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。     

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。     

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.     

Assisted reproductive technologies in conjunction with conservatively treated endometrial adenocarcinoma. A case report

This case report illustrates the successful use of assisted reproductive technologies (ARTs) in a patient receiving conservative treatment for endometrial adenocarcinoma. A 31-year-old infertile woman, diagnosed as FIGO stage Ia endometrial adenocarcinoma (grade 1), received oral medroxyprogesterone acetate 400 mg/day for 12 weeks. Endometrial curettage was performed and the absence of endometrial carcinoma was confirmed. A single pregnancy was achieved with in vitro fertilization and embryo transfer. A healthy female infant was born via cesarean section at 42 weeks' gestation. The carcinoma has not recurred, and the patient now desires a second child. We conclude that ART combined with progesterone treatment might be a powerful option for the treatment of infertile patients with early stage, well-differentiated endometrial adenocarcinoma.     

高分化子宫内膜样癌及子宫内膜重度不典型增生患者孕激素治疗的临床分析

目的探讨35岁以下高分化子宫内膜样癌及子宫内膜重度不典型增生患者采用孕激素治疗以保留患者子宫的疗效,并随访其治疗后的生育情况.方法采用回顾性分析的方法对1991年至2005年北京协和医院收治的35岁以下、接受孕激素治疗（以醋酸甲羟孕酮为主）的25例高分化子宫内膜样癌及子宫内膜重度不典型增生患者的临床病理资料进行研究.其中,子宫内膜样癌8例（内膜癌组）,子宫内膜重度不典型增生17例（不典型增生组）.孕激素治疗前对患者进行全面的分期评估,治疗后每1～6个月诊刮以评价疗效,对有生育要求者随访其生育情况.结果内膜癌组患者孕激素治疗前经全面的分期评估,证实为早期、高分化子宫内膜样癌.除1例子宫内膜样癌患者尚未评估疗效外,内膜癌组其他7例及不典型增生组17例患者治疗后有效者分别为6例（6/7）、17例（100%）;缓解者分别为5例（5/7）、14例（82%）;缓解后复发者分别为1例（1/5）、3例（21%）,复发时间为缓解后6～30个月;随访缓解后要求生育的14例患者中,内膜癌组4例患者尚未生育,不典型增生组10例患者中4例妊娠共7次.1例自然受孕后失访;3例经促排卵治疗后受孕并足月分娩,其中1例产后人工流产3次.结论对于要求保留子宫的高分化子宫内膜样癌及子宫内膜重度不典型增生的年轻患者,孕激素治疗是一种治疗选择.孕激素治疗前应对子宫内膜样癌患者进行详细全面的分期评估,辅助生殖措施的介入有望提高治疗后的妊娠率.     

Successful pregnancies in 2 infertile patients with endometrial adenocarcinoma

Two infertile patients with well-differentiated endometrial adenocarcinoma succeeded in having their own babies with assisted reproductive technology following treatment with a high dose of medroxyprogesterone acetate and repeated endometrial curettages. Their follow-up pathological examinations revealed no evidence of recurrent disease. Consequently, conservative treatment may be indicated in patients with well-differentiated endometrial adenocarcinoma at an early stage who desire to preserve their fertility.     

Progression of conservatively treated endometrial carcinoma after full term pregnancy: a case report

INTRODUCTION: We describe a case of conservatively treated endometrial endometrioid (EE) adenocarcinoma which showed an aggressive clinical outcome after pregnancy. CASE: A 30-year-old woman with a well differentiated EE adenocarcinoma decided to attempt a conservative approach and underwent progestin treatment with subsequent negative ultrasound and hysteroscopic controls. After 3 months, she conceived and at 36 weeks of gestation, a cesarean section was performed with multiple negative biopsies. Eight 8 months after delivery, an exploratory laparotomy documented disseminated poorly differentiated EE adenocarcinoma. Staging work up revealed diffuse metastatic disease. Despite chemotherapy, the patient experienced progression of disease with fatal acute respiratory syndrome due to massive neoplastic pulmonary lymphangitis. CONCLUSION: Conservative medical management of endometrial cancer in young women willing to preserve their reproductive potential, carries on potential risks. Careful selection of cases, informed consent, and strict follow up procedures are mandatory.     

