冻存卵巢组织移植成功——首次报道
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摘要
目的通过卵巢组织冻存技术及自体移植手术保护癌症患者生育力与内分泌功能。方法对1例40岁宫颈鳞癌IIb期患者在放化疗前进行卵巢组织取材、冻存,待其癌症痊愈后进行冻存卵巢组织自体移植手术,随访监测患者的激素水平、卵泡发育情况、月经恢复情况以及绝经相关症状。结果卵巢组织移植4个月后,改良Kupperman评分由20分降低至<5分,绝经相关症状基本消失,卵泡刺激素(FSH)降低至22.79 IU/L,此后继续下降至6 IU/L,雌二醇(E_2)由<11.8 ng/L升高至84.46 ng/L,B超监测到有卵泡发育且月经恢复。结论卵巢组织冻存移植4个月后卵巢功能恢复正常,证明卵巢组织在临床上移植成功。
Objective To preserve fertility and endocrine function of a cervical cancer patient by ovarian tissue cryopreservation and auto-transplantation. Methods Part of ovary was harvested and cryopreserved before chemo-and radio-therapy for a 40-year-old woman who was diagnosed with cervical squamous carcinoma. After the cervical cancer reached to remission, the patient underwent cryopreserved ovarian tissue transplantation. The endocrine hormone, follicle growth, restoration of menstruation and menopausal syndromes were detected.Results Four months after the surgery of transplatation, the modified Kupperman scores decreased from 20 to less than 5, and the menopausal syndrome disappeared. The concentration of follicle-stimulating hormone(FSH) decreased to 22.79 IU/L and then decline to 6 IU/L, the concentration of estradiol(E_2) increasedfrom <11.8 ng/L to 84.46 ng/L. Follicle growth was observed by ultrasound and the menstruation has been restored. Conclusion After the transplantation of cryopreserved ovarian tissue, the ovarian function has returned to normal, which demonstrated the success of transplantation of frozen-thawed ovarian tissue.
Objective To preserve fertility and endocrine function of a cervical cancer patient by ovarian tissue cryopreservation and auto-transplantation. Methods Part of ovary was harvested and cryopreserved before chemo-and radio-therapy for a 40-year-old woman who was diagnosed with cervical squamous carcinoma. After the cervical cancer reached to remission, the patient underwent cryopreserved ovarian tissue transplantation. The endocrine hormone, follicle growth, restoration of menstruation and menopausal syndromes were detected.Results Four months after the surgery of transplatation, the modified Kupperman scores decreased from 20 to less than 5, and the menopausal syndrome disappeared. The concentration of follicle-stimulating hormone(FSH) decreased to 22.79 IU/L and then decline to 6 IU/L, the concentration of estradiol(E_2) increasedfrom <11.8 ng/L to 84.46 ng/L. Follicle growth was observed by ultrasound and the menstruation has been restored. Conclusion After the transplantation of cryopreserved ovarian tissue, the ovarian function has returned to normal, which demonstrated the success of transplantation of frozen-thawed ovarian tissue.
引文
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[11]Ovarian tissue cryopreservation:a committee opinion[J].Fertil Steril,2014,101(5):1237-1243.DOI:10.1016/j.fertnstert.2014.02.052.
[12]Wallace WH,Smith AG,Kelsey TW,et al.Fertility preservation for girls and young women with cancer:population-based validation of criteria for ovarian tissue cryopreservation[J].Lancet Oncol,2014,15(10):1129-1136.DOI:10.1016/S1470-2045(14)70334-1.
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[14]阮祥燕,杜娟,卢丹,等.中国首例冻存卵巢组织移植报告[J].首都医科大学学报,2016(6):840-842.DOI:10.3969/j.issn.1006-7795.2016.06.025.
[15]Bastings L,Liebenthron J,Westphal JR,et al.Efficacy of ovarian tissue cryopreservation in a major European center[J].J Assist Reprod Genet,2014,31(8):1003-1012.DOI:10.1007/s10815-014-0239-7.
