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Email: enquiry@medicyatra.comFertility In Cancer Patients           22-06 2012        Copyright @ Forever Medic
Email: enquiry@medicyatra.comThe speaker declares that specific brand-name medications and/or  off-label, non-FDA-approved...
Email: enquiry@medicyatra.com     Cancer and Future Fertility• Patients of reproductive age often find prospect of  infert...
Email: enquiry@medicyatra.com         Fertility after cancer poses       challenging medical issues and          emotional...
Email: enquiry@medicyatra.com   Fertility Concerns Common• 57% of women age 40 and younger at  diagnosis of breast cancer ...
Email: enquiry@medicyatra.com Providers May Neglect to Discuss             Fertility• Only 68% of women age 50 or younger ...
American Society of Clinical Oncology                                     Email: enquiry@medicyatra.com  Recommendations o...
American Society of Clinical Oncology                                     Email: enquiry@medicyatra.com  Recommendations o...
Email: enquiry@medicyatra.com          Risk of Infertility in Men• Male infertility can result from:   –   Disease   –   A...
Email: enquiry@medicyatra.comAll Cancer Treatments Are not Equal• Alkylating agents appear to be most gonadotoxic; cis-  p...
Email: enquiry@medicyatra.com         Men Have Sperm Banking!• Sperm cryopreservation  – involves freezing and banking spe...
Email: enquiry@medicyatra.com            Other “Options” for Men• Hormonal Gonadoprotection (e.g. GnRH analogs)   – The ef...
Email: enquiry@medicyatra.com      Risk of Infertility in Women• Female fertility can be compromised by  any treatment tha...
Email: enquiry@medicyatra.comNatural Decline of Oocytes with Age           Copyright @ Forever Medic                      ...
Email: enquiry@medicyatra.comChemotherapy-related Amenorrhea• CRA may be permanent or temporary• CRA is an imperfect surro...
Email: enquiry@medicyatra.comRisk of amenorrhea is related to       age and treatment         Copyright @ Forever(Goodwin ...
Email: enquiry@medicyatra.com Ovarian Failure Risk with Cancer Treatments• High risk:  – Total body irradiation, high dose...
Email: enquiry@medicyatra.com    Risk of Chemotherapy-Related Amenorrhea      with Common Breast Cancer Regimens   Treatme...
Email: enquiry@medicyatra.com  Effects of Newer Treatments: Paclitaxel, Dose       Density, and Trastuzumab on CRA• Premen...
Email: enquiry@medicyatra.com  Effects of Paclitaxel, Dose Density, and           Trastuzumab on CRA       Variable       ...
Email: enquiry@medicyatra.com      Issues for Women Who      Remain Premenopausal• Will a woman be less fertile, even if s...
Email: enquiry@medicyatra.comOvarian Reserve in Women Who RemainPremenopausal After Chemotherapy For       Early Stage Bre...
Email: enquiry@medicyatra.com              Ovarian Reserve in Survivors                 Compared to Controls              ...
Age of Menopause Among Women Who               Email: enquiry@medicyatra.com  Remain Premenopausal Following  Treatment fo...
Email: enquiry@medicyatra.com      Effects of Endocrine Therapy• Adjuvant endocrine therapy for breast  cancer (tamoxifen ...
Email: enquiry@medicyatra.comFertility Preservation Considerations       for Women with Cancer The obvious: weigh the “nec...
Email: enquiry@medicyatra.com   Options for Fertility Preservation     in Women- Anatomic Fixes• Pelvic shielding during r...
Email: enquiry@medicyatra.com     Other Options for Preserving    Fertility for Women with Cancer•   Ovarian suppression (...
Email: enquiry@medicyatra.com Ovarian Sensitivity to Chemotherapy      Normal premenopausal ovaryLow level recruitment of ...
Email: enquiry@medicyatra.com Ovarian Sensitivity to Chemotherapy      Normal premenopausal ovaryLow level recruitment of ...
Email: enquiry@medicyatra.com      Summary of Phase II Trials          and Case Series• GnRH agonist coadministration with...
