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。     

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.     

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.     

Endometrial cancer

Endometrial carcinoma is the most common gynaecological malignancy in the Western world. The standard management of endometrial carcinoma is total hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymph-node dissection. Increasingly, endometrial cancer is being diagnosed in younger women in whom preserving fertility may be an important consideration when deciding optimal management. Conservative management of endometrial carcinoma may be a therapeutic option in carefully selected women with well-differentiated endometrial cancer in the absence of any myometrial invasion or adnexal disease seen on imaging. The biggest concern with conservative management of endometrial carcinoma is disease progression while on treatment or after initial response to medical treatment. Women opting for conservative management should be aware that hormonal therapy is not the standard form of management. Potential adverse outcomes should be taken into consideration.     

A rare case of choroidal metastasis presented after conservative management of endometrial cancer

Hematogenous dissemination from endometrial cancer is quite rare. We report a 31-year-old woman who developed choroidal metastasis following conservative management of early-stage endometrial carcinoma. She had received kidney transplantation and was taking steroids and cyclosporine. Three years after hysterectomy for persistent endometrial carcinoma, she developed multiple metastatic disease (to both lungs and right pelvis), and while on treatment with paclitaxel and carboplatin, she complained of a rapid visual deterioration. Ophthalmologic evaluation revealed a metastatic choroidal tumor associated with multiple central nervous system metastases. The patient refused further treatment and died 1 month after diagnosis of choroidal involvement. In conclusion, this is the first reported case of choroidal metastasis from endometrial cancer and highlights the need to consider immunosuppressive treatment as an absolute contraindication to conservative fertility-sparing treatment in gynecological malignancies.     

Successful in vitro fertilization pregnancy after conservative management of endometrial cancer

OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after conservative management of endometrial cancer. INTERVENTION(S): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts. RESULT(S): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.     

Fertility-sparing management of endometrial adenocarcinoma

Approximately 15% of patients with endometrial cancer are premenopausal. Previous studies largely support the conservative treatment of endometrial cancer in women desiring future fertility. From these studies, 75% to 80% of patients demonstrate a complete response to progestin therapy and the average recurrence rate is 30% to 35%. Conservative therapy should be reserved for women with International Federation of Gynecology and Obstetrics grade I tumors. Before conservative management, patients should be informed of the elevated risk (11%-29%) of concurrent ovarian cancer in cases of premenopausal endometrial cancer, and screening and ongoing surveillance during the treatment period is mandatory. A suggestion of myometrial invasion or metastatic disease is a contraindication to conservative management. Individuals meeting criteria for Lynch syndrome testing should be referred to genetic counseling. Fertility treatment should be individualized, and close surveillance is required during treatment. Staging hysterectomy is recommended after the completion of the childbearing period. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After participating in this activity, physicians should be better able to select appropriate candidates with endometrial cancer for fertility-sparing treatment. Educate patients with endometrial cancer regarding the risks and benefits of standard of care therapy and conservative therapy and screen appropriate patients for Lynch syndrome.     

Young patients with endometrial carcinoma selected for conservative treatment: a need for vigilance for synchronous ovarian carcinomas, case report and literature review

BACKGROUND: The aim of this paper is to report a case of synchronous ovarian malignancy in a very young patient with early endometrial cancer who desired fertility-sparing management. CASE: Twenty one-year-old patient presented with an apparent early stage endometrial cancer and desiring conservative management. After failure of conservative management for 3 years, surgery was performed. An incidentally small papillary serous ovarian tumor of low malignant potential was found. CONCLUSION: Careful preoperative and intraoperative assessment of the adnexa is mandatory in young women with endometrial cancer. Those who desire ovarian preservation should be counseled regarding the high potential for coexisting ovarian malignancy.     

Outcomes from assisted reproductive technology

The use of assisted reproductive technology (ART) for treating the infertile couple is increasing in the United States. The purpose of this paper is to review the short-term outcomes after ART. Pregnancy rates after ART have shown nearly continuous improvement in the years since its inception. A number of factors affect the pregnancy rate, with the most important being a woman's age. Certain clinical diagnoses are associated with a poorer outcome from ART, including the presence of hydrosalpinges, uterine leiomyomata that distort the endometrial cavity, and decreased ovarian reserve. Multiple gestations are the major complication after ART. New laboratory techniques, including extended embryo culture, may allow the transfer of fewer embryos to maintain pregnancy rates while reducing the risk of multiple gestations. Although much of the morbidity in children born after ART is the result of multiples, recent analysis suggests that even singletons are at higher risk for perinatal morbidity, including preterm delivery and small for gestational age infants. In vitro fertilization may be associated with a slight increased risk for birth defects. The major short-term complication of ART in women is the development of ovarian hyperstimulation syndrome. This syndrome is difficult to predict, but new treatments are being developed that may limit its frequency. Because of its high pregnancy rate, couples are moving to ART more quickly in the management of their infertility. All outcomes of ART, including pregnancy rates and adverse complications, need to be compared with standard non-ART therapy when deciding the appropriate course of treatment for a given couple.     

