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。     

早期子宫内膜癌和子宫内膜非典型增生患者保留生育功能治疗后的助孕策略研究进展

近年来,早期子宫内膜癌及子宫内膜非典型增生在年轻女性中的发病率逐渐升高,大剂量孕激素保留生育功能治疗为年轻患者提供了生育机会.本文将围绕近年的研究分析此类患者保留生育功能治疗后合适的妊娠时机及助孕方式,探讨适合此类患者安全有效的助孕策略,旨在提升此类患者保育治疗后的妊娠成功率.     

不孕症合并子宫内膜非典型增生及早期高分化子宫内膜样腺癌保守治疗后体外受精助孕的临床分析

目的探讨不孕症合并子宫内膜非典型增生(AEH)及早期高分化子宫内膜样腺癌(EC)药物保守治疗后体外受精(IVF)助孕时机、疗效及安全性。方法回顾性分析本中心不孕症合并AEH及EC保守治疗后行IVF助孕患者的临床资料,根据患者首次子宫内膜病理证实病变完全消退(CR)后开始IVF助孕时间分为≤3个月组(A组,n=35)和3个月组(B组,n=25),比较组间患者的临床结局。结果共纳入60例患者,AEH患者45例,EC患者15例,首次CR后随访时间(39.6±26.9)个月。共行95个取卵周期,新鲜胚胎移植(IVF-ET)67个周期,周期妊娠率为38.8%(26/67),冻融胚胎移植(FET)54个周期,周期妊娠率为25.9%(14/54)。共有36例患者妊娠47次,25例患者分娩32个活婴。患者IVF-ET周期妊娠率及FET周期妊娠率组间比较差异均无统计学意义,而B组复发率(48.0%)明显高于A组(17.1%,P=0.022)。多因素分析显示仅IVF助孕时间与复发有关(P=0.002,OR=1.078,95%CI=1.027~1.132)。随访期间总复发率为30.0%(18/60),无疾病进展及死亡不良事件。结论不孕症合并AEH及早期EC患者药物保守治疗后IVF助孕是相对安全有效的,复发与首次CR后IVF助孕时间有关,为降低复发宜尽早行IVF助孕。     

大剂量孕激素治疗子宫内膜不典型增生及早期子宫内膜癌的疗效及妊娠结局分析

目的:探讨大剂量孕激素治疗子宫内膜不典型增生及早期子宫内膜癌的疗效及妊娠结局。方法:选择2014年1月至2018年12月广州医科大学附属第三医院就诊的年轻且有生育要求的子宫内膜不典型增生患者24例及早期子宫内膜样腺癌患者6例,分析应用大剂量孕激素保守治疗的临床效果及妊娠结局。结果:24例子宫内膜不典型增生患者中完全缓解20例(83.33%),部分缓解0例,疾病稳定1例(4.17%),疾病进展1例(4.17%),疾病复发2例(8.33%);20例完全缓解中1例未婚,余19例中成功妊娠10例(52.63%),其中4例足月分娩,3例孕中期双胎流产,2例孕早期流产,1例孕早期随访中;2例疾病复发患者继续药物治疗后均完全缓解,其中1例自然受孕后足月分娩。6例早期高分化子宫内膜样腺癌完全缓解3例(50.00%),部分缓解0例,疾病稳定2例(33.33%),疾病进展0例,疾病复发1例(16.67%);疾病稳定2例最终行子宫内膜癌全面分期手术,余4例保留生育功能患者目前未成功妊娠。结论:密切随访下,大剂量孕激素治疗子宫内膜不典型增生和早期子宫内膜癌是安全有效的。     

未生育妇女卵巢早衰13例临床分析

目的:通过对未生育妇女卵巢早衰患者行激素周期治疗和促排卵治疗,评价其疗效,探讨可能有效的促排卵方案。方法:对13例患者行雌孕激素周期治疗3～6个周期,观察治疗前后患者临床症状、血清激素水平及盆腔超声相子宫的变化,并采用3种方案促排卵治疗。结果:13例患者经雌孕激素治疗3～6个周期后,血清卵泡刺激素(FSH)、黄体生成素(LH)水平明显下降(P<0.01),血清雌二醇(E2)与服药前相比差异无显著性(P>0.05),与治疗前比较B超子宫横切面的横径、前后径有增厚(P<0.05),但子宫纵切面的长径与治疗前相比差异无显著性(P>0.05),子宫内膜显著增厚(P<0.01)。以人绝经期促性腺激素(HMG)/人绒毛膜促性腺激素(HCG)方案和促性腺激素释放激素激动剂(GnRHa)/HMG/HCG方案促排卵治疗有成熟卵泡发育并各有1例妊娠。结论:卵巢早衰患者应尽可能查明病因,针对病因治疗,并尽早行激素周期治疗,有利于促排卵治疗成功,HMG/HCG和GnRHa/HMG/HCG这两种促排卵方案均有可行性。     

