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
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摘要
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。
Objective To investigate the timing, efficacy and safety of in vitro fertilization(IVF) in infertility patients with conservative treatment of atypical endometrium hyperplasia(AEH) and early well-differentiated endometrial adenocarcinoma(EC). Methods The clinical data of infertility patients with conservative treatment of AEH and early high differentiation EC, who underwent IVF treatment were retrospectively analyzed according to the time to start IVF after endometrial pathology confirmed that the lesion completely response(CR), the patients were divided into ≤ 3 months(group A, n=35) and > 3 months(group B, n=25). The clinical outcomes of the two groups were compared. Results A total of 60 patients were included, 45 with AEH and 15 with EC. The follow-up time from the first time to achieve CR was(39.6±26.9) months. Totally 95 IVF cycles were performed, including 67 fresh embryo transfer cycles, the rate of pregnancy per cycle was 38.8%(26/67), and 54 frozen-thawed embryo transfer(FET) cycles, the rate of pregnancy per cycle was 25.9%(14/54). A total of 36 patients were pregnant 47 times, 25 patients delivered 32 live births. There were no statistical differences in the IVF-ET cycle pregnancy rate and FET cycle pregnancy rate between the two groups, and the recurrence rate was significantly higher in group B(48.0%) than in group A(17.1%, P=0.022), with a statistical significance. Multifactorial analysis showed that only the time of IVF treatment after the first CR was related to recurrence(P=0.002, OR=1.078, 95% CI=1.027-1.132). The total recurrence rate was 30.0%(18/60) during the follow-up period, with no disease progression and adverse events. Conclusion Infertility patients with conservative treatment of AEH and early well-differentiated EC undergoing IVF treatment is relatively safe and effective. Recurrence is associated with the time of IVF treatment after the first time to achieve complete response, in order to reduce recurrence, IVF should be used as soon as possible.
Objective To investigate the timing, efficacy and safety of in vitro fertilization(IVF) in infertility patients with conservative treatment of atypical endometrium hyperplasia(AEH) and early well-differentiated endometrial adenocarcinoma(EC). Methods The clinical data of infertility patients with conservative treatment of AEH and early high differentiation EC, who underwent IVF treatment were retrospectively analyzed according to the time to start IVF after endometrial pathology confirmed that the lesion completely response(CR), the patients were divided into ≤ 3 months(group A, n=35) and > 3 months(group B, n=25). The clinical outcomes of the two groups were compared. Results A total of 60 patients were included, 45 with AEH and 15 with EC. The follow-up time from the first time to achieve CR was(39.6±26.9) months. Totally 95 IVF cycles were performed, including 67 fresh embryo transfer cycles, the rate of pregnancy per cycle was 38.8%(26/67), and 54 frozen-thawed embryo transfer(FET) cycles, the rate of pregnancy per cycle was 25.9%(14/54). A total of 36 patients were pregnant 47 times, 25 patients delivered 32 live births. There were no statistical differences in the IVF-ET cycle pregnancy rate and FET cycle pregnancy rate between the two groups, and the recurrence rate was significantly higher in group B(48.0%) than in group A(17.1%, P=0.022), with a statistical significance. Multifactorial analysis showed that only the time of IVF treatment after the first CR was related to recurrence(P=0.002, OR=1.078, 95% CI=1.027-1.132). The total recurrence rate was 30.0%(18/60) during the follow-up period, with no disease progression and adverse events. Conclusion Infertility patients with conservative treatment of AEH and early well-differentiated EC undergoing IVF treatment is relatively safe and effective. Recurrence is associated with the time of IVF treatment after the first time to achieve complete response, in order to reduce recurrence, IVF should be used as soon as possible.
引文
[1]俞梅,沈铿,杨佳欣,等.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[J].中华妇产科杂志,2006,41(4):242-245.DOI:10.3760/j.issn:0529-567X.2006.04.008.
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[7]Park JY,Kim DY,Kim JH,et al.Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer(KGOG 2002)[J].Eur J Cancer,2013,49(4):868-874.DOI:10.1016/j.ejca.2012.09.017.
[8]Kudesia R,Singer T,Caputo TA,et al.Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma[J].Am J Obstet Gynecol,2014,210(3):255.e1-4.DOI:10.1016/j.ajog.2013.11.001.
