不孕症合并子宫内膜非典型增生患者助孕治疗的临床分析

目的探讨不孕症合并子宫内膜非典型增生患者经保守治疗后助孕治疗的疗效和安全性。方法回顾性分析8例不孕症合并子宫内膜非典型增生患者，经孕激素或促性腺激素释放激素激动剂（GnRHa）治疗子宫内膜非典型增生缓解后，采用助孕治疗，观察助孕治疗的疗效及其对子宫内膜的影响。结果经孕激素或GnRHa治疗后，8例患者子宫内膜非典型增生全部缓解。共进行单纯促排卵治疗7个周期，促排卵联合人工授精2个周期，体外受精-胚胎移植（IVF—ET）7个周期，冻融胚胎移植2个周期。单纯促排卵周期均未妊娠，人工授精1个周期双胎妊娠；7个IVF—ET周期中，胚胎移植6个周期，3个周期获得临床妊娠；冻融胚胎移植1个周期获得临床妊娠。现足月分娩6活婴。1例未妊娠患者在促排卵后4个月发现子宫内膜癌变。结论不孕症合并子宫内膜非典型增生的患者经孕激素或GnRHa治疗缓解后，及时助孕治疗能提高妊娠率，但需严密观察，注意子宫内膜癌发生的可能。     

Letrozole as primary therapy for endometrial hyperplasia in young women.

OBJECTIVE: To study letrozole as a primary therapeutic agent for endometrial hyperplasia with or without atypia in young women. METHODS: Five premenopausal women presenting for infertility were diagnosed as having endometrial hyperplasia. A second biopsy was performed after they were treated for 3 months with 2.5 mg of letrozole per day. Serum levels of estradiol and progesterone were measured each month. RESULTS: Curettage of the endometrium at the end of treatment revealed no evidence of endometrial hyperplasia or atypia in any of the patients. Low serum levels of estradiol were found in all patients. CONCLUSION: This case series indicates that aromatase inhibitors deserve attention for the conservative treatment of endometrial hyperplasia. However, more studies are needed to confirm the efficacy and safety of this agent.     

Endometrial abnormalities in infertile women

OBJECTIVE: To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy. STUDY DESIGN: From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality. RESULTS: Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma. CONCLUSION: Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.     

Natural history of endometrial hyperplasia

Seventy-seven patients with endometrial hyperplasia, 48 with simple hyperplasia without atypia (SH), 17 with complex hyperplasia without atypia (CH), one with simple hyperplasia with atypia (SHA), and 11 with complex hyperplasia with atypia (CHA) were prospectively followed-up by total curettage every 12 months for 3 years. Progression to carcinoma occurred in only one of the 77 patients; she showed grade 1 adenocarcinoma. The overall regression rates were 79% for SH, 100% for SHA, 94% for CH, and 55% for CHA, respectively. In patients with CHA whose disease reverted to normal endometrium, regression was most likely to occur within the first year. Received: 28 August 2000 / Accepted: 19 October 2000     

Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women

The endometrial histology and endocrinologic and demographic characteristics of 556 asymptomatic postmenopausal women ,who attended the menopause outpatient clinic at Ankara Numune Education and Research Hospital were studied before initiating estrogen replacement therapy. Of these women ,486 (87.4%) had atrophic endometrium ,37 (6.65%) had proliferative endometrium ,27 (4.86%) had endometrial hyperplasia without atypia ,three (0.54%) had endometrial hyperplasia with atypia and three (0.54%) had endometrial adenocarcinoma on their biopsy specimens. When demographic characteristics of the patients were considered, we found that the patients with endometrial adenocarcinoma and endometrial hyperplasia with atypia had potential risk factors for endometrial pathology such as chronic anovulation ,diabetes or hypertension. This study confirms that routine endometrial sampling in asymptomatic postmenopausal women is not warranted ,but patients with associated risk factors should be screened for endometrial pathology before starting estrogen replacement therapy.     

Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women.

The endometrial histology and endocrinologic and demographic characteristics of 556 asymptomatic postmenopausal women, who attended the menopause outpatient clinic at Ankara Numune Education and Research Hospital were studied before initiating estrogen replacement therapy. Of these women, 486 (87.4%) had atrophic endometrium, 37 (6.65%) had proliferative endometrium, 27 (4.86%) had endometrial hyperplasia without atypia, three (0.54%) had endometrial hyperplasia with atypia and three (0.54%) had endometrial adenocarcinoma on their biopsy specimens. When demographic characteristics of the patients were considered, we found that the patients with endometrial adenocarcinoma and endometrial hyperplasia with atypia had potential risk factors for endometrial pathology such as chronic anovulation, diabetes or hypertension. This study confirms that routine endometrial sampling in asymptomatic postmenopausal women is not warranted, but patients with associated risk factors should be screened for endometrial pathology before starting estrogen replacement therapy.     