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.     

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 carcinoma remaining after term pregnancy following conservative treatment with medroxyprogesterone acetate

BACKGROUND: Successful pregnancies after conservative progestin treatment to young women with endometrial carcinoma have recently been reported. However, it is not known for certain whether the lesion is completely eradicated in such patients. We present a case of residual endometrial carcinoma after term pregnancy which had been treated conservatively before the pregnancy began. CASE: A 28-year-old woman with endometrial carcinoma received conservative treatment with high-dose medroxyprogesterone acetate (MPA) and then conceived. After delivery at term, atypical cells were found in the endometrial curettage specimen. A hysterectomy was performed 6 months after delivery and revealed the presence of a small focus of intramucosal, grade 1, endometrioid-type adenocarcinoma. Immunohistochemically, the tumor cells were positive for estrogen and progesterone receptors. CONCLUSION: We concluded that while MPA treatment had been effective, it had not completely eradicated the carcinomatous lesion, which remained during and after the term pregnancy.     

子宫内膜癌保留生育功能治疗的临床探讨

目的探讨早期子宫内膜癌患者保留生育功能治疗的适应证和治疗方法。方法对2003年11月至2007年9月佛山市第一人民医院接受保留生育功能治疗的6例早期子宫内膜癌患者,回顾性分析其临床资料、诊疗经过、近期疗效及妊娠结局。结果6例患者接受了以高效孕激素和反复宫腔镜检查与病灶去除为主的联合治疗,患者中位年龄31岁。子宫内膜样腺癌5例(高分化2例、中分化3例),中分化腺棘癌1例,6例雌、孕激素受体均阳性。1例治疗3个月获部分缓解,1例治疗不足3个月而未评估。其余4例均在治疗3～6个月内获完全缓解,其中2例患者分别于治疗结束后第2、4个月自然妊娠,新生儿均存活,其余2例暂未受孕。结论在严格掌握适应证的前提下对年轻且有强烈生育愿望的早期子宫内膜癌患者实施保留生育功能治疗是安全可行的,宫腔镜检查和定位活检可作为首选的评估和监测方法。肿瘤控制后应尽快妊娠,完成生育后应适时行手术治疗。     

Reevaluating the safety of fertility-sparing hormonal therapy for early endometrial cancer

OBJECTIVE: To evaluate the safety of fertility-sparing hormonal therapy for endometrial cancer in young patients. METHODS: Six patients diagnosed with endometrial adenocarcinoma grade I and had undergone progestin treatment were reviewed. Four patients failed progestin treatment and were then found at surgery to have both endometrial and ovarian cancers. A clonality assay using the human androgen receptor gene as the X-linked polymorphic marker and immunohistochemistry for steroid hormone receptor expression were used to delineate the relation between the endometrial and ovarian lesions and to explore possible causes of treatment failure. RESULTS: The patients were followed for a mean of 48.8 months. Four of the six responded to the treatment at a mean of 3.5 months. Two of these patients had a recurrence within a mean of 4.5 months after their initial response. Two patients did not respond to progestin treatment. At surgery in those 4, both endometrial and ovarian tumors were found. All 6 are still alive, and 2 successfully delivered healthy infants. The clonality assay revealed an independent cell origin for the endometrial and ovarian lesions in 2 of the 4 women who failed progestin treatment. Progesterone receptors were absent in both endometrial and ovarian tumors in 2 of these 4 patients. CONCLUSION: The absence of progesterone receptors may relate to the failure of progestin treatment. The use of progestin treatment for well-differentiated early endometrial carcinoma should be cautious and requires very careful clinical evaluation before and after treatment.     

