A Novel GnRH Agonist-Based Regimen for Reducing Recurrence in Fertility-Preserved Atypical Polypoid Adenomyoma: A Retrospective Study

A Novel GnRH Agonist-Based Regimen for Reducing Recurrence in Fertility-Preserved Atypical Polypoid Adenomyoma: A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Novel GnRH Agonist-Based Regimen for Reducing Recurrence in Fertility-Preserved Atypical Polypoid Adenomyoma: A Retrospective Study Jingwen Gan, Huili Zhang, Dongyan Cao, Huimei Zhou, Mei Yu, Tao Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7513445/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Atypical polypoid adenomyoma (APA) is an uncommon uterine lesion characterized by a potential for recurrence and malignant transformation. Fertility-sparing treatment represents a critical option for patients who wish to preserve reproductive capacity. Methods In this retrospective study, we analyzed 34 patients with APA (with or without concurrent endometrial lesions) who underwent hysteroscopic resection (HR) followed by either high-dose progestin or a GnRHa-based regimen (combined with letrozole) between January 2005 and January 2025. Clinicopathological characteristics, treatment outcomes, and reproductive results were evaluated. Results All patients diagnosed via HR, with a mean age of 31 years (range: 22–41). Among them, 31 had coexisting endometrial atypical hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). Eighteen patients (52.9%) were treated with high-dose progestin, and 16 (44.4%) received GnRHa plus letrozole. Complete response (CR) was achieved in all cases, with a median time to CR of 4.5 months (range: 3–15). The recurrence rate of endometrial lesions was 41.2%, with pathological progression observed in 14.7% of cases. Median disease-free survival was 37.5 months (range: 6–186), and 92.9% of recurrences occurred within five years. Factors associated with higher recurrence included age below 35 years, obesity, infertility, lesion location in the lower uterine segment and/or cervical canal. Although both the progestin and GnRHa groups showed similar CR rates and time to CR, the recurrence rate was relatively higher in the progestin group (52.6% vs. 26.7%). Uterine preservation was achieved in 31 patients (91.2%) during follow-up. Among 19 patients attempting conception, 11 pregnancies occurred in eight women, resulting in eight full-term live births. Conclusions Hormone therapy for APA demonstrates favorable initial response and reproductive outcomes. Given the high prevalence of coexisting endometrial hyperplastic lesions and a tendency for recurrence within 5 years, careful preoperative evaluation via HR and long-term follow-up are strongly recommended. GnRHa-based regimen may offer superior recurrence control compared to progestin therapy, although further studies are warranted to confirm these findings. Atypical polypoid adenomyoma Fertility-sparing Hormone therapy Highlights All 34 patients (100%) achieved complete response (CR) with fertility-sparing treatment, with a median time to CR of 4.5 months. Despite initial CR, 41.2% of patients developed recurrent endometrial lesions, with 14.7% showing pathological progression to EAH or EEC. Younger age (≤ 35 years), obesity, infertility, lower uterine/cervical lesion location, and progestin-only therapy were associated with higher recurrence rates, though not statistically significant after FDR correction. Patients receiving GnRHa plus letrozole had a lower recurrence rate (25% vs. 55.6%) and longer disease-free survival compared to those on high-dose progestin alone. Among 19 patients attempting conception, 8 achieved 11 pregnancies, resulting in 8 full-term live births, supporting the feasibility of fertility preservation. Recurrence occurred predominantly within 5 years (92.9%), underscoring the need for sustained surveillance. Introduction Atypical polypoid adenomyoma (APA) is a rare and clinically significant uterine lesion, first systematically described in 1981 [ 1 ]. Histologically, it is characterized by architecturally complex endometrial glands embedded within a fibromuscular stroma [ 2 , 3 ]. APA predominantly occurs in premenopausal women [ 4 ] and commonly presents with abnormal uterine bleeding or infertility [ 5 ]. Although its exact pathophysiology incompletely elucidated, the frequent expression of estrogen receptors in APA tissues suggests a potential role of prolonged estrogen exposure—such as in obesity—in its pathogenesis [ 6 , 7 ]. Although traditionally classified as benign, APA exhibits premalignant potential, with long-term studies reporting a 9–30% risk of concurrent or subsequent endometrial atypical hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC) [ 8 – 10 ]. Currently, there is no consensus on the optimal management of APA. Hysterectomy is generally recommended for women who have completed childbearing [ 10 ], while fertility-sparing interventions such as hysteroscopic resection (HR) may be considered for those wishing to preserve fertility. The role of hormone therapy after HR in improving oncological and reproductive outcomes remains uncertain. Given the substantial recurrence risk (30–45%) of APA associated endometrial lesions reported in previous studies [ 11 – 13 ], we conducted a retrospective analysis to evaluate the clinical characteristics, oncological outcomes, and reproductive results in patients with APA. This study also aimed to identify potential risk factors for lesion recurrence and to compare the efficacy of different hormonal regimens following resection. Materials and methods Study population Clinical data were retrospectively extracted from the electronic medical records of Peking Union Medical College Hospital (PUMCH). The inclusion criteria were as follows: (1) women aged 18–45 years who desired to preserve their fertility; (2) histologically confirmed APA by hysteroscopy, coexisting with EAH or Grade 1–2 EEC or not; (3) no signs of myometrial invasion or extra-uterine metastasis confirmed by enhanced magnetic resonance imaging (MRI); (4) have no contraindications to fertility-preserving treatment or pregnancy; (5) regular follow-up. Exclusion criteria were: patients who underwent hysterectomy with or without bilateral salpingo-oophorectomy. Between January 2005 and January 2025, a total of 35 patients diagnosed with APA via hysteroscopy at our hospital were identified. Of these, one patient was lost to follow-up after hysteroscopy, and the remaining 34 patients received fertility-preserving management at our institution and were followed up regularly until 30 June 2025. This study was approved by the Institutional Review Board of PUMCH (Approval No. 1-22PJ1091). The requirement for written informed consent was waived. Assessment and treatment Demographic, clinical, and pathological data at the time of the initial diagnosis, along with follow-up information, were systematically collected. Body mass index (BMI) was calculated, and a value ≥ 25 kg/m² was defined as overweight or obesity. Endometrial thickness was measured via ultrasonography, with the maximum diameter recorded. Lesion location was determined using MRI and hysteroscopy. Pathological diagnoses were confirmed by two experienced gynecological pathologists in accordance with the World Health Organization Classification of Tumors (2020). Cases with diagnostic discrepancies were resolved through consensus discussion among pathologists to establish a final diagnosis. Following hysteroscopic diagnosis, patients underwent medical management with one of two regimens: (1) High-dose oral progestin, consisting of either medroxyprogesterone acetate (MPA) 500 mg daily or megestrol acetate (MA) 160 mg twice daily; or (2) Gonadotropin-releasing hormone agonist (GnRHa)-based therapy which included subcutaneous injections of GnRHa (3.75 mg every 4 weeks) combined with oral letrozole 2.5 mg daily. Patients with APA, with or without concurrent EAH/EEC, received either high-dose progesterone (P group) or GnRHa plus letrozole (G group). Those with an enlarged uterus, obesity and/or a history of polycystic ovary syndrome were recommended to receive GnRHa-based therapy. Follow-up and Evaluation During the treatment period, monthly outpatient visits involved assessment of symptoms (such as vaginal spotting and abdominal pain), physical examination (including evaluation of weight loss), laboratory studies (including complete blood counts, biochemistry profiles, and CA125 level), and endometrial evaluation via ultrasound or MRI. Histological response was assessed every 3–4 months (aligning