The outcome of infertility treatment in patients undergoing assisted reproductive technology after conservative therapy for endometrial cancer

Purpose

To elucidate the problems in infertility treatment for women after conservative therapy for endometrial cancer (EC) or atypical complex endometrial hyperplasia (ACEH).

Methods

The clinical outcomes of 21 patients who underwent assisted reproductive technology after conservative therapy (group A) and 42 control women (group B) were retrospectively analyzed.

Results

There was no significant difference in the number of retrieved oocytes, fertilization rate or the number of transferred embryos between the two groups. Women in group A had a significantly thinner endometrium and a reduced implantation rate compared to those for women in group B. There was no significant difference in the cumulative clinical pregnancy and delivery rates between group A and B. The patients in group A required significantly more embryos for achieving a live-birth.

Conclusions

Our results indicate that a thin endometrium after repeated curettage may have a negative effect on endometrial receptivity of patients after conservative treatment for EC/ACEH. Clinicians should reconsider their present protocols and make efforts to minimize the damage to normal endometrium.     

Successful pregnancy in an infertile woman with endometrial hyperplasia and embryo transfer. A case report

BACKGROUND: Successful pregnancy in a woman with complex endometrial hyperplasia with atypia was treated conservatively with gestagens. CASE: The patient was initially diagnosed with complex hyperplasia of the endometrium with atypia by endometrial curettage and treated with several cycles of different gestagens. After repeated endometrial curettage, in vitro fertilization and embryo transfer were introduced for immediate treatment of the patient's infertility in order to avoid the risk of recurrent hyperplasia of the endometrium from estrogens. A single pregnancy was achieved after transfer of embryos obtained from intracytoplasmic sperm injection. This was performed due to poor semen characteristics. The patient delivered a normal, healthy male infant at term. CONCLUSION: Conservative treatment of complex endometrial hyperplasia with atypia in young women wishing to preserve fertility should be considered in carefully selected cases.     

Two successful pregnancies after in vitro fertilization and embryo transfer in a patient with endometrial atypical hyperplasia bordering on adenocarcinoma treated conservatively with high-dose progesterone

Women suffering from anovulatory infertility may develop endometrial hyperplasia and adenocarcinoma due to the unopposed estrogen effect. We present the case of a young infertile woman with endometrial atypical hyperplasia bordering on adenocarcinoma who refused hysterectomy and bilateral salpingo-oophorectomy and achieved two successful pregnancies after conservative treatment with high-dose progesterone followed by in vitro fertilization and embryo transfer. It is concluded that conservative treatment with high-dose progesterone for endometrial hyperplasia and well-differentiated early-stage adenocarcinoma followed by assisted reproductive technologies is an appropriate means for achieving pregnancy. However, the issue of hysterectomy and bilateral salpingo-oophorectomy after delivery or after fertility being no longer required is controversial. If surgery is not performed, close observation with endometrial sampling every 6 months is advisable.     

Endometrial hyperplasia with secretory changes

OBJECTIVE: Secretory changes in endometrial hyperplasia are uncommon. The aim of this study is to review the morphologic and clinical findings of 24 cases of endometrial hyperplasia with secretory changes. METHODS: In 24 patients diagnosed with endometrial hyperplasia with secretory changes during 6 years, clinical characteristics such as menopausal status and hormone treatment were correlated with morphological features. A matched age control group of 24 women with conventional endometrial hyperplasia was used to compare the hormonal effect. RESULTS: Nineteen patients were premenopausal. Nine women showed simple hyperplasia without atypia and 15 complex hyperplasia, 7 of them with atypia. Seventeen women were under hormonal treatment at the time of diagnosis, 10 of them with progestins. In 7 patients endometrial adenocarcinoma could be seen, 5 coexisting with endometrial hyperplasia with secretory changes and in 2 appearing after 1 and 4 months. In control group only 2 patients were undergoing progestin hormonal treatment. CONCLUSIONS: Secretory changes can be found in hyperplastic endometrium, particularly in premenopausal women under hormonal treatment with progestins, with the risk of misdiagnosis.     

