Atypical Endometrial Hyperplasia Patients Research Articles

Fertility-sparing treatment for endometrial cancer and atypical endometrial hyperplasia patients with progesterone resistance: A retrospective analysis of 61 cases

Fertility-sparing treatment for endometrial cancer and atypical endometrial hyperplasia patients with progesterone resistance: A retrospective analysis of 61 cases

Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients: a network meta-analysis.

Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89-8.46, p = 0.062; I2 = 71.3%), a higher nausea rate (RR 1.93, 95% CI 1.24-3.01, p = 0.187; I2 = 40.4%) than LNG-IUS in patients with EH. In contrast, LNG-IUS had a irregular vaginal bleeding rates (RR 0.76, 95% CI 0.64-0.90, p = 0.034; I2 = 77.7%) than OP in EH patients. In addition, as for AEH patients, OP has a higher persistence rate (RR 4.31, 95% CI 1.43-13.00, p = 0.93; I2 = 0.0%) than LNG-IUS. According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS.

Outcomes of extended progestin therapy in atypical endometrial hyperplasia patients without an initial response to progestin: a retrospective study from two tertiary centers in Korea and Taiwan.

In this study, we evaluated the role of prolonged progestin treatment on atypical endometrial hyperplasia (AEH) patients who did not achieve complete regression (CR) after at least 3 months of progestin treatment. Possible prognostic factors predicting disease regression and recurrence were also assessed. We retrospectively identified patients who had histologically confirmed persistent disease after at least 3 months of progestin treatment at two tertiary centers in Korea and Taiwan. Clinicopathologic factors and clinical outcomes were obtained from medical records. Logistic regression was used to analyze the relationship between covariates and the probability of CR and relapse. Fifty-two patients were included. Thirty-seven of 52 patients (71.2%) achieved CR after prolonged progestin treatment. Median time from starting progestin treatment to CR was 12.0 months. Daily administration of medroxyprogesterone acetate ≥200 mg or megestrol acetate ≥80 mg was associated with higher probability of regression. Nineteen of 37 patients (51.4%) experienced recurrence, with median time from CR to relapse of 15.0 months. Body mass index ≥27 was associated with higher relapse probability. Twelve of 16 patients with disease progression to endometrial carcinoma underwent surgery. The 12 cases had stage I tumors and lived without disease. Extension of progestin treatment course is feasible for AEH patients without an initial response to progestin. Higher daily progestin dosage was associated with higher probability of CR, and obesity was associated with higher risk of relapse. The patients without an initial response to progestins and whose AEH progressed to endometrial carcinoma had good prognoses.

Fertility-sparing re-treatment for endometrial cancer and atypical endometrial hyperplasia patients with progestin-resistance: a retrospective analysis of 61 cases

ObjectiveThis study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility.MethodsOur study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3–4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy.ResultsOverall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages.ConclusionGnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.

Impacts of ovarian reserve on conservative treatment for endometrial cancer and atypical hyperplasia.

Real-world data indicated that some endometrial atypical hyperplasia (EAH) and early endometrial carcinoma (EEC) patients of fertility preservation had a normal ovarian reserve, while some had a decreased ovarian reserve (DOR). This study was designed to investigate the effect of baseline ovarian reserve on the treatment of EAH and EEC patients who ask for preservation of fertility. This was a prospective cohort study conducted at a single university-affiliated fertility center. A total of 102 EAH and EEC patients who received fertility-preserving treatment between March 2019 and August 2020 were included and divided into a DOR group (n=22) and a non-DOR group (n=80). The 32-week CR rate of the non-DOR group was significantly higher than that of the DOR group (60.3% vs. 33.3%, P =0.028). The DOR group had a longer treatment duration to achieve CR than the non-DOR group (40.07 vs. 29.71 weeks, P=0.008, HR: 0.54, 95% CI: 0.36-0.86). Multivariate logistic regression analyses demonstrated that DOR (OR: 0.35, 95% CI: 0.13-0.99, P=0.049) and BMI ≥25 kg/m2 (OR: 0.40, 95% CI: 0.17-0.92, P=0.031) were negatively associated with 32-week CR. Decreased baseline ovarian reserve is negatively correlated with the efficacy of fertility-preserving treatment in EAH and EEC patients, as this group has a lower CR rate and a longer treatment duration to achieve CR than those without DOR.