[9]Chen M,Jin Y,Li Y,et al.Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer[J].Int J Gynecol Obstet,2016(132):34-38.DOI:10.1016/j.ijgo.2015.06.046.
[10]徐锋,王铁军.高分化子宫内膜样腺癌或子宫内膜不典型增生患者孕激素治疗的临床结局[J].江苏医药,2016,42(17):1889-1891.DOI:10.19460/j.cnki.0253-3685.2016.17.011.
[11]Simpson AN,Feigenberg T,Clarke BA,et al.Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin[J].Gynecol Oncol,2014(133):229-233.DOI:10.1016/j.ygyno.2014.02.020.
[12]Zhou R,Yang Y,Lu Q,et al.Prognostic factors of oncological and reproductive outcomes in fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin in Chinese patients[J].Gynecol Oncol,2015(139):424-428.DOI:10.1016/j.ygyno.2015.09.078.
[13]Suh DH,Kim JW,Aziz MF,et al.Asian society of gynecologic oncology workshop 2010[J].J Gynecol Oncol,2010,21(3):137-150.DOI:10.3802/jgo.2010.21.3.137.
[14]Kesterson JP,Fanning J.Fertility-sparing treatment of endometrial cancer:options,outcomes and pitfalls[J].J Gynecol Oncol,2012,23(2):120-124.DOI:10.3802/jgo.2012.23.2.120.
[15]Baker J,Obermair A,Gebski V,et al.Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma:a meta-analysis and systematic review of the literature[J].Gynecol Oncol,2012,125(1):263-270.DOI:10.1016/j.ygyno.2011.11.043.
[16]Kalogera E,Dowdy SC,Bakkum-Gamez JN.Preserving fertility in young patients with endometrial cancer:current perspectives[J].Int J Womens Health,2014,6:691-701.DOI:10.2147/IJWH.S47232.
[17]Gressel GM,Parkash V,Pal L.Management options and fertilitypreserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer[J].Intern J Gynecol Obstet,2015(131):234-239.DOI:10.1016/j.ijgo.2015.06.031.
[18] Park JY, Nam JH. Progestins in the fertility-sparing treatment and retreatment of patients with primary and recurrent endometrial cancer[J]. Oncologist, 2015(20):270-278. DOI: 10.1634/theoncologist.2013-0445
[19]Gallos ID,Yap J,Rajkhowa M,et al.Regression,relapse,and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia:a systematic review and metaanalysis[J].Am J Obstet Gynecol,2012,207(4):266.e1-266.e12.DOI:10.1016/j.ajog.2012.08.011.
[20]尚静,廖秦平,左文莉,等.子宫内膜非典型增生患者助孕策略分析[J].中国性科学,2013,22(11):52-55.DOI:10.3969/j.issn.1672-1993.2013.11.016.
[21]Ichinose M,Fujimoto A,Osuga Y,et al.The influence of infertility treatment on the prognosis of endometrial cancer and atypical complex endometrial hyperplasia[J].Intern J Gynecol Cancer,2013,23(2):288-293.DOI:10.1097/IGC.0b013e31827c18a1.
[22]Inoue O,Hamatani T,Susumu N,et al.Factors affecting pregnancy outcomes in young women treated with fertility preserving therapy for well-differentiated endometrial cancer or atypical endometrial hyperplasia[J].Reprod Biol Endocrinol,2016,14:2.DOI:10.1186/s12958-015-0136-7.
[23] Gadducci A, Spirito N, Baroni E, et al. The fertility-sparing treatment in patients with endometrial atypical hyperplasia and early end ometrial cancer:Adebated the rapeutic option[J]. Gynecol Endocrinol, 2009, 25(10):683-691. DOI: 10.1080/09513590902733733.
[24]Tong XM,Lin XN,Jiang HF,et al.Fertility-preserving treatment and pregnancy outcomes in the early stage of endometrial carcinoma[J].Chin Med J,2013,126(15):2965-2971.DOI:10.3760/cma.j.issn.0366-6999.20123534.
[25] Park JY, Seong SJ, Kim TJ, et al. Pregnancy outcomes after fertility-sparing management in young women with early endometrial[J]. Obstet Gynecol, 2013, 121(1):136-142. DOI: 10.1097/AOG.0b013e31827a0643.
[26]Koskas M,Uzan J,Luton D,et al.Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma:systematic review and meta-analysis[J].Fertil Steril,2014,101(3):785-794.DOI:10.1016/j.fertnstert.2013.11.028.
