimal luteal progesterone levels for pregnancy outcomes controversial in relation to progesterone resistance in endometriosis and/or adenomyosis patients undergoing HRT- FET cycles. Considering the latest meta-analysis results, pregnancy rates after surgery in adenomyosis are promising [79]. Meta-analyses have shown favourable results after uterus-sparing surgeries, with a range of pregnancy rates (38.5-49.1%) depending on the extent of adenomyosis. Postoperative GnRH agonist therapy has been shown to improve outcomes, however, results have been inconsistent. IVF/ICSI in conjunction with surgery showed im - proved outcomes in one meta-analysis, while it showed compa- rable outcomes to natural conception after surgery in another [79]. Perhaps with a greater advantage among younger patients with focal adenomyosis [80]. Pregnancy rates after HIFU are promising. Surgery may increase the risk of rupture and not ef- fective as a fertility treatment for women over the age 40 years. Based on curent evidence, surgery should only be considered for symptomatic women with repeated IVF/ICSI failure after the transfer of high quality embryos [51,52,55]. A meta-analysis by Ge Li et al. [67], showed that the ultra-long GnRH-a protocol may positively influence fresh ET outcomes in women with adenomyosis by possibly correcting implantation defects. There is another study that previously supported these

[70]. However, Ge’s meta-analysis, lacked randomiza - tion, did not phenotypically determined adenomyosis before IVF/ICSI, and while CPR were high and miscarriage rates similar in fresh cycles, this was not reflected in LBR. The latest ESHRE guidance does not recommend ultra-long GnRH agonist before IVF [6]. In terms of pregnancy outcomes, pregnancy complications are increased in both endometriosis and adenomyosis. DIE has www.jcimcr.org Page 13 been identified as a risk factor plasenta previa and for spon - taneous hemoperitoneum during gestation. Specific conditions that may arise for both situations should be considered during pregnancy monitoring. As early diagnosis and careful monitor - ing can help prevent or reduce the risk of complications for both the mother and the fetus.

LBR after IVF/ICSI is comparable in women with and with - out endometriosis. Laparoscopy routine is not recommended except in symptomatic cases before IVF/ICSI. DIE and adeno - myosis itself are thought to contribute to suboptimal IVF-ICSI outcomes in endometriosis. Surgical treatment of DIE before IVF/ICSI is controversial. The phenotypic effect of adenomyosis on IVF/ICSI outcomes is mixed. The answer remains unclear for which type of ad - enomyosis has the worst fertility outcome. Disturbance in the uterine junctional zone have been implicated as potential con - tributers to AD associated miscarriage. Junctional zone involve- ment impairs fertility regardless of phenotypic characteristics. Particularly symptomatic and diffuse adenomyosis adversely af- fected IVF/ICSI outcomes. Women with the most severe forms of adenomyosis have a trend toward worse outcomes. In endometriosis and adenomyosis, the presence of adeno - myosis reduces LBR. While both conditions may independently impair IVF/ICSI success, the percentages of women with both diseases remain a matter of debate. Based on current evidence, adenomyosis has a more prominent negative impact on LBR and miscarriage rates. The exclusion of adenomyosis with cur - rent TV USG and MRI