Oncologic, fertility, and obstetric outcomes with MPA therapy in women with endometrial cancer and atypical endometrial hyperplasia.

Medroxyprogesterone acetate (MPA) is one of the treatments of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) to preserve the fertility. Efficacy of MPA therapy and fertility and obstetric outcomes after remission were evaluated in EC or AEH patients. Among patients diagnosed with EC or AEH at Tokushima University Hospital between January 2002 and October 2020, we retrospectively analyzed patients, ages range from 26 to 40, who underwent conservative management using MPA (400-600 mg/day). In total, 19 patients underwent MPA therapy. The 18 (94%) patients achieved complete response (CR), and 1 (5%) patient achieved partial response (PR). Relapse occurred in 6 (32%) patients who had achieved CR. Of the patients who relapsed, 4 patients resumed MPA therapy and were in remission. Among 19 patients, 13 patients attempted pregnancy after CR. All of them underwent ovulation induction or assisted reproductive technology. As a result, 20 pregnancies in 10 (77%) patients and 12 live births in 9 (69%) patients were achieved. Rate of spontaneous abortion was 35% (7/20). MPA therapy can produce a high remission rate, and be considered an effective treatment for patients who wish fertility preservation. Around 70% patients who attempt to pregnancy can have at least one baby by infertility treatments. Because recurrence rate after MPA therapy is high, it may be desirable to aim for early pregnancy by active intervention.

Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

Serum lipidomic profiling by UHPLC-MS/MS may be able to detect early-stage endometrial cancer.

Nowadays, screening for endometrial cancer (EC) primarily relies on clinical symptoms and imaging, which makes it difficult to detect early-stage disease. Here, we conducted a widely targeted lipidomic analysis of 38 human serum samples in a discovery set and 40 human serum samples in a validation set to profile the dysregulated lipid species and establish lipid biomarkers for early-stage EC. This comprehensive lipidomic determination of 616 serum lipids indicated significant differences between early-stage EC patients and healthy controls. Three phases of lipid biomarker investigation (discovery, validation, and determination of the lipid biomarker panel) were performed, which revealed the upregulation of some sphingolipid, glycerophospholipid, and glycerolipids and downregulation of some carnitine. Consistently, the perturbation of sphingolipid and glycerophospholipid metabolism was also observed from pathway enrichment analysis. Moreover, a lipid biomarker panel, including ursodeoxycholic acid, PC(O-14:0_20:4), and Cer(d18:1/18:0), was established. This panel was assessed as an effective diagnostic model to distinguish early-stage EC patients from healthy controls and atypical endometrial hyperplasia patients within the area under the receiver operating characteristic curve (AUC) reaching 0.903 and 0.928, respectively. In particular, the comparison results of the diagnostic efficacy indicated that the lipid biomarker panel was superior to clinically established indicators for EC diagnosis, including HE4, CA125, CA153, and CA199, suggesting that it could be used as an excellent supplementary method for the diagnosis of early-stage EC. In conclusion, we established a novel and non-invasive lipid biomarker for early-stage EC detection and these findings may provide new insight into the pathological mechanisms of EC.