A randomized trial using the GnRH agonist                                  Email: enquiry@medicyatra.com        (triptorel...
Gonadotropin-releasing hormone agonists for                              Email: enquiry@medicyatra.com prevention of chemo...
Email: enquiry@medicyatra.com      Ongoing Study: SWOG 0230                “POEMS”II, IIIA            Premenopausal Stage ...
Email: enquiry@medicyatra.comIVF/Embryo Cryo        Copyright @ Forever Medic
Email: enquiry@medicyatra.com•    Cryopreservation of Embryos    Standardly available: 20-30% pregnancy rate per transfer ...
Comparison of Cycle Characteristics and Embryo Yield Among Tam-                                                Email: enqu...
Tamoxifen or aromataseEmail: enquiry@medicyatra.com                          inhibitor   stimulation protocols for IVF• In...
Email: enquiry@medicyatra.com        Oocyte Cryopreservation• Requires time and stimulation prior to treatment• No require...
Email: enquiry@medicyatra.com             Oocyte Cryopreservation• Technically difficult• MII oocytes: extremely sensitive...
Email: enquiry@medicyatra.com            Cryopreservation of              Ovarian Tissue• Requires surgical procedure to r...
Email: enquiry@medicyatra.com     Ovarian Cryopreservation• Ovarian cortex is frozen in thin slices• Primordial follicles ...
Email: enquiry@medicyatra.com     Ovarian Cryopreservation• Resumption of endocrine function has been  reported after orth...
Email: enquiry@medicyatra.com              Ovarian Cryopreservation  • Heterotopic tranplantation technique:      – Optima...
Email: enquiry@medicyatra.com        Ovarian Cryopreservation• Xenotransplantation:  – Has been shown feasible in several ...
Email: enquiry@medicyatra.com     Ovarian Cryopreservation• Transplanting complete, intact ovary:  – Has been demonstrated...
Email: enquiry@medicyatra.com     Sphingosine-1-Phosphate• Apoptotic inhibitor  – blocks pro-apoptotic messenger:    ceram...
Email: enquiry@medicyatra.comSafety and Timing of Pregnancy          after Cancer• Conventional wisdom is to wait until pa...
Conclusions: Fertility Concerns in                        Email: enquiry@medicyatra.com       Cancer Survivors• Very compl...
Email: enquiry@medicyatra.comConclusions: Fertility Concerns in    Cancer Survivors (cont.)• Address fertility issues up f...
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Fertility In Cancer Patients Treatment

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MedicYatra provides the safe & best Fertility In Cancer Patients Treatment and procedure at its affiliate & trusted hospitals & clinics in various metro cities of India, like Mumbai, Delhi, Bangalore, Chennai, Pune etc.Our Associate Board certified doctors are extensively trained and vastly experienced and have performed hundreds of such cases at our state of the art JCI accredited hospitals & Clinics. Our aim is to provide you the best of the services at the most affordable costs. Don't forget to say hi at info@medicyatra.com

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  • Over 12,000 women under age 40 are diagnosed with invasive breast cancer annually in the US alone Future fertility may be of critical importance, and may affect treatment decisions
  • Over 12,000 women under age 40 are diagnosed with invasive breast cancer annually in the US alone Future fertility may be of critical importance, and may affect treatment decisions
  • Over 12,000 women under age 40 are diagnosed with invasive breast cancer annually in the US alone Future fertility may be of critical importance, and may affect treatment decisions
  • The risk of premature menopause is related to patient age, chemotherapeutic agents, and the total dose received Review of several studies including women under the age of 40 has revealed that the risk of treatment-related menopause is relatively low though not negligible. In women under the age of 30, premature ovarian failure with standard regimens is uncommon, with at least two studies finding a 0% incidence in this age group with every 3 week AC. 29-32 The impact of treatment duration and dose intensity, as well as newer drugs (e.g. the taxanes) remains uncertain While adjuvant endocrine therapy, such as tamoxifen or lhrh agonists, do not generally cause infertility, they usually entail year of treatment during which time a pregnancy is contraindicated.
