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.     

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.     

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.     

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。     

Resectoscopic surgery in 10 women with abnormal uterine bleeding and atypical endometrial hyperplasia

STUDY OBJECTIVE: To evaluate the role of the resectoscope in the diagnosis and treatment of women with abnormal uterine bleeding (AUB) and atypical endometrial hyperplasia. DESIGN: Retrospective case series (Canadian Task Force classification III-3). SETTING: University-affiliated teaching hospital. PATIENTS: Ten women. Intervention. Hysteroscopic evaluation after preoperative endometrial biopsy indicated simple hyperplasia without atypia, complex hyperplasia with atypia, or inadequate specimen. MEASUREMENTS AND MAIN RESULTS: Atypical hyperplasia was confirmed in eight patients after total endomyometrial resection. Hysterectomy was offered to all patients but accepted by only two: one for bilateral ovarian serous cystadenomas and the second for a granulosa cell ovarian tumor. No residual endometrium was found in hysterectomy specimens. Seven women were amenorrheic and well 1 to 9 years after resection. An additional patient with amenorrhea died from colon cancer 2 years after resection. CONCLUSION: Resectoscopic surgery confirmed or detected atypical endometrial hyperplasia in eight women and excluded it in two patients with AUB and a previous diagnosis of simple hyperplasia, atypical hyperplasia, or inadequate specimen. Skillful resectoscopic surgery may be an alternative to hysterectomy in selected patients with atypical hyperplasia who are compliant with regular and long-term follow-up.     

Serum and tissue angiogenin in patients with endometrial hyperplasia

ObjectiveTo evaluate angiogenin levels in both tissue and serum of patients with endometrial hyperplasia with and without atypia.MethodsSixty women were classified according to the histopathological findings of endometrium into three groups. The control group consisted of 20 women with normal non-hyper plastic endometrium. The second group included 20 women diagnosed as complex endometrial hyperplasia without atypia. The third group included 20 women diagnosed as complex endometrial hyperplasia with atypia. Serum and tissue angiogenin were measured by enzyme immunoassay (EIA) technique and confirmed in tissues with Western Blotting (WB) technique.ResultsThere was a statistically significant increase in serum and tissue angiogenin levels of endometrial hyperplasia groups compared to those of control group (P<0.001). Serum and tissue angiogenin levels were with a statistically significant higher (P<0.001) in group III compared to group II. The sensitivity of serum angiogenin to detect the potential possibility of endometrial hyperplasia with atypia in endometrial hyperplasia patients was 100%, specificity 85%, positive predictive value 86.9%, negative predictive value 100%, positive likelihood ratio 6.6%, negative likelihood ratio 0% and accuracy 91.7%.ConclusionElevated levels of serum angiogenin in endometrial hyperplasia could assist in determining which patients are at high risk for atypical change requiring aggressive treatment.     

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.     

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.     

Clear cells of the endometrium: an indicator of estrogen level

We examined 70 cases of curettage (24 in normal proliferative phase and 46 with endometrial hyperplasia) and determined the percentage of clear cells among all glandular cells. The number of clear cells was increased in endometrium with hyperplasia without atypia or with minimal atypia (Grade of the endometrial hyperplasia I-IV. Classification of Hendrickson and Kempson 1979). It decreased as the hyperplasia became more severe. Besides we noticed an increase of clear cells in late proliferative phase. The relation of clear cells to estrogen level has been discussed.     

Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent.

Endometrial cancer and hyperplasia have long been associated with diabetes. Hyperinsulinemia may have a direct mitogenic effect on the endometrium and may inhibit the effect of progestogen therapy. This case report describes the treatment of a patient with atypical endometrial hyperplasia with an insulin-sensitizing agent. A 37-year-old patient presented after failed treatment of endometrial hyperplasia with progestogen therapy. One month after initiating metformin therapy the patient's endometrial biopsy demonstrated proliferative endometrium. This patient's atypical endometrial hyperplasia regressed after the initiation of treatment with an insulin-sensitizing agent. This relatively new class of drugs may provide an adjunct to the therapy of endometrial hyperplasia.     