Pregnancy induced with menotropins in a woman with polycystic ovaries, endometrial hyperplasia, and adenocarcinoma

A 31-year-old woman is described with PCOD associated with endometrial hyperplasia and well-differentiated adenocarcinoma. Conservative treatment with ovulation induction was pursued for a total of 3 1/2 years. After CC treatment failed to achieve conception, treatment with menotropins resulted in a twin pregnancy that aborted spontaneously and a singleton term pregnancy. Hysterectomy was performed 4 1/2 years after the initial diagnosis of well-differentiated endometrial adenocarcinoma was made. Histologic examination of the endometrium showed no progression of the disease. Ovulation induction of patients with polycystic ovaries and well-differentiated and noninvasive endometrial adenocarcinoma may be justified in properly selected cases.     

40岁以下子宫内膜腺癌患者的孕激素治疗--附六例报告及文献复习

目的 评价孕激素治疗40岁以下高分化、早期子宫内膜腺癌患者的有效性和安全性.方法回顾性分析复旦大学附属肿瘤医院1996年至2004年以孕激素治疗作为初次治疗的6例 40岁以下的高分化、早期子宫内膜腺癌患者的临床病理资料;同时检索近10年的国内外相关研究报道,发现相关病例56例,对以上两组资料进行综合分析.结果本组6例患者中,4例孕激素治疗有效,2例无效者行手术治疗.4例有效者中,2例分别于治疗后10个月和12个月出现复发而行手术治疗,故共有4例行子宫切除术,术后病理检查均未发现子宫外转移.6例患者随访至今均无瘤生存.文献报道的56例患者中,46例孕激素治疗有效,其中11例复发者中7例再次采用孕激素治疗,且5例再次获得完全缓解.此56例中,共有16例行手术治疗,15例无瘤生存,1例术后出现盆腔复发.本组6例患者治疗后无妊娠和分娩;文献报道的56例患者中,共有41次妊娠,并分娩40个婴儿,其中双胎4例,三胎2例.结论孕激素治疗40岁以下高分化、早期子宫内膜腺癌我们的经验尚少,虽难作评价,但国内外文献报道是安全可行的,并可达到妊娠和分娩的目的.     

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.     

年轻早期高分化子宫内膜样腺癌患者保守治疗新进展

子宫内膜癌（EC）是常见的妇科恶性肿瘤,对年轻未生育的早期高分化子宫内膜样腺癌患者来说,保守治疗显得尤为重要。传统保守治疗药物包括孕激素、促性腺激素释放激素类似物（GnRHa）和芳香化酶抑制剂（AIs）等。宫腔镜电切术联合孕激素治疗是年轻子宫内膜样腺癌患者保留生育功能的新型治疗方式,在缓解率、妊娠率、不良反应发生率和复发率等方面优于传统保守治疗,但目前关于手术操作及术后激素治疗尚无统一标准。肥胖EC患者应治疗肥胖以降低复发风险,其中以减重手术效果最为显著、持久。现已证实减重手术对体质量指数（BMI）≥35 kg/m2的早期高分化子宫内膜样腺癌患者是有效干预。建议BMI≥35 kg/m2或BMI≥30 kg/m2且合并代谢综合征/2型糖尿病的年轻早期高分化子宫内膜癌患者,若经非手术治疗肥胖疗效不佳,可考虑以减重手术作为辅助治疗     

Clinicopathologic study of uterine endometrial carcinoma in young women aged 40 years and younger

To clarify what constitutes the adequate management of uterine endometrial carcinoma in young women, we reviewed clinicopathologically 31 patients aged 40 years and younger between January 1991 and June 2004. As a primary treatment, 12 cases chose hormonal treatment with medroxyprogesterone acetate (MPA; 600 mg/day) due to no findings of myometrial invasion and diagnosis of a grade 1, well-differentiated adenocarcinoma. In remaining 19 cases, surgery was performed. All the 19 patients who received surgery as a primary treatment are alive, with no evidence of a recurrence of the disease. In the 12 patients who received hormonal treatment, 8 patients eventually received a hysterectomy because of recurrence or no response to MPA. Of these eight patients, myometrial invasion was recognized in three patients. One of the eight patients died of the metastasized disease to the liver and brain after hysterectomy. After hormonal treatment, 4 of the 12 patients were exempted from surgery and showed no evidence of recurrence. Two patients had viable children. Progesterone receptor was negative in one case that died. Careful consideration should be given to hormonal treatment with MPA for the conservative management of endometrial carcinoma in young women. Moreover, MPA is not always a consistent management for every patient.     