  • The risk of premature menopause is related to patient age, chemotherapeutic agents, and the total dose received Review of several studies including women under the age of 40 has revealed that the risk of treatment-related menopause is relatively low though not negligible. In women under the age of 30, premature ovarian failure with standard regimens is uncommon, with at least two studies finding a 0% incidence in this age group with every 3 week AC. 29-32 The impact of treatment duration and dose intensity, as well as newer drugs (e.g. the taxanes) remains uncertain While adjuvant endocrine therapy, such as tamoxifen or lhrh agonists, do not generally cause infertility, they usually entail year of treatment during which time a pregnancy is contraindicated.
  • Over 12,000 women under age 40 are diagnosed with invasive breast cancer annually in the US alone Future fertility may be of critical importance, and may affect treatment decisions
  • It is not entirely clear why the ovary is so sensitive to the effects of chemotherapy since in the normal adult premenopausal ovary, primordial follicle recruitment occurs at a fairly low level. One theory that is supported by changes in hormone levels observed during chemotherapy, suggests that initial toxicity of the chemotherapy to the oocytes results an a decrease in estradiol and an increase in FSH with leads to an increase in follicular recruitment putting more oocytes at risk and setting up a sort of vicious cycle.
  • And if indeed this is the case, use of a GnRH analog prior to chemotherapy could potentially avoid that increase in follicular recruitment that may be putting ovarian tissue at particular risk.
  • So in general, it does appear that coadministration of the GnRH agonist with chemotherapy is associated with a higher than expected rate of resumption of menses after chemotherapy. In addition, successful pregnancies have occurred following this approach. Howerver, the lack of randomized data really limits our ability to draw firm conclusions about the efficacy of this approach.
  • I would like to draw your attention to this abstract that will be discsussed Monday in a poster discussion session. This was randomized study that does not show any clear benefit to the GnRH analog in terms of amenorrhea rates, however, it was a small study and probably lacks power to detect a modest to moderate effect.
  • I would like to draw your attention to this abstract that will be discsussed Monday in a poster discussion session. This was randomized study that does not show any clear benefit to the GnRH analog in terms of amenorrhea rates, however, it was a small study and probably lacks power to detect a modest to moderate effect.
  • So hopefully more conclusive information will be available with completion of the S0230 or POEMS (Prevention of early menopause study). This is a larger randomized study we are conducting through the SWOG with invovlement of the US Intergroup and IBCSG. This study is open to early stage breast cancer patients with ER/PR-negative disease. This is a population in whom induction of early menopause may be an unwanted toxicity of chemotherapy even if fertility is not a concern. Subjects will be randomized to receive essentially any appropriate cyclophosphamide-containing adjuvant or neoadjuvant chemotherapy with or without the addition of monthly goserelin beginning about a week prior to chemotherapy.
