Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Fertility-sparing surgeries without adjuvant therapy through term pregnancies in a patient with low-grade endometrial stromal sarcoma:A case report

BACKGROUND Low-grade endometrial stromal sarcoma(LGESS)is a rare indolent tumor with a favorable prognosis.With the importance of improving quality of life recognized,fertility-sparing surgery may be an option for those young women.However,most of the reports suggested that stage IA patients might be candidates for fertility-sparing surgery,and adjuvant hormonal treatment was considered a feasible adjuvant therapy for reducing the recurrence risk of patients with LGESS and hysterectomy was recommended after the completion of pregnancy and delivery.CASE SUMMARY A 28-year-old pregnant woman diagnosed with stage IB LGESS was treated by fertility-sparing surgery when term cesarean section delivery was performed.Without any adjuvant treatment,she had the other successful term pregnancy and cesarean section 45 mo after first fertility-sparing surgery.Moreover,only hysteroscopic resection was performed to retain fertility again even when the tumor recurred after 6 years.So far the patient’s fertility and disease-free status have remained for more than 8 years without any adjuvant therapy despite local resection of the sarcoma.And the two babies were in good health.CONCLUSION For young patients with stage I LGESS,it seems that repeated fertility-sparing surgeries could be performed even after two term deliveries and the tumor recurrence,and it might be attempted without adjuvant therapy but the counseling should be considered as mandatory.

Postrecurrence Clinical Outcome of Patients with Stage I Epithelial Ovarian Cancer Who Underwent Fertility-Sparing Surgery Compared to Those with Radical Surgery

Background: To examine the difference in the survival of patients with recurrent ovarian cancer who received fertility-sparing surgery (FSS) and those receiving radical surgery. Methods: Clinicopathologic data on a total of 90 patients with stage I recurrent ovarian cancer collected under the central pathological review system were subjected to survival analyses. Patients were divided into 2 groups: 1) FSS (N = 11), 2) Radical (N = 79). Results: Five-year overall survival rates of patients in the two groups were as follows: 40.8% (FSS)/44.2% (Radical), respectively. There was no significant difference in overall survival among the groups (P = 0.887). Additionally, three-year postrecurrence survival rates of patients in the two groups were 24.8% (FSS) and 25.3% (Radical) (P = 0.730). Furthermore, we accumulated 137 patients {FSS (N = 58), Radical group (N = 79)} with stage I recurrent ovarian cancer from the current study and six representative reports in the literature. Patients who experienced recurrence in the remaining ovary alone (FSS) showed a more favorable prognosis than those who had extra-ovarian site recurrence (overall survival: P = 0.021, postrecurrence survival: P = 0.069). Conclusions: Although our retrospective analysis was very preliminary, we could propose the hypothesis that patients with stage I recurrent ovarian cancer who undergo FSS may not show poorer survival rates than patients who receive radical surgery.

Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

Objective:To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC).Methods:A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions.Results:Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months.As histologic grade increased,overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined.Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS.Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group.Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups.Conclusions:Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients.The surgical procedure and surgical route might not significantly influence the prognosis.Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

Characteristics of molecular classification in 52 endometrial cancer and atypical hyperplasia patients receiving fertility-sparing treatment