A successful pregnancy after intracytoplasmic sperm injection and embryo transfer in a patient with endometrial cancer who was treated conservatively

OBJECTIVE: To describe a patient with polycystic ovary syndrome (PCOS) conceiving with intracytoplasmic sperm injection (ICSI) and embryo transfer after conservative treatment of early stage endometrial cancer. DESIGN: Case report. SETTING: Tertiary center for assisted reproductive technologies.A 32-year-old woman with PCOS, primary infertility of 4 years duration, and grade 1 endometrioid endometrial cancer. INTERVENTION(S): Assessment of myometrial invasion and extrauterine spread with magnetic resonance imaging (MRI) and explorative laparotomy. High-dose progestin treatment and ICSI and embryo transfer. MAIN OUTCOME MEASURE(S): Successful take-home baby and no residual endometrial cancer. RESULT(S): A healthy normal female infant with a birth weight of 1740 g was born by cesarean section at 30 weeks' gestation. No residual cancer was detected at the follow-up curettage performed 2 months after the delivery. CONCLUSION(S): Conservative uterus-preserving treatment may be considered in patients with early stage endometrial cancer. Assisted reproductive technologies may be used in such patients for immediate achievement of pregnancy.     

Ovarian metastasis in a nulliparous woman with endometrial adenocarcinoma failing conservative hormonal treatment

BACKGROUND: There have been several reports about successful fertility-preserving treatment of endometrial carcinoma with subsequent pregnancy. However, conservative hormonal treatment for early-stage endometrial cancer still entails some risk. CASE: We present a 36-year-old nulliparous woman, initially diagnosed as clinical stage IA, grade 1 endometrial adenocarcinoma, receiving 6-month conservative treatment with remission achieved at 4 months from diagnosis. Recurrence at the endometrium was documented at the end of treatment. She underwent a definitive surgery including total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. The final pathology revealed well-differentiated endometrioid adenocarcinoma with inner one-third myometrial invasion and right ovarian metastasis. CONCLUSION: This case report signals a warning that negative preoperative imaging studies are not reassuring for a relapsing low-grade, early-stage endometrial carcinoma failing conservative treatment.     

Endometrial cancer and fertility

PURPOSE OF REVIEW: Endometrial cancer can affect reproductive-age women who may desire fertility preservation. This article discusses the current, available data about conservative management of endometrial cancer in young women. RECENT FINDINGS: Reproductive-age women with well differentiated endometrial carcinoma have an overall favorable prognosis provided that the tumor is identified at an early, noninvasive stage; however, advanced disease can be present. This article discusses current modalities to evaluate and clinically stage endometrial cancer including hysteroscopy, dilation and curettage, pelvic ultrasound, abdominopelvic computed tomography scan, pelvic magnetic resonance imaging, tumor marker CA125 level, and surgical exploration with laparoscopy or laparotomy. Thorough evaluation is critical as 10 to 29% of young women with endometrial cancer have a synchronous ovarian malignancy. Detailed counseling about the risks and benefits of conservative management, and expectations for fertility after treatment, surveillance, and definitive surgical management is essential. Multiple effective protocols exist for conservative treatment of endometrial cancer, and the initial response rates are as high as 57 to 75%. Successful pregnancies have occurred after conservative management, spontaneously, and with assisted reproductive technologies. SUMMARY: There are no standard recommendations for selection of appropriate women, treatment protocols, or long-term surveillance for conservative management of clinical stage I endometrial adenocarcinoma, and larger prospective clinical studies are warranted.