  • Transcript of "Fertility In Cancer Patients Treatment"

    1. 1. Email: enquiry@medicyatra.comFertility In Cancer Patients 22-06 2012 Copyright @ Forever Medic
    2. 2. Email: enquiry@medicyatra.comThe speaker declares that specific brand-name medications and/or off-label, non-FDA-approved uses are discussed in the lecture.• Letrozole or tamoxifen for ovarian stimulation• I will attempt to avoid bias by discussing the published researchin this area only and limitations of it Copyright @ Forever Medic
    3. 3. Email: enquiry@medicyatra.com Cancer and Future Fertility• Patients of reproductive age often find prospect of infertility one of the most difficult components of their disease and treatment• Oncology providers focus on survival• Can be difficult to assess who is interested in future fertility Copyright @ Forever Medic
    4. 4. Email: enquiry@medicyatra.com Fertility after cancer poses challenging medical issues and emotional consequences• Surveys of cancer survivors have identified an increased risk of emotional distress in those who become infertile because of their treatment• Long-term quality of life is affected by unresolved grief and depression Copyright @ Forever Medic
    5. 5. Email: enquiry@medicyatra.com Fertility Concerns Common• 57% of women age 40 and younger at diagnosis of breast cancer recalled concerns about fertility• 29% reported that infertility concerns influenced treatment decisions (Partridge et al., JCO 2004) Copyright @ Forever Medic
    6. 6. Email: enquiry@medicyatra.com Providers May Neglect to Discuss Fertility• Only 68% of women age 50 or younger at diagnosis of breast cancer recalled physician discussion of early menopause• 34% of women recalled discussion of infertility risk (Duffy et al., JCO 2005) Copyright @ Forever Medic
    7. 7. American Society of Clinical Oncology Email: enquiry@medicyatra.com Recommendations on Fertility Preservation in People Treated for Cancer • Assessment of risk for infertility •Communication with patient • Patient at risk for treatment induced infertility - • Patient interested in fertility preservation options Refer to specialist with expertise in fertility preservation methods Eligible for proven fertility preservation method Investigational fertility preservation technique*Male: Female: • ryopreservation of Cspermcryopreservation embryocryopreservation testicular or ovarian tissue conservative gynecologic surgery • ryopreservation ofoocytes C oophoropexy • Ovarian suppression *Clinical trial participation encouraged Copyright @ Forever Medic www.asco.org (Lee et al., J Clin Onc; 2006)
    8. 8. American Society of Clinical Oncology Email: enquiry@medicyatra.com Recommendations on Fertility Preservation in People Treated for Cancer • Assessment of risk for infertility •Communication with patient • Patient at risk for treatment induced infertility - • Patient interested in fertility preservation options Refer to specialist with expertise in fertility preservation methods Eligible for proven fertility preservation method Investigational fertility preservation technique*Male: Female: • ryopreservation of Cspermcryopreservation embryocryopreservation testicular or ovarian tissue conservative gynecologic surgery • ryopreservation ofoocytes C oophoropexy • Ovarian suppression *Clinical trial participation encouraged Copyright @ Forever Medic www.asco.org (Lee et al., J Clin Onc; 2006)
    9. 9. Email: enquiry@medicyatra.com Risk of Infertility in Men• Male infertility can result from: – Disease – Anatomic problems – Primary or secondary hormonal insufficiency – Damage or depletion of the germinal stem cells• The effects of chemotherapy or radiotherapy include compromised sperm number, motility, morphology, and DNA integrity• Azospermia typically surrogate for infertility Copyright @ Forever Medic