Significance of molecular classification in fertility-sparing treatment of endometrial carcinoma and atypical endometrial hyperplasia

Objective: To investigate the molecular classification of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) treated with fertility-sparing therapy, and to analyze its relationship with clinicopathological factors and treatment efficacy. Methods: A total of 46 EC and AEH patients who received fertility-sparing therapy and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2021, were retrospectively collected. The relationships between molecular classification and clinicopathological factors and treatment outcomes were analyzed. Results: (1) Of the 46 patients, including 40 EC and 6 AEH patients, 32 cases (71%, 32/45) had complete response (CR) after treatment, with median CR time of 8 months, 6 cases (13%, 6/45) had partial response, and 8 cases (25%, 8/32) had recurrence. (2) The cases were distributed as no specific molecular profile (NSMP) 34 cases (74%, 34/46) subtype mainly, high microsatellite instability (MSI-H) 7 cases (15%, 7/46), POLE ultra-mutated 3 cases (7%, 3/46), and copy number high (CNH) 2 cases (4%, 2/46). Patients with CNH had the hightest serum cancer antigen 125 (CA125) level [(34.3±35.2) kU/L]. MSI-H subtype had more family history of tumors (6/7), more with loss of mismatch repair (MMR) protein expression by immunohistochemical (7/7), and higher nuclear antigen associated with cell proliferation (Ki-67) expression level (3/3). (3) Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6; P=0.019), and survival analysis showed that they were less likely to achieve CR than those with NSMP subtype (P=0.022). Subgroup analysis of patients with NSMP showed that age ≥30 years related with longer treatment time to CR (P=0.010). In addition, CR was obtained after treatment in 2/3 POLE ultra-mutated cases and 2/2 CNH, respectively. Conclusions: Molecular classification relates with the treatment response in patients with EC and AEH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy, and patients with NSMP need to be further studied and predict treatment benefit. However, there are few cases in POLE ultra-mutated and CNH subtypes, which need further clinical research.

Comparatively analyzed quality of life in patients with atypical endometrial hyperplasia and endometrial cancer during various rehabilitation activities

Introduction. Radical surgery for recurrent atypical endometrial hyperplasia (AEH) allows to fully assess pathological changes of the endometrium, a risk of concomitant cancer, and provides insight into proposing a definitive therapy. However, after ovariohysterectomy, young women develop postovariectomy syndrome (POES) and psychosexual disorders profoundly decreasing quality of life (QoL) that requires rehabilitation measures.Aim: to conduct a comparative analysis of QoL in patients with recurrent AEH after hysterectomy with bilateral salpingooophorectomy based on the management tactics in the rehabilitation period.Materials and Methods. In the second part of the prospective randomized comparative study, 58 women diagnosed with recurrent AEH (mean patient age 44.25 ± 3.40 years) underwent a one-year-follow-up, divided into 2 groups according to the management tactics in the rehabilitation period: group 1 – 27 patients with "active" rehabilitation according to the complex rehabilitation and therapeutic protocol proposed by our research group; group 2 – 31 patients with "passive" rehabilitation. To assess the overall QoL, a questionnaire the Functional Assessment of Cancer Therapy for Patients with Endometrial Cancer (FACT-En) was used, analyzing a level of anxiety and depressive disorders with the Hospital Anxiety and Depression Scale (HADS) as well as manifestations of surgical menopause using Kupperman–Uvarova modified menopausal index (MMI) and sexual function – with the Female Sexual Function Index (FSFI) on day 3–7 as well as 3, 6, 12 months after surgical treatment.Results. It was found that inter-group difference was significant in the FACT-En questionnaire observed as early as by 3 months of the study, whereas by 12 months the QoL score in the "active" rehabilitation group increased by 39.36 points based on the FACT-En questionnaire, but only by 17.38 points in the "passive" rehabilitation cohort (p &lt; 0.001). Analyzing Kupperman–Uvarova MMI, the degree of manifested surgical menopause decreased over time in both groups. However, as early as 6 and 12 months after onset, “active” rehabilitation was featured with surgical menopause parameters corresponding to a mild course, whereas “passive” rehabilitation was associated with moderate severity (p &lt; 0.001). Over the entire follow-up period, "active" rehabilitation group was shown to have anxiety parameters decreased from 10.77 ± 2.36 score (subclinical anxiety) to 4.55 ± 1.50 score (normal range), whereas at 6 and 12 months of follow-up the "passive" rehabilitation group was found to have anxiety parameters corresponding to subclinical manifestations. Over time, sexual function improved in both groups, however, the parameters in the "active" vs. "passive" rehabilitation group were significantly higher as early as 3 months after the onset, with similar pattern observed at 6 and 12 months (p &lt; 0.05).Conclusion. The set of rehabilitation measures proposed by us improves psycho-emotional state, corrects POES manifestations, improves sexual function of AEH patients, thereby increasing overall QoL. This is comparable to the results of medical rehabilitation of women after radical treatment with endometrial cancer.

