FERTILITY PRESERVATION PROGRAM

Transcription

1 FERTILITY PRESERVATION PROGRAM The University of Illinois Fertility Preservation Program offers a comprehensive team approach to help women faced with serious conditions which may impair future fertility. Our team consists of reproductive endocrinologists, medical and surgical oncologists, rheumatologists, pathologists, embryologists, research and clinical nurses, social workers and clinical ethics consultants who are here to help. Drs. Bert Scoccia and Jennifer Hirshfeld-Cytron at the University of Illinois Fertility Center are Board Certified/Eligible specialists in Reproductive Endocrinology and Infertility. 1. Bert Scoccia, MD Professor of Obstetrics and Gynecology Director of the Division of Reproductive Endocrinology and Infertility Medical Director of the University of Illinois IVF Program. 2. Jennifer Hirshfeld-Cytron, MD Assistant Professor of Obstetrics and Gynecology Director of the University of Illinois Fertility Preservation Program We will be happy to discuss our Fertility Preservation Program and any other issues with you during an office consultation West Taylor Street, Suite 4A, Chicago, IL To make a new patient appointment, please call: UIC Call Center at or visit Existing patients please call: UIC Fertility Center at Page 1 of 16

2 INTRODUCTION The American Cancer Society estimates that in 2008, 700,000 women will have a cancer diagnosis. More than 11,000 breast cancer patients are diagnosed under the age of 40 each year. 21% of gynecologic cancer patients are diagnosed under the age of 45. The number of cancer survivors in the United States has increased from 3 million in 1971 to 10 million in 2001! Over the past few decades 80-90% of patients with Systemic Lupus Erythematosus (SLE) survive at least 10 years Women of reproductive age with severe SLE are sometimes treated with Cyclophosphamide, an Alkylating agent which may cause premature ovarian failure (POF) and loss of future reproductive potential Other severe Autoimmune Diseases such as Rheumatoid Arthritis, Systemic Sclerosis, and Sjogren Syndrome are sometimes treated with Cyclophosphamide, putting women of reproductive age at risk for POF PATIENT CONSIDERATIONS Patients of reproductive age with cancer and severe autoimmune disease need to be informed about future fertility options as they undergo their treatment. The American Society of Clinical Oncologists has issued Fertility Preservation Guidelines which state: As part of informed consent, prior to therapy, oncologists should address the possibility of infertility with patients as early in treatment planning as possible. Page 2 of 16

3 INDICATIONS FOR FERTILITY PRESERVATION A patient who is faced with a decision to preserve future fertility due to malignant or non-malignant conditions must take into account her age at diagnosis, ovarian involvement, time available prior to treatment initiation, type of cancer or severe autoimmune or rheumatic disease, and proposed treatment plan. This is a partial list of conditions which are amenable to fertility preservation: Breast Cancer Cervical Cancer Severe Autoimmune Disease Patients Undergoing Pelvic Radiation Stem Cell Transplantation Leukemia Non-Hodgkin Lymphoma Severe Endometriosis Turner Syndrome (Mosaic) FERTILITY PRESERVATION OPTIONS 1. Patients who want to address future fertility concerns need to take into account the timing during their treatment process, since this will impact the fertility preservation options available. Options are listed according to their medical status (Routine or Investigational Procedure). Before treatment starts: o Stimulated Egg Retrieval, In Vitro Fertilization and Embryo Freezing (Routine Procedure) o Unstimulated Egg Retrieval, In Vitro Maturation, In Vitro Fertilization and Embryo Freezing (Investigational Technique) o Ovarian Transposition (Surgical repositioning of the ovaries away from the radiation field Routine Procedure) o Stimulated Egg Retrieval and Egg Freezing (Investigational Technique) o Unstimulated Egg Retrieval, In Vitro Maturation and Egg Freezing (Investigational Technique) o Ovarian Tissue Freezing (Investigational Technique) o Radical Trachelectomy (Surgical removal of the cervix in patients with cervical cancer while retaining the uterus Routine Procedure) Page 3 of 16

