Pregnancy Outcomes Of Fertility-sparing Treatment For Early-stage Endometrial Cancer And Severe Atypical Hyperplasia

Background & Objectives:About 3%-14%of the endometrial cancer occurs in young women aged 40 years or younger and 70%-85% of them are nulligravid. No prediction of pregnancy outcomes for fertility-sparing therapy can be found from the previous reports based on clinical observations of a few cases. The purpose of this study is to provide evidence of fertility-preserving therapy for endometrial carcinoma and severe atypical hyperplasia. We also try to find some clues to predict the pregnancy outcomes of fertility-preserving therapy.Subjects & Methods:A systematic review and meta-analysis is studied to summarise the status and evaluate the efficacy and safety of progestin therapy for early-stage endometrial carcinoma and severe atypical hyperplasia. The clinical data of 95 patients, who accepted fertility-preserving therapy for early endometrial carcinoma and severe atypical hyperplasia, in Peking Union Medical College Hospital during last 20 years is studied to analyze the treatment effect, pregnancy outcomes and the related factors. A preliminary explore of HOX A10, APOD, SCD, LEPR, SREBP1 and FASN as molecular markers in the relationship between the expression of endometrial cancer and pregnancy is taken out. And a logistic regression model is built to predict the pregnancy outcome through the analysis of the factors associated with pregnancy.Results:25 studies in a total of 445 patients are included in the meta-analysis, resulting in the resgression rate 82.4%, relapse rate 25.0%, pregnancy rate 28.8% and live-birth rate 19.6%. Weight gain, abnormal liver function and abnormal blood coagulation test are the most common treatment related adverse events, while 2 disease-related deaths were occurred during follow-up.49 patients, mean age 29.3±3.5 years old, with fertility intentions, are included in the study. All the patients get complete regression, median time of complete regression is 6 months, resulting in a 50.0% pregnancy rate and among which 70.8% patients successfully delivered. During the mean follow-up time 62.5 ± 41.7 months,57.1% relapse, having a mean relapse time of 21.9 ± 18.9 months. Infertility and thickness of endometrium before treatment are the only two factors found associated with pregnancy. Low expression of HOX A10 is found on tumor tissues while the expression of HOX A10 in endometrial stromal cells is found significantly higher in patients successfully pregnant than who fails. High expression of APOD, SCD, LEPR, SREBP1 and FASN in tumor tissues is observed in all the patients, there is no statistic difference. Through the analysis of factors, like infertility, thickness of endometrium, expression of HOX A10 and BMI, with pregnancy, we build a logistic regression model, P value of which is more than 0.05, indicating there is no statistical significance.Conclusions:Fertility-preserving therapy for patients with early endometrial cancer and severe atypital hyperplasia can reach a satisfied complete regression rate, based on which pregnancy should become an important prognostic indicator in the future. High expression of HOX A10 may be a marker judging the pregnancy outcome. There is a long way for using mathematical model to predict the pregnancy outcome, with the adcantages of evaluating the patients’reproductive status in all aspects, it can be a fresh way to screen the patients and predict pregnancy outcome.