Severe atypical hyperplasia and early endometrial cancer are common gynecological diseases with a high incidence in postmenopausal women, and some studies have shown that 5% of patients with these diseases are women of reproductive age [1], whose reproductive health and fertility are seriously threatened. In order to investigate the pregnancy and outcome of patients with severe atypical hyperplasia and early-stage endometrial cancer after fertility-preserving treatment, we retrospectively analyzed the clinical data of patients with severe atypical hyperplasia and early-stage endometrial cancer who were admitted to our hospital.
Data and Methods
1. General data
Among 100 patients with severe atypical hyperplasia and early endometrial cancer admitted to our hospital between 2001 and 2011, 37 cases were randomly selected, aged between 20 and 43 years old, with an average of (28.9±12.4) years old, including 31 cases with severe atypical hyperplasia and 6 cases with endometrial cancer, with clinical stages of stage I in 3 cases, stage II in 2 cases, and stage III in 1 case.
2. Methods.
The clinical data of the selected study subjects were compiled, and retrospective analysis was performed for the general data, treatment methods, treatment effects, and pregnancy and delivery of the patients. Firstly, a comprehensive examination was performed to accurately assess the extent of the disease, including the patient’s family history and medical history, scraping or direct hysteroscopic scraping, estrogen and progesterone receptor testing, appropriate imaging, laparoscopy, etc. Then, reasonable treatments were adopted according to the examination results and the patient’s requirements, such as progesterone therapy, GNRHa therapy, and Mannorrhea therapy. GNRHa therapy, Mannorrhea therapy and GNRHa combined with Mannorrhea therapy, etc. Progestin is mostly used as medroxyprogesterone acetate and medroxyprogesterone acetate, while some patients are treated with hydroxyprogesterone caproate, and the dosage is determined on a case-by-case basis [2]. During the treatment period, the patient’s condition is closely monitored and the patient’s menstruation and pelvic ultrasound findings are recorded in detail after 3-12 months of follow-up. If abnormalities are detected, effective measures are taken to deal with them in a timely manner.
3. Indications for fertility preservation treatment
① Patient’s age <45 years old.
② The pathological type of endometrial cancer is adenocarcinoma and the adenocarcinoma is highly differentiated.
③ Immunohistochemical examination confirms that the patient’s progesterone receptor is positive.
④ The patient’s serum CA125 level was within the normal range, i.e., not more than 35 kU.
⑤ There is no myometrial infiltration.
⑥ No extra-uterine lesions were present.
⑦The patient strongly requested to preserve the reproductive function. ⑧ The results of liver and kidney function tests showed normal [3].
4, Statistical methods: SPSS14.0 software was used for data analysis, and the count data Χ2 test was used, and the difference was considered statistically significant when P<0.05.
RESULTS
Among the 37 patients, 25 patients received progestin therapy, 2 patients received GNRHa therapy, 5 patients received Mannorrhea therapy, and 5 patients received combined GNRHa and Mannorrhea therapy. (See Table 1 for details)
In 6 patients with endometrial cancer, the number of pregnancies was 7, with 4 pregnancies and 3 successful deliveries; in 31 patients with severe atypical hyperplasia of the endometrium, the number of pregnancies was 11, with 9 pregnancies and 4 successful deliveries. The differences in pregnancy and successful delivery rates between the two groups were statistically significant (P<0.05 Table 1).
DISCUSSION
Endometrial cancer is a common gynecologic malignancy, and most patients are usually in the early stage when diagnosed, with most histological types presenting as polymerized endometrioid adenocarcinoma. The results of many clinical studies confirm that patients with this type of disease have a good prognosis, a low recurrence rate, a long recurrence time, and a long patient survival [4]. Young patients have a strong requirement to preserve their reproductive function and therefore need to be treated aggressively with strict indications for preservation of reproductive function in order to obtain a more optimal outcome.
Endometrial hyperplasia is a precancerous lesion of endometrial cancer, and numerous studies have confirmed that endometrial atypical hyperplasia often co-exists with endometrial cancer, and the results of relevant surveys show that about 43% of patients with endometrial hyperplasia have endometrial adenocarcinoma. If patients with endometrial hyperplasia are not treated promptly and effectively, it will easily induce endometrial hyperplasia to become cancerous and eventually develop into endometrial adenocarcinoma. For a long time, the treatment of endometrial hyperplasia was mainly based on the application of cyclic progestins, which gradually evolved into the use of continuous high-dose progestins to initiate aggressive treatment of early endometrioid adenocarcinoma, thereby delaying the progression of the disease and buying time for further treatment [5]. However, the use of high-dose progestin conservative therapy is associated with significant adverse drug reactions and the risk of disease progression, and this treatment method has been controversial. Severe atypical hyperplasia of the endometrium often occurs in combination with early endometrioid carcinoma, and the two are located in close proximity to each other and can be transformed into each other, and due to the limitations of the pathological specimens obtained by diagnostic scraping, the two cannot be accurately distinguished by histological examination in most cases, which makes the principles of treatment, treatment outcome and prognosis of the two similar.
Currently, the standard treatment for endometrial cancer is surgical excision of both uterine adnexa, supplemented by radiotherapy for high-risk patients. Although this approach is more effective, patients will lose their reproductive function. There is a strong demand for the implementation of fertility preservation, therefore, in the process of initiating fertility preservation treatment for them, attention should be paid to the strict selection of treatment indications, the rational application of progestins and other related means, and the adjustment of treatment protocols and doses of drugs, etc., according to the specific conditions of the patients [6]. In this study, 37 patients were treated with progestin therapy, GNRHa therapy, Mannorrhea therapy and GNRHa combined with Mannorrhea therapy to preserve fertility, and the results showed that the pregnancy rate was 35.1% (13/37) and the successful delivery rate was 19.1% (7/37) in 37 patients. Among them, the pregnancy rate was 29.0% and the successful delivery rate was 12.9% in patients with severe endometrial atypia, and the pregnancy rate was 66.7% and the successful delivery rate was 50.0% in patients with endometrial cancer.
The relatively low rate of successful delivery after conservative treatment of endometrial cancer patients is mainly due to the presence of other factors that affect fertility in most of these patients, such as obesity, polycystic ovary syndrome, and prolonged anovulation [7]. During conservative treatment, patients should be induced to ovulate rapidly, safely and effectively, and assisted with appropriate fertility treatment techniques to increase the pregnancy and delivery rates after fertility preservation treatment.
In conclusion, the rational selection of therapeutic drugs, treatment protocols and indications for fertility preservation therapy is important for improving treatment outcomes and increasing pregnancy and successful delivery rates, and deserves attention.