[16]Sanfilippo S,Canis M,Ouchchane L,et al.Viability assessment of fresh and frozen/thawed isolated human follicles:reliability of two methods(Trypan blue and Calcein AM/ethidium homodimer-1)[J].J Assist Reprod Genet,2011,28(12):1151-1156.DOI:10.1007/s10815-011-9649-y.
[17]El IM,Giorgione V,Mamsen LS,et al.Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years[J].Fertil Steril,2016,106(7):1757-1762.DOI:10.1016/j.fertnstert.2016.09.001.
[18]Imbert R,Moffa F,Tsepelidis S,et al.Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility:a 12-year retrospective analysis[J].Hum Reprod,2014,29(9):1931-1940.DOI:10.1093/humrep/deu158.
[19]Dillon KE,Sammel MD,Prewitt M,et al.Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery:acute changes in ovarian reserve during and after chemotherapy[J].Fertil Steril,2013,99(2):477-483.DOI:10.1016/j.fertnstert.2012.09.039.
[20]国际妇科内分泌学会中国妇科内分泌学分会及共识专家.卵巢组织冻存与移植中国专家共识[J].中国临床医生杂志,2018,46(4):496-500.
[21]Donnez J,Dolmans MM.Transplantation of ovarian tissue[J].Best Pract Res Clin Obstet Gynaecol,2014,28(8):1188-1197.DOI:10.1016/j.bpobgyn.2014.09.003.
[22]Kim SS.Revisiting the role of heterotopic ovarian transplantation:futility or fertility[J].Reprod Biomed Online,2014,28(2):141-145.DOI:10.1016/j.rbmo.2013.09.028.
[23]Stern CJ,Gook D,Hale LG,et al.First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy[J].Hum Reprod,2013,28(11):2996-2999.DOI:10.1093/humrep/det360.
[24]Donnez J,Dolmans MM.Ovarian cortex transplantation:60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice[J].J Assist Reprod Genet,2015,32(8):1167-1170.DOI:10.1007/s10815-015-0544-9.
[25]Dittrich R,Hackl J,Lotz L,et al.Pregnancies and live births after20 transplantations of cryopreserved ovarian tissue in a single center[J].Fertil Steril,2015,103(2):462-468.DOI:10.1016/j.fertnstert.2014.10.045.
[26]Gellert SE,Pors SE,Kristensen SG,et al.Transplantation of frozenthawed ovarian tissue:an update on worldwide activity published in peer-reviewed papers and on the Danish cohort[J].J Assist Reprod Genet,2018,35(4):561-570.DOI:10.1007/s10815-018-1144-2.
[27]Meirow D,Ra’Anani H,Shapira M,et al.Transplantations of frozenthawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria[J].Fertil Steril,2016,106(2):467-474.DOI:10.1016/j.fertnstert.2016.04.031.
[28]Donnez J,Dolmans MM,Pellicer A,et al.Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue:a review of 60 cases of reimplantation[J].Fertil Steril,2013,99(6):1503-1513.DOI:10.1016/j.fertnstert.2013.03.030.
[29]Lee J,Kong HS,Kim EJ,et al.Ovarian injury during cryopreservation and transplantation in mice:a comparative study between cryoinjury and ischemic injury[J].Hum Reprod,2016,31(8):1827-1837.DOI:10.1093/humrep/dew144.
[30]Kolusari A,Okyay AG,Kockaya EA.The effect of erythropoietin in preventing ischemia-reperfusion injury in ovarian tissue transplantation[J].Reprod Sci,2018,25(3):406-413.DOI:10.1177/1933719117715127.
[31]Donnez J,Dolmans MM.Fertility preservation in women[J].N Engl J Med,2017,377(17):1657-1665.DOI:10.1056/NEJMra1614676.
[32]Jensen AK,Kristensen SG,Macklon KT,et al.Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark[J].Hum Reprod,2015,30(12):2838-2845.DOI:10.1093/humrep/dev230.
