FERTILITY PRESERVATION Hesham Al-Inany, M.D, PhD
WHY THIS TALK  <ul><li>Increase incidence of cancer during the reproductive age. </li></ul><ul><li>Survival and cure rates...
BREAST CANCER <ul><li>The commonest malignancy   in women during reproductive age.  </li></ul><ul><li>One out of every 228...
AUTO IMMUNE  DISEASES TREATED WITH CHEMOTHERAPY.   <ul><li>SLE ;  systemic lupus erythematosus (incidence 3 per 1000 peopl...
HAEMATOPOIETIC STEM CELL TRANSPLANTATION  ( HSCT ) <ul><li>Pre-existing bone marrow ablation using cytotoxic chemotherapy ...
CONSEQUENCES OF MULTI-AGENT  CHEMOTHERAPY AND RADIOTHERAPY <ul><li>Premature ovarian failure (POF). </li></ul><ul><li>Earl...
FACTORS AFFECTING THE EXTENT OF CHEMOTHERAPY INDUCED GONADOTOXICITY.   <ul><li>Type, duration, dose. </li></ul><ul><li>Gon...
FACTORS AFFECTING THE EXTENT OF RADIOTHERAPY INDUCED GONADOTOXICITY <ul><li>1.  Patient’s age. </li></ul><ul><li>2. Dose o...
AMENORRHEA <ul><li>Temporary amenorrhea or permanent. </li></ul><ul><li>Older women have a shorter duration of onset of am...
Lee et al. JCO, 2006 Agents Effect on sperm <ul><li>Radiation to the testes, Chlorambucil, Cyclophosphamide, Procarbazine,...
SO WHAT TO DO??
ASAP <ul><li>The decision for fertility preservation should be considered as soon as possible to maximize the likelihood o...
FERTILITY PRESERVATION STRATEGIES  <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryo...
PHARMACOLGIC PROTECTION  <ul><li>A) GnRH agonists. </li></ul><ul><ul><li>Premenarchal gonads appear to be least sensitive ...
Potentially relevant RCTs identified and screened for retrieval (n= 1439) RCTs excluded,  Duplicate publication (n=78) RCT...
VALUE OF GNRH AGONIST IN REDUCING POF
FERTILITY PRESERVATION STRATEGIES  <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryo...
IVF <ul><li>IVF before cancer treatment and cryopreservation of Embryos.  </li></ul><ul><li>IVF after cancer treatment. </...
CRYOPRESERVATION OF PREIMPLANTATION EMBRYOS <ul><li>18.6% success rates. </li></ul><ul><li>Survival rates of embryos betwe...
LIMITATIONS <ul><li>Some female treatments are dependent upon phase of the menstrual cycle and can be initiated only at mo...
LIMITATIONS <ul><li>Requires 10–14 days of ovarian stimulation from the beginning of menstrual cycle  </li></ul><ul><li>It...
FERTILITY PRESERVATION STRATEGIES  <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryo...
OOCYTE CRYOPRESERVATION. <ul><li>for single women, ethically accepted. </li></ul><ul><li>Alternative strategy is to freeze...
LIMITATIONS  <ul><li>Still experimental </li></ul><ul><li>(3-4 times  lower  success rate than standard IVF)  </li></ul><u...
Vitrification   1min, 37 ℃   WS1,2 5min×2 3min DS TS LN 2 Thawing WS  + ES1 + ES2 3min ES3 9min VS1  VS2  VS3  VS4 P1 2hrs...
FERTILITY PRESERVATION STRATEGIES  <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryo...
OVARIAN TRANSPOSITION <ul><li>(The ovarian dose is reduced by transposition  to 5–10% ) </li></ul><ul><li>A) Medial transp...
REPRODUCTIVE FUNCTION OF TRANSPOSED OVARIES. <ul><li>89% spontaneous pregnancy with 75%   </li></ul><ul><li>occurring with...
REPRODUCTIVE FUNCTION OF TRANSPOSED OVARIES. <ul><li>Controversies regarding pregnancy  outcomes   </li></ul><ul><li>after...
COMPLICATIONS OF OOPHROPEXY <ul><li>Fallopian tube infarction. </li></ul><ul><li>Chronic ovarian pain. </li></ul><ul><li>O...
