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Fertility Preservation and Infertility Treatments in Breast Cancer Patients. How to Stimulate and What Are

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Fertility Preservation and Infertility Treatments in Breast Cancer Patients. How to Stimulate and What Are Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Michael von W olff 1 FertilityDies ist derpreservation Titel der Präsentationand infertility treatments in breast cancer patients Prof. Michael von Wolff University Women`s Hospital Division of Gynecological Endocrinology and Reproductive Medicine 1 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern I (M.v.W.) have nothing to declare Michael von W olff 3 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Agenda • General remarks • Fertility preservation techniques • Infertility/pregnancy after Breast cancer Michael von W olff 4 2 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Agenda • General remarks • Fertility preservation techniques • Infertility/pregnancy after Breast cancer Michael von W olff 5 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Frequency of breast cancer counselings (>5.000 cases in FertiPROTEKT) Michael von W olff von Wolff et al., RBM online, 2015 6 3 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Michael von W olff Schüring….von Wolff, Arch Gynecol OBstet, in press 7 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Disease free survival Overall survival Good prognosis? 2010 Cancello et al., Ann Oncol Oncol Ann al., et Cancello Michael von W olff Schüring….von Wolff, Arch Gynecol OBstet, in press 8 4 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Risk of infertility high? Michael von W olff Sukumvanich et a., Cancer, 2010 9 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Diagnosis Breast cancer ≤ 40 y Decision criteria 5-years survival 5-years survival Therapy ≥50% <50%, Stage IV POI-risk high and age ≥38y at POI-risk low and age <38y at Rather no the time of the expected the time of the expected fertility pregnancy pregnancy preservation Estrogen-sensitive Not estrogen-sensitive Info: limited data 1 week 2 weeks 1 week ≥2 weeks 1 week GnRHa Stimulation plus Cryo ovarian Stimulation GnRHa aromatase-inhibitors tissue Indikation und Durchführung fertilitätsprotektiver Massnahmen bei onkologischen und nicht- Michael von W olff 10 onkologischen Erkrankungen, Hrsg.: von Wolff, Schmidt & Klaunig-Verlag, 1. Auflage, 2016 5 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Agenda • General remarks • Fertility preservation techniques • Infertility/pregnancy after Breast cancer Michael von W olff 11 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern The efficacy of GnRH agonists Breast cancer: Odds ratios for POI/amenorrhoea with and without GnRHagonists Michael von W olff Senra et al., Ultrasound OBst Gynecol, 201712 6 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Long term efficacy of GnRH agonists Analysis of the ovarian reserve after a chemotherapy in hodgkins lymphoma patient with (n=32) and without (n=35) GnRH-agonists. Conclusion: GnRHa do have a short term But possiBly not a long term effect, requiring an individual decision concerning its use. Demeestere et al., J Clin Oncol, 08 2016 Michael von W olff 13 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Risk of GnRH agonists in Breast cancer? Disease free suvival with vs. without GnRHa in 257 premenopausal receptor negative women receiving standard chemotherapy Michael von W olff Halle et al., N Eng J Med, 2015 14 7 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Risk of GnRH agonists in hormone receptor positive breast cancer? TEXT: GnRHa with chemotherapy, SOFT: GnRHa after chemotherapy Michael von W olff Regan et al., Ann Oncol, 2017 15 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Cryopreservation of ovarian tissue Risk of ovarian metastasis Study Patients Stage Metastasis No No No Indikation und Durchführung fertilitätsprotektiver Massnahmen bei onkologischen und nicht- Michael von W olff 16 onkologischen Erkrankungen, Hrsg.: von Wolff, Schmidt & Klaunig-Verlag, 1. Auflage, 2016 8 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Further risks in case of tissue freezing Risk of ovarian metastasis increased in stage IV carcinoma: o Lobular carcinoma: 5/14 women = 36% o Ductal carcinoma: 2/75 women = 3% Harris et al., Br. J Cancer, 1994 Up to 20% of women <35y are BRCA positive Life time risk of developing ovarian cancer o BRCA 1: 45% (2% <40y, 14% <50y) o BRCA 2: 12% ( 1% <50y) Jacobs et al., Lancet 2016 Michael von W olff 17 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Transplantation techniques Into the pelvic wall Into the ovary Onto the ovary University women`s hospital Berne Michael von W olff 18 9 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Life birth rate following transplantation of ovarian tissue Michael von W olff 19 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Efficacy