    10. 10. Email: enquiry@medicyatra.comAll Cancer Treatments Are not Equal• Alkylating agents appear to be most gonadotoxic; cis- platin – cumulative dose important• Radiation is very damaging: – >=2.5 Gy to testis area results in prolonged azospermia – External beam to field that includes ovaries Copyright @ Forever Medic
    11. 11. Email: enquiry@medicyatra.com Men Have Sperm Banking!• Sperm cryopreservation – involves freezing and banking sperm collected through masturbation, rectal electroejacualtion, testicular aspiration or post-masturbation urine – If patient sick or with certain cancers (e.g., testicular cancer and Hodgkins)- sperm quality may be poor prior to treatment – Many patients have to start chemotherapy soon enough to limit the number of ejaculates – Still reasonable to make every effort to bank sperm- intracytoplasmic sperm injection (ICSI) allows the successful freezing and future use of small sample Copyright @ Forever Medic
    12. 12. Email: enquiry@medicyatra.com Other “Options” for Men• Hormonal Gonadoprotection (e.g. GnRH analogs) – The efficacy of gonadoprotection through hormonal manipulations has only been evaluated in very small studies in male cancer patients – Evidence suggests hormonal therapy in men is not successful in preserving fertility when highly sterilizing chemotherapy is given• Potential future options (not tested in humans yet) – Testicular tissue cryopreservation or reimplantation Copyright @ Forever Medic – Testis grafting with maturation in SCID mice
    13. 13. Email: enquiry@medicyatra.com Risk of Infertility in Women• Female fertility can be compromised by any treatment that: – Decreases the number of primordial follicles – Affects hormonal balance – Interferes with the functioning of the ovaries, fallopian tubes, uterus or cervix. Copyright @ Forever Medic
    14. 14. Email: enquiry@medicyatra.comNatural Decline of Oocytes with Age Copyright @ Forever Medic (Lobo, NEJM 2005)
    15. 15. Email: enquiry@medicyatra.comChemotherapy-related Amenorrhea• CRA may be permanent or temporary• CRA is an imperfect surrogate for menopause and infertility• Accurate assessment of ovarian function has implications for – family planning, contraception – treatment in hormone sensitive tumors – other survivorship@concerns Copyright Forever Medic Online Pvt. Ltd
    16. 16. Email: enquiry@medicyatra.comRisk of amenorrhea is related to age and treatment Copyright @ Forever(Goodwin et al., J Clin Oncol 1999) Medic
    17. 17. Email: enquiry@medicyatra.com Ovarian Failure Risk with Cancer Treatments• High risk: – Total body irradiation, high dose cyclophosphamide, chlorambucil, melphalan, busulfan, nitrogen mustard, procarbazine• Intermediate risk: – Cisplatin, carboplatin, doxorubicin• Low or no risk: – Methotrexate, 5-fluorouracil, vincristine, vinblastine, bleomycin, actinomycin• Unknown risk: – Taxanes, oxaliplatin, irinotecan, monoclonal antibodies, Copyright @ Forever Medic Tyrosine kinase inhibitors (Sonmezer and Oktay, Hum Reprod Update, 2004)
    18. 18. Email: enquiry@medicyatra.com Risk of Chemotherapy-Related Amenorrhea with Common Breast Cancer Regimens Treatment Age <30 Age 30-40 Age>40 None ~0 <5 20-25 AC x 4 -- 13 57-63 CMF x 6 19 31-38 76-96 CAF/CEF x 6 23-47 80-89 TAC x 6 51 AC x 4, T x 4 38 (15% age <40)(Goodwin et al., JCO 1999; Burstein, H. J. et al. NEJM 2000; Nabholtz et al., ASCO 2002; Copyright @ Forever MedicParulekar et al., JCO 2005; Fornier et al., Cancer 2005; Petrek et al, JCO 2006)
    19. 19. Email: enquiry@medicyatra.com Effects of Newer Treatments: Paclitaxel, Dose Density, and Trastuzumab on CRA• Premenopausal women who received adjuvant chemotherapy• N=451• Age at diagnosis, mean: 42 years (range 25-55)• Follow-up, mean: 34 months (range 6-93) Copyright @ Foreveret al., Breast Cancer Res Treat 2006) (Abusief Medic