人绝经期促性腺激素联合氯米芬或来曲唑用于多囊卵巢综合征患者促排卵疗效比较

的探讨人绝经期促性腺激素（HMG）＋氯米芬（CC）、HMG和来曲唑（LE）＋HMO对多囊卵巢综合征（PCOS）患者宫腔内供精人工授精的治疗效果。方法将2007年12月-2008年5月期间在我中心就诊的114例PCOS妇女的114个宫腔内人工授精（AID）周期分为3组：CC＋HMG周期组38个周期，HMG周期组38个周期，LE＋HMG周期组38个周期。分析比较3组的年龄、血清T水平、绒毛膜促性腺激素肌肉注射日（HCG日）平均卵泡直径（MFD）≥14mm的卵泡（成熟卵泡）个数、平均卵泡E2水平、子宫内膜厚度、HCG日单优势卵泡发育成熟百分率、HMG用量和周期妊娠率。结果CC＋HMG组、HMG组和LE＋HMG组患者年龄和血清T水平比较，差异无显著性（P〉0．05），CC＋HMG组HCG日成熟卵泡个数为（2．9±1．6）个，明显多于其他两组[HMG组为（1．6±1．0）个，LE＋HMG组为（1．9±1．2）个]，差异有显著性（P〈0．05），而内膜厚度较其他两组薄，差异有显著性（P〈0．05），HMG组与LE＋HMG组HCG日成熟卵泡个数和子宫内膜厚度比较，差异无显著性（P〉0．05）。3组HCG日单优势卵泡发育成熟百分率分别21．05％、78．95％和52．63％，差异有显著性（P〈0．05）。CC＋HMG组、HMG组和LE＋HMG组HMG用量分别为（4．89±1．59）支和（9．88±4．59）支、（9．68±4．67）支（75IU／支），CC＋HMG组与后两组比较，差异有显著性（P=0．00）。HMG组、LE＋HMG组HMG用量比较，差异无显著性（P〉0．05）。3组的周期妊娠率分别为36．84％、39．48％和31．57％，差异无显著性（P〉0．05）。结论HMG促排卵周期更易得到单优势卵泡发育成熟；CC＋HMG促排卵HMG用药量最少；CC＋HMG、HMG和LE＋HMG均可获得满意的周期妊娠率。     

促排卵治疗后子宫内膜厚度及妊娠率的临床分析

目的 探讨不同促排卵治疗后子宫内膜厚度及妊娠率。方法 采用宫颈粘液评分(CMS)、放射免疫法测定雌激素(E2)水平,阴道超声观察用克罗米芬(CC)、CC/戊酸雌二醇(CC/E)、CC联合绝经期促性腺激素(CC/HMG)及促性腺激素激动剂联合HMG(GnRH-a/HMG)促排卵方案治疗后的卵泡成熟情况,并测量注射HCG日的子宫内膜厚度,分析不同促排卵方案子宫内膜的厚度及其受孕率。结果 子宫内膜厚度≥7 mm者,周期妊娠率为17.1％,明显高于子宫内膜<7 mm者(3.45％)(P<0.05);应用CC、CC/E促排卵方案注射HCG日子宫内膜厚度≥7 mm的比率明显小于CC/HMG及GnRH—a/HMG方案;CC及CC/E促排卵方案注射HCG日,子宫内膜厚度差异无显著性(P>0.05);GnRH—a/HMG方案LH值小于CC、CC/E及C/HMG方案,而E2值明显大于CC及CC/E方案,小于CC/HMG方案,CC及CC/E的E2水平差异无显著性(P>0.05)。结论 CC对子宫内膜的周期性增殖具有不良影响。而GnRH—a及HMG的使用则可提高子宫内膜的厚度,增加受孕能力。     

三维超声参数对IVF/ICSI-ET妊娠结局的预测价值

目的:探讨三维超声参数对体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSIET)妊娠结局的预测价值。方法:回顾性分析697例行IVF/ICSI助孕患者h CG注射日子宫内膜及内膜下超声参数,根据临床妊娠与否分组,比较妊娠组与非妊娠组的资料,并进一步根据促排卵方案行分层分析,研究各项超声参数与妊娠结局的关联。结果:1妊娠组的年龄、不孕年限和IVF周期数显著低于非妊娠组(P0.05),而妊娠组的子宫内膜厚度、内膜体积大于非妊娠组(P0.05),妊娠组螺旋动脉收缩期速度(PSV)和舒张末期速度(EDV)、内膜下1 mm血流指数(FI)、内膜下3 mm的FI和血管血流指数(VFI)高于非妊娠组,差异均有统计学意义(P0.05)。2超声参数与长方案患者妊娠结局无明显关联,而在短方案促排卵患者中,妊娠组和非妊娠组的内膜厚度及螺旋动脉EDV存在统计学差异(P0.05)。3Logistic回归显示周期数和内膜厚度可作为短方案患者妊娠结局的预测指标,受试者工作特征(ROC)曲线分析也提示内膜厚度对妊娠具有一定的预测价值。结论:IVF/ICSI患者h CG注射日子宫内膜和内膜下三维超声参数对妊娠结局的预测价值十分有限,内膜厚度对短方案患者妊娠具有一定的预测作用。     

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.     