diagnostic criteria has provided an advan- tage in terms of pure endometriosis IVF results. Surgical pallia - tive treatments in adenomyosis are yielding promising results. Pregnancy complications are increased in both endometriosis and adenomyosis. Declarations Ethics committee: Support not used. Due to the review, no ethics committee approval was received. Credit authorship contribution statement: CK: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing - original draft. Funding statement: The author received no external funding or assistance for this study. Conflict of interest statement for all authors: The author has no conflict to declare. Attestation statements: Data regarding any of the subjects in the study has not been previously published unless specified. Data will be made available to the editors of the journal pre and/ or post publication for review or query upon request. Artificial intelligence and artificial intelligence-supported technologies were not used. Data sharing statement: All the data is shared in the manuscript.

1. Carey ET, Wong JMK, Khan Z. Comprehensive Revire of Endometriosis Care. Obstet Gynecol. 2025; 146(3): 323-340. doi: 10.1097/AOG.0000000000006004.PMID: 40674745 2. Orr NL, Albert A, Liu YD, Lum A, Hong J, et al. KRAS mutations and endometriosis burden of disease. J. Pathol. Clin. Res. 2023; 9: 302-312. doi: 10.1002/cjp2.317. 3. Li YF, Li WW, Yang XH, Yang YB, Ye QJ. Clinical characteristics of endometriosis with and without dysmenorrhea diagnosed by laparoscopy. Front Med Lausanne. 2025; 12: 1635960. doi: 10.3389/fmed.2025.1635960. eCollection 2025.PMID: 41020245 4. Tomassetti C, Johnson NP , Petrozza J, Abrao MS, Einarsson JI, et al. An International Terminology for Endometriosis. International working group of AAGL, ESGE, ESHRE and WES; J Minim Invasive Gynecol. 2021; 28(11): 1849-1859. doi: 10.1016/j.jmig.2021.08.032. PMID: 34690084 5. Alonso A, Gunther K, Maheux-Lacroix S, Abbott J Medical management of endometriosis. Curr Opin Obstet Gynecol. 2024; 36(5): 353-361. doi: 10.1097/GCO.0000000000000983. PMID: 39159261 6. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, et al. ESHRE Endometriosis Guideline Group. ESHRE guideline: Endometriosis.Hum Reprod Open. 2022; 2022(2): 009. doi: 10.1093/ 2022.PMID: 35350465 7. Skorupskaite K, Hardy M, Bhandari H, Yasmin E, Saab W, et al. Evidence based management of patients with endometriosis undergoing assisted conception: British fertility soCiety policy and practice recommendations. Hum Fertil (Camb). 2024; 27(1): 2288634. doi: 10.1080/14647273.2023.2288634. Epub 2024 Jan 16.PMID: 38226584. 8. Kuan KKW, Omoseni S, Tello JA Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian stimulation: A systematic review. Ther Adv Endocrinol Metab. 2023; 14: 20420188231173324. 10.1177/20420188231173325. 9. Han Y , Liu C, Liu D, Wu L, Huang W. Pregnancy outcomes in freeze-all versus fresh embryo transfer cycles of women with adenomyosis and endometriosis: A systemic review and meta- analysis.Front Endocrinol (Lausanne). 2025; 16: 1507252. doi: 10.3389/fendo.2025.1507252. eCollection 2025.PMID: 40438397. 10. Qi Q, Luo J, Wang Y , Xie Q. Effects of artifiCial cycles with and without gonadotropin-releasing hormone agonist pretreatment on frozen embryo transfer outcomes. The Journal of International Medical Research, 2020; 48(6): 300060520918474. https://doi. org/10.1177/0300060520918474 11. Georgiou EX, Melo P , Baker PE, Sallam HN, AriCi A, et al. Long- term GnRH agonist therapy before İn Vitro Fertilisation (IVF) for improving fertility outcomes in women with endometriosis. The Cochrane Database of Systematic Reviews. 