Prognosis of patients with endometrial cancer or atypical endometrial hyperplasia after complete remission with fertility-sparing therapy.

PURPOSE: Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR. METHODS: We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy. RESULTS: The median follow-up duration was 34 months (range: 1-179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities. CONCLUSIONS: We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children.

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

PURPOSE: 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. METHODS: 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 3 months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed. RESULTS: There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91 months. BMI ≤ 30 kg/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). CONCLUSION: 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.

Analysis of pregnancy-associated factors after fertility-sparing therapy in young women with early stage endometrial cancer or atypical endometrial hyperplasia.

BACKGROUND: Fertility-sparing therapy is an alternative conservative treatment for patients with early stage endometrioid cancer or atypical endometrial hyperplasia. In this study, we investigated pregnancy outcomes and pregnancy-associated factors in young patients receiving hormonal therapy. METHODS: We retrospectively analyzed 68 patients who attempted to conceive after fertility-sparing therapy and achieving complete remission (CR). They were divided into a pregnancy group and a non-pregnancy group. A Cox proportional hazard regression model was applied for univariate and multivariate analysis to determine factors associated with pregnancy. Kaplan-Meier analysis, combined with the log-rank test, was used to calculate a patient's pregnancy probability and the distribution of recurrence-free survival (RFS). RESULTS: A total of 36 patients became pregnant with 47 pregnancies. Univariate and multivariate Cox analysis revealed that several factors were associated with pregnancy, including BMI at the time of pregnancy permission, the time to CR, prolonged treatment time, the number of hysteroscopy procedures, the endometrium thickness after CR, and relapse before pregnancy. The mean RFS of patients who achieved pregnancy, and those who did not, was 27.6 months and 14.8 months, respectively (P = 0.002). No significant difference was detected in terms of cumulative RFS when compared between assisted reproductive technology (ART) cases and those involving natural conception (NC) (P = 0.707). CONCLUSIONS: Normal BMI, a shorter time to CR, a prolonged three-month treatment, fewer hysteroscopy procedures, and a thicker endometrium may be positive indicators for successful pregnancies, while relapse before pregnancy may have a negative effect on conception. Moreover, a successful pregnancy protects the endometrium while ART does not increase the risk of recurrence.

Efficacy of medroxyprogesterone acetate treatment and retreatment for atypical endometrial hyperplasia and endometrial cancer.

AIM: Medroxyprogesterone acetate (MPA) is used to preserve fertility in patients with Grade 1 endometrial cancer without myometrial invasion (G1EA) and those with atypical endometrial hyperplasia (AEH). However, the efficacy of retreatment with MPA has not been sufficiently established for patients who experience recurrence but wish to retain their fertility. This study aimed to show the effectiveness of MPA treatment and retreatment for AEH and G1EA. METHODS: A total of 39 patients received MPA treatment between 2005 and 2015, including nine with G1EA and 30 with AEH. The patients received high-dose (600 mg/day) MPA for 26 weeks. If a complete response was not achieved, MPA treatment was continued. After complete remission, if there was a recurrence, the patient was offered a choice of a hysterectomy or retreatment with MPA. The gynecologic and obstetric outcomes were retrospectively analyzed. RESULTS: The median age was 34 years, and the median body mass index was 23.3 kg/m2 . The median follow-up period was 52 months. Complete response rates for the initial treatment were 89% for G1EA and 93% for AEH. Recurrence occurred in 88% of patients with G1EA (7/8) and 50% of those with AEH (14/28). Seven patients with G1EA and 11 with AEH received MPA retreatment, and 100% and 92% of these achieved a complete response. During the study period, a total of 14 pregnancies were recorded with 10 live births. CONCLUSION: MPA can be effective for G1EA and AEH treatment even when they recur.

Curative Polyendocrine Therapy in a 21-year-Old Patient with Endometrial Carcinoma: Case Report and Review of the Literature.

INTRODUCTION: As the numbers of young patients diagnosed with early-stage endometrial carcinoma continue to rise, the question regarding fertility-preserving therapeutic options will increasingly gain significance in the future. CASE PRESENTATION: Here, we present the case of a 21-year-old patient diagnosed with symptomatic atypical endometrial hyperplasia. After 4 months of treatment with medroxyprogesterone acetate, a follow-up dilatation and curettage revealed early-stage, well-differentiated endometrioid endometrial carcinoma. Despite national guidelines recommending hysterectomy, the nulliparous patient expressed a desire to preserve her fertility. Subsequently, she underwent polyendocrine therapy with letrozole, everolimus, metformin, and Zoladex. Forty-three months after diagnosis, the patient successfully gave birth to a healthy child, and there have been no indications of recurrence thus far. DISCUSSION: This case suggests that triple endocrine therapy may be an option for selected patients with early endometrial cancer and a desire for fertility-sparing therapy.

Contemporary Fertility-Sparing Management Options of Early Stage Endometrioid Endometrial Cancer in Young Nulliparous Patients.