[33]张红,马文叶,杨延周,等.小鼠卵巢玻璃化冻融过程中重组人卵泡刺激素干预对血管内皮生长因子(VEGF)及整合素αvβ3表达的影响[J].生殖与避孕,2015,35(4):230-236.DOI:10.7669/j.issn.0253-357X.2015.04.0230.
[2]Anderson RA,Wallace WH.Antimüllerian hormone,the assessment of the ovarian reserve,and the reproductive outcome of the young patient with cancer[J].Fertil Steril,2013,99(6):1469-1475.DOI:10.1016/j.fertnstert.2013.03.014.
[3]Schmidt R,Richter D,Sender A,et al.Motivations for having children after cancer—a systematic review of the literature[J].Eur J Cancer Care(Engl),2016,25(1):6-17.DOI:10.1111/ecc.12276.
[4]Bellizzi KM,Smith A,Schmidt S,et al.Positive and negative psychosocial impact of being diagnosed with cancer as an adolescent or young adult[J].Cancer,2012,118(20):5155-5162.DOI:10.1002/cncr.27512.
[5]李扬璐,阮祥燕,Mueck AO.人卵巢组织冻存与移植研究进展[J].首都医科大学学报,2017(4):485-491.DOI:10.3969/j.issn.1006-7795.2017.04.001.
[6]Ruan XY.Chinese Society of Gynecological Endocrinology affiliated to the International Society of Gynecological Endocrinology Guideline for ovarian tissue cryopreservation and transplantation[J].Gynecol Endocrinol,2018,21:1-6.DOI:10.1080/09513590.2018.1488957.
[7]Donnez J,Dolmans MM,Diaz C,et al.Ovariancortex transplantation:time to move on from experimental studies to open clinical application[J].Fertil Steril,2015,104(5):1097-1098.DOI:10.1016/j.fertnstert.2015.08.005.
[8]Oktay K,Harvey BE,Loren AW.Fertility preservation in patients with cancer:ASCO clinical practice guideline update summary[J].J Oncol Pract,2018:P1800160.DOI:10.1200/JOP.18.00160.
[9]Donnez J,Dolmans MM,Demylle D,et al.Livebirth after orthotopic transplantation of cryopreserved ovarian tissue[J].Lancet,2004,364(9443):1405-1410.DOI:10.1016/S0140-6736(04)17222-X.
[10]Donnez J,Dolmans MM.Fertility preservation in women[J].N Engl J Med,2017,377(17):1657-1665.DOI:10.1056/NEJMra1614676.
[11]Ovarian tissue cryopreservation:a committee opinion[J].Fertil Steril,2014,101(5):1237-1243.DOI:10.1016/j.fertnstert.2014.02.052.
[12]Wallace WH,Smith AG,Kelsey TW,et al.Fertility preservation for girls and young women with cancer:population-based validation of criteria for ovarian tissue cryopreservation[J].Lancet Oncol,2014,15(10):1129-1136.DOI:10.1016/S1470-2045(14)70334-1.
[13]Liebenthron J,Montag M.Chapter 15 development of a nationwide network for ovarian tissue cryopreservation[J].Methods Mol Biol,2017,1568:205-220.DOI:10.1007/978-1-4939-6828-2_15.
[14]阮祥燕,杜娟,卢丹,等.中国首例冻存卵巢组织移植报告[J].首都医科大学学报,2016(6):840-842.DOI:10.3969/j.issn.1006-7795.2016.06.025.
[15]Bastings L,Liebenthron J,Westphal JR,et al.Efficacy of ovarian tissue cryopreservation in a major European center[J].J Assist Reprod Genet,2014,31(8):1003-1012.DOI:10.1007/s10815-014-0239-7.
[16]Sanfilippo S,Canis M,Ouchchane L,et al.Viability assessment of fresh and frozen/thawed isolated human follicles:reliability of two methods(Trypan blue and Calcein AM/ethidium homodimer-1)[J].J Assist Reprod Genet,2011,28(12):1151-1156.DOI:10.1007/s10815-011-9649-y.