Objective To investigate the molecular classification of endometrial cancer(EC)and atypical endometrial hyperplasia(AEH)patients treated with fertility-sparing treatment(FST),and its relationship with clinicopathological factors and treatment efficacy.Methods:A total of 52EC and AEH patients who received FST and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2022,were retrospectively collected.We analyzed the relationship between molecular classification and clinicopathological factors and treatment outcomes.Results(1)Of the 52 patients,including 46EC and 6 AEH patients,42(80.8%)achieved complete remission(CR)after FST,with a median time to achieve CR of 9 months.Ten cases(23.8%)had recurrence.(2)Patients were distributed into 4 molecular subgroups as 39 cases(75%)of copy number low(CNL),7 cases(13.5%)of microsatellite instability-high(MSI-H),4 cases(7.7%)of POLE mutations(POLEmut),and 2 cases(3.8%)of copy number high(CNH).Patients with MSI-H subgroup had more family history of tumor(6/7),more with loss of expression of mismatch repair(MMR)protein(7/7),and higher expression level of Ki-67(3/3).(3)Patients with MSI-H subgroup had the lowest CR rate at 6 months(0/7,P=0.014),and survival analysis showed that such patients were less likely to achieve CR than those with CNL(P=0.022).For CNL patients,median 6-month CR rate was 40.6%.In addition,CR was obtained in 3(3/4)POLEmut patients and 2(2/2)CNH patients,respectively.Conclusions Molecular classification relates with the treatment response in patients with EC and AEH receiving FST.Patients with MSI-H subgroup have poor treatment efficacy,and patients with CNL need to be further divided to predict treatment benefit.There are also a few successful cases in POLEmut and CNH subtgroups,which needs further research.

Clinicopathological Evaluation of Ovarian Juvenile Granulosa Cell Tumor: Is Fertility-Sparing Surgery Safe?

Objective:To retrospectively investigate the clinicopathological characteristics of ovarian juvenile granulosa cell tumors(JGCTs)and to evaluate the safety of fertility-sparing surgery.Methods:In this study,surgically treated patients with JGCTs diagnosed between January 2004 and October 2018 in our center were identified.Clinicopathological data,survival outcomes,and recurrence rates were examined in these patients.Results:A total of 8 patients were included.All patients were premenarchal girls or young women(age range,9-32 years).Irregular vaginal bleeding was the most common presenting symptom.Of them,seven patients were classified with Stage I JGCTs,and they underwent fertility-sparing surgery.One patient who had Stage IIIC JGCT and had completed childbearing underwent complete surgery.Seven patients received adjuvant chemotherapy.The median follow-up duration in the total cohort was 64 months(range,2-117 months).The overall survival rate in the fertility-sparing group was 100%,whereas the patient with Stage IIIC JGCT died 1 month after the treatment.Conclusions:Fertility-sparing surgery might not show a negative impact on oncologic outcomes.Fertility sparing could be considered a modified option for patients with Stage I JGCTs.However,due to the limited number of patients,the conclusion must be interpreted with caution,and larger or multicenter studies are needed before conclusions can be drawn.

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

Objective To investigate the clinical features and outcome of recurrent endometrial cancer(EC)or atypical endometrial hyperplasia(AEH)patients who underwent hysterectomy after fertility-sparing therapy.Methods Clinical 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.Conclusion For 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.

Oncology and reproductive outcomes over 16 years of malignant ovarian germ cell tumors treated by fertility sparing surgery

BACKGROUND Malignant ovarian germ cell tumors(MOGCT)are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery(FSS)for this disease are still limited.AIM To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS.METHODS All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed.RESULTS Sixty-two patients were recruited for this study.The median age was 22 years old and over 77%were nulliparous.The three most common histology findings were immature teratoma(32.2%),dysgerminoma(24.2%),and yolk sac tumor(24.2%).The distribution of stage was as follows;Stage I,74.8%;stage II,9.7%;stage III,11.3%;and stage IV,4.8%.Forty-three(67.7%)patients received adjuvant chemotherapy.With a median follow-up time of 96.3 mo,the 10-year progressionfree survival and overall survival were 82.4%and 91%,respectively.For reproductive outcomes,of 43 patients who received adjuvant chemotherapy,18(41.9%)had normal menstruation,and 17(39.5%)resumed menstruation with a median time of 4 mo.Of about 14 patients who desired to conceive,four were pregnant and delivered good outcomes.Only one case was aborted.Therefore,the successful pregnancy rate was 28.6%CONCLUSION The oncology and reproductive outcomes of MOGCT treated by FSS are excellent.Many patients show a long survival time with normal menstruation.However,the obstetric outcome is not quite satisfactory.