    20. 20. Email: enquiry@medicyatra.com Effects of Paclitaxel, Dose Density, and Trastuzumab on CRA Variable Odds 95% CI p-value ratio*Chemotherapy AC-T 1.27 0.70-2.32 0.61 AC 1.00 Referent --Regimen DD 1.30 0.66-2.57 0.56 q3wk 1.00 Referent --Trastuzumab AC-TH 0.49 0.21-1.17 0.11 AC 1.00 Referent --Tamoxifen yes 2.14 1.16-3.97 0.02 no 1.00 Referent --Age at diagnosis 1.39 1.30-1.49 <0.0001 Copyright @ Forever Medic (Abusief et al., Breast Cancer Res Treat 2006)
    21. 21. Email: enquiry@medicyatra.com Issues for Women Who Remain Premenopausal• Will a woman be less fertile, even if she continues to menstruate?• Will a woman go through menopause earlier (“delayed, premature menopause”) Copyright @ Forever Medic
    22. 22. Email: enquiry@medicyatra.comOvarian Reserve in Women Who RemainPremenopausal After Chemotherapy For Early Stage Breast Cancer• 20 breast cancer survivors who remained premenopausal after chemotherapy• 20 age, gravidity-matched controls• Day 2-4 of cycle, measured ovarian reserve (Ruddy et@ Forever Medicand Sterility, In Press) Copyright al., Fertility
    23. 23. Email: enquiry@medicyatra.com Ovarian Reserve in Survivors Compared to Controls Survivors (n=20) Controls (n=20) P-valueAntral Follicle 5.2 11.3 0.0042Count (AFC)Anti-Mullerian 0.57 1.77 0.0004Hormone(AMH)Follicle 11.56 8.04 0.02StimulatingHormoneInhibin B (InB) 24.3 46.6 0.02Estradiol (E2) 126.0 38.8 0.14 Prospective studies are needed to determine the predictive value of these tests for pregnancy after Copyright @ Forever Medic chemotherapy (Ruddy et al., Fertility and Sterility, In Press)
    24. 24. Age of Menopause Among Women Who Email: enquiry@medicyatra.com Remain Premenopausal Following Treatment for Early Breast Cancer• Long-term data from the International Breast Cancer Study Group (IBCSG) Trials V and VI• Included women who had reported menses in months 12-24 after diagnosis• N= 767 women – 540 women randomized to PeCT (1 cycle CMF) or No CT – 227 randomized to CMF x 6 or 7 Copyright @ Forever Medic (Partridge et al, Eur J Ca 2007)
    25. 25. Email: enquiry@medicyatra.com Effects of Endocrine Therapy• Adjuvant endocrine therapy for breast cancer (tamoxifen or ovarian suppression) does not appear to cause permanent amenorrhea or infertility• BUT… endocrine therapy usually entails years of treatment when pregnancy contraindicated, and aging during that time compromises fertility Copyright @ Forever Medic
    26. 26. Email: enquiry@medicyatra.comFertility Preservation Considerations for Women with Cancer The obvious: weigh the “necessity” of systemic therapy Copyright @ Forever Medic
    27. 27. Email: enquiry@medicyatra.com Options for Fertility Preservation in Women- Anatomic Fixes• Pelvic shielding during radiation• Ovarian Transposition – surgical repositioning of ovaries away from the radiation field• Conservative Gynecologic Surgery (Radical Trachelectomy) – surgical removal of the cervix while preserving the uterus Copyright @ Forever Medic
    28. 28. Email: enquiry@medicyatra.com Other Options for Preserving Fertility for Women with Cancer• Ovarian suppression (LHRH agonists) during treatment• Cryopreservation of embryos• Cryopreservation of ovarian tissue• Cryopreservation of oocytes• Pharmaceutical protection with anti-apoptotic agents (eg. Sphingosine-1-phosphate)• Oocyte donation and gestational surrogacy Copyright @ Forever Medic
    29. 29. Email: enquiry@medicyatra.com Ovarian Sensitivity to Chemotherapy Normal premenopausal ovaryLow level recruitment of primordial follicles Cytotoxic chemotherapy Oocyte toxicity Decreased estradiol Increased FSH Increased follicular recruitment More oocytes at risk Copyright @ Forever Medic
    30. 30. Email: enquiry@medicyatra.com Ovarian Sensitivity to Chemotherapy Normal premenopausal ovaryLow level recruitment of primordial follicles Cytotoxic chemotherapy Oocyte toxicity Decreased estradiol Increased FSH GnRHa Increased follicular recruitment More oocytes at risk Copyright @ Forever Medic