Incidence of endometrial cancer (EC) has been increasing in recent years, especially in high-income countries. The disease commonly affects peri- and postmenopausal women; however, about 5% of women are diagnosed with EC in their reproductive age. Due to both the increasing incidence of EC among reproductive age women and trends to delayed childbearing, fertility-sparing treatment for young patients with EC has become extremely important for researchers and practitioners. Because the classic treatment with total hysterectomy and bilateral saplingo-oophorectomy is not an appropriate approach for young women demanding fertility preservation, several fertility-sparing options have been developed and summarized in this review. Utilization of different medications and their combination (progestagens, gonadotropin releasing hormones analogues, and metformin in different formulations) are tested and found as efficient for fertility-sparing treatment. New minimally invasive surgical techniques, combined with progestagens, are also confirmed as valuable. There are many novel conservative and surgical treatment approaches under investigation. Assuming that molecular biomarkers can be both diagnostic and prognostic to assist in prediction of response to a certain therapy, prognostic risk groups' stratification along with specific biomarkers' identification will ensure low recurrence and decrease mortality rates in young women with EC.

Weight Loss Improves Pregnancy and Livebirth Outcomes in Young Women with Early-Stage Endometrial Cancer and Atypical Hyperplasia.

PURPOSE: To evaluate the effects of body weight loss on reproductive outcomes in young women with early-stage endometrial cancer (EC) and atypical hyperplasia (AH) who underwent fertility-sparing therapy. PATIENTS AND METHODS: Patients with well-differentiated EC (n=8, FIGO stage Ia) and AH (n=36) who achieved complete regression after fertility-sparing therapy were retrospectively reviewed. Patients were divided into a weight loss group (n=25) and a non-weight loss group (n=19). Subgroup analysis according to body mass index and relative weight loss were performed to investigate the effect of weight loss on pregnancy and live birth outcomes. Univariate and multivariate logistic regression analyses were undertaken to determine pregnancy-associated factors. RESULTS: Mean body weight and body mass index at pre-progestin treatment and at fertility treatment initiation were 70.63±12.03 and 67.08±8.18 kg, respectively, 27.06±4.44 and 25.73±3.15 kg/m2, respectively. Twenty-five patients (56.82%) lost weight, the median absolute weight loss was 5.00 kg (1.00-34.50), and the median relative weight loss was 6.70% (1.00-36.00%) over a median of 12 months (5.00-97.00). A favorable pregnancy rate (65.91%) and live birth rate (50.00%) were achieved. The pregnancy and live birth rates were meaningfully higher in the weight loss group than in the non-weight loss group (88.00% vs 36.84%, P=0.000; 64.00% vs 31.58%, P=0.033); weight loss ≥5% significantly increased pregnancy and live birth rate in patients with BMI ≥25 kg/m2. The risk ratio of weight loss ≥5% in multivariate logistic analysis for pregnancy was 10.448 (1.102, 99.056, P=0.041). CONCLUSION: Weight loss could positively affect pregnancy rate and improve live birth rate in overweight and obese women with early-stage EC and AH during/after fertility-sparing therapy. Weight loss ≥5% increased pregnancy and livebirth rates significantly in overweight and obese women.

Comparison among fertility-sparing therapies for well differentiated early-stage endometrial carcinoma and complex atypical hyperplasia.

OBJECTIVE: To compare fertility-sparing therapies including oral progestogens, hysteroscopic resection (HR), and the levonorgestrel- releasing intrauterine system (LNG-IUS) in achieving disease regression, recurrence and live birth rate in well differentiate early-stage endometrial carcinoma (eEC) and complex atypical hyperplasia(CAH). STUDY DESIGN: This was a meta-analysis of previous studies focus on the fertility-sparing therapy for well differentiate early-stage endometrial carcinoma (eEC) and complex atypical hyperplasia (CAH). DATE SOURCES: Medline, the Cochrane Library and Embase was searched with the terms and Synonyms: words similar to eEC and CAH with therapies associated with fertility-sparing. MAIN OUTCOME MEASURES: The number of all patients accepted fertility sparing therapies, patients got regressed, relapsed and delivered were extracted from each study, and the regression, recurrence, and live birth rate of each study were calculated. The regression, recurrence and live birth rates between each two interventions were compared with the aid of meta-regression in packages of "meta" and "meta for" written in R. RESULTS: Fifty-four studies reported fertility sparing therapies in young women with eEC and CAH were included. Meta-analysis showed that HR followed by progestogens achieved a higher pooled regression (98.06% vs 77.20% P < 0.0001) and live birth rate (52.57% vs 33.38%, P = 0.0944) and a lower recurrence rate compared with oral progestogens alone (4.79% vs 32.17% P = 0.0004). At the same time, the pooled live birth rate (52.57% vs 18.09% P =0.0399) of HR followed by progestogens are significantly higher than the LNG-IUS alone. Which no statistical difference in regression (98.06% vs 94.24%; P = 0.4098) and recurrence rates (4.79% vs 3.90% P = 0.8561) was seen. CONCLUSIONS: Of the available fertility-sparing therapeutic options, HR followed by progestogens may be a more effective one.