with each treatment course) through HR or endometrial biopsy—the latter performed when no intrauterine occupying lesion was identified. Treatment response was classified into complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). CR was defined as the absence of any endometrial lesion on pathological examination. PR was characterized by pathological improvement, reflected as regression from EAH to complex or simple hyperplasia, or from EEC to atypical, complex, or simple hyperplasia. SD referred to persistence of lesions consistent with the original diagnosis. PD was defined as progression to more advanced pathology or evidence of myometrial invasion and/or extrauterine metastasis. Patients who did not achieve CR within 12 months were considered fertility-preservation failures and advised surgery. For those who declined hysterectomy, a conservative re-treatment strategy was offered after obtaining renewed written informed consent. Patients wishing to conceive after achieving CR received preconception counseling and were referred for assisted reproductive technology (ART). Others were maintained on prophylactic regimens (such as oral contraceptives, cyclic progestins, or levonorgestrel-releasing intrauterine devices) to prevent recurrence. The following outcomes were analyzed: Cumulative CR rates at 3, 6 months and by the end of treatment, median time to achieve CR, recurrence rate after CR, and incidence of histological progression. Reasons for hysterectomy and corresponding surgical histology were also collected. Fertility outcomes—including time to pregnancy, use of ART, and pregnancy outcomes—were documented. Statistical analysis Continuous variables were expressed as mean ± standard deviation or median (range), and compared using the student’s t-test and Mann–Whitney U tests, as appropriate. Categorical variables were summarized as numbers (percentages) and compared using Pearson’s chi-squared test. Univariate P-values were adjusted for multiplicity within each analysis set using the Benjamini–Hochberg false discovery rate (FDR) adjustment method. Variables with statistical significance in univariate analyses were incorporated into a multivariate Cox proportional hazards model. Results are presented as odds ratios (OR) with 95% confidence intervals (CIs). A two-sided p-value < 0.05 was considered statistically significant. All analyses were performed using SPSS version 25.0 (version 25.0; Chicago, IL, USA). Results Characteristics of patients with APA All patients initially underwent HR. The mean age of the APA cohort was 31.53 ± 4.71 years, with a mean BMI of 25.39 ± 5.30 kg/m². Among the 34 patients, 82.4% (28/34) were nulliparous and 29.4% (10/34) had a history of infertility. Preoperative ultrasound revealed a mean endometrial thickness of 2.29 ± 1.63 cm. Lesions were located in the uterine fundus in 76.5% (26/34) of cases, with the remainder involving the lower uterine segment and/or cervix. APA was accompanied by EAH in 58.8% (20/34) of cases and by EEC in 32.4% (11/34). Isolated APA was observed in only 8.8% (3/34) of patients (Table 1 ). Table 1 Characteristics of APA patients Variables Value (N = 34) Age, years 31 (22–41) BMI 23.85 (18.4–38.5) Nulliparity N 24 (70.6%) Y 10 (29.4%) CA125 (IU/ml) Normal 26 (76.5%) Elevated 8 (23.5%) Em (cm) 1.7 (0.2–7.5) APA localization Uterine fundus 26 (76.5%) Lower uterine segment and/or cervical canal 8 (23.5%) Endometrial pathology APA with EAH 20 (58.8%) APA with EEC 11 (32.4%) only APA 3 (8.8%) Treatment options MA or MPA 18 (52.9%) GnRHa 16 (47.1%) Note: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; BMI, body mass index; Em, endometrial thickness; EAH, endometrial atypical hyperplasia; EEC, endometrioid endometrial carcinoma; MPA medroxyprogesterone acetate; MA, megestrol acetate; GnRHa, Gonadotropin-releasing hormone agonist. Treatment regimen and oncological outcomes Within the cohort, 18 patients (52.9%) were treated with MPA or MA, and 16 patients (47.1%) received GnRHa. After 3 months of treatment, 6 patients (17.6%) achieved CR, which increased to 27 patients (79.4%) by 6 months. Only two patients required more than 12 months to attain CR. Notably, all patients (100%) eventually achieved an initial CR, with a median time to CR of 4.5 months (range: 3–15) and a median total treatment duration of six months (range: 3–15). At a mean follow up of 74 months (range: 18–191), no recurrence of APA was observed. However, endometrial lesions were detected in 14 patients (41.2%), including five who exhibited disease progression after initial CR. Among these, one patient with initial APA relapsed as EAH, and one progressed to EEC. Additionally, three patients initially diagnosed with APA coexisting with EAH later developed EEC. The median time from CR to the diagnosis of EAH or EEC was 37.5 months (range: 6–186) (Table 2 ). Among these 14 patients, recurrence occurred within 2 years in 8 (57.1%) and within 5 years in 13 (92.9%). Uterine preservation was achieved in 31 patients (91.2%). Two (8.8%) patients underwent hysterectomy due to progression to EEC and repeatedly failed assisted reproductive technology. One patient underwent ovarian cancer staging surgery following a diagnosis of well-differentiated ovarian endometrioid carcinoma. Table 2 Oncologic outcomes of APA patients Variables Value (N = 34) Total CR 34 (100%) 3-months CR 6 (17.65%) 6-months CR 27 (79.41%) Over 12-months CR 2 (5.88%) Time to CR, Mo 4.5 (3–15) Time of drug treatment, Mo 6 (3–15) Recurrence 14 (41.2%) Progression of pathology 5 (14.71%) DFS, Mo 37.5 (6–186) Follow up, Mo 74 (18–191) Hysterectomy 3 (8.8%) Note: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; CR, complete response. DFS, Disease-Free Survival. Risk factors for relapsed with EAH or EEC in patients with APA Potential risk factors for recurrence of EAH or EEC in APA patients were evaluated (Table 3 ). Age ≤ 35 years, obesity, comorbid infertility, and lesion located in the lower uterine segment and/or cervical canal were relatively associated with higher recurrence. Progesterone treatment had a higher recurrence rate compared with that of the GnRHa-based regimen. Yet, no statistical significance was observed. Table 3 Univariable analysis of recurrence risk factors with FDR correction Factors Rario Total (n = 34) OR Cl P FDR Age : ≤ 35 vs. >35 (Ref) 55.6% vs. 25.0% 5.8 0.8–16.2 0.014 0.274 BMI : N (Ref) vs. Overweight 38.9% vs. 43.8% 1.2 0.3–4.8 0.774 0.809 Infertility : N (Ref) vs. Y 33.3% vs. 60.0% 3.0 0.7–13.8 0.158 0.274 CA125 (U/ml) : Normal vs. Elevated (Ref) 42.3% vs. 37.5% 1.2 0.2–6.2 0.809 0.809 Em : ≤ 1 cm (Ref) vs. >1 cm 50.0% vs. 38.5% 1.6 0.3–7.9 0.564 0.752 APA localization : Uterine fundus (Ref) vs. Lower uterine segment and/or cervical canal 34.6% vs. 62.5% 3.7 0.6–16.3 0.171 0.274 Treatment Regimen : P vs. G (Ref) 52.6% vs. 26.7% 3.8 0.9–16.2 0.077 0.274 Consolidation therapy : N vs. Y (Ref) 33.3% vs. 60.0% 3.0 0.6–13.8 0.158 0.274 Note: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; BMI, body mass index; Em, endometrial thickness; EAH, endometrial atypical hyperplasia; EEC, endometrioid endometrial carcinoma; P, high-dose oral progestin therapy; G, Gonadotropin-releasing hormone agonist (GnRHa)-based therapy. Comparison between P and G groups No significant differences were observed in the baseline characteristics of patients between the two groups. At the first hysteroscopic evaluation after 3 months of treatment, CR rates were 22.22% in group P and 18.75% in group G. After 6 months of treatment, CR rates were comparable between the groups (77.78% vs. 81.25%). One patient in each group achieved CR after more than 12 months of treatment (5.56% in group P vs. 6.25% in group G). Although time to CR was similar between groups (P = 0.833), the median time from CR to diagnosis of EAH or EEC was longer in group P than in group G (3 months vs. 29 months, P = 0.082) (Table 4 ). Table 4 Characteristics and outcomes in diverse treatment regimen of Patients with APA Variables P group (N = 18) G group (N = 16) P Age, years 0.800 ≤ 35 12 (66.7%) 10 (62.5%) > 35 6 (33.3%) 6 (37.5%) BMI 0.746 N 10 (55.6%) 8 (50.0%) Overweight 8 (44.4%) 8 (50.0%) Infertility 0.824 N 13 (72.2%) 11 (68.8%) Y 5 (27.8%) 5 (31.3%) CA125 (IU/ml) 0.849 Normal 14 (77.8%) 12 (75.0%) Elevated 4 (22.2%) 4 (25.0%) Em (cm) 0.153 ≤ 1 cm 6 (33.3%) 2 (12.5%) > 1 cm 12 (66.7%) 14 (87.5%) APA localization 0.317 Uterine fundus 15 (83.3%) 11 (68.8%) Lower uterine segment and/or cervical canal 3 (16.7%) 5 (31.2%) Endometrial pathology 0.599 Only APA or with EAH 13 (72.2%) 9 (56.3%) APA