Immunohistochemical evaluation of PTEN protein in patients with endometrial intraepithelial neoplasia compared to endometrial adenocarcinoma and proliferative phase endometrium

OBJECTIVE: The aim of this study was to reclassify endometrial hyperplasia cases and examine PTEN protein immunoreactivity compared to cases with endometrial adenocarcinoma and proliferative endometrium. DESIGN: Endometrial samples from 37 women with endometrial hyperplasia with atypia were reclassified as endometrial intraepithelial neoplasia (EIN). Eighteen were complex and 19 were simple endometrial hyperplasia. Twenty-our cases of EIN, ten endometrial adenocarcinoma cases and ten proliferative phase endometrium sections were immunostained for PTEN expression. PTEN expression was documented according to the degree of immunoreactivity as complete loss, partial loss and present. RESULTS: Twenty-four of 37 (64%) women with endometrial hyperplasia were reclassified as EIN. Complete loss of PTEN immunoreactivity was found in only one of the 24 EIN patients (4.2%), partial loss in eight of 24 (33.3%) and present in 15 of 24 (62.5%). There were no difference in PTEN immunoreactivity between EIN, endometrial adenocarcinoma and endometrial proliferation (p = 0.342). PTEN immunoreactivity was partially lost in seven and present in three of the patients with endometrial adenocarcinoma. None of the patients expressed complete loss of PTEN immunoreactivity in this group. CONCLUSION: EIN classification may provide a better and more objective assessment of endometrial hyperplasia cases. PTEN expression showed no differences among the cases of EIN, endometrial carcinoma and proliferative phase endometrium.     

Significance of benign endometrial cells in Pap smears from postmenopausal women

OBJECTIVE: To assess the significance of benign exfoliated endometrial epithelial or stromal cells on cervicovaginal Pap smears obtained from postmenopausal women not receiving exogenous hormones. STUDY DESIGN: A computerized search of the cytology database at two institutions was performed for a five-year period, and all cervical cytology cases from postmenopausal patients diagnosed with benign endometrial cells were identified. Those cases with histologic follow-up within 12 months of the original cytologic evaluation were selected for analysis, and their cytology and surgical pathology slides were reviewed. RESULTS: A total of 227 postmenopausal women with benign endometrial cells were identified. Of the 61 patients with histologic follow-up, 25 (41%) had significant endometrial diseases, including hyperplasia without atypia (11), atypical endometrial hyperplasia (5), well-differentiated adenocarcinoma (8) and high grade serous carcinoma (1). Benign diagnoses, including atrophy (15), weakly proliferative endometrium (9) and proliferative endometrium (6), were noted in 30 patients (49%). Endometrial polyp was identified in three patients (5%). There were three cases of nondiagnostic histologic specimens that lacked endometrial tissue (5%). Two of nine women (22%) with proven carcinoma were asymptomatic. CONCLUSION: The diagnosis of endometrial cells, cytologically benign, in a postmenopausal woman not receiving hormone on Pap smears is associated with a significant number of cases of endometrial hyperplasia, atypical hyperplasia and carcinoma.     

Descriptive epidemiology of endometrial hyperplasia in patients with abnormal uterine bleeding

PURPOSE OF INVESTIGATION: To evaluate the prevalence and epidemiologic characteristics of endometrial hyperplasias in women with abnormal uterine bleeding. METHODS: We performed a retrospective analysis on data gained from 294 patients with histologically documented endometrial hyperplasia (with or without atypia), detected among 1,469 women who underwent fractional dilatation and curettage in our department due to abnormal uterine bleeding from 1986 to 1998. Epidemiologic characteristics were abstracted from the patients' medical charts. RESULTS: 294/1469 women were found with endometrial hyperplasia (258 without atypia and 36 atypical hyperplasias). Thirty-six of them were under 40 years of age. Four of the detected endometrial hyperplasias progressed to endometrial carcinoma (one with simple hyperplasia, two with complex and one with atypical hyperplasia). Obesity and hypertension were justified as risk factors in our study population. CONCLUSIONS: The prevalence of endometrial hyperplasia according to our data was 20%. There were statistically significant differences in most epidemiologic parameters between the two types of hyperplasia. The progression of four endometrial hyperplasias to endometrial adenocarcinoma indicates the need for intense follow-up even in cases where patients undergo conservative therapy.     