Identification of potential models for predicting progestin insensitivity in patients with endometrial atypical hyperplasia and endometrioid endometrial cancer based on ATAC-Seq and RNA-Seq integrated analysis.

Objective: The aim of this study was to establish predictive models based on the molecular profiles of endometrial lesions, which might help identify progestin-insensitive endometrial atypical hyperplasia (EAH) or endometrioid endometrial cancer (EEC) patients before progestin-based fertility-preserving treatment initiation. Methods: Endometrial lesions from progestin-sensitive (PS, n = 7) and progestin-insensitive (PIS, n = 7) patients were prospectively collected before progestin treatment and then analyzed by ATAC-Seq and RNA-Seq. Potential chromatin accessibility and expression profiles were compared between the PS and PIS groups. Candidate genes were identified by bioinformatics analyses and literature review. Then expanded samples (n = 35) were used for validating bioinformatics data and conducting model establishment. Results: ATAC-Seq and RNA-Seq data were separately analyzed and then integrated for the subsequent research. A total of 230 overlapping differentially expressed genes were acquired from ATAC-Seq and RNA-Seq integrated analysis. Further, based on GO analysis, REACTOME pathways, transcription factor prediction, motif enrichment, Cytoscape analysis and literature review, 25 candidate genes potentially associated with progestin insensitivity were identified. Finally, expanded samples were used for data verification, and based on these data, three predictive models comprising 9 genes (FOXO1, IRS2, PDGFC, DIO2, SOX9, BCL11A, APOE, FYN, and KLF4) were established with an overall predictive accuracy above 90%. Conclusion: This study provided potential predictive models that might help identify progestin-insensitive EAH and EEC patients before fertility-preserving treatment.

Nodal Assessment in Endometrial Atypical Hyperplasia

Objective: Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25–50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging. Methods: Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases. Design: This was a retrospective study. Results: Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (p = 0.01), hypertension (p < 0.01), and endometrial thickness ≥20 mm (p = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29–6.48) in AUB, 2.7 (95% CI: 1.06–6.92) in hypertension, and 3.1 (95% CI: 1.19–7.97) in endometrial thickness ≥20 mm cases. Limitations: The present study has limitations inherent in its retrospective nature. Conclusion: The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested.

Efficacy and pregnancy outcomes of hysteroscopic surgery combined with progestin as fertility-sparing therapy in patients with early stage endometrial cancer and atypical hyperplasia.

This study aims to evaluate the efficacy of hysteroscopic curettage combined with progestin therapy in young patients with early-stage endometrial cancer (EC) and endometrial atypical hyperplasia (EAH) who wished to preserve their fertility. This prospective cohort study included 16 patients with early-stage EC and 25 patients with EAH in Dalian Maternal and Child Health Hospital from August 2014 to October 2018. All patients received fertility-sparing therapy with hysteroscopic evaluation every 3months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed. There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91months. BMI ≤ 30kg/m2 was associated with shorter treatment duration to achieve CR (P = 0.003). Among the patients who attempted to conceive, 30.3% (10/33) had successful pregnancy, and 18.2% (6/33) delivered live births. The implementation of assisted reproductive technology (ART) is closely associated with pregnancy (P = 0.001). The fertility-sparing therapy, hysteroscopic curettage combined with progestin therapy, of early young EC and EAH patients is safe and effective. BMI is the main factor affecting the duration of CR. After achieving CR, ART can significantly improve the pregnancy rate of these patients.

Fertility-Sparing Treatment for Endometrial Cancer or Atypical Endometrial Hyperplasia Patients With Obesity.

