卵巢刺激和卵母细胞体外成熟在女性肿瘤患者生育力保存中的应用
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摘要
【目的】初步探讨在女性肿瘤患者生育力保存中,不同促排卵方案以及卵母细胞体外成熟技术的临床效果。【方法】分析中山大学附属第六医院生殖医学研究中心27例女性肿瘤患者冷冻卵子或胚胎的临床资料。【结果】纳入的女性肿瘤患者平均年龄为27.1岁,从就诊日开始算起,平均用6.8 d获卵,促性腺激素平均总用量为910 U。其中乳腺癌患者促排卵期间的最高雌激素水平约为360 pg/mL。促排卵周期卵子成熟率约为82.6%,而紧急取卵后行卵母细胞体外成熟的成熟率为38.1%。【结论】年轻女性肿瘤患者的卵巢反应性普遍较好,不同获卵方案均能达到可观的效果,卵子及胚胎质量无明显下降;联合应用来曲唑可较好地控制患者促排卵期间体内的雌激素水平;紧急取卵后行卵母细胞体外成熟的成熟率较低。在临床应用上,我们应根据患者的原发肿瘤疾病特点、就诊时机个性化选择获卵方案。
【Objective】To determine the effect of ovarian stimulation or in vitro maturation for fertility preservation in female cancer patients. 【Methods】 A retrospective study was conducted in 27 females who underwent fertility preservation procedures in our center.【Results】Female patients were included in this study with an average age of 27.1.Patients spent on average for 6.8 d to retrieve oocytes since their attendance day. Total amount of Gn was on average 910 U per patient and for patients with breast cancer,the average estrogen level on trigger day reached 360 pg/mL. The maturation rate of oocytes from ovarian stimulation cycles was 82.6%,which of that in emergency in-vitro maturation cycles was 38.1%.【Conclusion】The development capability of oocytes from cancer patients are comparable with those of other infertility patients. Peak estradiol levels were controlled by the administration of letrozole. In vitro maturation of oocytes performed at random time of the menstrual cycle may result in a lower maturation rate,which is associated with the time limit of the follow-up cancer treatment. In conclusion,clinicians should consider a more holistic approach for female cancer patients,which focuses not only on the characteristic of the primary cancer but also on the phase of the menstrual cycle at their attendance day.
【Objective】To determine the effect of ovarian stimulation or in vitro maturation for fertility preservation in female cancer patients. 【Methods】 A retrospective study was conducted in 27 females who underwent fertility preservation procedures in our center.【Results】Female patients were included in this study with an average age of 27.1.Patients spent on average for 6.8 d to retrieve oocytes since their attendance day. Total amount of Gn was on average 910 U per patient and for patients with breast cancer,the average estrogen level on trigger day reached 360 pg/mL. The maturation rate of oocytes from ovarian stimulation cycles was 82.6%,which of that in emergency in-vitro maturation cycles was 38.1%.【Conclusion】The development capability of oocytes from cancer patients are comparable with those of other infertility patients. Peak estradiol levels were controlled by the administration of letrozole. In vitro maturation of oocytes performed at random time of the menstrual cycle may result in a lower maturation rate,which is associated with the time limit of the follow-up cancer treatment. In conclusion,clinicians should consider a more holistic approach for female cancer patients,which focuses not only on the characteristic of the primary cancer but also on the phase of the menstrual cycle at their attendance day.
引文
[1]陈万青,郑荣寿,曾红梅,等. 2011年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2015,24(1):1-10.Chen WQ,Zheng RT,Zeng HM,et al. Report ofCancer Incidence and Mortality in China,2011[J].Chin Cancer,2015,24(1):1-10.
[2]陈万青,郑荣寿,张思维,等. 2012年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2016,25(1):1-8.Chen WQ,Zheng RT,Zhang SW,et al. Report ofCancer Incidence and Mortality in China,2012[J].Chin Cancer,2016,25(1):1-8.
[3]陈万青,郑荣寿,张思维,等. 2013年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2017,26(1):1-7.Chen WQ,Zheng RT,Zhang SW,et al. Report ofCancer Incidence and Mortality in China,2013[J].Chin Cancer,2017,26(1):1-7.
[4] Martinez F. Update on fertility preservation from theBarcelona International Society for FertilityPreservation-ESHRE-ASRM 2015 expert meeting:indications, results and future perspectives[J].Fertil Steril,2017,108(3):407-415.
[5] Collaborative Group on Hormonal Factors in BreastCancer. Breast cancer and breastfeeding:collaborative reanalysis of individual data from 47epidemiological studies in 30 countries,including50 302 women with breast cancer and 96 973women without the disease[J]. Lancet,2002,360(9328):187-195.
[6] Calderon-Margalit R,Friedlander Y,Yanetz R,etal. Cancer risk after exposure to treatments forovulation induction[J]. Am J Epidemiol,2009,169(3):365-375.
[7] Kallen B, Finnstrom O, Lindam A, et al.Malignancies among women who gave birth after invitro fertilization[J]. Hum Reprod,2011,26(1):253-258.
[8] Brinton LA,Scoccia B,Moghissi KS,et al. Long-term relationship of ovulation-stimulating drugs tobreast cancer risk[J]. Cancer Epidemiol BiomarkersPrev,2014,23(4):584-593.
[9] Wallace WH, Thomson AB, Kelsey TW. Theradiosensitivity of the human oocyte[J]. HumReprod,2003,18(1):117-121.
[10]Balduzzi A, Dalle JH, Jahnukainen K, et al.Fertility preservation issues in pediatrichematopoietic stem cell transplantation:practicalapproaches from the consensus of the PediatricDiseases Working Party of the EBMT and theInternational BFM Study Group[J]. Bone MarrowTransplant,2017,52(10):1406-1415.