[27]Ramirez PT,Frumovitz M,Bodurka DC,et al.Hormonal therapy for the management of grade1 endometrial adenocarcinoma:a literature review[J].Gynecol Oncol,2004,95(1):133-138.DOI:10.1016/j.ygyno.2004.06.045.
[28]Niwa K,Tagami K,Lian Z,et al.Outcome of fertility-preserving treatment in young women with endometrial carcinomas[J].BJOG,2005,112(3):317-320.DOI:10.1111/j.1471-0528.2004.00398.x.
[29]Gunderson CC,Fader AN,Carson KA,et al.Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma:a systematic review[J].Gynecol Oncol,2012,125(2):477-482.DOI:10.1016/j.ygyno.2012.01.003.
[30]Juretzka MM,O’Hanlan KA,Katz SL,et al.Embryo cryopreservation after diagnosis of stage IIB endometrial cancer and subsequent pregnancy in a gestational carrier[J].Fertil Steril,2005,83(4):1041.DOI:10.1016/j.fertnstert.2004.09.026.
[31]Azim A,Oktay K.Letrozole for ovulation induction and fertility preservation by embryo cryopreservation in young women with endometrial carcinoma[J].Ferti Steril,2007,88(3):657-664.DOI:10.1016/j.fertnstert.2006.12.068.
[2]Ushijima K,Yahata H,Yoshikawa H,et al.Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women[J].J Clin Oncol,2007(25):2798-2803.DOI:10.1200/JCO.2006.08.8344
[3]倪仁敏,杨冬梓.年轻早期内膜癌患者保守治疗后的生育结局[J].生殖与避孕,2015,35(10):715-718.DOI:10.7669/j.issn.0253-357X.2015.10.0715.
[4]李红真,乔杰.子宫内膜非典型增生18例保守治疗结局分析[J].中国妇产科临床杂志,2008(9):31-33.DOI:10.3969/j.issn.1672-1861.2008.01.010.
[5]王永学,潘玲亚,黄惠芳,等.年轻子宫内膜癌患者孕激素保守治疗临床分析[J].中华肿瘤防治杂志,2011,18(7):541-544.DOI:10.16073/j.cnki.cjcpt.2011.07.013.
[6]单波儿,任玉兰,孙建民,等.年轻早期高分化子宫内膜样腺癌或子宫内膜不典型增生保留生育功能的II期临床研究[J].中国癌症杂志,2012,22(6):424-429.DOI:10.3969/j.issn.1007-3969.2012.06.005.
[7]Park JY,Kim DY,Kim JH,et al.Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer(KGOG 2002)[J].Eur J Cancer,2013,49(4):868-874.DOI:10.1016/j.ejca.2012.09.017.
[8]Kudesia R,Singer T,Caputo TA,et al.Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma[J].Am J Obstet Gynecol,2014,210(3):255.e1-4.DOI:10.1016/j.ajog.2013.11.001.
[9]Chen M,Jin Y,Li Y,et al.Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer[J].Int J Gynecol Obstet,2016(132):34-38.DOI:10.1016/j.ijgo.2015.06.046.
[10]徐锋,王铁军.高分化子宫内膜样腺癌或子宫内膜不典型增生患者孕激素治疗的临床结局[J].江苏医药,2016,42(17):1889-1891.DOI:10.19460/j.cnki.0253-3685.2016.17.011.
[11]Simpson AN,Feigenberg T,Clarke BA,et al.Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin[J].Gynecol Oncol,2014(133):229-233.DOI:10.1016/j.ygyno.2014.02.020.
[12]Zhou R,Yang Y,Lu Q,et al.Prognostic factors of oncological and reproductive outcomes in fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin in Chinese patients[J].Gynecol Oncol,2015(139):424-428.DOI:10.1016/j.ygyno.2015.09.078.
[13]Suh DH,Kim JW,Aziz MF,et al.Asian society of gynecologic oncology workshop 2010[J].J Gynecol Oncol,2010,21(3):137-150.DOI:10.3802/jgo.2010.21.3.137.
[14]Kesterson JP,Fanning J.Fertility-sparing treatment of endometrial cancer:options,outcomes and pitfalls[J].J Gynecol Oncol,2012,23(2):120-124.DOI:10.3802/jgo.2012.23.2.120.