Measurement of endometrial volume and endometrial thickness for assessment of endometrial receptivity in assisted reproductive techniques

The authors investigated the role of 3D endometrial volume measurements as a predictor of clinical pregnancy in ART and comparison between endometrial volume and endometrial thickness in order to find the better predictor for endometrial receptivity in ART. Endometrial volume emerged recently as a new efficient predictor of endometrial response to hormonal stimulation and successful implantation. In this clinical study, participated 58 infertile patients undergoing IVF-treatment, during the period from 01.01.2004 till 01.01.2005. Endometrial volume of < 2 ml on the day of Embryotransfer (ET) was a better predictor for low endometrial receptivity, than Endometrial thickness on the same day and resulted in significant lower IVF clinical pregnancy and implantation rates. Endometrial volume > 2 ml on the day of ET was a positive predictor for ART outcome.     

The thin endometrium in assisted reproductive technology: An ongoing challenge

Thin endometrium is identified to adversely affect reproductive success rates after assisted reproductive technology (ART). Several treatment modalities have been presented to patients with thin endometrium, to improve endometrial thickness and the subsequent endometrial receptivity. These approaches comprising hormonal management by estradiol, tamoxifen, human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonist, vasoactive agents such as aspirin, vitamin E, pentoxifylline, nitroglycerin and sildenafil, intra-uterine infusion of growth factor such as Granulocyte Colony Stimulating Factor (G-CSF) and the latest application of platelet-rich plasma, electrical stimulation, regenerative medicine and presentation of endometrial receptivity array. In spite of the large variety of treatment, most of the choices achieve only minor modification in the endometrium thickness and have not been validated so far. Treatment of thin endometrium remains a challenge and future enormous investigations are required to further clarification and ideal management of patients with thin endometrium.     

不孕症合并子宫内膜息肉的临床处理及预后

子宫内膜息肉是最常见的良性子宫内膜病变之一,可能通过机械梗阻和炎症刺激影响妊娠的发生而导致不孕。经阴道超声是内膜息肉的主要筛查手段,宫腔镜检查及直视下病理活检则是内膜息肉诊断的金标准。宫腔镜手术切除息肉可以提高自然妊娠和辅助生殖技术的成功率,然而息肉切除是否作为辅助生殖技术实施前的常规治疗目前尚有争议。子宫内膜息肉术后复发的预防、促排卵过程中新发息肉的处理是目前的两个临床难题,需要一系列设计严谨的临床及基础研究为息肉的处理提供更有说服力的理论和实践依据。     

评估和改善子宫内膜容受性治疗反复种植失败的研究进展

反复种植失败(RIF)是困扰辅助生殖技术(ART)发展的难题,子宫内膜容受性是体外受精-胚胎移植(IVF-ET)成功的关键因素。如何提高RIF患者的子宫内膜容受性日益受到生殖医学界的关注。本文从子宫内膜容受性评价常用临床方法到宫腔镜治疗宫腔结构异常、子宫内膜机械性损伤、调节母-胎免疫容受性、药物抑制子宫收缩、改善子宫内膜厚度、改善子宫内膜血流等方面,对RIF的治疗方法进行了阐述与总结,以期为未来的科学研究及临床治疗提供参考。     

Endometrial stromal sarcoma diagnosed after hysteroscopic endometrial resection

Endometrial ablation and resection is now common therapy for dysfunctional uterine bleeding that is unresponsive to conservative management. Opponents argue that it may predispose patients to potentially hazardous malignancies of the uterus. In our patient, endometrial resection was performed to treat menorrhagia after a negative workup. Pathologic interpretation of the resected tissue showed a low-grade stromal sarcoma of the endometrium. The woman underwent definitive treatment, which included total abdominal hysterectomy, and has remained recurrence free over the past 3 years. Although rare, uterine malignancies have been documented after hysteroscopic management of menorrhagia. It is suggested that intraoperative endometrial resection or tissue sampling be done to prevent or diagnose endometrial hyperplasia and uterine malignancies.     