    31. 31. Email: enquiry@medicyatra.com Summary of Phase II Trials and Case Series• GnRH agonist coadministration with chemotherapy is associated with high rates of resumption of menses after chemotherapy• Successful pregnancies have occurred following chemotherapy with GnRHa• Lack of randomized data – Uncontrolled studies tended to have young patient populations Copyright @ Forever Medic
    32. 32. A randomized trial using the GnRH agonist Email: enquiry@medicyatra.com (triptorelin) during chemotherapy•N=49 (12-month f/u on 42 patients, and 18 month on 34 patients)•Median age 39 years, range 21–43•Median time to return of menses Triptorelin arm: 6.1 months (range 1–19) Control arm: 4.7 months (range 0–22) (p=0.79)•Menstruation resumed post chemotherapy in the respectivegroups as follows: triptorelin vs control 6 months: 44% vs 60%, 12 months 83% vs 79% Copyright @ Forever Medic (R. Ismail-Khan et al. ASCO 2008)
    33. 33. Gonadotropin-releasing hormone agonists for Email: enquiry@medicyatra.com prevention of chemotherapy-induced ovarian damage: prospective randomized study•N=80•Age range 18-40•Menstruation resumed post chemotherapy (3-8 months)in the respective groups as follows: GnRHa group Control group 35/39 resumed menses 13/39 resumed menses 27 resumed spontaneous ovulation Medic in control group Copyright @ Forever vs. 10 (Badawy et al., Fertility and Sterility, in Press)
    34. 34. Email: enquiry@medicyatra.com Ongoing Study: SWOG 0230 “POEMS”II, IIIA Premenopausal Stage I, ER-/PR- Breast Cancer Under age 50 CALGB 40401 Randomization Stratification: ECOG S0230 n=416 Age IBCSG 34-05 ChemotherapyStandard cyclophosphamide Standard cyclophosphamideContaining (neo)adjuvant Containing (neo)adjuvantchemotherapy chemotherapy Plus monthly goserelin Copyright @ Forever Medic
    35. 35. Email: enquiry@medicyatra.comIVF/Embryo Cryo Copyright @ Forever Medic
    36. 36. Email: enquiry@medicyatra.com• Cryopreservation of Embryos Standardly available: 20-30% pregnancy rate per transfer of 2-3 embryos• Requires medical stability, time, and partner/sperm, adequate ovarian reserve• Expensive, ethically problematic if patient dies• Requires ovarian stimulation prior to systemic breast cancer treatment- concerning in patients with hormone- sensitive cancer• Natural cycle IVF has low yield (Oktay et al, JCO, 2005; Partridge & Winer, JCO 2005) Copyright @ Forever Medic
    37. 37. Comparison of Cycle Characteristics and Embryo Yield Among Tam- Email: enquiry@medicyatra.com IVF (12 patients) TamFSH-IVF (seven patients), and Letrozole-IVF (11 patients) Patients (Oktay et al, JCO, 2005) Tam-IVF TamFSH-IVF Letrozole-IVF av bv Variable (a) (b) (c) b avc cAge, years 36.6 ± 1.6 38.3 ± 1.9 38.5 ± 1 NS NS NSBaseline FSH, mU/ 9.4 ± 1.5 9.4 ± 1.5 6.2 ± 1.1 NS NS NSmLPeakE2, pg/mL 419 ± 39 1,182 ± 271 380 ± 57 <. > .05 <. 05 05Total follicles, No. 2 ± 0.3 6±1 7.8 ± 0.9 <. <. >. 01 001 05Follicle > 17 mm, 1.2 ± 0.1 2.6 ± 0.4 3.2 ± 0.4 <. <. >.No. 05 001 05Total oocytes, No. 1.7 ± 0.3 6.9 ± 1.1 12.3 ± 2.5 <. <. >. 05 001 05Mature oocytes, 1.5 ± 0.3 5.1 ± 1.1 8.5 ± 1.6 <. <. >.No. 05 001 05Total embryos, No. 1.3 ± 0.2 Copyright @ Forever Medic ± 0.8 3.8 ± 0.8 5.3 <. <. >. 05 001 05
    38. 38. Tamoxifen or aromataseEmail: enquiry@medicyatra.com inhibitor stimulation protocols for IVF• Increase embryo yield, lower E2 levels with Letrozole, blockage of receptors with Tamoxifen – Unclear if mitigates potential risk• Preliminary safety data available• Number of babies resulting from such strategies that would have not been born otherwise remains unclear (Oktay et al, JCO 2005; Partridge & Winer, JCO 2005; Oktay et al., JCO 2008) Copyright @ Forever Medic
    39. 39. Email: enquiry@medicyatra.com Oocyte Cryopreservation• Requires time and stimulation prior to treatment• No requirement for sperm, less ethical concern• Experimental- approximately 2% pregnancy rate per thawed oocyte Copyright @ Forever Medic