[15]Baker J,Obermair A,Gebski V,et al.Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma:a meta-analysis and systematic review of the literature[J].Gynecol Oncol,2012,125(1):263-270.DOI:10.1016/j.ygyno.2011.11.043.
[16]Kalogera E,Dowdy SC,Bakkum-Gamez JN.Preserving fertility in young patients with endometrial cancer:current perspectives[J].Int J Womens Health,2014,6:691-701.DOI:10.2147/IJWH.S47232.
[17]Gressel GM,Parkash V,Pal L.Management options and fertilitypreserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer[J].Intern J Gynecol Obstet,2015(131):234-239.DOI:10.1016/j.ijgo.2015.06.031.
[18] Park JY, Nam JH. Progestins in the fertility-sparing treatment and retreatment of patients with primary and recurrent endometrial cancer[J]. Oncologist, 2015(20):270-278. DOI: 10.1634/theoncologist.2013-0445
[19]Gallos ID,Yap J,Rajkhowa M,et al.Regression,relapse,and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia:a systematic review and metaanalysis[J].Am J Obstet Gynecol,2012,207(4):266.e1-266.e12.DOI:10.1016/j.ajog.2012.08.011.
[20]尚静,廖秦平,左文莉,等.子宫内膜非典型增生患者助孕策略分析[J].中国性科学,2013,22(11):52-55.DOI:10.3969/j.issn.1672-1993.2013.11.016.
[21]Ichinose M,Fujimoto A,Osuga Y,et al.The influence of infertility treatment on the prognosis of endometrial cancer and atypical complex endometrial hyperplasia[J].Intern J Gynecol Cancer,2013,23(2):288-293.DOI:10.1097/IGC.0b013e31827c18a1.
[22]Inoue O,Hamatani T,Susumu N,et al.Factors affecting pregnancy outcomes in young women treated with fertility preserving therapy for well-differentiated endometrial cancer or atypical endometrial hyperplasia[J].Reprod Biol Endocrinol,2016,14:2.DOI:10.1186/s12958-015-0136-7.
[23] Gadducci A, Spirito N, Baroni E, et al. The fertility-sparing treatment in patients with endometrial atypical hyperplasia and early end ometrial cancer:Adebated the rapeutic option[J]. Gynecol Endocrinol, 2009, 25(10):683-691. DOI: 10.1080/09513590902733733.
[24]Tong XM,Lin XN,Jiang HF,et al.Fertility-preserving treatment and pregnancy outcomes in the early stage of endometrial carcinoma[J].Chin Med J,2013,126(15):2965-2971.DOI:10.3760/cma.j.issn.0366-6999.20123534.
[25] Park JY, Seong SJ, Kim TJ, et al. Pregnancy outcomes after fertility-sparing management in young women with early endometrial[J]. Obstet Gynecol, 2013, 121(1):136-142. DOI: 10.1097/AOG.0b013e31827a0643.
[26]Koskas M,Uzan J,Luton D,et al.Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma:systematic review and meta-analysis[J].Fertil Steril,2014,101(3):785-794.DOI:10.1016/j.fertnstert.2013.11.028.
[27]Ramirez PT,Frumovitz M,Bodurka DC,et al.Hormonal therapy for the management of grade1 endometrial adenocarcinoma:a literature review[J].Gynecol Oncol,2004,95(1):133-138.DOI:10.1016/j.ygyno.2004.06.045.
[28]Niwa K,Tagami K,Lian Z,et al.Outcome of fertility-preserving treatment in young women with endometrial carcinomas[J].BJOG,2005,112(3):317-320.DOI:10.1111/j.1471-0528.2004.00398.x.
[29]Gunderson CC,Fader AN,Carson KA,et al.Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma:a systematic review[J].Gynecol Oncol,2012,125(2):477-482.DOI:10.1016/j.ygyno.2012.01.003.
[30]Juretzka MM,O’Hanlan KA,Katz SL,et al.Embryo cryopreservation after diagnosis of stage IIB endometrial cancer and subsequent pregnancy in a gestational carrier[J].Fertil Steril,2005,83(4):1041.DOI:10.1016/j.fertnstert.2004.09.026.
[31]Azim A,Oktay K.Letrozole for ovulation induction and fertility preservation by embryo cryopreservation in young women with endometrial carcinoma[J].Ferti Steril,2007,88(3):657-664.DOI:10.1016/j.fertnstert.2006.12.068.