ObjectiveTo evaluate the efficacy and prognosis of fertility-sparing treatment on endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) patients with BMI ≥ 30 kg/m2.MethodsA total of 102 EC or AEH patients with obesity who received fertility-preserving therapy in the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital were included in our study. All patients were followed up regularly. Clinical characteristics, treatment outcomes, adverse events, and reproductive outcomes were collected and analyzed.ResultsA total of 88 (86.3%) patients achieved complete response (CR), 92.5% in AEH and 82.3% in EC, with 6 months (3–12 months) median CR time. High remission rates were found in patients who received gonadotropin-releasing hormone agonist (GnRHa)-based regimen, were younger than 35 years old, and lost more than 10% of their weight. Fifteen (17.0%) women had developed recurrence with a median recurrence time of 26 (8–52) months. Patients who received GnRHa regimen, lost more than 10% weight, received maintenance therapy, or conceived during the follow-up period had a low probability of recurrence. Of the patients with CR, 57 women attempted to get pregnant and 16 (28.1%) patients became pregnant, 7 (12.3%) of them successfully delivered and 4 (7.0%) were in pregnancy, while 5 (8.8%) of them miscarried.ConclusionFor obese patients with EC and AEH, fertility-preserving treatment can still achieve a promising response. Weight loss of more than 10% has a positive influence on response, recurrence, as well as pregnancy rates. GnRHa could be an option for obese women due to less effect on weight gain compared to progestin therapy.

Management of Recurrent Endometrial Cancer or Atypical Endometrial Hyperplasia Patients After Primary Fertility-Sparing Therapy.

ObjectiveTo evaluate the efficacy and prognosis of fertility-sparing re-treatment on patients with recurrent endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) who wish to preserve their uterus after complete remission (CR) for primary conservative therapy.MethodsWe performed a retrospective study on recurrent EC or AEH patients who received fertility-sparing re-treatment after achieving CR. Data regarding clinicopathological factors, adverse events, treatment efficacy, tumor prognosis, and reproductive outcome were analyzed.ResultsOf the 98 recurrent patients with a median disease-free interval period of 19 (3–96) months, 18 patients decided to receive hysterectomy directly, and 80 patients received fertility-preserving re-treatment. Seventy-one (88.6%) cases achieved CR, 96.0% in AEH and 75.8% in EC patients, with the 6 (3–16) months’ median CR time. Seven (8.8%) patients failed to achieve CR and then underwent the hysterectomy: one partial response (PR), four stable disease (SD), and two progressive disease (PD). Forty-nine women attempted to get pregnant after CR, 13 (26.5%) became pregnant, seven (14.3%) successfully delivered, and six (12.2%) miscarried. During the follow-up period, 22 (31.0%) women had developed a second relapse with the median recurrence time of 12 (4–90) months, and 10 patients decided to receive the third round of fertility-sparing treatment. Seven (70.0%) patients, 33.3% in EC and 85.7% in AEH, achieved CR again. Hysterectomy was performed in two (20.0%) patients due to SD. After the third-round treatment, six women had the desire to conceive but no one became pregnant successfully.ConclusionFor patients with recurrent EC and AEH after primary conservative treatment, fertility-preserving re-treatment can still achieve a promising response, and patients have possibilities of completing childbirth.

PPOS Protocol Effectively Improves the IVF Outcome Without Increasing the Recurrence Rate in Early Endometrioid Endometrial Cancer and Atypical Endometrial Hyperplasia Patients After Fertility Preserving Treatment.