with EEC 5 (27.8%) 7 (43.7%) Consolidation therapy 0.005* N 9 (50.0%) 15 (93.8%) Y 9 (50.0%) 1 (6.3%) 3-months Initial CR 4/18 (22.22%) 3/16 (18.75%) 0.597 6-months Initial CR 14/18 (77.76%) 13/16 (81.25%) 0.551 over 12-months Initial CR 1/18 (5.56%) 1/16 (6.25%) 0.316 Time to CR, Mo 6 (3–15) 4 (3–13) 0.833 Total time of treatment, Mo 7.5 (3–15) 4 (3–13) 0.233 DFS, Mo 43 (6–186) 29 (7–83) 0.082 Recurrence 0.071 N 8 (44.4%) 12 (75.0%) Y 10 (55.6%) 4 (25.0%) Follow up time, Mo 86.5 (42–191) 50.5 (18–126) 0.008* Pregnancy 0.824 N 13 (72.2%) 11 (68.8%) Y 5 (27.8%) 5 (31.2%) Note: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; BMI, body mass index; Em, endometrial thickness; EAH, endometrial atypical hyperplasia; EEC, endometrioid endometrial carcinoma; CR, complete response. DFS, Disease-Free Survival. Fertility outcomes During follow-up period, 19 patients expressed a desire to conceive. Eight patients achieved a total of 11 pregnancies, with a median time to conception of 8.5 months (range: 1–41). Six pregnancies resulted from in vitro fertilization, four were spontaneous, and one followed ovulation induction. Eight pregnancies ended in full-term live births, and three ended in early embryonic arrest (Table 5 ). Table 5 Reproductive outcomes of APA patients Variables Value Pregnancy Times 11 IVF 6 (54.5%) Natural 4 (36.4%) Ovulation induction 1 (9.1%) Time to pregnancy, Mo 8.5 (1–41) Pregnant outcomes Full-term birth 8 (72.7%) Embryo arrest 3 (27.3%) Note: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; IVF, In Vitro Fertilization. Discussion In this retrospective study, we evaluated the efficacy and reproductive outcomes of fertility-sparing treatment in 34 patients with APA, with or without concurrent endometrial hyperplastic lesions. Our findings demonstrate that hormone therapy following hysteroscopic resection is associated with favorable initial response and reproductive outcomes, albeit with a considerable risk of endometrial lesion recurrence. Consistent with previous reports, APA predominantly affected young premenopausal women in our cohort, with a median age of 31 years. A substantial proportion of patients were nulliparous (70.6%) and nearly one-third had a history of infertility. Notably, over 90% of APA cases were accompanied by EAH or EEC, a rate higher than previously documented (ranging from 9–59.9%) [ 10 , 14 ]. This may be attributed to the thorough diagnostic hysteroscopy and systematic histopathological review performed in our institution, underscoring the importance of comprehensive endometrial evaluation in these patients. For patients with APA without concurrent endometrial hyperplastic lesions, complete HR of the lesion is considered first-line treatment [ 15 ]. However, the role of hormone therapy in the prognostic outcomes of APA, with or without endometrial hyperplasia, remains poorly defined. Some investigators suggested that persistent estrogen stimulation combined with progesterone deficiency may represent key pathological mechanisms in APA development. This was supported by the strong immunohistochemical expression of estrogen receptor and progesterone receptor in the glandular components of APA, indicating a potential therapeutic benefit of hormonal intervention [ 16 , 17 ]. All patients achieved initial CR following hormone therapy, with a median time to CR of 4.5 months. The cumulative CR rate reached 79.4% at 6 months, superior to outcomes reported in studies where adjuvant hormone therapy was not administered [ 10 , 18 ]. These results supported the use of hormonal treatment following complete resection to enhance initial therapeutic response. Reported recurrence rates for APA ranged from 28.9–35.1% [ 9 , 19 , 20 ]. Multiple studies demonstrated that postoperative progesterone therapy was associated with significantly reduced recurrence and malignant transformation rates compared to no hormonal treatment [ 10 , 14 ]. Nomura et al. [ 21 , 22 ] also indicated that MPA therapy contributed to lower recurrence rates. Similarly, Wang et al. [ 18 ] reviewed 86 APA cases and concluded that high-dose progestin therapy following HR may delay or prevent disease recurrence. In our study, no recurrence of APA was observed after a median follow-up of 74 months (range: 18–191). However, recurrence of endometrial lesions occurred in 41.2% of patients, with nearly 15% showing pathological progression, consistent with recent literature [ 21 , 23 ]. Most recurrences (92.9%) were detected within 5 years, highlighting the necessity of long-term surveillance. Younger age (≤ 35 years), obesity, infertility, and lesion location in the lower uterine segment or cervix were associated with higher recurrence rates, although these did not reach statistical significance after FDR adjustment. Notably, patients receiving GnRHa plus letrozole had a lower recurrence rate (25% vs. 55.6%) and a longer disease-free interval compared to those receiving progestin alone. GnRHa induces profound hypoestrogenism and may exert direct anti-proliferative effects on endometrial tissue [ 17 ], while letrozole further reduces estrogen synthesis. These mechanisms may synergistically contribute to more effective suppression of endometrial hyperplasia and reduce recurrence risk. Further research is warranted to determine whether GnRHa represents a superior therapeutic option for APA patients with coexisting endometrial lesions. Reproductive outcomes were encouraging: among 19 patients attempting conception, 8 achieved 11 pregnancies, resulting in 8 full-term live births. This suggested that fertility-preserving treatment does not compromise pregnancy potential in appropriately selected patients [ 24 ]. The primary mechanism underlying stromal changes in APA involves metaplasia of normal endometrial stroma into smooth muscle, often exhibiting poorly defined borders at the interface with the myometrium. Although APA does not demonstrate true myometrial invasion histologically, it can be challenging to distinguish from myometrial invasion by endometrial carcinoma on MRI. Furthermore, due to its uncertain malignant potential, APA may complicate fertility-sparing decision-making. In our study, one patient presented with MRI findings suggestive of superficial myometrial invasion. However, given strong desire of this patient to preserve fertility and after exclusion of contraindications to conservative management, she underwent GnRHa plus letrozole. After six months of treatment, she achieved CR, and no endometrial lesion recurrence was observed during follow-up. Narumi et al. [ 25 ] also reported a case of APA with deep myometrial involvement where complete resection was not achievable via HR. The patient therefore underwent laparoscopic excision of the lesion followed by levonorgestrel-releasing intrauterine system (LNG-IUS) insertion. After six months, the LNG-IUS was removed, and no recurrence was detected during 26 months of follow-up. Therefore, how to establish fertility-preserving strategies for patients with APA complicated by endometrial lesions is an issue that warrants further discussion in the future. One limitation of this study is its retrospective design and relatively small sample size, which may limit the statistical power to identify significant risk factors. Moreover, treatment allocation was not randomized, which may introduce selection bias. Prospective studies with larger cohorts are needed to validate our findings and refine treatment strategies. In summary, hormone therapy following hysteroscopic resection represents an effective fertility-sparing approach for APA patients, with high initial response rates and promising reproductive outcomes. However, the substantial recurrence risk underscores the need for long-term monitoring. GnRHa-based regimens may offer superior recurrence control compared to progestin-alone therapy and warrant further investigation. Declarations Competing interests The authors declare no competing interests. Ethics approval This study involves human participants and was approved by the Institutional Review Board of Peking Union Medical College Hospital (Approval No. 1-22PJ1091). The requirement for informed consent was waived in accordance with the Declaration of Helsinki. Provenance and peer review Not commissioned; externally peer reviewed. Funding This work was supported by the National High Level Hospital Clinical Research Funding (Program Nos. 2022-PUMCH-B-082). Author Contribution Cao DY, Zhou HM, Yu M, and Wang T provided cases and confirmed the completeness and accuracy of the data and analyses, and the final approval of the version to be published. Gan JW have substantially contributed to the design and writing of the manuscript and data collection. Zhang HL contributed to the design and data collection. Cao DY accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish as a guarantor. 