卵泡期超长方案在高龄患者IVF/ICSI治疗中的应用
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摘要
目的评估卵泡期超长方案在高龄女性行体外受精/卵母细胞浆内单精子注射(IVF/ICSI)助孕治疗中的可行性。方法回顾性分析2016年7月～2018年7月在温州医科大学附属第二医院生殖中心行IVF/ICSI新鲜胚胎移植的高龄患者333例,其中143例采用微刺激方案,190例采用卵泡期超长方案。对比两种方案的实验室和临床结局。进一步将行卵泡期超长方案的患者分为>35～38岁组(107例)和>38～42岁组(83例),比较两组患者的实验室及临床结局。结果相比采用微刺激方案的患者,卵泡期超长方案的患者使用了更多的促性腺素和更长的超促排卵时间,但获得了更高的临床妊娠率和胚胎种植率。>38～42岁组的超高龄患者在使用卵泡期超长方案后,获得了与>35～38岁组高龄患者类似的临床妊娠率(P> 0.05),但胚胎种植率较>35～38岁组高龄患者低(P <0.05)。结论对于卵巢储备功能尚可的高龄患者(年龄≤42周岁、窦卵泡数≥5个、基础卵泡刺激素≤12 U/L),卵泡期超长方案是可行的并可作为首选的超促排卵方案。
Objective To assess the feasibility of prolonged protocol performed in aged patients undergoing in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI) treatment. Methods A Retrospective analysis was conducted on the data of 333 aged women who were given IVF/ICSI treatment with fresh embryo transplantation in the Reproductive Center of the Second Affiliated Hospital of Wenzhou Medical University from July 2016 to July 2018,of which 143 cases were given mild stimulation,and 190 cases were given prolonged protocol. The laboratory and clinical outcomes of two schemes were compared. Then patients in prolonged group were further divided into two groups according to their age. one included 107 cases aged >35-38 years old and the other contained 83 cases aged >38-42 years old,and laboratory and clinical outcomes were compared between the groups. Results Patients with the prolonged protocol used more doses of gonadotropin and longer treatment duration than those with mild stimulation, but patients with prolonged protocol achieved higher clinical pregnancy rates and embryo implantation rates. In patients with mild stimulation,the clinical pregnancy rate of patients aged >38-42 years old group was similar to that of the >35-38 year-old group(P >0.05),while the embryo implantation rate was lower than the >35-38 year-old group(P < 0.05). Conclusion The prolonged protocol is expected to be one of preferred option for elderly patients with tolerable ovarian reverse(≤ 42 years old, AFC≥5 and basic FSH≤12 U/L).
Objective To assess the feasibility of prolonged protocol performed in aged patients undergoing in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI) treatment. Methods A Retrospective analysis was conducted on the data of 333 aged women who were given IVF/ICSI treatment with fresh embryo transplantation in the Reproductive Center of the Second Affiliated Hospital of Wenzhou Medical University from July 2016 to July 2018,of which 143 cases were given mild stimulation,and 190 cases were given prolonged protocol. The laboratory and clinical outcomes of two schemes were compared. Then patients in prolonged group were further divided into two groups according to their age. one included 107 cases aged >35-38 years old and the other contained 83 cases aged >38-42 years old,and laboratory and clinical outcomes were compared between the groups. Results Patients with the prolonged protocol used more doses of gonadotropin and longer treatment duration than those with mild stimulation, but patients with prolonged protocol achieved higher clinical pregnancy rates and embryo implantation rates. In patients with mild stimulation,the clinical pregnancy rate of patients aged >38-42 years old group was similar to that of the >35-38 year-old group(P >0.05),while the embryo implantation rate was lower than the >35-38 year-old group(P < 0.05). Conclusion The prolonged protocol is expected to be one of preferred option for elderly patients with tolerable ovarian reverse(≤ 42 years old, AFC≥5 and basic FSH≤12 U/L).
引文
[1]经瑛,王倩,崔趁趁,等.高龄影响卵母细胞及早期胚胎线粒体功能的研究进展[J].中华生殖与避孕杂志,2017,37(7):598-601.
[2]王靖,邢琼,王超,等.3种不同促排卵方案在高龄不孕患者IVF/ICSI-ET中的临床应用分析[J].安徽医科大学学报,2018,53(7):1080-1084.
[3]张群芳,陈国勇,刘芸,等.促性腺激素释放激素激动剂不同降调节方案对子宫内膜异位症患者IVF结局的研究[J].生殖医学杂志,2015,24(9):732-736.