2019; (11): 013240. 12. Khalifa E, Mohammad H, Abdullah A, Abdel-Rasheed M, Khairy M, et al. Role of suppression of endometriosis with progestins before IVF-ET: A non-inferiority randomized controlled trial. BMC Pregnancy Childbirth. 2021; 21(1): 264. doi: 10.1186/ s12884-021-03736-2.PMID: 33784989 13. Kamath MS, Subramanian V, Antonisamy B, Sunkara SK. Endometriosis and oocyte quality: An analysis of 614 donor oocyte reCipient and autologous IVF cycles.Hum Reprod Open. 2022; 2022(3): 025. doi: 10.1093/hropen/hoac025. eCollection 2022.PMID: 35747401 14. Juneau C, Kraus E, Werner M. Patients with endometriosis have aneuploidy rates equivalent to their age-matched peers in the in vitro fertilization population. Fertil Steril. 2017; 108: 284-288. www.jcimcr.org Page 14 15. Robin C, Uk A, Decanter C, Behal H, Collinet P , et al. Impact of endometriosis on oocyte morphology in IVF-ICSI: Retrospective study of a cohort of more than 6000 mature oocytes.Reprod Biol Endocrinol. 2021; 19(1): 160. doi: 10.1186/s12958-021-00798-x. PMID: 34656130. 16. Gayete-Lafuente S, Vilà Famada A, Albayrak N, Espinós Gómez JJ, Checa Vizcaíno MÁ, et al. Indirect markers of oocyte quality in patients with ovarian endometriosis undergoing IVF/ICSI: A systematic review and meta-analysis. Reprod Biomed Online. 2024; 49(3): 104075. doi: 10.1016/j.rbmo.2024.104075. PMID: 38943812 17. Barcelos ID, Vieira RC, Ferreira EM, Araújo MC, Martins Wde P , et al. Meiotic abnormalities of oocytes from patients with endometriosis submitted to ovarian stimulation]. Rev Bras Ginecol Obstet. 2008; 30(8): 413-9. doi: 10.1590/s0100- 72032008000800007.PMID: 19142525 18. Houjin Dongye , Xiaofeng Ji , Xiaopei Ma, Jialun Song , Lei Yan. The Impact of Endometriosis on Embryo Quality in in vitro Fertilization/Intracytoplasmic Sperm Injection: A Systematic Review and Meta-Analysis Front Med (Lausanne). 2021; 8: 669342. doi: 10. 3389/fmed.2021.669342. PMCiD: PMC8206501 19. Bishop LA, Gunn J, Jahandideh S, Devine K, Decherney AH, et al. Endometriosis does not impact live-birth rates in frozen embryo transfers of euploid blastocysts. Fertility and Sterility. 2021; 115(2): 416-422. https://doi.org/10.1016/j. fertnstert.2020.07.050 20. Barnhart Kurt, Rebecca Dunsmoor-Su, Christos Coutifaris. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002; 77(6): 1148-55. doi: 10.1016/s0015-0282(02)03112-6.PMID: 12057720 21. Harb HM, I D Gallos, J Chu, M Harb, A Coomarasamy The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis BJOG. 2013; 120(11): 1308-20. doi: 10.1111/1471-0528.12366.PMID: 23834505 22. Qu H, Du Y , Yu Y , Wang M, Han T, et al. The effect of endometriosis on IVF/ICSI and perinatal outcome: A systematic review and meta-analysis. J. Gynecol. Obstet. Hum. Reprod. 2022; 51: 102446. doi: 10.1016/j.jogoh.2022.102446. 23. Latif S, Khanjani S, Saridogan E.Endometriosis and In Vitro Fertilization.MediCina (Kaunas). 2024; 60(8): 1358. doi:10.3390/ mediCina60081358.PMID: 39202639 24. Mappa I, Page ZP , Di MasCio D, Patelli C, D’ Antonio F, et al. The Effect of Endometriosis on In Vitro Fertilization Outcomes: A Systematic Review and Meta-Analysis. Healthcare (Basel). 