of transplantation - Life birth rate after transplantation ovarian tissue Jensen et al., Hum Reprod 2015 (Dänemark): Life birth rate/per patient 31% (incl. repeated transplant.) FertiProtekt: van der Veen et al., Hum Reprod 2016 Life birth rate/per transplantation: 23% Update FertiPROTEKT (updatated By J. LieBenthron): 162 transplantations in 125 women; 46 women with POI and follow uo >12 month: Life birth per 1st transplantation: 30% (plus 1 ongoing pregnancy) Michael von W olff 20 10 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Efficacy of transplantation – Success rate in relation to maternal age at the time of tissue freezing Best age: ≤ 35y Michael von W olff Van der Ven et al., Hum Reprod, 2016 21 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Ovarian stimulation The ovarian stimulation can Be performed within 2 weeks irrespective of day of the menstrual cycle von Wolff et al., Fertil Steril, 2009 Cakmak et al., Fertil Steril 2013 von Wolff et al., EJOG 2016 Risks: No relevant risks (6 out of 205 patients without a fertilited oocyte) Lawrenz et al., Arch Gy nec ol Obs tet, 2011 Michael von W olff 22 11 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Collected oocytes (FertiPROTEKT) Michael von W olff von Wolff et al., RBMonline, 2015 23 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Stimulation techniques Michael von W olff 24 12 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Efficacy of ovarian stimulation – theoretical calculation cased on the number of retrieved oocytes and registry data. Red numbers: Theoretical life birth rate 16 EntnommeneCollected oocytesOozyten 14 FertilisierteFertilized Oozyten oocytes 12 10 40% 8 35% 30% 6 25% 4 2 Lawrenz et al., 0 2010 Fertil Steril 18-25 26-30 31-35 36-40 v. Wol ff & Di an; (n=20) (n=42) (n=42) (n=21) Dsch Aerzteblatt Age Int., 2011 Michael von W olff 25 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Observational studies to calculate the Life Birth rate following the use of cryopreserved oocytes and emBryos 8 studies: •1203 women cryopreserved •90 women used their depot (7.5%) •196 emBryo transfers •35 women delivered ≥1 baby (Life Birth rate / women: 38.9%) •45 children total Alvarez & Ramanathan, Hum Reprod, 2016 Michael von W olff 26 13 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Stimulation techniques Michael von W olff von Wolff et al., Arch Gynecol Obstet, in press 27 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Addition of letrozole Michael von W olff 28 14 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Safety of letrozole 2014 Michael von W olff 29 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Agenda • General remarks • Fertility preservation techniques • Infertility/pregnancy after Breast cancer Michael von W olff 30 15 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern InfluenceWas tun of nach pregnancy der Chemotherapie? on the prognosis Survival rate Lymph node negative SS-Studie Lymph node positive Michael von W olff Azem et al., Eur J Cancer, 2011, 31 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern But……. Cancello et al., Ann Oncol 2010 Michael von W olff 32 16 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Infertility treatments In which cases is the risk of relapse lower after hormone dependant breast cancer? (Estimated success rates): High ovarian reserve: o 3 month treatment by IUI: Live birth rate 20% o 3 month treatment by NC-IVF: Live birth rate 30% o 3 month treatment by IVF: Live birth rate 60% Low ovarian reserve: o 3 month treatment by IUI: Live birth rate 20% o 3 month treatment by NC-IVF: Live birth rate 30% o 3 month treatment by IVF: Live birth rate 30% o E2 increasing medications should only Be used if necessary o IVF: co-treamtment with E2-reducing medications (Tam, letrozole) is useful Michael von W olff 33 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Is PGD a solution in case of BRCA mutation? Risk of developing cancer in BRCA carriers in different studies BRCA 1 - Breast BRCA 2 - Breast BRCA 1 - Ovary BRCA 2 - Ovary BRCA mutations follows autosomal dominant inheritance pattern: Polar body and embryo biopsy are both possible Michael von W olff Chen & Parmiginai, J Clin Oncol 2007 34 17 Abteilung Gynäkologische Endokrinologie und Reproduktions me dizi n, Bern Summary • Breast cancer tratment causes a low risk of infertility at young age But a high risk at high age, especially due to long lasting endocrine treatment. • GnRHa can also Be applied in hormone dependant Breast cancer. • In women <35y Both ovarian tissue freezing and ovarian stimulation are possiBle options. • In women >35y ovarian stimulation might Be more effective. • Pregnancy need to Be permitted By oncologists and risk of relapse should Be very low. • Infertility treatment: Short «Time to pregnancy» counts possibly more than gonadotropin free treatments. Michael von W olff 35 18.
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