[4]李游,伍琼芳,易迎春.超长方案降调节对多囊卵巢综合症不孕患者行IVF结局的影响[J].江西医药,2014,49(2):117-120.
[5]陈艳,周爱莲.卵巢低反应者减量降调节并控制Gn启动剂量的体外受精结局[J].国际生殖健康/计划生育杂志,2018,37(1):28-31.
[6]高龄女性不孕诊治指南[J].中华生殖与避孕杂志,2017,37(2):87-100.
[7] Gleicher N,Barad DH. Detection of infertility risk and premature ovarian aging:U.S. Patent 8,951,724[P]. 2015-2-10.
[8] Kato N,Iwase A,Sugita A,et al. Anti-Müllerian hormone as a possible predictor of fecundability in subfertile women over 38 years:a retrospective cohort study[J]. Gynecol Endocrinol,2015,31(1):22-25.
[9] González-Foruria I,Pe觡arrubia J,Borràs A,et al. Age,independent from ovarian reserve status,is the main prognostic factor in natural cycle in vitro fertilization[J]. Fertil Steril,2016,106(2):342-347. e2.
[10] May-Panloup P,Boucret L,Chao de la Barca JM,et al.Ovarian ageing:the role of mitochondria in oocytes and follicles[J]. Hum Reprod Update,2016,22(6):725-743.
[11] Babayev E,Seli E. Oocyte mitochondrial function and reproduction[J]. Current Opinion Obstet Gynecol,2015,27(3):175.
[12] Tal R,Tal O,Seifer BJ,et al. Antimüllerian hormone as predictor of implantation and clinical pregnancy after assisted conception:a systematic review and meta-analysis[J].Fertil Steril,2015,103(1):119-130. e3.
[13] Harada T,Khine YM,Kaponis A,et al. The impact of adenomyosis on women′s fertility[J]. Obstet Gynecol Surv,2016,71(9):557.
[14] Wang R,Wang F,Yang L,et al. Effects of long-acting GnRH:a prolonged protocol in assisted pregnancy via IVF-ET in infertile patients with PCOS[J]. Minerva Chir,2018,73(2):251-253.
[15] Surrey E,Katz-Jaffe M,Kondapalli LA,et al. Prolonged administration of GnRH agonist(GnRHa)prior to embryo transfer(ET)in endometriosis(ENDO)and integrin(INT)negative patients:the impact of freeze-all cycles[J]. Fertil Steril,2016,106(3):e269.
[16] Song J,Qian K. Endometrial,but not ovarian response affects clinical outcomes and can be improved by prolonged pituitary down-regulation in patients with thin and medium endometrium[J]. Fertil Steril,2018,110(4):e255-e256.
[17] Kashani L,Mohamadi M,Fattah-Ravandi BH,et al. Impact of prolonged versus ocp plus long protocol on IVFET outcomes in patients with gradeⅢ-Ⅳendometriosis:a randomized clinical trial[J]. Acta Medica Iranica,2018,56(5):308-313.
[18] Guo S,Zhang D,Niu Z,et al. Pregnancy outcomes and neonatal outcomes after pituitary down-regulation in patients with adenomyosis receiving IVF/ICSI and FET:results of a retrospective cohort study[J]. Int J Clin Exp Med,2016,9(7):14313-14320.
[19] Wang R,Wang F,Yang L,et al. Effects of long-acting GnRH:a prolonged protocol in assisted pregnancy via IVF-ET in infertile patients with PCOS[J]. Minerva Chirurgica,2018,73(2):251-253.
[20]李洁,詹雪君,高军,等.在IVF-ET中低剂量长效GnRH-a与短效GnRH-a长方案降调节的评价[J].生殖医学杂志,2015,24(10):828-833.
[21] Luo Y,Deng M,Xiaokun HU,et al. Relation between dosage of GnRH-a and serum LH levels and comparison of clinical outcomes among different GnRH-a long protocols[J].Journal of Sun Yat-sen University(Medical Sciences),2017,38(2):278-284.
[22] Shapiro BS,Daneshmand ST,Desai J,et al. The risk of embryo-endometrium asynchrony increases with maternal age after ovarian stimulation and IVF[J]. Reprod Biomed Online,2016,33(1):50-55.
[2]王靖,邢琼,王超,等.3种不同促排卵方案在高龄不孕患者IVF/ICSI-ET中的临床应用分析[J].安徽医科大学学报,2018,53(7):1080-1084.