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Hysteroscopic treatment of atypical polypoid adenomyoma diagnosed incidentally in a young infertile woman [J]. Fertil Steril. 2008;89(2):e4569–12. https://doi.org/10.1016/j.fertnstert.2007.02.061 . Terada T. Atypical polypoid adenomyoma of the uterus: an immunohistochemical study on 5 cases [J]. Annals of diagnostic pathology, 2011, 15(5): 338–41. https://doi.org/10.1016/j.anndiagpath.2011.03.008 Yahata T, Nonaka T, Watanabe A, Sekine M, Tanaka K. Fertil Steril. 2011;95(7):e24359–11. https://doi.org/10.1016/j.fertnstert.2011.03.067 . Complete hysteroscopic resection of a large atypical polypoid adenomyoma, followed by a successful pregnancy [J]. Wang Q, Shan W, Yang B, Xue Y, Lou Y, Chen X. Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma [J]. Front Oncol. 2024;14:1386931. https://doi.org/10.3389/fonc.2024.1386931 . Mikos, Tsolakidis G. Clinical presentation and management of atypical polypoid adenomyomas: Systematic review of the literature [J]. Eur J Obstet Gynecol Reprod Biol. 2019;236:14–21. https://doi.org/10.1016/j.ejogrb.2019.02.027 . Zhang Y, Duan H, Guo Ys. al. Hysteroscopy used in atypical polypoidadenomyoma treatment [J]. Chin jClin Obstet Gynecol, 2010, 11(4): 268 – 70. https://doi.org/ https://doi.org/10.1016/S0020-7292(09)61424-7 Nomura H, Sugiyama Y, Tanigawa T, Matoda M, Kanao H, Kondo E, Takeshima N. Long-term outcomes of fertility-sparing treatment of atypical polypoid adenomyoma with medroxyprogesterone acetate [J]. Arch Gynecol Obstet. 2016;293(1):177–81. https://doi.org/10.1007/s00404-015-3824-9 . Nomura H, Sugiyama Y, Tanigawa T, Matoda M, Okamoto S, Omatsu K, Kanao H, Kato K, Utsugi K, Takeshima N. Maintenance hormonal therapy after treatment with medroxyprogesterone acetate for patients with atypical polypoid adenomyoma [J]. Jpn J Clin Oncol. 2018;48(3):255–8. https://doi.org/10.1093/jjco/hyx193 . Domeniconi L, Amadori A, Maniglio P, Saragoni L. Atypical polypoid adenomyoma of the endometrium: diagnosis and treatment. A case report [J]. Pathologica. 2020;112(4):214–8. https://doi.org/10.32074/1591-951x-112 . Chiyoda T, Lin BL, Saotome K, Kiyokawa S, Nakada S. Hysteroscopic Transcervical Resection for Atypical Polypoid Adenomyoma of the Uterus: A Valid, Fertility-Preserving Option [J]. J Minim Invasive Gynecol. 2018;25(1):163. https://doi.org/10.1016/j.jmig.2017.08.659 . 9.e1. Narumi R, Takei Y, Morisawa H, Taneichi A, Matsubara S, Fujiwara H. Successful laparotomy tumor resection and levonorgestrel-releasing intrauterine system for atypical polypoid adenomyoma [J]. J Obstet Gynaecol Res. 2019;45(1):230–4. https://doi.org/10.1111/jog.13783 . Additional Declarations No competing interests reported. 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05:39:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1009913,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7513445/v1/f26f2596-81fd-4f6b-afdb-281c45e586cb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Novel GnRH Agonist-Based Regimen for Reducing Recurrence in Fertility-Preserved Atypical Polypoid Adenomyoma: A Retrospective Study","fulltext":[{"header":"Highlights","content":"\u003cp\u003e All 34 patients (100%) achieved complete response (CR) with fertility-sparing treatment, with a median time to CR of 4.5 months.\u003c/p\u003e\u003cp\u003e Despite initial CR, 41.2% of patients developed recurrent endometrial lesions, with 14.7% showing pathological progression to EAH or EEC.\u003c/p\u003e\u003cp\u003e Younger age (\u0026le;\u0026thinsp;35 years), obesity, infertility, lower uterine/cervical lesion location, and progestin-only therapy were associated with higher recurrence rates, though not statistically significant after FDR correction.\u003c/p\u003e\u003cp\u003e Patients receiving GnRHa plus letrozole had a lower recurrence rate (25% vs. 55.6%) and longer disease-free survival compared to those on high-dose progestin alone.\u003c/p\u003e\u003cp\u003e Among 19 patients attempting conception, 8 achieved 11 pregnancies, resulting in 8 full-term live births, supporting the feasibility of fertility preservation.\u003c/p\u003e\u003cp\u003e Recurrence occurred predominantly within 5 years (92.9%), underscoring the need for sustained surveillance.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eAtypical polypoid adenomyoma (APA) is a rare and clinically significant uterine lesion, first systematically described in 1981 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Histologically, it is characterized by architecturally complex endometrial glands embedded within a fibromuscular stroma [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. APA predominantly occurs in premenopausal women [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and commonly presents with abnormal uterine bleeding or infertility [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Although its exact pathophysiology incompletely elucidated, the frequent expression of estrogen receptors in APA tissues suggests a potential role of prolonged estrogen exposure\u0026mdash;such as in obesity\u0026mdash;in its pathogenesis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough traditionally classified as benign, APA exhibits premalignant potential, with long-term studies reporting a 9\u0026ndash;30% risk of concurrent or subsequent endometrial atypical hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC) [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Currently, there is no consensus on the optimal management of APA. Hysterectomy is generally recommended for women who have completed childbearing [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], while fertility-sparing interventions such as hysteroscopic resection (HR) may be considered for those wishing to preserve fertility. The role of hormone therapy after HR in improving oncological and reproductive outcomes remains uncertain. Given the substantial recurrence risk (30\u0026ndash;45%) of APA associated endometrial lesions reported in previous studies [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], we conducted a retrospective analysis to evaluate the clinical characteristics, oncological outcomes, and reproductive results in patients with APA. This study also aimed to identify potential risk factors for lesion recurrence and to compare the efficacy of different hormonal regimens following resection.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003eClinical data were retrospectively extracted from the electronic medical records of Peking Union Medical College Hospital (PUMCH). The inclusion criteria were as follows: (1) women aged 18\u0026ndash;45 years who desired to preserve their fertility; (2) histologically confirmed APA by hysteroscopy, coexisting with EAH or Grade 1\u0026ndash;2 EEC or not; (3) no signs of myometrial invasion or extra-uterine metastasis confirmed by enhanced magnetic resonance imaging (MRI); (4) have no contraindications to fertility-preserving treatment or pregnancy; (5) regular follow-up. Exclusion criteria were: patients who underwent hysterectomy with or without bilateral salpingo-oophorectomy. Between January 2005 and January 2025, a total of 35 patients diagnosed with APA via hysteroscopy at our hospital were identified. Of these, one patient was lost to follow-up after hysteroscopy, and the remaining 34 patients received fertility-preserving management at our institution and were followed up regularly until 30 June 2025. This study was approved by the Institutional Review Board of PUMCH (Approval No. 1-22PJ1091). The requirement for written informed consent was waived.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAssessment and treatment\u003c/h3\u003e\n\u003cp\u003eDemographic, clinical, and pathological data at the time of the initial diagnosis, along with follow-up information, were systematically collected. Body mass index (BMI) was calculated, and a value\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u0026sup2; was defined as overweight or obesity. Endometrial thickness was measured via ultrasonography, with the maximum diameter recorded. Lesion location was determined using MRI and hysteroscopy. Pathological diagnoses were confirmed by two experienced gynecological pathologists in accordance with the World Health Organization Classification of Tumors (2020). Cases with diagnostic discrepancies were resolved through consensus discussion among pathologists to establish a final diagnosis.