2024; 12(23): 2435. doi: 10.3390/healthcare12232435.PMID: 39685057 25. van Hoogenhuijze NE, Lahoz Casarramona G, Lensen S, Farquhar C, Kamath MS, et al. Endometrial scratching in women undergoing IVF/ICSI: An individual partiCipant data meta-analysis. Hum Reprod Update. 2023; 29(6): 721-740. doi: 10.1093/humupd/dmad014.PMID: 37336552 26. GarCia-Velasco JA, Fassbender A, Ruiz-Alonso M, Blesa D, D’Hooghe T, et al. Is endometrial receptivity transcriptomics affected in women with endometriosis? A pilot study. Reprod Biomed Online. 2015; 31(5): 647-54. doi: 10.1016/j. rbmo.2015.07.014.PMID: 26385059 27. Pirtea P , de Ziegler D, Ayoubi JM. Endometrial receptivity in adenomyosis and/or endometriosis.Fertil Steril. 2023; 119(5): 741-745. doi: 10.1016/j.fertnstert.2023.03.004. PMID: 36914148 28. Omland AK, Abyholm T, Fedorcsák P et al Pregnancy outcome after IVF and ICSI in unexplained, endometriosis-associated and tubal factor infertility. Hum Reprod Oxf Engl. 2005; 20: 722-727. 10.1093/humrep/deh664 29. Research and Dataset Publications. https://www.sart.org/ professionals-and-providers/research/. Accessed 27 Feb 2025. 30. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y .Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: A systematic review and meta-analysis. Hum Reprod Update. 2019;25:592-632. doi: 10.1093/humupd/dmz012. 31. Liao L, Pan Z, Li Y . Endometriosis as a risk factor: Impact on IVF outcomes and reproductive parameters: A systematic review and meta-analysis. Arch Gynecol Obstet. 2025; 312(4): 1085- 1093. doi: 10.1007/s00404-025-08137-w. PMID: 40748500 32. Paffoni A, Maíra Casalechi, Dominique De Ziegler, Ettore CiCinelli, Edgardo Somigliana, et al. Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2024; 7(1): 2354249. doi:10. 1001/jamanetworkopen.2023. 54249. PMID: 38294811 33. Hamdan M, Omar SZ, Dunselman G, Cheong Y . Influence of endometriosis on assisted reproductive technology outcomes: A systematic review and meta-analysis. Obstet Gynecol. 2015; 125(1): 79-88. doi: 10.1097/AOG.0000000000000592.PMID: 25560108 34. Rossi AC, Prefumo F. The effects of surgery for endometriosis on pregnancy outcomes following in vitro fertilization and embryo transfer: A systematic review and meta-analysis. Arch. Gynecol. Obstet. 2016; 294: 647-655. doi: 10.1007/s00404-016-4136-4. 35. Morcel K, Merviel P , Bouée S, Le Guillou M, Carlier M, et al. What is the impact of endometriosis and the AFS stage on cumulative pregnancy rates in IVF programs? Reprod Health. 2024; 21(1): 13. doi: 10.1186/s12978-024-01747-8.PMID: 38287446 36. Leonardi M, Gibbons T, Armour M, Wang R, Glanville E, et al.When to Do Surgery and When Not to Do Surgery for Endometriosis: A Systematic Review and Meta-analysis. J Minim Invasive Gynecol. 2020; 27(2): 390-407.e3. doi: 10. 1016/j. jmig.2019.10.014.PMID: 31676397 37. Hodgson RM, Lee HL, Wang R, Mol BW, Johnson N.Interventions for endometriosis-related infertility: A systematic review and network meta-analysis. Fertil Steril. 2020; 113(2): 374-382.e2. doi: 10.1016/j.fertnstert.2019.09.031.PMID: 32106991 38. Jin X, Ruiz Beguerie J. Laparoscopic surgery for subfertility related to endometriosis: A meta-analysis. Taiwan J Obstet Gynecol. 2014; 53(3): 303-8. doi: 10.1016/j.tjog.2013.02.004. PMID: 25286781 39. Opoien HK, Fedorcsak P , Byholm T, Tanbo T. Complete surgical removal of minimal and mild endometriosis improves outcome of subsequent IVF/ICSI treatment. Reprod Biomed Online. 