恶性肿瘤患者卵巢功能的保护

放化疗严重损害患者的卵巢功能和生育能力。保护卵巢功能和生育能力的方法有药物、卵巢移位、卵巢移植和冷冻保存技术等。最有效的药物为促性腺激素释放激素激动剂（GnRHa），对化疗引起的卵巢损害有效。卵巢移位对盆腔放疗引起的卵巢损害有效。胚胎冷冻技术成熟。卵巢冷冻移植、卵母细胞冷冻和未成熟卵母细胞体外成熟（IVM）技术尚不成熟，成功率低。     

放疗对宫颈癌根治术患者卵巢功能影响

目的 在保留并移位卵巢的ⅠB1-ⅡA2期根治术后需辅助放疗的年轻宫颈癌患者中,评估移位卵巢剂量学参数与临床不同卵巢功能状态之间相关性。方法 回顾2015-2017年间86例患者疗前和疗后2年内移位卵巢功能和临床相关症状,并评价放疗技术中移位卵巢的剂量学参数以及移位卵巢的功能状态之间的相关性。术后放疗采用不同体外保护移位卵巢,68例IMRT或VMAT,18例二维等中心放疗。结果 卵巢和PTV最近距离与卵巢剂量≥V5Gy呈负相关(P=0.025)。V8Gy、Dmean与疗后FSH(为卵巢血清卵泡刺激素,FSH)呈正相关(P=0.011、0.020)。即V8Gy体积越大Dmean越高,疗后FSH越高卵巢功能越差。二维技术中≥V5Gy低于三维技术,剂量降低明显。疗后卵巢功能正常者平均年龄33.4岁,而卵巢功能衰竭者平均年龄39.6岁(P=0.007)。不同卵巢状态患者间保留卵巢数目、是否同步化疗均相近,但与疗前FSH、E2(雌二醇)水平相关,即疗前FSH水平越高E2越低,疗后卵巢FSH水平越高E2越低。疗前保留卵巢但功能衰竭者均进行了新辅助化疗且年龄略高。结论 年龄,卵巢 V_{8 Cy}、D_mean,悬吊卵巢与 PTV 最近距离,疗前有无新辅助化疗及放疗技术均会影响移位卵巢功能的保护。     

宫颈癌患者卵巢移位手术后放射治疗对卵巢功能的作用分析

目的探讨卵巢移位术对宫颈癌患者放射治疗后卵巢功能的作用。方法选取2008年5月至2012年5月收治的40例宫颈癌患者为研究对象,行卵巢移位术治疗,并按照患者放射治疗指征在手术后进行放射性治疗,观察其手术前、手术后和放射治疗结束1个月后和放射治疗结束6个月后血清中性激素水平以及随访情况。结果手术后患者血清性激素水平无明显变化,化疗结束1个月后垂体分泌卵泡刺激素（FSH）和促黄体生成素（LH）水平明显上升,雌二醇（E2）和孕酮（P）水平明显下降（P〈0．05）,并于化疗结束6个月后恢复手术前水平。放射治疗结束6个月后,25例患者出现潮热、盗汗、烦躁、失眠等围绝经期症状,性生活满意度为37．5％,且复发1例,手术后生活质量（QOL）满意度为51．2％,无死亡病例。放射治疗结束1年后围绝经期症状自行消失,仅3例患者存在围绝经期症状,性生活满意度为95．0％,QOL满意度96．4％,2例复发,患者全部生存。放射治疗结束6个月与1年后两组在围绝经期症状、性生活满意度和QOL满意度差异均具有统计学意义（P〈0．05）。结论卵巢移位术能够有效保护宫颈癌患者放射治疗后卵巢功能,操作方便、疗效可靠,且明显降低了复发率,对患者手术后生活质量的提高具有重要意义,值得临床广泛推广。     

年轻宫颈癌患者卵巢功能保护的临床研究

目的 探讨年轻宫颈癌患者保留卵巢适应征范围及提高保留卵巢功能的方法 。方法 58例45岁以下宫颈癌患者实施了卵巢移位术,其中53例在根治术同时行卵巢移位术,包括6例宫颈腺癌病例及12例术前行髂内动脉介入化疗病例。术后辅助放疗16例。5例在根治性放疗前行单纯卵巢移位术。通过血清性激素水平的测定及随访性生活状况等评估术后卵巢功能。结果 58例卵巢移位术前术后血清性激素水平无统计学差别（P〉0.05）。卵巢移位术后放疗组雌、孕激素水平虽较未放疗组低（P〈0.05）,但仍显著高于根治性放疗组（P〈0.05）。随访中,无1例因卵巢转移复发。结论 卵巢移位术是保留年轻宫颈癌患者卵巢功能安全有效的方法 。恰当选择宫颈腺癌病例及通过新辅助化疗使部分中、晚期患者保留卵巢成为可能,尽可能的将卵巢移至远离放射野是提高保留卵巢功能的主要方法 。     