Preserving fertility before assisted reproduction in women with endometrial carcinoma: case report and literature review

Fertility-preserving treatment with progestin may be considered in nulliparous women with well-differentiated endometrial carcinoma. Recently, assisted reproductive treatments have been performed to achieve a rapid pregnancy in such cases. This report evaluates a 39-year-old woman who admitted with menorrhagia and primary infertility. Owing to persistent menstrual irregularity and thick endometrium, a diagnostic office hysteroscopy with endometrial biopsy was performed and revealed a well-differentiated adenocarcinoma. Although the woman wished to retain her childbearing potential with conservative management followed by an assisted reproduction cycle, the repeated endometrial biopsies during progestin treatment revealed persistent adenocarcinoma. Complementary surgery was performed due to persistent endometrial malignancy, which noted well-differentiated endometrioid adenocarcinoma without myometrial invasion or extrauterine disease. A review of cases with endometrial carcinoma that have been treated with conservative management and a subsequent assisted cycle is also presented here. To date, there are 14 such reports, including 15 women and 21 healthy infants. However, obtaining remission and maintaining the reproductive capability may not always be possible, even in early-stage cases. Therefore, patient and physician should always consider carefully if fertility-preserving management is preferred after diagnosis of endometrial carcinoma.     

Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome

OBJECTIVE: To assess the role of endometrial thickness on vaginal ultrasound assessment and menstrual history in predicting endometrial hyperplasia in women with polycystic ovary syndrome (PCOS) who presented with infertility due to anovulation. METHODS: This was a prospective study in a university referral-based fertility and endocrine clinic. Fifty-six women with PCOS presenting with infertility due to anovulation underwent both vaginal ultrasound assessments and endometrial biopsies. The main outcome measures were the predictive value of sonographic endometrial thickness (primary objective) and the menstrual history with other clinical characteristics (secondary objective) for proliferative endometrium and endometrial hyperplasia in logistic regression analysis. Their predictive value was further examined by receiver operating characteristic curve analysis. RESULTS: Thirty-six PCOS patients (64.3%) had proliferative endometrium and 20 (35.7%) had endometrial hyperplasia. Five of the latter (25%) had cytologic atypia. Endometrial thickness less than 7 mm or intermenstrual interval less than 3 months (corresponding to more than four menstrual periods yearly) was associated with proliferative endometrium only. The endometrial thickness correlated positively with endometrial hyperplasia (P =.018) and, together with the average intermenstrual interval, were significant predictors of endometrial hyperplasia (P <.001). CONCLUSION: These findings point to the usefulness of obtaining a detailed menstrual history in women with PCOS by identifying those at increased risk of endometrial hyperplasia and who require an endometrial biopsy. The endometrial thickness corroborates this clinical impression and is particularly useful when the menstrual history is uncertain. Endometrial hyperplasia in this population is effectively excluded when the endometrial thickness is less than 7 mm.     

Development of metastatic endometrial endometrioid adenocarcinoma while on progestin therapy for endometrial hyperplasia

BACKGROUND: Conservative treatment with progestins is a reasonable treatment option for endometrial complex atypical hyperplasia and, in the experimental setting, for some women with grade 1 endometrial endometrioid adenocarcinoma. The risk of progression to a high-stage endometrial cancer is quite low, with only two previously reported cases in the English literature. CASE: A 40-year-old woman with endometrial complex atypical hyperplasia diagnosed by dilatation and curettage was managed conservatively with progestin therapy (initially, megesterol acetate; then, a combination oral contraceptive). More than 2 years after her original diagnosis, she developed endometrial endometrioid adenocarcinoma, FIGO grade 2, with lymph node metastasis. The tumor was microsatellite instability-high due to methylation of MLH1 and loss of MLH1 protein. CONCLUSION: Currently, there are no good criteria for predicting which patients with complex atypical hyperplasia/grade 1 endometrioid adenocarcinoma will optimally respond to progestin therapy. There is some evidence that endometrial complex hyperplasia demonstrating loss of MLH1 protein by immunohistochemistry is strongly related to subsequent or concurrent endometrial cancer, especially tumors of higher grade and stage. In a woman with a biopsy diagnosis of endometrial hyperplasia, evaluation of MLH1 protein status by immunohistochemistry may provide useful information when medical management is being considered.     

Tratamiento conservador del cáncer de endometrio en una pareja estéril

Successful conservative management for early-stage low-grade endometrial cancer in young women wishing to preserve fertility has been reported in small series. Although few data are available on assisted reproductive technology (ART) outcomes after conservative management of endometrial carcinoma, ART does not seem to worsen prognosis. We report the case of a 29-year-old woman with a history of primary infertility, who was diagnosed with a well-differentiated endometrial adenocarcinoma (stage Ia), which was treated with high doses of oral progesterone. A successful pregnancy was achieved after ART.     