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.     

Hysteroscopic Resection of Endometrial Polyps and Assisted Reproductive Technology Pregnancy Outcomes Compared with No Treatment: A Systematic Review

Endometrial polyps are frequently encountered in the uterine cavity of infertile women. There is much debate regarding the treatment of endometrial polyps in patients who are undergoing assisted reproductive technology (ART). A systematic review was performed by searching PubMed, Embase, and the Cochrane Library for retrospective or prospective studies that compared the effect of hysteroscopic resection of polyps with no treatment on pregnancy outcomes of patients who underwent ART. The primary outcomes were clinical pregnancy, live birth, miscarriage, and implantation rates after ART. Eight studies with a total of 2267 patients were included. The results showed that hysteroscopic resection of endometrial polyps (mean size <2 cm) was associated with an increased rate of clinical pregnancy in patients who underwent intrauterine insemination. No clear benefit was observed for clinical pregnancy, live birth, miscarriage, or implantation rates in patients who underwent in vitro fertilization/intracytoplasmic sperm injection cycles. In conclusion, the effect of hysteroscopic polypectomy on pregnancy outcomes of patients who have undergone ART remains unclear. More prospective, randomized controlled trials are warranted to determine appropriate treatment.     

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.     

A need for laparoscopic evaluation of patients with endometrial carcinoma selected for conservative treatment

BACKGROUND: The aim of this paper was to report two cases of extrauterine disease in patients with early stage endometrial cancer (EC) who desired fertility-sparing management. CASES: Two patients presenting an apparent early stage EC and desiring conservative management. The two patients, aged 35 and 36 years old, had a grade 1 and grade 2 EC diagnosed after curettage or hysteroscopic resection of a polyp. Ultrasound (US) imaging was normal (ovary). Once informed about the risk of recurrence, both patients opted for conventional therapy (hysterectomy with bilateral salpingo-oophorectomy). A small ovarian carcinoma was found in one patient and isolated positive peritoneal cytology in the other. CONCLUSIONS: These cases seem to suggest that laparoscopic evaluation including adnexal exploration and peritoneal cytology (and possibly pelvic lymphadenectomy) should be performed in patients with early stage EC selected for conservative management to confirm the absence of extrauterine disease.     

Fertility sparing therapy for ovarian cancer has inherent risks and benefits

Introduction: Fertility sparing therapy for epithelial ovarian cancer has been suggested for well-selected patients with early stage disease. The overall recurrence rate of 10% and 5-year disease free survival greater than 90% is similar in conservative and traditional surgical management of epithelial ovarian cancer. Thus, conservative approaches may be considered in young women diagnosed with FIGO stage I cancer who wish to preserve reproductive function. Subsequent use of assisted reproductive technologies (ART) may facilitate production of biologic offspring in these cancer survivors. However, each candidate requires unique consideration by subspecialists to avoid potentially fatal management errors. Case report: We present two cases in which fertility sparing therapy for early stage epithelial ovarian cancer was considered. The first case delineates the comprehensive work-up required to identify candidates for this therapy, while the second case illustrates the successful application of a fertility sparing approach. Discussion: The conservative management of early epithelial ovarian cancer and use of ART to obtain offspring are reviewed.     

子宫内膜不典型增生和早期子宫内膜癌保守治疗方案分析

随着癌症发病的年轻化,患有子宫内膜癌的育龄期女性越来越多。为了保留生育能力,大部分患者倾向于保守治疗。故而众多研究者提出了子宫内膜不典型增生和早期子宫内膜癌的保守治疗方案,并在临床上进行了小样本研究。传统治疗以口服大剂量孕激素为主,然而多数口服孕激素治疗的患者复发率高、并发症多。左炔诺孕酮宫内缓释节育系统通过局部作用于子宫内膜,可减少大量孕激素对机体造成的不良反应。宫腔镜能够精准切除病灶,保护正常子宫内膜,相对降低了发生不孕、流产风险。二甲双胍的抗肿瘤作用能增加孕激素的有效率。通过综述子宫内膜不典型增生和早期子宫内膜癌各种保守治疗后的缓解率、复发率和妊娠结局,为临床上在治疗前对每位患者的自身因素及疾病特点进行评估,以采取对患者最有益的治疗方案及管理模式提供依据。