2011; 23(3): 389-95. doi: 10.1016/j.rbmo.2011.06.002.PMID: 21764382 40. Alshehre SM, Narice BF, Fenwick MA, Metwally M. The impact of endometrioma on in vitro fertilisation/intra-cytoplasmic injection IVF/ICSI reproductive outcomes: A systematic review and meta-analysis. Archives of Gynecology and Obstetrics. 2021; 303(1): 3-16. https://doi.org/10.1007/s00404-020-05796-9 41. Kwon SK, Kim SH, Yun SC, Kim DY , Chae HD, Kim, et al. Decline of serum antimüllerian hormone levels after laparoscopic ovarian cystectomy in endometrioma and other benign cysts: A prospective cohort study. Fertility ant Sterility. 2014; 101(2): 435-441. https://doi.org/10.1016/j.fertnstert.2013.10.043 www.jcimcr.org Page 15 42. M. Nickkho-Amiry, R. Savant, K. Majumder, E. Edi-O’sagie, M. Akhtar. The effect of surgical management of endometrioma on the IVF/ICSI outcomes when compared with no treatment? A systematic review and meta-analysis Arch Gynecol Obstet. 2028; 297(4); 1043-1057. 43. Wu CQ, Albert A, Alfaraj S, Taskin O, Alkusayer GM, et al. Live Birth Rate after Surgical and Expectant Management of Endometriomas after In Vitro Fertilization: A Systematic Review, Meta-Analysis, and Critical Appraisal of Current Guidelines and Previous Meta-Analyses. J Minim Invasive Gynecol. 2019; 26(2): 299-311.e3. doi: 10.1016/j.jmig.2018.08.029.PMID: 30717864 44. Pszczołowska M, Walczak K, Kołodziejczyk W, Kozłowska M, Kozłowski G, et al. Understanding Deep Endometriosis: From Molecular to Neuropsychiatry Dimension.Int J Mol SCi. 2025; 26(2): 839. doi: 10.3390/ijms26020839.PMID: 3985955 45. Alborzi S, Askary E, Poordast T, Ghavas R, Fakharmoghadam F, et al. Relation of endometrioma and deep infiltrating endometriosis surgery on ovarian reserve: A Large Single- Centre, Cross-Sectional Study. 46. Maignien C, Santulli P , Bourdon M, Korb D, Marcellin L, et al. Deep Infiltrating Endometriosis: A Previous History of Surgery for Endometriosis May Negatively Affect Assisted Reproductive Technology Outcomes.Reprod SCi. 2020; 27(2): 545-554. doi: 10.1007/s43032-019-00052-1. PMID: 32046438 47. Liang Y , Min Liu, Jianmei Zhang2, Zenghui Mao. First-line surgery versus first-line assisted reproductive technology for women with deep infiltrating endometriosis: A systematic review and meta-analysis Front Endocrinol Lausanne. 2024; 15: 1352770. doi: 10.3389/fendo.2024.1352770. eCollection 2024. PMID: 38699387 48. Casals G, Carrera M, Domínguez JA, Abrão MS, Carmona F.Impact of Surgery for Deep Infiltrative Endometriosis before In Vitro Fertilization: A Systematic Review and Meta-analysis. J Minim Invasive Gynecol. 2021; 28(7): 1303-1312.e5. doi: 10.1016/j. jmig.2021.02.007.PMID: 33582380 49. Daniilidis A, Angioni S, Di Michele S, Dinas K, Gkrozou F, et al. Deep Endometriosis and Infertility: What Is the Impact of Surgery? J Clin Med. 2022; 11(22): 6727. doi: 10.3390/jcm11226727.PMID: 36431203 50. Bourdon M, Peigné M, Maignien C, de Villardi de Montlaur D, Solignac C, et al. Impact of Endometriosis Surgery on In Vitro Fertilization/IntracytoplasmicSperm Injection Outcomes: A Systematic Review and Meta-analysis. Reprod SCi. 2024; 31(6): 1431-1455. doi: 10.1007/s43032-023-01421-7. PMID: 3816885765. 51. Pai AH, Chen LH, Huang SY , Wu HM, Chang CL, et al. The Art of Managing Infertile Patients with Adenomyosis. Gynecol Minim Invasive Ther. 2024; 13(4): 205-208. doi: 10.4103/gmit.gmit-53- 24. eCollection 2024 Oct-Dec.PMID: 39660232 52. Cozzolino M, Bulun S, De Ziegler D, Exacoustos C, Fatemi H, et al. The First Lugano Workshop on the role of adenomyosis in ART. Reprod Biomed Online. 