\u003c/p\u003e\u003cp\u003eFollowing hysteroscopic diagnosis, patients underwent medical management with one of two regimens: (1) High-dose oral progestin, consisting of either medroxyprogesterone acetate (MPA) 500 mg daily or megestrol acetate (MA) 160 mg twice daily; or (2) Gonadotropin-releasing hormone agonist (GnRHa)-based therapy which included subcutaneous injections of GnRHa (3.75 mg every 4 weeks) combined with oral letrozole 2.5 mg daily. Patients with APA, with or without concurrent EAH/EEC, received either high-dose progesterone (P group) or GnRHa plus letrozole (G group). Those with an enlarged uterus, obesity and/or a history of polycystic ovary syndrome were recommended to receive GnRHa-based therapy.\u003c/p\u003e\n\u003ch3\u003eFollow-up and Evaluation\u003c/h3\u003e\n\u003cp\u003eDuring the treatment period, monthly outpatient visits involved assessment of symptoms (such as vaginal spotting and abdominal pain), physical examination (including evaluation of weight loss), laboratory studies (including complete blood counts, biochemistry profiles, and CA125 level), and endometrial evaluation via ultrasound or MRI. Histological response was assessed every 3\u0026ndash;4 months (aligning with each treatment course) through HR or endometrial biopsy\u0026mdash;the latter performed when no intrauterine occupying lesion was identified. Treatment response was classified into complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). CR was defined as the absence of any endometrial lesion on pathological examination. PR was characterized by pathological improvement, reflected as regression from EAH to complex or simple hyperplasia, or from EEC to atypical, complex, or simple hyperplasia. SD referred to persistence of lesions consistent with the original diagnosis. PD was defined as progression to more advanced pathology or evidence of myometrial invasion and/or extrauterine metastasis. Patients who did not achieve CR within 12 months were considered fertility-preservation failures and advised surgery. For those who declined hysterectomy, a conservative re-treatment strategy was offered after obtaining renewed written informed consent. Patients wishing to conceive after achieving CR received preconception counseling and were referred for assisted reproductive technology (ART). Others were maintained on prophylactic regimens (such as oral contraceptives, cyclic progestins, or levonorgestrel-releasing intrauterine devices) to prevent recurrence.\u003c/p\u003e\u003cp\u003eThe following outcomes were analyzed: Cumulative CR rates at 3, 6 months and by the end of treatment, median time to achieve CR, recurrence rate after CR, and incidence of histological progression. Reasons for hysterectomy and corresponding surgical histology were also collected. Fertility outcomes\u0026mdash;including time to pregnancy, use of ART, and pregnancy outcomes\u0026mdash;were documented.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (range), and compared using the student\u0026rsquo;s t-test and Mann\u0026ndash;Whitney U tests, as appropriate. Categorical variables were summarized as numbers (percentages) and compared using Pearson\u0026rsquo;s chi-squared test. Univariate P-values were adjusted for multiplicity within each analysis set using the Benjamini\u0026ndash;Hochberg false discovery rate (FDR) adjustment method. Variables with statistical significance in univariate analyses were incorporated into a multivariate Cox proportional hazards model. Results are presented as odds ratios (OR) with 95% confidence intervals (CIs). A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were performed using SPSS version 25.0 (version 25.0; Chicago, IL, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eCharacteristics of patients with APA\u003c/h2\u003e\u003cp\u003eAll patients initially underwent HR. The mean age of the APA cohort was 31.53\u0026thinsp;\u0026plusmn;\u0026thinsp;4.71 years, with a mean BMI of 25.39\u0026thinsp;\u0026plusmn;\u0026thinsp;5.30 kg/m\u0026sup2;. Among the 34 patients, 82.4% (28/34) were nulliparous and 29.4% (10/34) had a history of infertility. Preoperative ultrasound revealed a mean endometrial thickness of 2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63 cm. Lesions were located in the uterine fundus in 76.5% (26/34) of cases, with the remainder involving the lower uterine segment and/or cervix. APA was accompanied by EAH in 58.8% (20/34) of cases and by EEC in 32.4% (11/34). Isolated APA was observed in only 8.8% (3/34) of patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of APA patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValue (N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (22\u0026ndash;41)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.85 (18.4\u0026ndash;38.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNulliparity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (70.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (29.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCA125 (IU/ml)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (76.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (23.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEm (cm)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.7 (0.2\u0026ndash;7.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAPA localization\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUterine fundus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (76.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLower uterine segment and/or cervical canal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (23.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEndometrial pathology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPA with EAH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (58.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPA with EEC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (32.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eonly APA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (8.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment options\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMA or MPA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (52.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGnRHa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (47.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eNote: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; BMI, body mass index; Em, endometrial thickness; EAH, endometrial atypical hyperplasia; EEC, endometrioid endometrial carcinoma; MPA medroxyprogesterone acetate; MA, megestrol acetate; GnRHa, Gonadotropin-releasing hormone agonist.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTreatment regimen and oncological outcomes\u003c/h3\u003e\n\u003cp\u003eWithin the cohort, 18 patients (52.9%) were treated with MPA or MA, and 16 patients (47.1%) received GnRHa. After 3 months of treatment, 6 patients (17.6%) achieved CR, which increased to 27 patients (79.4%) by 6 months. Only two patients required more than 12 months to attain CR. Notably, all patients (100%) eventually achieved an initial CR, with a median time to CR of 4.5 months (range: 3\u0026ndash;15) and a median total treatment duration of six months (range: 3\u0026ndash;15). At a mean follow up of 74 months (range: 18\u0026ndash;191), no recurrence of APA was observed. However, endometrial lesions were detected in 14 patients (41.2%), including five who exhibited disease progression after initial CR. Among these, one patient with initial APA relapsed as EAH, and one progressed to EEC. Additionally, three patients initially diagnosed with APA coexisting with EAH later developed EEC. The median time from CR to the diagnosis of EAH or EEC was 37.5 months (range: 6\u0026ndash;186) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Among these 14 patients, recurrence occurred within 2 years in 8 (57.1%) and within 5 years in 13 (92.9%). Uterine preservation was achieved in 31 patients (91.2%). Two (8.8%) patients underwent hysterectomy due to progression to EEC and repeatedly failed assisted reproductive technology. One patient underwent ovarian cancer staging surgery following a diagnosis of well-differentiated ovarian endometrioid carcinoma.