轻度子宫内膜异位症患者供精人工授精治疗方案的比较

目的:探讨轻度子宫内膜异位症患者在腹腔镜诊治术后2年内,自然周期和促排卵周期供精人工授精(AID)的妊娠结局。方法:回顾性分析303周期(168例)无排卵障碍的轻度子宫内膜异位症患者AID情况,比较在腹腔镜诊治术后2年内,自然周期(78例,195周期)与促排卵周期(90例,108周期)AID助孕后的周期妊娠率;同时比较在促排卵周期中,单卵泡排卵与多卵泡排卵的周期妊娠率。结果:在所有研究患者中,妊娠47例,其中自然周期妊娠率为16.9%(33/195),促排卵周期妊娠率为13.0%(14/108),二者比较差异无统计学意义(P=0.362)。在促排卵周期中,单卵泡排卵周期妊娠率13.5%(7/52),多卵泡排卵周期妊娠率12.5%(7/56),二者比较差异无统计学意义(P=0.882)。结论:对于排卵正常的轻度子宫内膜异位症患者,在助孕方式的选择中,可以优先选择自然周期人工授精。     

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.     

Young women with atypical endometrial hyperplasia or endometrial adenocarcinoma stage I: will conservative treatment allow pregnancy? Results of a French multicentric survey

OBJECTIVES: To analyse the carcinological and obstetrical results of young women with atypical endometrial hyperplasia or endometrial adenocarcinoma, treated in a conservative way to allow pregnancy. PATIENTS AND METHODS: A retrospective analysis of 13 cases (5 adenocarcinomas and 8 atypical hyperplasias) followed in 8 French centers between 1997 and 2004. RESULTS: After 4.6 months of conservative treatment, there were no residual lesions in 61.5% of the cases. Progestatives seem to be the most effective treatment. Tumoral regression makes it possible to plan a pregnancy, with childbirth in 25% of the cases. In these frequently infertile patients, all the techniques of assisted reproduction can be used. Recurrences are not rare after hormonal treatment (37.5%), so, total hysterectomy is justified after delivery. DISCUSSION AND CONCLUSION: Conservative treatment for young women with atypical endometrial hyperplasia or endometrial adenocarcinoma stage I can be considered in some cases to enable pregnancy.     

Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate

OBJECTIVE: To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. DESIGN: Prospective trial in infertility patients treated with CC. SETTING: Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates. RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.     

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.     

Update in polycystic ovary syndrome: new criteria of diagnosis and treatment in Japan

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women of reproductive age. In 2006 the Japanese Society of Obstetrics and Gynecology (JSOG) proposed new, revised diagnostic criteria that in the future could also be valued internationally. Based on the new diagnostic criteria, the JSOG has also proposed the revised treatment criteria in 2008. In PCOS obese patients desiring children, weight loss and exercise is recommended. Nonobese patients, or those obese women who do not ovulate after lifestyle changes, are submitted to ovulation-induction therapy with clomiphene citrate (CC). Obese CC-resistant patients who have impaired glucose tolerance or insulin resistance are treated with a combination of metformin and CC. If these treatments options are unsuccessful, ovulation induction with exogenous gonadotropin therapy or laparoscopic ovarian drilling (LOD) is recommended. A low-dose step-up regimen is recommended with careful monitoring in order to reduce the risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Alternatively, with LOD high successful pregnancy rates of around 60 % are expected with a low risk of multiple pregnancies. If ovulation induction is unsuccessful, IVF-ET treatment is indicated. In high OHSS-risk patients, systematic embryo freezing and subsequent frozen embryo transfer cycles are recommended. In nonobese, anovulatory PCOS patients not desiring children, pharmacological treatments such as Holmström, Kaufmann regimens or low-dose oral anticonceptives are used to induce regular withdrawal bleeding. These treatments are especially important for preventing endometrial hyperplasia and endometrial cancer. These new diagnostic and treatment criteria hopefully will contribute to an improved care of PCOS patients in Japan.     

自然及促排卵周期子宫内膜整合素α4β1的表达

目的 了解氯米芬（CC）、绝经期促性腺激素（hMG）对黄体中期子宫内膜整合素α4β1表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术检测48例正常妇女自然周期以及48例正常妇女、30例多囊卵巢综合征患者应用CC／绒毛膜促性腺激素（hCG）及CC／hMG/hCG方案促卵治疗后黄体中期子宫内膜整合素α4β1的表达。结果 子宫内膜整合素α4β1在正常妇女自然周期着床窗口期呈现强阳性表达,而CC、hMG抑制整合率α4β1的表达,两者比较,差异有极显著性（P＜0．01）;妊娠者较妊娠者整合素α4β1表达强度高。结论 促排卵周期黄体中期整合素α4β1表达下降或缺失,子宫内膜容受性下降,妊娠率降低。     

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.     

The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study

In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75?mg gonadotropin-releasing hormone agonist (GnRHa) ? leuproreline acetate depot every 4 weeks. After the third injection of 3.75?mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52?mg levonorgestrel (Mirena^®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75?mg of GnRHa every 4 weeks. After the third injection of 3.75?mg of GnRHa, we also inserted a GnRH-IUS (Mirena^®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.