[3]张群芳,陈国勇,刘芸,等.促性腺激素释放激素激动剂不同降调节方案对子宫内膜异位症患者IVF结局的研究[J].生殖医学杂志,2015,24(9):732-736.
[4]李游,伍琼芳,易迎春.超长方案降调节对多囊卵巢综合症不孕患者行IVF结局的影响[J].江西医药,2014,49(2):117-120.
[5]陈艳,周爱莲.卵巢低反应者减量降调节并控制Gn启动剂量的体外受精结局[J].国际生殖健康/计划生育杂志,2018,37(1):28-31.
[6]高龄女性不孕诊治指南[J].中华生殖与避孕杂志,2017,37(2):87-100.
[7] Gleicher N,Barad DH. Detection of infertility risk and premature ovarian aging:U.S. Patent 8,951,724[P]. 2015-2-10.
[8] Kato N,Iwase A,Sugita A,et al. Anti-Müllerian hormone as a possible predictor of fecundability in subfertile women over 38 years:a retrospective cohort study[J]. Gynecol Endocrinol,2015,31(1):22-25.
[9] González-Foruria I,Pe觡arrubia J,Borràs A,et al. Age,independent from ovarian reserve status,is the main prognostic factor in natural cycle in vitro fertilization[J]. Fertil Steril,2016,106(2):342-347. e2.
[10] May-Panloup P,Boucret L,Chao de la Barca JM,et al.Ovarian ageing:the role of mitochondria in oocytes and follicles[J]. Hum Reprod Update,2016,22(6):725-743.
[11] Babayev E,Seli E. Oocyte mitochondrial function and reproduction[J]. Current Opinion Obstet Gynecol,2015,27(3):175.
[12] Tal R,Tal O,Seifer BJ,et al. Antimüllerian hormone as predictor of implantation and clinical pregnancy after assisted conception:a systematic review and meta-analysis[J].Fertil Steril,2015,103(1):119-130. e3.
[13] Harada T,Khine YM,Kaponis A,et al. The impact of adenomyosis on women′s fertility[J]. Obstet Gynecol Surv,2016,71(9):557.
[14] Wang R,Wang F,Yang L,et al. Effects of long-acting GnRH:a prolonged protocol in assisted pregnancy via IVF-ET in infertile patients with PCOS[J]. Minerva Chir,2018,73(2):251-253.
[15] Surrey E,Katz-Jaffe M,Kondapalli LA,et al. Prolonged administration of GnRH agonist(GnRHa)prior to embryo transfer(ET)in endometriosis(ENDO)and integrin(INT)negative patients:the impact of freeze-all cycles[J]. Fertil Steril,2016,106(3):e269.
[16] Song J,Qian K. Endometrial,but not ovarian response affects clinical outcomes and can be improved by prolonged pituitary down-regulation in patients with thin and medium endometrium[J]. Fertil Steril,2018,110(4):e255-e256.
[17] Kashani L,Mohamadi M,Fattah-Ravandi BH,et al. Impact of prolonged versus ocp plus long protocol on IVFET outcomes in patients with gradeⅢ-Ⅳendometriosis:a randomized clinical trial[J]. Acta Medica Iranica,2018,56(5):308-313.
[18] Guo S,Zhang D,Niu Z,et al. Pregnancy outcomes and neonatal outcomes after pituitary down-regulation in patients with adenomyosis receiving IVF/ICSI and FET:results of a retrospective cohort study[J]. Int J Clin Exp Med,2016,9(7):14313-14320.
[19] Wang R,Wang F,Yang L,et al. Effects of long-acting GnRH:a prolonged protocol in assisted pregnancy via IVF-ET in infertile patients with PCOS[J]. Minerva Chirurgica,2018,73(2):251-253.
[20]李洁,詹雪君,高军,等.在IVF-ET中低剂量长效GnRH-a与短效GnRH-a长方案降调节的评价[J].生殖医学杂志,2015,24(10):828-833.
[21] Luo Y,Deng M,Xiaokun HU,et al. Relation between dosage of GnRH-a and serum LH levels and comparison of clinical outcomes among different GnRH-a long protocols[J].Journal of Sun Yat-sen University(Medical Sciences),2017,38(2):278-284.
[22] Shapiro BS,Daneshmand ST,Desai J,et al. The risk of embryo-endometrium asynchrony increases with maternal age after ovarian stimulation and IVF[J]. Reprod Biomed Online,2016,33(1):50-55.