Uterine sarcoma. Case report

55 years female patient who is sent to the New Hospital Durango management fibroids and anemia, why not start the study protocol for hysterectomy, preoperative presenting within normal parameters, transvaginal ultrasound uterine fibroids and endometrial hyperplasia, biopsy endometrium with endometrial hyperplasia without atypia simple, and is scheduled for total abdominal hysterectomy with bilateral salpingo-oophorectomy. Surgical procedure is performed with the incident of tearing the uterine body on the right side with extension to the neck and externalization of endometrial tissue, the event is completed without complications. Histopathologic endometrial stromal sarcoma of high grade. Management in a row by the oncology department by 25 sessions of radio and brachytherapy.     

Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent

Endometrial cancer and hyperplasia have long been associated with diabetes. Hyperinsulinemia may have a direct mitogenic effect on the endometrium and may inhibit the effect of progestogen therapy. This case report describes the treatment of a patient with atypical endometrial hyperplasia with an insulin-sensitizing agent. A 37-year-old patient presented after failed treatment of endometrial hyperplasia with progestogen therapy. One month after initiating metformin therapy the patient's endometrial biopsy demonstrated proliferative endometrium. This patient's atypical endometrial hyperplasia regressed after the initiation of treatment with an insulin-sensitizing agent. This relatively new class of drugs may provide an adjunct to the therapy of endometrial hyperplasia.     

c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial cancer

Purpose

To evaluate the expression of c-kit (CD117) in endometrial hyperplasia and endometrial cancer.

Methods

Expression of c-kit in 10 normal endometrium, 18 simple endometrial hyperplasia, 16 complex endometrial hyperplasia (10 cases with atypia and 6 cases without atypia), and 6 endometrial cancer were investigated by immunohistochemistry.

Results

c-Kit expression decreased as the lesion progressed to endometrial cancer. Immunostaining was mostly focal and weak in the normal endometrium and was mostly diffuse and strong in the simple and complex endometrial hyperplasia.

Conclusions

Simple and complex hyperplastic endometrial tissues express diffuse cytoplasmic staining for c-kit and the expression decreases with the progression of the lesion.     

Endometrial hyperplasia: a clinician's review

Endometrial hyperplasia is considered present when the ratio of glandular to stromal tissue of the endometrium is greater than 1:1. Further differentiation is made into simple or complex hyperplasia with or without the presence of cytological atypia. Such changes are caused by excess or unopposed oestrogenic stimulation. Clinically endometrial hyperplasia is often asymptomatic but can present as abnormal uterine bleeding. Many cases are detected incidentally or following abnormal vaginal bleeding by an increase in the normal endometrial thickness on transvaginal ultrasonography (TVS). An endometrial biopsy can be obtained using a pipelle or at hysteroscopy, and examination of this allows a histological diagnosis. Cytological atypia mandates active intervention as its presence correlates with both a significant risk of progression to endometrial cancer as well as an increased rate of occult endometrial cancer. Hysterectomy is therefore the treatment of choice. The absence of cytological atypia confers a lower risk of malignant change. Thus management is more conservative. Progestogens are used to oppose the oestrogenic stimuli, coupled with ongoing surveillance.     

Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia with atypia

OBJECTIVE: The objective was to report a series of infertility therapy outcomes following conservative management of endometrial adenocarcinoma and/or complex hyperplasia with atypia. METHODS: A retrospective review of the University of Iowa assisted reproductive technology database was performed. All women presenting with International Federation of Obstetrics and Gynecology (FIGO) grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were assessed for type and duration of medical management, initial, interim treatment, and preinfertility treatment endometrial biopsy (BX) findings. Assessment of infertility treatment outcomes and postinfertility endometrial biopsy findings were performed. All of the pathology samples were re-reviewed at the Gynecologic Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular expertise in gynecologic pathology. RESULTS: Four infertile women, three nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade 1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were successfully treated with high-dose progestational agents resulting in normal proliferative endometrium. In addition, both women with complex hyperplasia with atypia were successfully treated with progestins and/or ovulation induction. Successful pregnancy outcomes were achieved for three of the four women with assisted reproductive technology. A total of five successful pregnancies and eight healthy live-born infants were achieved among three women. One of the four women was unable to conceive despite three cycles of in vitro fertilization. Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to obtain benign endometrium preceding infertility therapy. CONCLUSION: This report demonstrates that conservative management of well-differentiated endometrial adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive assisted reproduction is an option to highly motivated and carefully selected women.     