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOncologic outcomes of APA patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValue (N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal CR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (100%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e3-months CR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (17.65%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e6-months CR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (79.41%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOver 12-months CR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (5.88%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTime to CR, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.5 (3\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTime of drug treatment, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (3\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRecurrence\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (41.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProgression of pathology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (14.71%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDFS, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37.5 (6\u0026ndash;186)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFollow up, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (18\u0026ndash;191)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHysterectomy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (8.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eNote: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; CR, complete response. DFS, Disease-Free Survival.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eRisk factors for relapsed with EAH or EEC in patients with APA\u003c/h3\u003e\n\u003cp\u003ePotential risk factors for recurrence of EAH or EEC in APA patients were evaluated (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Age\u0026thinsp;\u0026le;\u0026thinsp;35 years, obesity, comorbid infertility, and lesion located in the lower uterine segment and/or cervical canal were relatively associated with higher recurrence. Progesterone treatment had a higher recurrence rate compared with that of the GnRHa-based regimen. Yet, no statistical significance was observed.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariable analysis of recurrence risk factors with FDR correction\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRario\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFDR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e: \u0026le; 35 vs. \u0026gt;35 (Ref)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55.6% vs. 25.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.8\u0026ndash;16.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.274\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e: N (Ref) vs. Overweight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.9% vs. 43.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3\u0026ndash;4.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.774\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.809\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInfertility\u003c/b\u003e: N (Ref) vs. Y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.3% vs. 60.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.7\u0026ndash;13.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.158\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.274\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCA125 (U/ml)\u003c/b\u003e: Normal vs. Elevated (Ref)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.3% vs. 37.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.2\u0026ndash;6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.809\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.809\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEm\u003c/b\u003e: \u0026le; 1 cm (Ref) vs. \u0026gt;1 cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50.0% vs. 38.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3\u0026ndash;7.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.564\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.752\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAPA localization\u003c/b\u003e: Uterine fundus (Ref) vs. Lower uterine segment and/or cervical canal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.6% vs. 62.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6\u0026ndash;16.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.171\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.274\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment Regimen\u003c/b\u003e: P vs. G (Ref)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52.6% vs. 26.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.9\u0026ndash;16.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.077\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.274\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eConsolidation therapy\u003c/b\u003e:\u0026nbsp;N vs. Y (Ref)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.3% vs. 60.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6\u0026ndash;13.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.158\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.274\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; BMI, body mass index; Em, endometrial thickness; EAH, endometrial atypical hyperplasia; EEC, endometrioid endometrial carcinoma; P, high-dose oral progestin therapy; G, Gonadotropin-releasing hormone agonist (GnRHa)-based therapy.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eComparison between P and G groups\u003c/h2\u003e\u003cp\u003eNo significant differences were observed in the baseline characteristics of patients between the two groups. At the first hysteroscopic evaluation after 3 months of treatment, CR rates were 22.22% in group P and 18.75% in group G. After 6 months of treatment, CR rates were comparable between the groups (77.78% vs. 81.25%). One patient in each group achieved CR after more than 12 months of treatment (5.56% in group P vs. 6.25% in group G). Although time to CR was similar between groups (P\u0026thinsp;=\u0026thinsp;0.833), the median time from CR to diagnosis of EAH or EEC was longer in group P than in group G (3 months vs. 29 months, P\u0026thinsp;=\u0026thinsp;0.082) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics and outcomes in diverse treatment regimen of Patients with APA\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eP group (N\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eG group (N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.800\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (62.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.746\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (55.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverweight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (44.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInfertility\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.824\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (72.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (27.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCA125 (IU/ml)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.849\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (77.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEm (cm)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.153\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;1 cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;1 cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (87.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAPA localization\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUterine fundus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLower uterine segment and/or cervical canal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEndometrial pathology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.599\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnly APA or with EAH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (72.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (56.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPA with EEC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (27.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (43.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eConsolidation therapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.005*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (93.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e3-months Initial CR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4/18 (22.22%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3/16 (18.