MALE: SPERM CRYOPRESERVATION  <ul><li>Outpatient procedure;  </li></ul><ul><li>Cost approximately 1,500 for three samples ...
SAFETY <ul><li>no  detectable increased risk of disease  recurrence  associated with most fertility preservation methods a...
OFFSPRING <ul><li>no  evidence that a history of cancer therapy, or fertility interventions increase the risk of cancer  o...
FERTILITY PRESERVATION STRATEGIES  <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryo...
Jeruss and Woodruff (2009) New England Journal of Medicine. What Technique is Appropriate ?
CONCLUSION. <ul><li>GnRH analogues are the only available  </li></ul><ul><li>medical protection for chemotherapy. </li></u...
THANK YOU!
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Fertility preservation

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  • Fertility preservation

    1. 1. FERTILITY PRESERVATION Hesham Al-Inany, M.D, PhD
    2. 2. WHY THIS TALK <ul><li>Increase incidence of cancer during the reproductive age. </li></ul><ul><li>Survival and cure rates of cancer are improving. </li></ul><ul><li>One in 1000 adults is a survivor of childhood cancer. </li></ul>
    3. 3. BREAST CANCER <ul><li>The commonest malignancy in women during reproductive age. </li></ul><ul><li>One out of every 228 women will develop breast cancer befor 40 years of age. </li></ul><ul><li>15% of all breast cancer occur at <40 years. </li></ul>
    4. 4. AUTO IMMUNE DISEASES TREATED WITH CHEMOTHERAPY. <ul><li>SLE ; systemic lupus erythematosus (incidence 3 per 1000 people ) </li></ul><ul><li>Behcet’s disease. </li></ul><ul><li>Autoimmune glomerulonephritis. </li></ul><ul><li>Crhon’s disease. </li></ul><ul><li>Ulcerative colitis </li></ul><ul><li>Using cyclophosphamide , methotrexate , 5 fluoro-uracil . </li></ul>
    5. 5. HAEMATOPOIETIC STEM CELL TRANSPLANTATION ( HSCT ) <ul><li>Pre-existing bone marrow ablation using cytotoxic chemotherapy is a pre-requisit before HSCT. (for example: treatment of leukaemia ) </li></ul>
    6. 6. CONSEQUENCES OF MULTI-AGENT CHEMOTHERAPY AND RADIOTHERAPY <ul><li>Premature ovarian failure (POF). </li></ul><ul><li>Early pregnancy loss. </li></ul>
    7. 7. FACTORS AFFECTING THE EXTENT OF CHEMOTHERAPY INDUCED GONADOTOXICITY. <ul><li>Type, duration, dose. </li></ul><ul><li>Gonatotoxicity induced by chemotherapy is almost irreversible. </li></ul>
    8. 8. FACTORS AFFECTING THE EXTENT OF RADIOTHERAPY INDUCED GONADOTOXICITY <ul><li>1. Patient’s age. </li></ul><ul><li>2. Dose of radiation (Breaking point 300cGy). </li></ul><ul><li>3. Extent. </li></ul><ul><li>4. Type of radiation (abdominal, pelvic external beam, brachytherapy). </li></ul>
    9. 9. AMENORRHEA <ul><li>Temporary amenorrhea or permanent. </li></ul><ul><li>Older women have a shorter duration of onset of amenorrhea </li></ul><ul><li><40years 6-16 months. </li></ul><ul><li>>40years 2-4 months. </li></ul>
    10. 10. Lee et al. JCO, 2006 Agents Effect on sperm <ul><li>Radiation to the testes, Chlorambucil, Cyclophosphamide, Procarbazine, Melphalan, Cisplatin </li></ul>Prolonged azoospermia <ul><li>BCNU, CCNU </li></ul>Azoospermia in adulthood after treatment before puberty <ul><li>Busulfan, Ifosfamide, BCNU, Nitrogen Mustard, Actinomycin D </li></ul>Azoospermia likely, but always given with other highly sterilizing agents <ul><li>Carboplatin </li></ul>Prolonged azoospermia not often observed at indicated dose <ul><li>Doxorubicin, Thiotepe, Cytosine arabinoside, Vinblastine, Vincristine </li></ul>Can be additive with above agents in causing prolonged azoospermia, but cause only temporary reductions in counts when used alone <ul><li>Amacrine, Bleomycine, Dacarbazine, Daunorubicin, Epirubicin, Etoposide, Fludarabine, 5-Fluorouracil, 6-Mercaptopurine, Methotrexate, Mitoxantrone, Thioguanine </li></ul>Only temporary reductions in counts at doses used in conventional regimens, but additive effects are possible <ul><li>Newer agents </li></ul>?
