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.

Atypical endometrial hyperplasia in a 35-year-old woman:A case report and literature review

BACKGROUND Atypical endometrial hyperplasia(AEH)is a common precancerous lesion of endometrial carcinoma(EC).The risk factors for AEH and EC directly or indirectly related to estrogen exposure include early menarche,nulliparity,polycystic ovarian syndrome,diabetes,and obesity.Both AEH and EC rarely occur in young patients(<40-years-old),who may desire to maintain their fertility.Evaluating the cancer risk of AEH patients is helpful for the determination of therapeutic plans.CASE SUMMARY We report a rare case of AEH in a 35-year-old woman who presented to the Hunan Provincial Maternal and Child Health Care Hospital with a large mass in the uterus.She married at 20-years-old,and had been married for more than 15 years to date.Several characteristics of this patient were observed,including nulliparity,limited sexual activity(intercourse 1-2 times a year)in recent years,and irregular vaginal bleeding for 2 years.Gynecological examination revealed an enlarged uterus,similar to the uterus size in the fourth month of pregnancy,and the uterine wall was relatively hard.Curettage was performed based on transvaginal sonography and magnetic resonance imaging results.Findings from the pathological examination were typical for AEH.The patient was cured after treatment with the standard therapy of high-dose progesterone.CONCLUSION In patients with intrauterine lumps that may be malignant,a pathological report should be obtained.

Pregnancy outcomes after fertility preservation in women with endometrial carcinoma and atypical endometrial hyperplasia:A systematic review and meta-analysis

Objective:The objective of the study was to compare the effects of assisted reproductive technology(ART)and spontaneous pregnancy on pregnancy outcomes in women with endometrial carcinoma(EC)and atypical endometrial hyperplasia(AEH)following fertility-sparing treatments.Methods:Relevant studies published through July 2020 were identified from PubMed and Web of Science literature searches.The pregnancy outcomes of ART and spontaneous pregnancy were summarized and compared for women with complete remission of EC/AEH after fertility-sparing treatments.A subgroup analysis was performed based on whether patients had received in vitro fertilization and embryo transfer(IVF-ET)treatment.The complete remission and recurrence rates of EC/AEH following fertility-sparing treatments were estimated.The effect of pregnancy on recurrence rates of EC/AEH was also calculated.Results:Sixteen observational studies reporting pregnancy outcomes or recurrence with ART or spontaneous pregnancy for women with EC/AEH after fertility-sparing treatments were included.The complete remission rate of EC/AEH was 81.5%(95%CI,78%–85%).Compared with spontaneous pregnancy,the pregnancy rate of ART was significantly higher(66.8%vs.43.7%,OR=2.64,95%CI 1.71–4.05,P<0.00001,I^(2)=14%).Subgroup analysis showed that the pregnancy rate of IVF-ET was significantly higher than that of spontaneous pregnancy(62.7%vs.35.1%,OR=2.85,95%CI 1.44-5.63,P=0.003,I^(2)=29%).The live birth rate of ART was significantly higher than that of spontaneous pregnancy(75.3%vs.47.8%,OR=3.96,95%CI1.76-8.77,P=0.0009,I^(2)=45%).The recurrence rate of EC/AEH was 31%(95%CI 24%–39%).Clinical pregnancy could reduce the recurrence rate of EC/AEH,but there was no significant evidence of an association.Conclusions:ART,especially IVF-ET,could significantly improve pregnancy outcomes in women with EC/AEH receiving fertility-sparing treatments.Following complete remission,ART treatment might be a better option for women with EC/AEH than spontaneous pregnancy.

Analysis on Reverse of Atypical Endometrial Hyperplasia by Drugs in Patients with Polycystic Ovary Syndrome

Objective To analyze the efficacy and safety of drugs on reverse of atypical endometrial hyperplasia in patients with polycystic ovary syndrome （PCOS）. Methods Seventeen patients with PCOS complicated by atypical endometrial hyperplasia （9 patients who were treated with progestin but not reversed were considered as group A; 8 patients who were untreated were considered as group B） were retrospectively analyzed Both groups received oral glucose tolerance test （OGTT） and insulin release test, to check whether the patients had insulin resistance （IR） or hyperinsulinemia. The 17 patients were treated with oral contraceptives combined with metformin. Results After the 17 patients with PCOS complicated by IR and hyperinsulinemia received drug treatment for 3 -6 cycles, atypical endometrial hyperplasia was success- fully reversed Conclusion Oral contraceptives combined with metformin is a clinically practical and effective method for treatment of PCOS complicated by atypical insulin-resistant endometrial hyperplasia.

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.