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.597\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e6-months Initial CR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14/18 (77.76%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13/16 (81.25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.551\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eover 12-months Initial CR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1/18 (5.56%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1/16 (6.25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.316\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTime to CR, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (3\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.833\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal time of treatment, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.5 (3\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.233\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDFS, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43 (6\u0026ndash;186)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (7\u0026ndash;83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.082\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRecurrence\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.071\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (44.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (55.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFollow up time, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e86.5 (42\u0026ndash;191)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50.5 (18\u0026ndash;126)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.008*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePregnancy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.824\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (72.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (27.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; BMI, body mass index; Em, endometrial thickness; EAH, endometrial atypical hyperplasia; EEC, endometrioid endometrial carcinoma; CR, complete response. DFS, Disease-Free Survival.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eFertility outcomes\u003c/h2\u003e\u003cp\u003eDuring follow-up period, 19 patients expressed a desire to conceive. Eight patients achieved a total of 11 pregnancies, with a median time to conception of 8.5 months (range: 1\u0026ndash;41). Six pregnancies resulted from in vitro fertilization, four were spontaneous, and one followed ovulation induction. Eight pregnancies ended in full-term live births, and three ended in early embryonic arrest (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eReproductive outcomes of APA patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePregnancy Times\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (54.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNatural\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (36.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOvulation induction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTime to pregnancy, Mo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.5 (1\u0026ndash;41)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePregnant outcomes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFull-term birth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (72.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmbryo arrest\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (27.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eNote: Data are shown as number (%) or median (range). APA, atypical polypoid adenomyoma; IVF, In Vitro Fertilization.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective study, we evaluated the efficacy and reproductive outcomes of fertility-sparing treatment in 34 patients with APA, with or without concurrent endometrial hyperplastic lesions. Our findings demonstrate that hormone therapy following hysteroscopic resection is associated with favorable initial response and reproductive outcomes, albeit with a considerable risk of endometrial lesion recurrence.\u003c/p\u003e\u003cp\u003eConsistent with previous reports, APA predominantly affected young premenopausal women in our cohort, with a median age of 31 years. A substantial proportion of patients were nulliparous (70.6%) and nearly one-third had a history of infertility. Notably, over 90% of APA cases were accompanied by EAH or EEC, a rate higher than previously documented (ranging from 9\u0026ndash;59.9%) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This may be attributed to the thorough diagnostic hysteroscopy and systematic histopathological review performed in our institution, underscoring the importance of comprehensive endometrial evaluation in these patients.\u003c/p\u003e\u003cp\u003eFor patients with APA without concurrent endometrial hyperplastic lesions, complete HR of the lesion is considered first-line treatment [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, the role of hormone therapy in the prognostic outcomes of APA, with or without endometrial hyperplasia, remains poorly defined. Some investigators suggested that persistent estrogen stimulation combined with progesterone deficiency may represent key pathological mechanisms in APA development. This was supported by the strong immunohistochemical expression of estrogen receptor and progesterone receptor in the glandular components of APA, indicating a potential therapeutic benefit of hormonal intervention [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAll patients achieved initial CR following hormone therapy, with a median time to CR of 4.5 months. The cumulative CR rate reached 79.4% at 6 months, superior to outcomes reported in studies where adjuvant hormone therapy was not administered [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These results supported the use of hormonal treatment following complete resection to enhance initial therapeutic response.\u003c/p\u003e\u003cp\u003eReported recurrence rates for APA ranged from 28.9\u0026ndash;35.1% [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Multiple studies demonstrated that postoperative progesterone therapy was associated with significantly reduced recurrence and malignant transformation rates compared to no hormonal treatment [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Nomura et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] also indicated that MPA therapy contributed to lower recurrence rates. Similarly, Wang et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] reviewed 86 APA cases and concluded that high-dose progestin therapy following HR may delay or prevent disease recurrence. In our study, no recurrence of APA was observed after a median follow-up of 74 months (range: 18\u0026ndash;191). However, recurrence of endometrial lesions occurred in 41.2% of patients, with nearly 15% showing pathological progression, consistent with recent literature [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Most recurrences (92.9%) were detected within 5 years, highlighting the necessity of long-term surveillance. Younger age (\u0026le;\u0026thinsp;35 years), obesity, infertility, and lesion location in the lower uterine segment or cervix were associated with higher recurrence rates, although these did not reach statistical significance after FDR adjustment.\u003c/p\u003e\u003cp\u003eNotably, patients receiving GnRHa plus letrozole had a lower recurrence rate (25% vs. 55.6%) and a longer disease-free interval compared to those receiving progestin alone. GnRHa induces profound hypoestrogenism and may exert direct anti-proliferative effects on endometrial tissue [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], while letrozole further reduces estrogen synthesis. These mechanisms may synergistically contribute to more effective suppression of endometrial hyperplasia and reduce recurrence risk. Further research is warranted to determine whether GnRHa represents a superior therapeutic option for APA patients with coexisting endometrial lesions.