2025; 50(1): 104444. doi: 10. 1016/j. rbmo.2024. 104444. Epub 2024 Sep 12.PMID: 39672080 53. Trinchant R, Cruz M, Requena A, García-Velasco JA Adenomyosis, espeCially in its focal nature, hampers implantation and live birth rate after single euploid embryo transfer. Int J Gynaecol Obstet. 2025; 169(2): 759-765. doi: 10.1002/ijgo.16082.PMID: 3967329 54. Mishra I, Melo P , Easter C, Sephton V, Dhillon-Smith R, et al. Prevalence of adenomyosis in women with subfertility: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2023 Jul;62(1):23-41. doi: 10.1002/uog.26159.PMID: 36647238 55. Dueholm M. Uterine adenomyosis and infertility, review of reproductive outcome after in vitro fertilization and surgery. Acta Obstet Gynecol Scand. 2017; 96: 715-726. doi: 10.1111/ aogs.13158. 56. Younes G, Tulandi T.Effects of adenomyosis on in vitro fertilization treatment outcomes: A meta-analysis. Fertil Steril. 2017; 108(3): 483-490.e3. doi: 10.1016/j.fertnstert.2017.06.025.PMID: 28865548 57. Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, Spaanderman M, Kramer BW, et al. Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: A systematic review and meta- analysis..Reprod Biomed Online. 2021; 42(1): 185-206. doi: 10.1016/j.rbmo.2020.09.023.PMID: 33191131 58. Bourdon M, Mimouni A, Maignien C, Casalechi M, Vigano P , et al. Reduced live birth rates following ART in adenomyosis patients: A matched control study.Hum Reprod. 2025; 40(5): 855-864. doi: 10.1093/humrep/deaf052.PMID: 40159349 59. Neal S, Morin S, Werner M. Three-dimensional ultrasound diagnosis of adenomyosis is not associated with adverse pregnancy outcome following single thawed euploid blastocyst transfer: Prospective cohort study. Ultrasound Obstet Gynecol. 2020; 56: 611-617. 60. Mavrelos D, Holland TK, O’Donovan O, Khalil M, Ploumpidis G, et al. The impact of adenomyosis on the outcome of IVF- embryo transfer. Reprod. Biomed. Online. 2017; 35: 549-554. doi: 10.1016/j.rbmo.2017.06.026. 61. Vercellini P , Consonni D, Barbara G, Buggio L, Frattaruolo MP , et al. Adenomyosis and reproductive performance after surgery for rectovaginal and colorectal endometriosis: A systematic review and meta-analysis. Reprod. Biomed. Online. 2014; 28: 704-713 62. Cozzolino M, Alsbjerg B, Pellicer A. The adenomyosis/ endometriosis IVF patient - call for clinical focus Reproductive BioMediCine Online. 2024; 48: 103737. 63. Martínez-Conejero JA, Maika Morgan, Manel Montesinos, Sara Fortuño, Marcos Meseguer, et al. Adenomyosis does not affect implantation, but is associated with miscarriage in patients undergoing oocyte donation Fertil Steril. 2011; 96(4): 943-50. doi: 10.1016/j.fertnstert.2011.07.1088. 64. Sachs-Guedj N, Coroleu B, Pascual MA, Rodríguez I, Polyzos N. Presence of Adenomyosis Impairs Clinical Outcomes in Women Undergoing Frozen Embryo Transfer: A Retrospective Cohort Study. J. Clin. Med. 2023; 12: 6058. doi: 10.3390/jcm12186058. 65. Wang XL, Xu Z-W, Huang Y-Y , Lin S, Lyu G-R. Different subtypes of ultrasound- diagnosed adenomyosis and in vitro fertilization outcomes: A systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2023; 102(6): 657-68. 10.1111/aogs.14580 66. Bourdon M, Santulli P , Maignien C, Bordonne C, Millischer AE, et al. The “freeze-all” strategy seems to improve the chances of birth in adenomyosis-affected women. Fertil Steril. 2024; 121(3): 460-469. doi: 10.1016/j.fertnstert.2023.11.039.PMID: 38056519 67. Ge L, Li Y , Zhou J, Zhao X, Chen X, et al. Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: A systematic review and meta-analysis. BMJ Open. 2024; 14(7): 077025. doi: 10.1136/bmjopen-2023-077025.PMID: 39025820 68. González-Comadran M, Olmos EA, Mariño MAA, Vizcaíno MAC Utility of GnRH Agonists before embryo transfer in women with adenomyosis: Systematic review and meta-analysis. .JBRA Assist Reprod. 2025; 29(3): 507-519. doi: 10.5935/1518- www.jcimcr.org Page 16 0557.20250012.PMID: 40674550 69. Galati G, Olivieri C, Cosentino M, Azenkoud I, Cugini S, et al. J Medical treatment before in-vitro fertilization in patients with adenomyosis: A systematic review and meta-analysis. Assist Reprod Genet. 2025; 42(2): 381-388. doi: 10.1007/s10815-024- 03323-2.PMID: 39666211 70. Lan J, Wu Y , Wu Z, Wu Y , Yang R, et al. Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study. Front Endocrinol (Lausanne). 2021; 12: 609771. doi: 10.3389/ fendo.2021.609771.PMID: 34135858 71. Steinmann M, Anthon C, Kohl Schwartz AS, Mackens S, Blockeel C, et al. GnRH agonist pretreatment prior to frozen embryo transfer in women with adenomyosis: A systematic review and meta-analysis.Reprod Biomed Online. 2025; 51(5): 105075. doi: 10.1016/j.rbmo.2025.105075.PMID: 4107542 72. Badawy AM, Elnashar AM, Mosbah AA. Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: A randomized controlled trial. Acta Obstet Gynecol Scand. 2012; 91(4): 489-95. doi:10.1111/j.1600- 0412.2012.01350.x.PMID: 22229256 73. Sharma S, RoyChoudhury S, Bhattacharya MP , Hazra S, Majhi AK, et al. Low-dose letrozole - an effective option for women with symptomatic adenomyosis awaiting IVF: A pilot randomized controlled trial. Reprod Biomed Online. 2023; 47(1): 84-93. doi: 10.1016/j.rbmo.2023.03.010.PMID: 37149412 74. Liang Y , Zhu M, Sun F, Liu X, Liu J, et al. Phenotypic heterogeneity in adenomyosis: Internal and external subtypes. Arch Gynecol Obstet. 2025. doi: 10.1007/s00404-025-08166-5.PMID: 40886209 75. Sharma S, Bathwal S, Agarwal N, Chattopadhyay R, Saha I, et al. Does presence of adenomyosis affect reproductive outcome in IVF cycles? A retrospective analysis of 973 patients. Reprod Biomed Online. 2019; 38: 13-21. doi: 10.1016/j. rbmo.2018.09.014. 76. Liu M, Yan Li, Yuan Yuan, Min Jiang, Ping Yin, et al. Peri- implantation treatment with TNF-α inhibitor for endometriosis and/or adenomyosis women undergoing frozen-thawed embryo transfer: A retrospective cohort study. J Reprod Immunol. 2025; 167: 104415. doi: 10.1016/j.jri.2024.104415.PMID: 39700679 77. Rees CO, Rupert IAM, Nederend J, Consten D, Mischi M, et al. Women with combined adenomyosis and endometriosis on MRI have worse IVF/ICSI outcomes compared to adenomyosis and endometriosis alone: A matched retrospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2022; 271: 223-234. doi: 10.1016/j.ejogrb.2022.02.026.PMID: 35231748 78. Alson S, Stenqvist A, SladkeviCius P .Cumulative live birth rates under three consecutive IVF/ICSI treatment cycles are reduced in women with endometriosis and/or adenomyosis diagnosed by ultrasonography. Hum Reprod. 2025; 184. doi: 10.1093/ humrep/deaf184.PMID: 40974212 79. Liu L, Wang T, Li Y , Tian H, Zhou C, et al. Reproductive outcomes after fertility-sparing interventions for symptomatic adenomyosis: A systematic review and meta-analysis. BMC Pregnancy Childbirth. 