Objective: To investigate the effectiveness and recurrence risk of different ovulation stimulation protocols in early-stage endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients after successful fertility preserving treatment.Design: A retrospective review of clinical files between June 2012 and July 2018.Setting: University hospital.Patients: Ninety seven women (74 AEH and 23 early-stage EEC patients) underwent in vitro fertilization (IVF) and frozen-thawed embryo transfer (FET) after successful fertility preserving treatment. All patients received megestrol acetate which was initiated immediately after AEH or EEC diagnosis by hysteroscopy. Fertility treatment was initiated after confirmation of complete response by two consecutive hysteroscopic evaluations and endometrium biopsy in a 3-month interval. Women with tubal factors underwent IVF treatment directly. Women who failed to conceive spontaneously within 12 months or after other infertility treatments like ovulation induction for 6 consecutive months or 2 consecutive artificial insemination failures were also offered IVF treatment.Main Outcome Measure (s): The clinical and laboratory embryo data, clinical pregnancy outcomes and endometrial disease recurrence rates.Results: Compared with the standard regimen group, the good-quality embryo rate was higher in progestin primed ovarian stimulation (PPOS) regimen group (P = 0.034). Univariate analysis showed significant differences in age (P = 0.033), treatment time of endometrial lesions (P < 0.001), and duration of Gn treatment (P = 0.018) between the recurrent and non-recurrent groups. In the adjusted model of multivariate logistic regression analysis, the age (P = 0.014) at ovulation induction and treatment time of endometrial lesions (P < 0.001) were significantly correlated with the recurrence of endometrial disease.Conclusions: The PPOS protocol is a feasible and safe strategy to stimulate ovulation during IVF after fertility preservation therapy, and the age at ovulation induction and treatment time of endometrial lesions are two stable predictors of recurrence in endometrial diseases.

Significance of serum and pathological biomarkers in fertility-sparing treatment for endometrial cancer or atypical hyperplasia: a retrospective cohort study

BackgroundThis study analyzed the changes of serum and pathological biomarkers during fertility-sparing therapy of endometrial cancer (EC) or endometrial atypical hyperplasia (EAH), to investigate their implications for early prediction of treatment efficacy.MethodsA retrospective analysis of EC or EAH patients who received fertility-sparing therapy between 2012 and 2016 was performed. Serum and endometrium sampling were obtained for each patient at three time points: at baseline, at 3–6 months' treatment and at the end of conservative treatment. Serum biomarkers including insulin resistance (HbA1c, HOMA-IR), sex hormones and thyroid hormones were measured. Meanwhile expression of endometrial pathological biomarkers including ER, PR, PRB and Ki-67 was also assessed by immunohistochemistry.ResultsFor the 53 recruited patients, overall complete response, recurrence and pregnancy rates were 94%, 26% and 36.4%. During the treatment, the serum biomarkers of HOMA-IR remained stable, while pathological markers including PR, PRB and Ki67 diminished significantly. Patients who achieved remission faster had significant lower HOMA-IR level and higher PRB expression at baseline. We also found a more remarkable down-regulation of PRB related with faster remission. Further multivariate analysis confirmed that baseline HOMA-IR ≥ 2.5 negatively affected treatment time to remission (OR 0.206; p = 0.017). While marked reduction of PRB (≥ 30%) at 3–6 months' treatment correlated with faster remission (OR 5.788; p = 0.010).ConclusionFor EC and EAH patients who received fertility-sparing therapy, baseline status of insulin resistance predicted poor response to progestin, while marked reduction of PRB following the initial 3–6 months' treatment predicted fast remission.

Characteristics of progestin-insensitive early stage endometrial cancer and atypical hyperplasia patients receiving second-line fertility-sparing treatment.

ObjectiveThis study investigated the characteristics of progestin-insensitive endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients receiving fertility-sparing treatments and assessed the therapeutic effects of second-line fertility-preserving treatments.MethodsThree hundred and thirty-eight patients with EEC (n=75) or AEH (n=263) receiving fertility-preserving treatment were retrospectively analyzed. ‘Progestin-insensitive’ was defined as meeting one of the following criteria: 1) presented with progressed disease at any time during conservative treatment, 2) remained with stable disease after 7 months of treatment, and/or 3) did not achieve complete response (CR) after 10 months of treatment. Clinical characteristics and treatment results of progestin-insensitive patients receiving second-line treatment and those of progestin-sensitive patients were compared.ResultsEight-two patients (59 AEH and 23 EEC) were defined as progestin-insensitive and 256 as progestin-sensitive. In multivariate analysis, body mass index ≥28.0 kg/m2 (odds ratio [OR]=1.898) and lesion size >2 cm (OR=2.077) were independent predictors of progestin-insensitive status. Compared to AEH patients, progestin-insensitive EEC patients had poorer second-line treatment responses (28-week cumulative CR rate after changing second-line treatment, 56.3% vs. 85.4%, p=0.011). No statistical difference was found in CR rate among different second-line treatments.ConclusionObesity and larger lesion size were independent risk factors associated with progestin-insensitive status. In progestin-insensitive patients receiving second-line treatment, EEC patients had lower CR rate comparing with AEH patients. Further study with larger sample size is needed to evaluate efficacy of different second-line treatments for progestin insensitive patients.