    11. 11. SO WHAT TO DO??
    12. 12. ASAP <ul><li>The decision for fertility preservation should be considered as soon as possible to maximize the likelihood of success. </li></ul>
    13. 13. FERTILITY PRESERVATION STRATEGIES <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryos. </li></ul><ul><li>Oocyte cryopreservation. </li></ul><ul><li>Ovarian transposition. </li></ul><ul><li>Cyropreservation and transplantation of ovarian tissue. </li></ul>
    14. 14. PHARMACOLGIC PROTECTION <ul><li>A) GnRH agonists. </li></ul><ul><ul><li>Premenarchal gonads appear to be least sensitive to cytotoxic drugs. </li></ul></ul><ul><ul><li>By suppressing gonadotrophin. </li></ul></ul><ul><ul><li>No protection effect of radiation therapy. </li></ul></ul><ul><ul><li>No protetive effect on male gonads. </li></ul></ul><ul><li>B) GnRH Antagonists. </li></ul>
    15. 15. Potentially relevant RCTs identified and screened for retrieval (n= 1439) RCTs excluded, Duplicate publication (n=78) RCTs retrieved for more detailed evaluation (n=1361) RCTs excluded Does not fulfill the inclusion criteria (n= 1336) Potentially appropriate RCTs to be included in the meta-analysis (n=25) RCTs excluded from meta-analysis: - GNRH agonist was begun after chemotherapy; no concomitant treatment of GnRH agonist and chemotherapy (n= 6) - Majority of patients had oophorectomy prior to treatment (n= 1) - Ovarian suppression performed reversibly (GnRH agonist for 3 years) or irreversibly (oophorectomy or radiotherapy). Data not provided separately (n= 1) RCTs included in meta-analysis (n=17) RCTs withdrawn, by outcome: - No data available for inclusion (n= 13) RCTs with usable information, by outcome (n= 4)
    16. 16. VALUE OF GNRH AGONIST IN REDUCING POF
    17. 17. FERTILITY PRESERVATION STRATEGIES <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryos . </li></ul><ul><li>Oocyte cryopreservation. </li></ul><ul><li>Ovarian transposition. </li></ul><ul><li>Cyropreservation and transplantation of ovarian tissue. </li></ul>
    18. 18. IVF <ul><li>IVF before cancer treatment and cryopreservation of Embryos. </li></ul><ul><li>IVF after cancer treatment. </li></ul><ul><li>(poorer responses) </li></ul>
    19. 19. CRYOPRESERVATION OF PREIMPLANTATION EMBRYOS <ul><li>18.6% success rates. </li></ul><ul><li>Survival rates of embryos between 35 and 90%. </li></ul><ul><li>8 – 30% implantation rates. </li></ul><ul><li>Not acceptable to prepubertal, adolescent and </li></ul><ul><li>women without a partner. </li></ul>
    20. 20. LIMITATIONS <ul><li>Some female treatments are dependent upon phase of the menstrual cycle and can be initiated only at monthly intervals </li></ul>
    21. 21. LIMITATIONS <ul><li>Requires 10–14 days of ovarian stimulation from the beginning of menstrual cycle </li></ul><ul><li>It is a surgical procedure </li></ul><ul><li>Requires husband </li></ul><ul><li>Cost: per cycle, storage fees </li></ul>
    22. 22. FERTILITY PRESERVATION STRATEGIES <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryos. </li></ul><ul><li>Oocyte cryopreservation . </li></ul><ul><li>Ovarian transposition. </li></ul><ul><li>Cyropreservation and transplantation of ovarian tissue. </li></ul>
    23. 23. OOCYTE CRYOPRESERVATION. <ul><li>for single women, ethically accepted. </li></ul><ul><li>Alternative strategy is to freeze immature oocytes ( primordial follicle ) . </li></ul>
    24. 24. LIMITATIONS <ul><li>Still experimental </li></ul><ul><li>(3-4 times lower success rate than standard IVF) </li></ul><ul><li>Vetrification can be a good option </li></ul>