2025; 25(1): 1178. doi: 10.1186/s12884- 025-08323-3.PMID: 41206447 80. Tan J, Moriarty S, Taskin O, Allaire C, Williams C, et al. Reproductive Outcomes after Fertility-Sparing Surgery for Focal and Diffuse Adenomyosis: A Systematic Review.J Minim Invasive Gynecol. 2018; 25(4): 608-621. doi: 10.1016/j.jmig.2017.12.020. PMID: 29305234 81. Huang YF, Deng J, Wei XL, et al. A comparison of reproductive outcomes of patients with adenomyosis and infertility treated with high-intensity focused ultrasound and laparoscopic exCision. Int J Hyperthermia. 2020; 37(1): 301-7. 82. Youssef Y , Alkatout I, Ayoubi JM, Feki A, Moawad G Robotic- assisted exCision of diffuse adenomyosis. Facts Views Vis Obgyn. 2024; 16(3): 365-368. doi: 10.52054/FVVO.1 83. Matsuzaki S, Nagase Y , Ueda Y , Lee M, Matsuzaki S, et al. The assoCiation of endometriosis with placenta previa and postpartum hemorrhage: A systematic review and meta- analysis. Am J Obstet Gynecol MFM. 2021; 3(5): 100417. doi: 10.1016/j.ajogmf.2021.100417.PMID: 3409817784. 84. Leone Roberti Maggiore, A Racca, F Barra, V G Vellone, P L Venturini, et al. Influence of adenomyosis on pregnancy and perinatal outcomes in women with endometriosis Ultrasound Obstet Gynecol. 2018; 52(5): 666-671. doi: 10.1002/uog.18989. PMID: 29266553 85. Cozzolino M, Cosentino M, Loiudice L, Martire FG, Galliano D, et al. Impact of adenomyosis on in vitro fertilization outcomes in women undergoing donor oocyte transfers: A prospective observational study. Fertil. Steril. 2024; 121: 480-488. doi: 10.1016/j.fertnstert.2023.11.034 86. Lin PW, Chyi-Uei Chern, Chia-Jung Li, Pei-Hsuan Lin, Kuan-Hao Tsui, et al. Improvement of early miscarriage rates in women with adenomyosis via oxytoCin receptor antagonist during frozen embryo transfer-a propensity score-matched study. Reprod Biol Endocrinol. 2024; 22(1): 79. doi: 10.1186/s12958- 024-01255-1.PMID: 38997744 87. Xia Y , Hongbiao Yu. Systematic review and meta-analysis of adverse pregnancy outcomes with different types of adenomyosis. Int J Gynaecol Obstet. 2025; 171(3): 1054-1065. doi: 10.1002/ijgo.70272 88. Juárez-Barber E, Cozzolino M, Corachán A, Alecsandru D, Pellicer N, et al. Adjustment of progesterone administration after endometrial transcriptomic analysis does not improve reproductive outcomes in women with adenomyosis. accessed on 29 August 2024. Reprod. BioMed. Online. 2023; 46: 99-106. doi: 10.1016/j.rbmo.2022.09.007 89. Alsbjerg B, Kesmodel US, Humaidan P . Endometriosis patients benefit from high serum progesterone in hormone replacement therapy-frozen embryo transfer cycles: A cohort study. Reprod Biomed Online 2023;46:92-98 90. Bourdon M, Sorel M, Maignien C, Guibourdenche J, Patrat C, et al. Progesterone levels do not differ between patients with or without endometriosis/adenomyosis both in those who conceive after hormone replacement therapy-frozen embryo transfer cycles and those who do not. Hum Reprod. 2024; 39(8): 1692-1700. doi: 10.1093/humrep/deae114.PMID: 38850031 91. Sharma S, RoyChoudhury S, Karan M, Shaw K, Paladhi P , et al. Impact of Localization of Diffuse Adenomyosis on Frozen Embryo Transfer Outcomes and Perinatal Outcomes: A Prospective Cohort Study of 585 Patients. Gynecol Obstet Invest. 2025: 1-9. doi: 10.1159/000546437.PMID: 40435981 92. Exacoustos C, Morosetti G, Conway F, Camilli S, Martire FG, et al. New Sonographic Classification of Adenomyosis: Do Type and Degree of Adenomyosis Correlate to Severity of Symptoms?.J Minim Invasive Gynecol. 2020; 27(6): 1308-1315. doi: 10.1016/j. jmig.2019.09.788.PMID: 31600574