    40. 40. Email: enquiry@medicyatra.com Oocyte Cryopreservation• Technically difficult• MII oocytes: extremely sensitive to temperature changes• Crystal formation can cause cytoplasmic damage• Cryoprotectants – depolymerize meiotic spindle – cause aneuploidy• Hardening of zona pellucida – barrier to fertilization Copyright @ Forever Medic
    41. 41. Email: enquiry@medicyatra.com Cryopreservation of Ovarian Tissue• Requires surgical procedure to remove ovary or piece of ovary• May increase risk of infertility in low risk situation• Potential for reintroduction of malignant cells at reimplantation• Highly experimental- few babies born to date Copyright @ Forever Medic
    42. 42. Email: enquiry@medicyatra.com Ovarian Cryopreservation• Ovarian cortex is frozen in thin slices• Primordial follicles are less sensitive to cryodamage because of – low metabolic rate – absence of zona pellucida – high surface-volume ratio Copyright @ Forever Medic
    43. 43. Email: enquiry@medicyatra.com Ovarian Cryopreservation• Resumption of endocrine function has been reported after orthotopic and heterotopic transplantation• Embryo was generated from oocytes retrieved from sc transplanted ovarian tissue• Two live births reported after orthotopic transplantation of frozen-banked ovarian tissue in lymphoma@survivors Copyright Forever Medic
    44. 44. Email: enquiry@medicyatra.com Ovarian Cryopreservation • Heterotopic tranplantation technique: – Optimal site unknown – Most have been to arm or forearm (or suprapubic area)- No need for abdominal surgery- Easy monitoring of follicular dvelopment- Easy removal if necessary (Oktay K, et al, JAMA, 2001;286:1490-3)@ Forever Medic Copyright
    45. 45. Email: enquiry@medicyatra.com Ovarian Cryopreservation• Xenotransplantation: – Has been shown feasible in several animal models into immunodeficient mice – Concerns: • Retroviruses, prions • Abnormal oocyte development • Abnormal chromatin patterns – Benefits: • Easier to repeat grafting if needed • Easier access for IVF Copyright @ Forever Medic
    46. 46. Email: enquiry@medicyatra.com Ovarian Cryopreservation• Transplanting complete, intact ovary: – Has been demonstrated in rats and sheep – Recently demonstrated in human, but high risk for ischemia-reperfusion injury – No pregnancy demonstrated (Bedaiwy M, et al, Hum Reprod, 2006) Copyright @ Forever Medic
    47. 47. Email: enquiry@medicyatra.com Sphingosine-1-Phosphate• Apoptotic inhibitor – blocks pro-apoptotic messenger: ceramide (early messenger that signals apoptosis in response to stress) – shown to be beneficial in mice when injected into ovarian bursa sac prior to radiation – has not been evaluated in humans Copyright @ Forever Medic al, Nat Med 1997;3:1228-32) (Perez G, et
    48. 48. Email: enquiry@medicyatra.comSafety and Timing of Pregnancy after Cancer• Conventional wisdom is to wait until patient gets through the period of highest risk recurrence – Receive optimal therapy (endocrine therapy may be prolonged)• No data to suggest harm in pregnancy sooner• No evidence for increased risk of disease recurrence associated with most fertility preservation methods and pregnancy- little data!• Aside from hereditary genetic syndromes and in-utero exposure to chemotherapy, no evidence for increased risk of cancer or abnormality in progeny Copyright @ Forever Medic
    49. 49. Conclusions: Fertility Concerns in Email: enquiry@medicyatra.com Cancer Survivors• Very complex and difficult issues• Limited available data• Patient preferences critical in some settings• Managing expectations often necessary Copyright @ Forever Medic
    50. 50. Email: enquiry@medicyatra.comConclusions: Fertility Concerns in Cancer Survivors (cont.)• Address fertility issues up front; include fertility concerns in the risk-benefit analysis – Refer to fertility specialists early• In the event of pregnancy, consider “high risk” obstetrics management Copyright @ Forever Medic
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