子宫内膜非典型增生18例保守治疗结局分析

目的探讨孕激素治疗子宫内膜非典型增生的结局及适宜的辅助生育策略。方法回顾性分析2002年1月～2007年4月18例不孕合并子宫内膜非典型增生的患者应用大剂量孕激素保守治疗的结果及妊娠结局。结果①14例患者在应用大剂量孕激素治疗3～36个月后病灶消退，4例病灶持续存在；②3例患者在停止治疗5～15个月后发展为子宫内膜癌。内膜非典型增生病变的再现率为33．3％；③8例患者接受了辅助生育治疗．5例分别经CC＋HMG促排卵治疗3～6周期无优势卵泡发育．1例在第6个促排卵周期获宫内单胎妊娠。4例（包括1例CC＋HMG促排卵未孕者）患者接受了5个周期IVF助孕，1例输卵管妊娠。1例自然流产。另2例冻存胚胎等待移植。结论多数子宫内膜非典型增生的患者对大剂量孕激素治疗有效。对这类患者．一旦内膜病变消退，应积极助孕．可以适当放宽IVF—ET指征。     

Preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia

OBJECTIVES: To determine the preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia. MATERIAL AND METHODS: One hundred and three patients with endometrial hyperplasia detected by surgical curettage performed due to various gynecologic pathologies were treated by hysterectomy. We compared retrospectively the histopathological diagnoses found on curettage with those found on hysterectomy specimens. The classification scheme endorsed by the International Society of Gynecological Pathologists was used to classify the endometrial hyperplasia. The histologic findings found on the endometrial tissue of curettage specimens were correlated with those from hysterectomy specimens. Histopathologic evaluation was performed by a single skilled gynecologic pathologist. RESULTS: A total number of 103 women--76 (73.8%) premenopausal and 27 (26.2%) postmenopausal--were determined to have endometrial hyperplasia on histopathological evaluation of endometrial tissues obtained by endometrial curettage performed for evaluation of various bleeding abnormalities. These included 94 patients with simple hyperplasia without atypia (91.3%), two patients with simple hyperplasia with atypia (1.9%), five patients with complex hyperplasia without atypia (4.9%), and two patients with complex hyperplasia with atypia (1.9%). Histopathological evaluation of endometrial tissue obtained from hysterectomy specimens (of patients diagnosed with hyperplasia on curettage) revealed a total number of 65 cases (63.1%) with endometrial hyperplasia, and 38 cases (36.9%) with various histopathological findings. The correlation between preoperative and postoperative endometrial histologic findings was found to be statistically insignificant (r = 0.105, p = 0.29). Among 94 patients who were found to have simple hyperplasia without atypia on curettage specimens, 55.3%, were found to have simple hyperplasia without atypia, 1.1% simple hyperplasia with atypia, 5.3% complex hyperplasia without atypia, 9.6% secretory endometrium, 4.3% proliferative endometrium, 21.3% disorganized proliferative endometrium, 1.1% corpus luteum persistency, 1.1% basal endometrium, and 1.1% endometrium cancer on final hysterectomy specimens. CONCLUSION: Postoperative diagnosis of endometrial pathology might be different from that of preoperative especially in cases with simple endometrial hyperplasia without atypia.     

Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women

OBJECTIVE: To investigate the effect of differences in endometrial thickness and pattern as visualized with present-day high-resolution transvaginal ultrasound equipment on the outcome of assisted reproductive treatment. DESIGN: Prospective cohort study. SETTING: Two large infertility units in university hospitals. PATIENT(S): The endometrial characteristics of 981 patients during 1,600 assisted reproductive treatment cycles were compared with those of 205 untreated women. In addition, abnormal echogenic patterns of the endometrium were characterized histologically in 44 patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): The endometrium was significantly thinner in untreated women and women treated with IUI than in women treated with IVF or intracytoplasmic sperm injection. The exponential proliferation of the endometrium was similar in conception and nonconception cycles. The odds for a successful pregnancy were significantly lower in the presence of a thin endometrium in women treated with IUI but not in women treated with the long stimulation protocol for IVF or intracytoplasmic sperm injection. Singleton pregnancies were more common than multiple pregnancies in patients with thin endometria. CONCLUSION(S): The pregnancy rates of assisted reproductive procedures are influenced only marginally by the degree of endometrial proliferation, and treatment should not be canceled because of inadequate endometrial thickness.