[17]El IM,Giorgione V,Mamsen LS,et al.Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years[J].Fertil Steril,2016,106(7):1757-1762.DOI:10.1016/j.fertnstert.2016.09.001.
[18]Imbert R,Moffa F,Tsepelidis S,et al.Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility:a 12-year retrospective analysis[J].Hum Reprod,2014,29(9):1931-1940.DOI:10.1093/humrep/deu158.
[19]Dillon KE,Sammel MD,Prewitt M,et al.Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery:acute changes in ovarian reserve during and after chemotherapy[J].Fertil Steril,2013,99(2):477-483.DOI:10.1016/j.fertnstert.2012.09.039.
[20]国际妇科内分泌学会中国妇科内分泌学分会及共识专家.卵巢组织冻存与移植中国专家共识[J].中国临床医生杂志,2018,46(4):496-500.
[21]Donnez J,Dolmans MM.Transplantation of ovarian tissue[J].Best Pract Res Clin Obstet Gynaecol,2014,28(8):1188-1197.DOI:10.1016/j.bpobgyn.2014.09.003.
[22]Kim SS.Revisiting the role of heterotopic ovarian transplantation:futility or fertility[J].Reprod Biomed Online,2014,28(2):141-145.DOI:10.1016/j.rbmo.2013.09.028.
[23]Stern CJ,Gook D,Hale LG,et al.First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy[J].Hum Reprod,2013,28(11):2996-2999.DOI:10.1093/humrep/det360.
[24]Donnez J,Dolmans MM.Ovarian cortex transplantation:60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice[J].J Assist Reprod Genet,2015,32(8):1167-1170.DOI:10.1007/s10815-015-0544-9.
[25]Dittrich R,Hackl J,Lotz L,et al.Pregnancies and live births after20 transplantations of cryopreserved ovarian tissue in a single center[J].Fertil Steril,2015,103(2):462-468.DOI:10.1016/j.fertnstert.2014.10.045.
[26]Gellert SE,Pors SE,Kristensen SG,et al.Transplantation of frozenthawed ovarian tissue:an update on worldwide activity published in peer-reviewed papers and on the Danish cohort[J].J Assist Reprod Genet,2018,35(4):561-570.DOI:10.1007/s10815-018-1144-2.
[27]Meirow D,Ra’Anani H,Shapira M,et al.Transplantations of frozenthawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria[J].Fertil Steril,2016,106(2):467-474.DOI:10.1016/j.fertnstert.2016.04.031.
[28]Donnez J,Dolmans MM,Pellicer A,et al.Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue:a review of 60 cases of reimplantation[J].Fertil Steril,2013,99(6):1503-1513.DOI:10.1016/j.fertnstert.2013.03.030.
[29]Lee J,Kong HS,Kim EJ,et al.Ovarian injury during cryopreservation and transplantation in mice:a comparative study between cryoinjury and ischemic injury[J].Hum Reprod,2016,31(8):1827-1837.DOI:10.1093/humrep/dew144.
[30]Kolusari A,Okyay AG,Kockaya EA.The effect of erythropoietin in preventing ischemia-reperfusion injury in ovarian tissue transplantation[J].Reprod Sci,2018,25(3):406-413.DOI:10.1177/1933719117715127.
[31]Donnez J,Dolmans MM.Fertility preservation in women[J].N Engl J Med,2017,377(17):1657-1665.DOI:10.1056/NEJMra1614676.
[32]Jensen AK,Kristensen SG,Macklon KT,et al.Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark[J].Hum Reprod,2015,30(12):2838-2845.DOI:10.1093/humrep/dev230.
[33]张红,马文叶,杨延周,等.小鼠卵巢玻璃化冻融过程中重组人卵泡刺激素干预对血管内皮生长因子(VEGF)及整合素αvβ3表达的影响[J].生殖与避孕,2015,35(4):230-236.DOI:10.7669/j.issn.0253-357X.2015.04.0230.