Endometrial hyperplasia

Endometrial hyperplasia is an abnormal glandular proliferation of the endometrium resulting from exposure to unopposed oestrogens of endogenous and exogenous sources. Endometrial hyperplasia is rare in women under the age of 30 with an increasing incidence with age and an overall peak incidence in women aged 50–54 years. Most women diagnosed with endometrial hyperplasia present with abnormal uterine bleeding including menorrhagia, inter menstrual bleeding or postmenopausal bleeding. The classification of endometrial hyperplasia is currently debated but the most widely used classification system (WHO 1994) defines endometrial hyperplasia as simple or complex with or without atypia. Treatment of endometrial hyperplasia can be medical or surgical and is dependent on cause, malignant potential, fertility requirements and medical co-morbidities as well as patient preference.     

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     

Which surgical procedure for patients with atypical endometrial hyperplasia?

OBJECTIVE: To determine the occult coexistence of endometrial carcinoma in patients with atypical endometrial hyperplasia and to compare histological prognostic factors according to lymph node status in occult endometrial carcinoma. MATERIALS AND METHODS: Two hundred and four patients from two referral centers (during the period 1990-2003) who were operated on within 1 month of endometrial biopsy for symptomatic endometrial hyperplasia without receiving any medical treatment were included retrospectively. Patients having preoperative endometrial biopsy results of concomitant endometrial hyperplasia and carcinoma were excluded from the study. Fifty-six patients having atypia in preoperative biopsy (group I) were compared with 148 patients without atypia (group II). Chi-square and Mann-Whitney U-tests were used for statistical analyses. RESULTS: No significant difference was observed between the two groups according to age or menopausal status. Patients in group II had significantly higher parity than patients in group I. In group I, 62.5% of the patients had endometrial carcinoma, 21.4% had endometrial hyperplasia, and 16.1% had normal endometrium in hysterectomy specimens. In group II, the percentages were 5.4, 38.5, and 56.1%, respectively. Complete surgical staging was performed in 20 patients. Four patients had metastatic lymph nodes. All of them had grade 2 tumors with lymphovascular space involvement. Three of them had nonendometrioid tumors. CONCLUSION: Careful intraoperative and preoperative evaluation of the endometrium must be the sine qua non for patients with atypical endometrial hyperplasia. It is reasonable to do frozen section at the time of hysterectomy for atypical endometrial hyperplasia, and if grade 2/3 of nonendometrioid cancer with lymphovascular space involvement is found, complete surgical staging should be performed.     

Endometriumhyperplasie und -karzinom

Endometrial hyperplasia can cause bleeding disorders and some are also precancerous lesions of an endometrial cancer. Vaginal sonography plays an important role in the diagnosis of endometrial hyperplasia. This can be combined with a sonographically supported progestin test for further differential diagnosis. For a definitive diagnosis, hysteroscopy and curettage is the method of choice. An exact histological classification of endometrium hyperplasia is necessary. For medical treatment of endometrial hyperplasia without atypia, cyclic or continuous treatment with an oral progestin or alternatively intrauterine progestin treatment by a levonorgestrel intrauterine system (LNG-IUS) may be useful. After treatment of complex or atypical hyperplasia, control of histological specimen is necessary. In atypical hyperplasia or early stage of endometrial cancer in patients who desire a pregnancy, conservative therapy should be used cautiously and only in combination with strict clinical and sonographical controls.