Clinical features and outcome of 15 patients with recurrent endometrial cancer or atypical endometrial hyperplasia received primary fertility-sparing therapy followed by hysterectomy

ObjectiveTo investigate the clinical features and outcome of recurrent endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) patients who underwent hysterectomy after fertility-sparing therapy. MethodsClinical data was retrospectively collected for 15 recurrent endometrial cancer or atypical endometrial hyperplasia patients who underwent hysterectomy in six hospitals from 2003 to 2019. According to the indicators of hysterectomy, patients were divided into four groups: 7 patients who underwent direct hyesterectomy after the first relapse, 4 due to re-treatment failure, 1 after full term live birth, and 3 because of multiple recurrence. Clinical coexisting conditions, regimen and outcome of fertility-sparing therapy, pre- and post-operative pathological results, and prognosis were analyzed. Results(1) Fertility-spraring treatment was given to a total of 15 eligible patients, including 6 with EC and 9 with AEH. Median time interval from remission to recurrence was 12 months (range 3–92). Oral progestin-based medicine was the main fertility-sparing therapy in both primary treatment and re-treatment after recurrence. Six (6/8) patients received progestin combined with gonadotrophin releasing hormone agonist or metformin in three re-treatment groups. (2) Nine patients underwent hysterectomy and 6 staging surgery. Three patients had pathological upgrade after surgery. Five (5/10) EC patients had superficial myometrial invasion in postoperative pathology. All patients showed no evidence of disease in the median follow-up of 17 months (range 3–118). (3) Among seven patients who failed to re-treatment and had multiple recurrence, six were overweight/obesity and six had insulin resistance. Two of these patients had synchronous ovarian cancer in the postoperative pathology. ConclusionFor the patients with recurrent EC or AEH after primary fertility-sparing therapy, overweight/obesity and insulin resistance might be the risk factors for re-treatment failure. Hysterectomy is recommended when patients had re-treatment failure or multiple recurrence; and generally the prognosis is favorable.

Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial.

To assess the efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC). A randomised, single-centre, open-label, controlled trial conducted between October 2013 and December 2017. Shanghai OBGYN Hospital of Fudan University, China. A total of 150 patients (18-45years old) with primary AEH or well-differentiated EEC were randomised into an MA group (n=74) and an MA plus metformin group (n=76). Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160mg orally, daily) or MA (160mg orally, daily) plus metformin (500mg orally, three times a day). The primary efficacy parameter was the cumulate complete response (CR) rate within 16weeks of treatment (16w-CR rate); the secondary efficacy parameters were 30w-CR rate and adverse events. The 16w-CR rate was higher in the metformin plus MA group than in the MA-only group (34.3 versus 20.7%, odds ratio [OR]2.0, 95% confidence interval [CI]0.89-4.51, P=0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR2.56, 95% CI 1.06-6.21, P=0.04). This effect of metformin was also significant in non-obese (51.4 versus 24.3%, OR3.28, 95% CI1.22-8.84, P=0.02) and insulin-sensitive (54.8 versus 28.6%, OR3.04, 95% CI1.03-8.97, P=0.04) subgroups of AEH women. No significant result was found in secondary endpoints. As a fertility-sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients. For AEH patients, metformin plus MA might be a better fertility-sparing treatment to achieve a higher early CR rate compared with MA alone.