    25. 25. Vitrification 1min, 37 ℃   WS1,2 5min×2 3min DS TS LN 2 Thawing WS + ES1 + ES2 3min ES3 9min VS1 VS2 VS3 VS4 P1 2hrs Cryotop (20μl for each drop, at R.T.) 3min 15sec x 4 Before ICSI (7.5%EG,7.5%DMSO in ES) (15%EG,15%DMSO,0.5M Suc in VS) (1M Suc in TS, 0.5M Suc in DS)
    26. 26. FERTILITY PRESERVATION STRATEGIES <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryos. </li></ul><ul><li>Oocyte cryopreservation. </li></ul><ul><li>Ovarian transposition. </li></ul><ul><li>Cyropreservation and transplantation of ovarian tissue. </li></ul>
    27. 27. OVARIAN TRANSPOSITION <ul><li>(The ovarian dose is reduced by transposition to 5–10% ) </li></ul><ul><li>A) Medial transposition </li></ul><ul><li>Behind the uterus. </li></ul><ul><li>B) Lateral transposition </li></ul><ul><li>up to the pelvic sidewall at least 3cm </li></ul><ul><li>from the upper border of the radiation </li></ul><ul><li>field. </li></ul><ul><li>techniques * by laparotomy during surgery. </li></ul><ul><li>* by laparoscopy </li></ul><ul><li>- higher doses of radiation are more likely associated </li></ul><ul><li>with vascular damage of transposed ovaries. </li></ul>
    28. 28. REPRODUCTIVE FUNCTION OF TRANSPOSED OVARIES. <ul><li>89% spontaneous pregnancy with 75% </li></ul><ul><li>occurring without repositioning. </li></ul><ul><li>11% conceived with IVF . </li></ul>
    29. 29. REPRODUCTIVE FUNCTION OF TRANSPOSED OVARIES. <ul><li>Controversies regarding pregnancy outcomes </li></ul><ul><li>after pelvic irradiation . </li></ul><ul><li>? Increase fetal wastage </li></ul><ul><li>? Birth defects </li></ul><ul><li>? Low birth weight </li></ul><ul><li>? Abnormal karyotype </li></ul><ul><li>? Cancer in the offspring </li></ul><ul><li>? Spontaneous abortions </li></ul><ul><li>advice: delay pregnancy for a year after completing radiation therapy. </li></ul>
    30. 30. COMPLICATIONS OF OOPHROPEXY <ul><li>Fallopian tube infarction. </li></ul><ul><li>Chronic ovarian pain. </li></ul><ul><li>Ovarian cyst formation. </li></ul><ul><li>Migration of ovaries back to their original </li></ul><ul><li>position. </li></ul><ul><li>Ovarian metastasis (No increased risk ) . </li></ul>
    31. 31. MALE: SPERM CRYOPRESERVATION <ul><li>Outpatient procedure; </li></ul><ul><li>Cost approximately 1,500 for three samples stored for 3 years </li></ul><ul><li>Most effective way </li></ul>
    32. 32. SAFETY <ul><li>no detectable increased risk of disease recurrence associated with most fertility preservation methods and pregnancy, even in hormonally sensitive tumors. </li></ul>
    33. 33. OFFSPRING <ul><li>no evidence that a history of cancer therapy, or fertility interventions increase the risk of cancer or congenital abnormalities in the offspring. </li></ul>
    34. 34. FERTILITY PRESERVATION STRATEGIES <ul><li>Pharamacolgical protection. </li></ul><ul><li>IVF and cryopreservaion of embryos. </li></ul><ul><li>Oocyte cryopreservation. </li></ul><ul><li>Ovarian transposition. </li></ul><ul><li>Cyropreservation and transplantation of ovarian tissue. </li></ul>
    35. 35. Jeruss and Woodruff (2009) New England Journal of Medicine. What Technique is Appropriate ?
    36. 36. CONCLUSION. <ul><li>GnRH analogues are the only available </li></ul><ul><li>medical protection for chemotherapy. </li></ul><ul><li>Laparoscopic ovarian transposition is a good option if radiotherapy is to be used. </li></ul>
    37. 37. THANK YOU!
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