宫颈癌放疗时保留卵巢功能的研究进展

目前国内外研究报道均提示移位卵巢放疗后成功保留内分泌功能概率不高。宫颈癌放疗后卵巢功能与多种因素相关,如放疗剂量和方式、患者年龄、移位位置、同期化疗药物。因此对不同患者来说,放疗时需要控制卵巢组织在个体化剂量限制内才可能更加有效保留卵巢功能。     

腹腔镜手术对卵巢良性肿瘤创伤指标及卵巢功能的影响

目的探讨腹腔镜手术对卵巢良性肿瘤创伤及卵巢功能的影响。方法选取卵巢良性肿瘤患者120例,按门诊号编号,采用随机数字法分为观察组和对照组,每组60例。对照组实施开腹手术治疗,观察组实施腹腔镜手术治疗。比较两组患者围手术期相关指标,术后创伤指标及雌二醇(E2),促卵泡雌激素(FSH),促黄体素(LH)等卵巢功能检查指标水平变化。结果观察组术中出血量、手术时间、术后镇痛率与对照组相比均有统计学意义(P<0.05),而术后排气时间与对照组相比差异无统计学意义(P>0.05)。观察组患者治疗后WBC、CRP、IL-6与对照组相比,差异有统计学意义(P<0.05),而TNF-Α与对照组相比差异无统计学意义(P>0.05)。观察组患者治疗前后E2、FSH、LH水平变化不显著,差异无统计学意义(P>0.05),但治疗后1、3、6个月与对照组比较均有统计学意义(P<0.05)。结论腹腔镜手术治疗卵巢良性肿瘤对患者机体创伤影响较小,恢复较好,且不会对卵巢功能造成显著影响。     

腹腔镜下卵巢良性肿瘤剥除术对卵巢功能的影响分析

目的探索腹腔镜下卵巢良性肿瘤剥除术对卵巢功能的影响。方法将90例卵巢良性肿瘤(单侧)患者,按照随机数字表法分为腹腔镜组和开腹手术组,各45例。测定2组患者在术前和术后3、6个月及术后1年的卵泡刺激素(FSH)、雌二醇(E2)、黄体生成素(LH)水平,采用三维超声检测患者的窦状卵泡数(Fo)、巢体积(VOL)及卵巢髓质平均血流指数(FI),评价患者卵巢的储备功能以及随访记录患者术后1年内经量和月经周期的变化。结果 FSH、E2、LH以及VOL、Fo、FI在术前、术后3、6个月及术后1年水平组间差异无统计学意义(P>0.05),开腹组和传统手术组分别在术前、术后3、6个月及术后1年水平有轻微变化,但差异无统计学意义(P>0.05)。住院时间组间差异具有统计学意义(P<0.05),随访月经恢复情况组间具有统计学意义(P<0.05)。术后1年2组患者月经规律,无卵巢良性肿瘤复发现象。结论卵巢良性肿瘤采取不同手术方式治疗效果无明显差异性,但是腹腔镜手术的损伤小,患者住院时间短,术后恢复快,值得临床推荐。     

化疗致卵巢功能损伤的研究进展

化疗药物对女性癌症患者的卵巢功能造成损害,可引起卵巢功能早衰。损伤发生率及机制尚需进一步的研究,促性腺激素释放激素激动剂(GnRHa)似能够保护化疗时的卵巢功能,卵巢组织移植保护卵巢功能技术上可行,但尚需解决一些问题。     

化疗致卵巢功能损伤的研究进展

化疗药物对女性癌症患者的卵巢功能造成损害,可引起卵巢功能早衰。损伤发生率及机制尚需进一步的研究,促性腺激素释放激素激动剂（GnRHa）似能够保护化疗时的卵巢功能,卵巢组织移植保护卵巢功能技术上可行,但尚需解决一些问题。     

自体造血干细胞移植治疗恶性肿瘤进展

自体造血干细胞移植 ( AHSCT)是现阶段最常用的造血干细胞移植之一 ,近 1 0多年来 ,自体外周血造血干细胞移植 ( APBSCT)基础和临床研究发展迅猛 ,已基本取代早年常用的自体骨髓移植( ABMT)。目前 ,AHSCT主要应用于治疗恶性血液病和恶性实体肿瘤等。1　恶性淋巴瘤1 .1　霍奇金病 ( HD)　目前常规 MOPD/ ABVD方案结合放射治疗 HD的治愈率超过 60 % ,但对于复发 ,特别是难治性的 HD,常规化疗效果不佳。英国淋巴瘤协作组 ( BNLl) 1 993年报道采用常规化疗与自体骨髓移植治疗复发耐药 HD的前瞻性随机对照研究 ,结果常规化疗组 3…     

Ovarian preservation with gonadotropin-releasing hormone analog during chemotherapy

Objective: After the improved long‐term survival in young women with cancer undergoing chemotherapy, the preservation of their future fertility has been the focus of recent interest. We studied whether gonadotropin‐releasing hormone (GnRH) analogs could prevent the early onset of ovarian insufficiency post‐chemotherapy and protect fertility. Methods: The patients were divided into two groups. Group A consisted of post‐menarche patients aged 12–45 years (n = 15), who received chemotherapy but no GnRH analog protection. Group B consisted of post‐menarche patients aged 12–45 years (n = 15), who received chemotherapy with GnRH analog. The gonadotropin values in the two groups were checked. Both groups received a multi‐agent chemotherapy regimen (bleomycin, etoposide, cisplation, Taxol, carboplatin), (Taxol, cisplatinum) and (vincristin, actinomycin, cyclophosphamide) In group B, the GnRH analog was diphereline (3/75 mg). It was administered each month before and during treatment with chemotherapy. The first dose was administered 7 days before starting chemotherapy. Result: In group A, five patients (33%) had amenorrhea and premature ovarian failure. The laboratory values in these five patients showed increased gonadotropin. In group B, the most of patient resumed menstruation after 2–4 months. All these patients had a normal titer of gonadotropin. Conclusion: The GnRH analog co‐treatment should be considered in every woman of reproductive age receiving chemotherapy.     

流式细胞术检测肿瘤相关蛋白在人卵巢上皮性肿瘤裸鼠冻融卵巢组织移植中的意义

目的 通过对人卵巢上皮性肿瘤裸鼠原位移植瘤的癌旁组织相关蛋白的检测,探讨癌旁正常卵巢组织筛选的标准及冻融卵巢组织移植的可行性.方法 将人卵巢上皮性肿瘤OVCAR3细胞于裸小鼠颈背部近腋窝处皮下种植获取瘤源,行卵巢原位移植后,取癌组织、癌旁近端组织、癌旁中段组织、癌旁远端组织及正常裸鼠卵巢组织,采用流式细胞术检测各组织中的细胞角蛋白-7（CK-7）、CA125、p53、Survivin、基质金属蛋白酶-2（MMP-2）、金属蛋白酶组织抑制物-2（T1MP-2）的表达量;分别取全部指标阴性组、CK-7（-）CA125（-）Survivin（-）组、CK-7（＋）CA125（＋）Survivin（＋）组的组织、癌组织和冻融正常裸鼠卵巢组织进行移植,分析各组移植后的癌变率及CA125水平变化,同时检测原位移植后不同病变程度的裸鼠血清CA125水平.结果 从52份人卵巢上皮性肿瘤裸鼠原位移植瘤模型中获取46份（88.5％）活组织检查正常的癌旁残余卵巢组织;仅卵巢种植裸鼠血清CA125水平高于正常裸鼠（P＜0.01）,低于卵巢外种植裸鼠（P＜0.05）.原位移植瘤组织中CK-7、CA125、p53、Survivin、MMP-2及TIMP-2的表达率分别为93.3 ％（28/30）、93.3 ％（28/30）、86.7％（26/30）、86.7％（26/30）、83.3％（25/30）、83.3％（25/30）,癌旁近端组织的表达率分别为70.0％（21/30）、70.0％（21/30）、63.3％（19/30）、63.3％（19/30）、60.0％（18/30）、56.7％（17/30）,癌旁中段组织的表达率分别为33.3％（10/30）、30.0％（9/30）、30.0％（9/30）、30.0％（9/30）、26.7％（8/30）、23.3％（7/30）,癌旁远端组织的表达率分别为26.7％（8/30）、23.3％（7/30）、26.7％（8/30）、26.7 ％（8/30）、30.0％（9/30）、30.0％（9/30）;20份原位移植正常卵巢组织上述指标均为阴性.癌旁近端组织中CK-7、CA125、p53、Survivin、MMP-2及TIMP-2的表达率低于癌组织（P＜0.05）,高于癌旁中段组织及癌旁远端组织（P＜0.01）;癌旁中段组织及癌旁远端组织表达率差异无统计学意义（P＞0.05）.癌旁组织CK-7、CA125、Survivin的强阳性表达率明显高于p53、MMP-2、TIMP-2（P＜ 0.05）.全部指标表达阴性组或CK-7（-）CA125（-）Survivin（-）组的组织移植后,未发现癌变,其癌变率及CA125水平低于CK-7（＋）CA125（＋）Survivin（＋）组（P＜0.01,P＜0.05）.结论 CK-7、CA125、p53、Survivin、MMP-2及TIMP-2等分子指标的表达向无癌方向呈递减趋势,这些肿瘤相关基因表达全部阴性或主要指标CK-7、CA125、Survivin阴性均可作为筛选癌旁残余正常卵巢组织的标准,流式细胞术可作为筛查残留癌灶及隐匿转移的有效方法;人卵巢上皮性肿瘤裸鼠冻融卵巢组织移植安全、可行.     

The valencia programme for fertility preservation

INTRODUCTION: Fertility preservation needs have increased dramatically in recent years due to a rising cancer incidence and also a significant increase in survival rates. MATERIALS AND METHODS: We report on 200 women participating in the Valencia Programme for Fertility Preservation, of whom 55% were breast cancer patients, 25% Hodgkin's disease patients, and the remaining 20% suffered from other nonmalignant and malignant diseases. Mean age was 28.2 years (11-39). Before patients were submitted to oncological treatment, the right ovarian cortex was extracted by laparoscopy and cryopreserved. Once the patient was free of disease, the right ovarian cortex was thawed and implanted onto the left ovarian medulla (after extraction at the same surgical time of left ovarian cortex). RESULTS: In 95% of cases, a piece approximately 2 x 3 cm was obtained. The procedure did not cause any change in the cancer therapy schedule. Four implants had been performed (all of them in women who underwent chemotherapy prior to ovarian cortex extraction), from which two of the case achieved ovarian function resumption, in one case a month after the implant and in the other 5.5 months after. The remaining two implanted cases were performed 5 and 6 months prior to the writing of this paper, respectively. CONCLUSIONS: Ovarian tissue cryopreservation is a feasible option to preserve ovarian function and possibly fertility in adolescents and young women at risk of developing premature ovarian failure (POF) due to chemotherapy and/or radiotherapy.     

Fertility preservation in cancer patients: The global framework

Cancer treatment is the most frequent cause of reduced fertility in cancer patients, with up to 80% of survivors affected. None of the established or experimental fertility preservation methods can assure parenthood, rather they may provide a future opportunity to overcome treatment induced sterility. Around 70–75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. Lack of time and knowledge about existing options, delay in potentially useful treatment, patient’s age, partnership status, existing children, sexual orientation and socioeconomic situation are the main barriers to effective fertility preservation. Patient’s fears, expectations and priorities shaped by personal values have to be addressed in the framework of medical necessities, realistic survival probabilities, socio-cultural environment and resources availability. We call for a need of patient centred fertility counselling within a framework that should include patients understanding of medical aspects of their cancer, realistic fertility preservation options, preferences based on personal values and goals. Optional support services could also include legal guidance, psychological and spiritual support and financial counselling.     

Safety Assessment of Ovarian Cryopreservation and Transplantation in Nude Mice Bearing Human Epithelial Ovarian Cancer

Objective: Nude mice with orthotopic transplantation of human ovarian epithelial cancer were used toinvestigate screening criteria for paraneoplastic normal ovarian tissue and the security of the freezing andthawing for ovarian tissue transplantation. Methods: Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP-2 in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as immunohistochemistry. Thetissues of the groups with all negative indicators of RT-PCR, all negative indicators of immunohistochemistry,negative expression of CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancertissues and normal ovarian tissues of nude mice were used for freezing and thawing transplantation, to analyzeovert and occult carcinogenesis rates after transplantation. Results: When all indicators or the main indicators,CK-7, CA125 and survivin, were negative, tumorigenesis did not occur after transplantation. In addition theoccult carcinogenesis rate was lower than in the group with positive expression of CK-7, CA125 and survivin(P<0.01). After subcutaneous and orthotopic transplantation of ovarian tissues, rates did not change (P>0.05).There was no statistical significance among rates after transplantation of ovarian tissues which were obtainedunder different severity conditions (P>0.05). Conclusion: Negative expression of CK-7, CA125 and survivin canbe treated as screening criteria for security of ovarian tissues for transplantation. Immunohistochemical methodscan be used as the primary detection approach. Both subcutaneous and orthotopic transplantation are safe. Theinitial severity does not affect the carcinogenesis rate after tissue transplantation. Freezing and thawing ovariantissue transplantation in nude mice with human epithelial ovarian carcinoma is feasible and safe.     

Phase II study of gonadotropin-releasing hormone analog for ovarian function preservation in hematopoietic stem cell transplantation patients

Purpose.

Premature ovarian failure occurs in 40%–70% of patients who receive conventional chemotherapy alone. However, the incidence is higher, 70%–100%, in patients who undergo myeloablative chemotherapy with hematopoietic stem cell transplantation (HSCT). Gonadotropin-releasing hormone (GnRH) analogs, such as leuprolide, in a continuous-release formulation, may protect the ovaries from the gonadotoxic effects of chemotherapy. In non-HSCT settings, GnRH analogs have reduced the risk for premature ovarian failure to <10%. We conducted a phase II clinical trial based on the hypothesis that giving leuprolide before conditioning chemotherapy in HSCT patients reduces premature ovarian failure incidence.

Patients and Methods.

Eligible patients were women aged ≤40 years who were HSCT candidates, were premenopausal, and had both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels ≤20 IU/L. Two 22.5-mg leuprolide doses were delivered in 3-month depot i.m. injections, the first within 2 months before HSCT. Patients were monitored for menstruation return, and ovarian function tests (FSH, LH, and estradiol) were done every 2 months starting 90 days after the last leuprolide dose.

Results.

Sixty eligible patients were enrolled, 59 underwent HSCT, and 44 were evaluable (median age, 25 years; median follow-up, 355 days). Only seven of 44 patients (16%) regained ovarian function. Of the 33 who received myeloablative regimens, six (18%) regained ovarian function. However, among the 11 who received nonmyeloablative regimens, only one (9%) regained ovarian function (p = .66).

Conclusion.

Leuprolide did not preserve ovarian function in patients who underwent HSCT using either myeloablative or nonmyeloablative regimens. Other measures that protect ovarian function need to be investigated.     

Options on fertility preservation in female cancer patients

Infertility following treatment of cancer is a quality of survival's recognized issue and efforts should be made to help young cancer patients retaining their fertility potential. Options to preserve fertility in female patients include well established methods such as shielding to reduce radiation damage to reproductive organs, fertility-sparing surgery and emergency in vitro fertilization after controlled ovarian stimulation, aiming at freezing embryos. Transfer of frozen/thawed embryos today is a clinical routine in fertility clinics worldwide and it has been used for over 25 years. Mature oocytes after ovarian stimulation can also be frozen unfertilized, nevertheless overall pregnancy rates after fertilization of frozen-thawn oocytes are still relatively lower than those with embryo freezing. Remaining fertility preservation options are still in development and include the freezing of immature oocytes aiming at later in vitro maturing and fertilizing them and the cryopreservation of ovarian tissue for future retransplantation or for in vitro growth and maturation of follicles, both still experimental.     

Protecting female fertility in cancer patients

Aim: The preservation of fertility in female patients diagnosed with cancer has recently been an area of intensive investigation. This review summarizes available options and discusses recently published data concerning experimental methods. Specific strategies for fertility preservation in women with gynecologic malignancies are also presented. Method: The MEDLINE database was reviewed for all publication on medication, surgery or assisted reproductive technology that could potentially preserve fertility in women who are receiving cancer therapy. Conclusion: There are many modalities that are available to a patient undergoing a treatment that will negatively impact on her fertility. While many procedures and medical interventions have been proven successful both in terms of ovarian function and pregnancy rates, other techniques have great potential but do not have long‐term clinical data. gonadotropin‐releasing hormone (GnRH) analogs prevent chemotherapy‐induced ovarian damage in animals, however, human results are controversial. Anti‐apoptotic agents may present an innovative treatment to prevent oocyte destruction during cancer therapy. The cryopreservation of embryo, oocyte and ovarian tissue is one option to preserve fertility. It is important that the patients’ primary‐care physician understand the methods available to preserve fertility in a cancer patient and communicate this information to the patient. The improvement of these techniques as well as a better characterization of their success rates and risks await further investigation.