\u003c/p\u003e\u003cp\u003eReproductive outcomes were encouraging: among 19 patients attempting conception, 8 achieved 11 pregnancies, resulting in 8 full-term live births. This suggested that fertility-preserving treatment does not compromise pregnancy potential in appropriately selected patients [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe primary mechanism underlying stromal changes in APA involves metaplasia of normal endometrial stroma into smooth muscle, often exhibiting poorly defined borders at the interface with the myometrium. Although APA does not demonstrate true myometrial invasion histologically, it can be challenging to distinguish from myometrial invasion by endometrial carcinoma on MRI. Furthermore, due to its uncertain malignant potential, APA may complicate fertility-sparing decision-making.\u003c/p\u003e\u003cp\u003eIn our study, one patient presented with MRI findings suggestive of superficial myometrial invasion. However, given strong desire of this patient to preserve fertility and after exclusion of contraindications to conservative management, she underwent GnRHa plus letrozole. After six months of treatment, she achieved CR, and no endometrial lesion recurrence was observed during follow-up. Narumi et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] also reported a case of APA with deep myometrial involvement where complete resection was not achievable via HR. The patient therefore underwent laparoscopic excision of the lesion followed by levonorgestrel-releasing intrauterine system (LNG-IUS) insertion. After six months, the LNG-IUS was removed, and no recurrence was detected during 26 months of follow-up. Therefore, how to establish fertility-preserving strategies for patients with APA complicated by endometrial lesions is an issue that warrants further discussion in the future.\u003c/p\u003e\u003cp\u003eOne limitation of this study is its retrospective design and relatively small sample size, which may limit the statistical power to identify significant risk factors. Moreover, treatment allocation was not randomized, which may introduce selection bias. Prospective studies with larger cohorts are needed to validate our findings and refine treatment strategies.\u003c/p\u003e\u003cp\u003eIn summary, hormone therapy following hysteroscopic resection represents an effective fertility-sparing approach for APA patients, with high initial response rates and promising reproductive outcomes. However, the substantial recurrence risk underscores the need for long-term monitoring. GnRHa-based regimens may offer superior recurrence control compared to progestin-alone therapy and warrant further investigation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003cp\u003eThis study involves human participants and was approved by the Institutional Review Board of Peking Union Medical College Hospital (Approval No. 1-22PJ1091). The requirement for informed consent was waived in accordance with the Declaration of Helsinki.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eProvenance and peer review\u003c/h2\u003e\u003cp\u003e Not commissioned; externally peer reviewed.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work was supported by the National High Level Hospital Clinical Research Funding (Program Nos. 2022-PUMCH-B-082).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eCao DY, Zhou HM, Yu M, and Wang T provided cases and confirmed the completeness and accuracy of the data and analyses, and the final approval of the version to be published. Gan JW have substantially contributed to the design and writing of the manuscript and data collection. Zhang HL contributed to the design and data collection. Cao DY accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish as a guarantor.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets are not publicly available due to privacy reasons but are available from the corresponding author ( [[email protected]](mailto:[email protected]) ) on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMazur MT. 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Hysteroscopic Transcervical Resection for Atypical Polypoid Adenomyoma of the Uterus: A Valid, Fertility-Preserving Option [J]. J Minim Invasive Gynecol. 2018;25(1):163. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jmig.2017.08.659\u003c/span\u003e\u003cspan address=\"10.1016/j.jmig.2017.08.659\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 9.e1.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNarumi R, Takei Y, Morisawa H, Taneichi A, Matsubara S, Fujiwara H. Successful laparotomy tumor resection and levonorgestrel-releasing intrauterine system for atypical polypoid adenomyoma [J]. J Obstet Gynaecol Res. 2019;45(1):230\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jog.13783\u003c/span\u003e\u003cspan address=\"10.1111/jog.13783\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Atypical polypoid adenomyoma, Fertility-sparing, Hormone therapy","lastPublishedDoi":"10.21203/rs.3.rs-7513445/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7513445/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAtypical polypoid adenomyoma (APA) is an uncommon uterine lesion characterized by a potential for recurrence and malignant transformation. Fertility-sparing treatment represents a critical option for patients who wish to preserve reproductive capacity.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIn this retrospective study, we analyzed 34 patients with APA (with or without concurrent endometrial lesions) who underwent hysteroscopic resection (HR) followed by either high-dose progestin or a GnRHa-based regimen (combined with letrozole) between January 2005 and January 2025. Clinicopathological characteristics, treatment outcomes, and reproductive results were evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAll patients diagnosed via HR, with a mean age of 31 years (range: 22\u0026ndash;41). Among them, 31 had coexisting endometrial atypical hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). Eighteen patients (52.9%) were treated with high-dose progestin, and 16 (44.4%) received GnRHa plus letrozole. Complete response (CR) was achieved in all cases, with a median time to CR of 4.5 months (range: 3\u0026ndash;15). The recurrence rate of endometrial lesions was 41.2%, with pathological progression observed in 14.7% of cases. Median disease-free survival was 37.5 months (range: 6\u0026ndash;186), and 92.9% of recurrences occurred within five years. Factors associated with higher recurrence included age below 35 years, obesity, infertility, lesion location in the lower uterine segment and/or cervical canal. Although both the progestin and GnRHa groups showed similar CR rates and time to CR, the recurrence rate was relatively higher in the progestin group (52.6% vs. 26.7%). Uterine preservation was achieved in 31 patients (91.2%) during follow-up. Among 19 patients attempting conception, 11 pregnancies occurred in eight women, resulting in eight full-term live births.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eHormone therapy for APA demonstrates favorable initial response and reproductive outcomes. Given the high prevalence of coexisting endometrial hyperplastic lesions and a tendency for recurrence within 5 years, careful preoperative evaluation via HR and long-term follow-up are strongly recommended. GnRHa-based regimen may offer superior recurrence control compared to progestin therapy, although further studies are warranted to confirm these findings.\u003c/p\u003e","manuscriptTitle":"A Novel GnRH Agonist-Based Regimen for Reducing Recurrence in Fertility-Preserved Atypical Polypoid Adenomyoma: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-18 05:31:27","doi":"10.21203/rs.3.rs-7513445/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-10-29T09:15:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-24T08:52:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"281401909165566627315579140032607013441","date":"2025-10-16T06:32:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"33206187447526045573018353395048163158","date":"2025-10-16T06:19:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-06T08:02:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-09T15:58:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-04T06:28:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-04T06:27:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2025-09-02T04:56:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"33c7c478-59ee-4f22-b845-a8c8129b3b6d","owner":[],"postedDate":"October 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-10-18T05:31:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-18 05:31:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7513445","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7513445","identity":"rs-7513445","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}