[11]Azim AA,Costantini-Ferrando M,Oktay K. Safetyof fertility preservation by ovarian stimulation withletrozole and gonadotropins in patients with breastcancer:A prospective controlled study[J]. J ClinOncol,2008,26(16):2630-2635.
[12]Rodgers RJ,Reid GD,Koch J,et al. The safetyand efficacy of controlled ovarian hyperstimulationfor fertility preservation in women with early breastcancer:A systematic review[J]. Hum Reprod,2017,32(5):1033-1045.
[13]Pereira N, Kelly AG, Stone LD, et al.Gonadotropin-releasing hormone agonist triggerincreases the number of oocytes and embryosavailable for cryopreservation in cancer patientsundergoing ovarian stimulation for fertilitypreservation[J]. Fertil Steril,2017,108(3):532-538.
[14]von Wolff M, Thaler CJ, Frambach T, et al.Ovarian stimulation to cryopreserve fertilized oocytesin cancer patients can be started in the luteal phase[J]. Fertil Steril,2009,92(4):1360-1365.
[15]Prasath EB,Chan ML,Wong WH,et al. Firstpregnancy and live birth resulting fromcryopreserved embryos obtained from in vitromatured oocytes after oophorectomy in an ovariancancer patient[J]. Hum Reprod,2014,29(2):276-278.
[16]Abir R, Ben-Aharon I, Garor R, et al.Cryopreservation of in vitro matured oocytes inaddition to ovarian tissue freezing for fertilitypreservation in paediatric female cancer patientsbefore and after cancer therapy[J]. Hum Reprod,2016,31(4):750-762.
[17]Johnson EK, Finlayson C, Rowell EE, et al.Fertility preservation for pediatric patients:currentstate and future possibilities[J]. J Urol,2017,198(1):186-194.
[2]陈万青,郑荣寿,张思维,等. 2012年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2016,25(1):1-8.Chen WQ,Zheng RT,Zhang SW,et al. Report ofCancer Incidence and Mortality in China,2012[J].Chin Cancer,2016,25(1):1-8.
[3]陈万青,郑荣寿,张思维,等. 2013年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2017,26(1):1-7.Chen WQ,Zheng RT,Zhang SW,et al. Report ofCancer Incidence and Mortality in China,2013[J].Chin Cancer,2017,26(1):1-7.
[4] Martinez F. Update on fertility preservation from theBarcelona International Society for FertilityPreservation-ESHRE-ASRM 2015 expert meeting:indications, results and future perspectives[J].Fertil Steril,2017,108(3):407-415.
[5] Collaborative Group on Hormonal Factors in BreastCancer. Breast cancer and breastfeeding:collaborative reanalysis of individual data from 47epidemiological studies in 30 countries,including50 302 women with breast cancer and 96 973women without the disease[J]. Lancet,2002,360(9328):187-195.
[6] Calderon-Margalit R,Friedlander Y,Yanetz R,etal. Cancer risk after exposure to treatments forovulation induction[J]. Am J Epidemiol,2009,169(3):365-375.
[7] Kallen B, Finnstrom O, Lindam A, et al.Malignancies among women who gave birth after invitro fertilization[J]. Hum Reprod,2011,26(1):253-258.
[8] Brinton LA,Scoccia B,Moghissi KS,et al. Long-term relationship of ovulation-stimulating drugs tobreast cancer risk[J]. Cancer Epidemiol BiomarkersPrev,2014,23(4):584-593.
[9] Wallace WH, Thomson AB, Kelsey TW. Theradiosensitivity of the human oocyte[J]. HumReprod,2003,18(1):117-121.
[10]Balduzzi A, Dalle JH, Jahnukainen K, et al.Fertility preservation issues in pediatrichematopoietic stem cell transplantation:practicalapproaches from the consensus of the PediatricDiseases Working Party of the EBMT and theInternational BFM Study Group[J]. Bone MarrowTransplant,2017,52(10):1406-1415.
[11]Azim AA,Costantini-Ferrando M,Oktay K. Safetyof fertility preservation by ovarian stimulation withletrozole and gonadotropins in patients with breastcancer:A prospective controlled study[J]. J ClinOncol,2008,26(16):2630-2635.
[12]Rodgers RJ,Reid GD,Koch J,et al. The safetyand efficacy of controlled ovarian hyperstimulationfor fertility preservation in women with early breastcancer:A systematic review[J]. Hum Reprod,2017,32(5):1033-1045.
[13]Pereira N, Kelly AG, Stone LD, et al.Gonadotropin-releasing hormone agonist triggerincreases the number of oocytes and embryosavailable for cryopreservation in cancer patientsundergoing ovarian stimulation for fertilitypreservation[J]. Fertil Steril,2017,108(3):532-538.
[14]von Wolff M, Thaler CJ, Frambach T, et al.Ovarian stimulation to cryopreserve fertilized oocytesin cancer patients can be started in the luteal phase[J]. Fertil Steril,2009,92(4):1360-1365.
[15]Prasath EB,Chan ML,Wong WH,et al. Firstpregnancy and live birth resulting fromcryopreserved embryos obtained from in vitromatured oocytes after oophorectomy in an ovariancancer patient[J]. Hum Reprod,2014,29(2):276-278.
[16]Abir R, Ben-Aharon I, Garor R, et al.Cryopreservation of in vitro matured oocytes inaddition to ovarian tissue freezing for fertilitypreservation in paediatric female cancer patientsbefore and after cancer therapy[J]. Hum Reprod,2016,31(4):750-762.
[17]Johnson EK, Finlayson C, Rowell EE, et al.Fertility preservation for pediatric patients:currentstate and future possibilities[J]. J Urol,2017,198(1):186-194.