Recurrent postmenopausal bleeding - just endometrial disease or ovarian sex cord-stromal tumor? A case report

BACKGROUND Postmenopausal bleeding(PMB)is a common gynecologic complaint among elderly women,and endometrial hyperplasia is a common cause of this bleeding.Ovarian fibromas are the most common type of ovarian sex cord-stromal tumor(SCST).They arise from non-functioning stroma,rarely show estrogenic activity,and stimulate endometrial hyperplasia,causing abnormal vaginal bleeding.CASE SUMMARY We report herein the case of a 64-year-old Chinese woman who presented with recurrent PMB.A sex hormone test revealed that her estrogen level was significantly higher than normal,and other causes of hyperestrogenism had been excluded.The patient had undergone four curettage and hysteroscopy procedures in the past 7 years due to recurrent PMB and endometrial hyperplasia.The culprit behind the increase in estrogen level—an ovarian cellular fibroma with estrogenic activity—was eventually found during the fifth operation.CONCLUSION Ovarian cellular fibromas occur insidiously,and some may have endocrine functions.Postmenopausal patients with recurrent PMB and endometrial thickening observed on ultrasonography are recommended to undergo sex hormone testing while waiting for results regarding the pathology of the endometrium.If the estrogen level remains elevated,the clinician should consider the possibility of an ovarian SCST and follow-up the patient closely,even if the imaging results do not indicate ovarian tumors.Once the tumor is found,it should be removed as soon as possible no matter the size to avoid endometrial lesions due to long-term estrogen stimulation.More studies are needed to confirm whether preventive total hysterectomy with bilateral salpingo-oophorectomy should be recommended for women with recurrent PMB exhibiting elevated estrogen levels,despite the auxiliary examination results not indicating ovarian mass.The physical and psychological burden caused by repeated curettage could be prevented using this technique.

Reproductive advance of fertility preservation in patients with early endometrial carcinoma or endometrial atypical hyperplasia

Endometrial cancer(EC)is the fourth common cancer in women worldwide with its incidence rising each year.10%–15%young patients are diagnosed of EC.For patients of childbearing age with early endometrial cancer or atypical hyperplasia,it is necessary to consider surgical removal of uterus after they have given birth.It is a big challenge for reproductive doctors and oncologists to help such patients get pregnant safely as soon as possible.In this article,we will review the latest progress in conservative treatment and candidates for fertility preservation,application of molecular detection,the fertility outcome and follow-up treatment which aims to stimulate more thinking.

Microscale endometrial sampling biopsy in detecting endometrial cancer and atypical hyperplasia in a population of 1551 women:a comparative study with hysteroscopic endometrial biopsy

Background:Endometrial cancer is one of the most common malignancies of the reproductive system.Effective and cost-effective screening method for populations at high risk is not available.This study aimed to investigate specimen adequacy and the influencing factors in microscale endometrial sampling biopsy and to evaluate the diagnostic accuracy and medical cost of biopsy in endometrial cancer and atypical hyperplasia screenings in comparison with hysteroscopic endometrial biopsy.Methods:A total of 1551 patients at high risk for endometrial lesions who required hysteroscopic endometrial biopsy from November 2017 to August 2018 were included.Microscale endometrial sampling biopsy was performed,followed by hysteroscopic endometrial biopsy.We evaluated the specimen adequacy and influencing factors of microscale endometrial sampling.Diagnostic consistency between microscale endometrial sampling biopsy and hysteroscopic endometrial biopsy was evaluated.The sensitivity,specificity,positive predictive value,and negative predictive value of microscale endometrial sampling biopsy in screening for endometrial cancer and atypical hyperplasia were analyzed,and the medical costs of the two procedures were compared.Results:The specimen adequacy was 81.2%.Patient age,menopausal status,endometrial thickness,and endometrial lesion type were correlated with specimen adequacy.There was good consistency in distinguishing benign and malignant endometrial diseases between microscale endometrial sampling biopsy and hysteroscopic biopsy(kappa 0.950,95%CI 0.925-0.975).The sensitivity,specificity,positive predictive value,and negative predictive value of microscale endometrial sampling biopsy were 91.7%,100.0%,100.0%,and 99.3%for endometrial cancer screening,respectively,and 82.0%,100.0%,100.0%,and 99.4%for atypical hyperplasia screening.The medical cost of endometrial sampling biopsy was only 22.1%of the cost of hysteroscopic biopsy.Conclusions:Microscale endometrial sampling biopsy is a minimally invasive alternative technique for obtaining adequate endometrial specimens for histopathological examination.It has the potential to be used in detecting endometrial cancer and atypical hyperplasia with high efficiency and low cost.

Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions

Background： Liquid-based cytology （LBC） offers an alternative method to biopsy in screening endometrial cancer. Cell block （CB）, prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. Methods： A total of 198 women with high risks of endometrial carcinoma （EC） from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler （SAP-1 ） followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. Results： The specimen inadequate rate of CB was significantly higher than that of LBC （22.2% versus 7.1%, P 〈 0.01）. There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia （ 11 cases） or carcinoma （18 cases） confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. Conclusions： CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions.