Fertility Preservation In Cancer Pt Fin (1)Presentation Transcript
Fertility preservation in cancer patient 如何保留癌症病患的生育能力 楊曉君醫師 2004 年台中榮總專科醫師講座
Fertility preservation in cancer patient
Who is appropriate
In vivo protection
Conservative surgery and surgery technique
Mature, immature oocytes freeze
Ovarian tissue banking
Six distinct issues should be considered Fertility preservation in cancer patient
The risk of sterility with the proposed treatment program
The overall prognosis for the patient
The potential risks of delaying chemotherapy
The impact of any future pregnancy upon the risk of tumor recurrence
The impact of any required hormonal manipulation on tumor itself
The possibility of tumor contamination of the harvested tissue
C/T and R/T in Prepubertal girl(I)
Pre-pubertal ovary extremely resistant to the gonadotoxic chemotherapy agents, such as cyclophosphamide and nitrogen mustard
High rates of perservation of fertility among pre-pubertal girls exposed to MOPP C/T for Hodgkin’s disease.
The mechanisms of resistance: the quiescent cell-cycle status of germ cell in prepubertal ovary?
Oral pills and LHRHa: encouraging early report(chapman and Sutcliffe 1981. Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin’s disease.)
C/T and R/T in Prepubertal girl(II )
The extremely high doses of C/T prior to bone marrow transplantation for treatment of hematological malignancies frequently result in long term sterility .—ovarian cryopreservation should be considered, when the underlying disease may remission and unlikely to contamination the harvest tissue.
prepubertal ovary remain extremely sensitive to radiation ->with doses of 5-20Gy ->ovarian failure.
Prognosis of early stage Breast cancer
The prognosis for women with ostensibly surgically resectable, early stage breast cancer has improved with the increased application of adjuvant C/T and hormone therapy.
The likelihood of woman with node-negative disease remaining free of recurrence at 5 yrs is approximately 85%, 75% for one lymph node is involved, 65% of five nodes are involved.
Dr.Cha 在 1991 年首先報告使用不成熟卵子體外培養後體外授精 (IVM-IVF) ，再將胚胎植入而成功懷孕。他們所使用的不成熟卵子來源是接受開腹手術病人（例如： c/s, ectopic pregnancy or ATH 等）。利用開腹同時，以空針抽取卵巢上的卵泡 (2~10mm) 抽出後再放入培養液中培養。待卵子培養到 M2 stage 時，再與精蟲結合。再把受精卵取出培養使發育為胚胎後植入母體子宮。
Cryopreservation of oocytes
Traditional slow cooling
Vitrification: a process that produces a glasslike solidification of living cells that completely avoids ice crystal formation during colling.
Success rate of slow oocytes freezing
The most consistent and long-term study resulted in only 9 pregnancies and the birth of 11 babies from transfers after the insemination of 1502 thawed eggs, giving a success rate of 0.7%.
Porcul. Cycle of human oocytes cryopreservation and intracytoplasmic sperm injection: result of 112 cycles. Fertil & Steril 1999;72: 2
Tucker et al ,conducted an elegant study on slow-cooled human oocytes and reports viable pregnancies involving several advanced fetuses with success rate: 1%
-Tucker. Clinical application of human egg cryopreservation. Hum Reprod 1998;13: 3156-9
from the University of Bologna studied 11 pregnancies from frozen eggs, which resulted in 13 children. In all but one of the pregnancies, amniocentesis was performed, showing that all of the fetuses were normal. They report that the gestational age at delivery was normal, and post-natal growth and development have all been reported normal.
Frozen–thawed and grafted ovarian tissue can restore ovulatory cycles in sheep study.
Primordial follicles are relatively robust to freezing and thawing.
2000, Dr. Kutluk Oktay from Cornell University, reported the first case of laparoscopic transplantation of frozen-thrawed ovarian tissue to the pelvic sidewall with subsequent ovulation.
No one has achieved a pregnancy from frozen human ovarian tissue yet.
Ovarian tissue autotransplantation
2001, Dr. Kutluk Oktay transplanted a section of a woman's ovary into her forearm. Egg development and normal hormone production was achieved. Theoretically, the eggs could be removed and used for in vitro fertilization to achieve a pregnancy. Dr. Oktay had similar results with a second patient.
Consideration of Ovarian tissue autotransplantation
Safety : the residual disease in autografted ovarian tissues might cause recrudescence of disease.
kim et. al. : total 30 non-obese diabetic severe combined immunodeficient (SCID) mice were individually xenografted s.c. with frozen-thawed ovarian tissue from 18 patients with lymphoma,
Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm(I) oktay, JAMA, september 26, 2001-286: 1490-3
Patient A , 35y/o woman, stage IIIb squamous cell Cx Ca. she consulted to fresh transplantation prior to pelvic radiotherapy.
Both ovaries were removed laparoscopically, and after frozen section showed no metastasis, their cortices were prepared in 16 strips were of 5x50x1-3mm.
Ovarian strips were wedged subcutaneously to the forearm prior to pelvic radiotherapy.
Patient B , 37 y/o woman with recurrent serous cyct in her only one ovary. Dense pelvic adhesion was noted.
Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm(II)
Menopause was confirmed immediately after the transplantation in both Pt(A: 47mIU/ml, B:50.7mIU/ml)
Patient A : follicle development was noted by physical and ultrasound examination approximately 10 weeks after transplantation. The mean FSH, LH decreased to 8.6mIU/ml and 12.8 mIU/ml. The peripheral E2 showed cyclical variation, dominant follicle developed each months. Percutaneous oocyte aspiration yielded a mature oocyte after COH. Fertilization failure after ICSI
Patient B: spontaneous MC since 6 months after transplantation. mid-cycle LH surge and USG:a 9 mm follicle. Ovulation was confirmed via progesterone level after LH surge.