4 During treatment: o Radiation Shielding of the Ovaries (Routine Technique) o Ovarian Medical Suppression (Investigational Technique) After treatment completion: o Frozen Embryo Thawing and Transfer (Routine Procedure) o In Vitro Fertilization with Donor Eggs (Routine Procedure) o Frozen Egg Thawing, In Vitro Fertilization and Embryo Transfer (Investigational Technique) o Embryo Transfer with Frozen Donor Embryos (Routine Procedure) o Embryo Transfer to a Gestational Surrogate (Routine Technique) o Adoption (Routine Practice) o Frozen Ovarian Tissue Thawing and Transplantation with or without In Vitro Fertilization and Embryo Transfer (Investigational Technique) 2. Patients need to take into account their current status with respect to a partner or sperm donor. Options are listed according to medical status (Standard or Investigational). Women without a male partner may wish to consider: o In Vitro Fertilization with Anonymous Donor Sperm and Embryo Freezing (Standard Technique) o Egg Freezing (Investigational Technique ) o Ovarian Tissue Freezing (Investigational Technique) Women with a male partner may wish to consider: o In Vitro Fertilization and Embryo Freezing (Standard Technique) o Egg Freezing (Investigational Technique) o Ovarian Tissue Freezing (Investigational Technique) 3. Patients should also discuss with a fertility specialist the decrease in future fertility which occurs with advancing maternal age. In particular, there is a significant decrease in the number of eggs available (about 25,000 per ovary) at the age of 37 years. Page 4 of 16

5 RISK of PREMATURE OVARIAN FAILURE The risk of permanent lack of menstrual cycles (amenorrhea and/or premature ovarian failure) in a woman of reproductive age following treatment for cancer or severe rheumatologic and autoimmune diseases depends on factors such as a patient s age, chemotherapy agent used and/or pelvic radiation therapy dosage. Chemotherapy and radiation therapy may directly damage or destroy the eggs in the ovaries, which can lead to premature menopause. Radiation to the pelvis can also lead to impairment in the lining of or blood flow to the uterus. The following are estimated risks of premature ovarian failure (listed from highest to lowest) and, consequently, loss of future fertility potential in a patient of reproductive age: RISK TREATMENT High >80% 1. High Dose External Beam Radiation to the Ovaries: Adult women > 6 Gy Post-Pubertal girls> 10 Gy Pre-Pubertal girls > 15 Gy (Gy-Gray: Absorbed Dose of Radiation) 2. Bone Marrow Transplant or Stem Cell Transplant Alkylating Agent Chemotherapy (Cyclophosphamide, Busulfan or Melaphan) in preparation for transplant 3. Breast Cancer Combination Chemotherapy in Women over 40 Yrs: Alkylating Agent Chemotherapy (Cyclophosphamide, Busulfan or Melaphan) plus Methotrexate, Fluorouracil, Doxorubicin plus Epirubicin Page 5 of 16

6 RISK Intermediate ~ 30-70% TREATMENT 1. Breast Cancer or Severe Autoimmune Disease Chemotherapy in Women Yrs: Alkylating Chemotherapy (Cyclophosphamide, Busulfan Melphalan or Chlorambucil) 2. Breast Cancer Combination Chemotherapy in Women over 40 yrs: Alkylating Agent Chemotherapy (Cyclophosphamide, Busulfan or Melaphan) plus Doxorubicin RISK Low <20% TREATMENT 1. Breast Cancer or Severe Autoimmune Disease Chemotherapy in Women less than 30 Yrs: Alkylating Agent Chemotherapy (Cyclophosphamide, Busulfan, Melaphan or Chlorambucil) 2. Breast Cancer Combination Chemotherapy in Women less than 40 Yrs: Alkylating Agent Chemotherapy (Cyclophosphamide, Busulfan or Melaphan) plus Doxorubicin 3. Cancer Chemotherapy for : Leukemia (ALL, AML) Non Hodgkin Lymphoma Page 6 of 16

7 RISK Very Low/ None TREATMENT Individual Chemotherapy or Radiotherapy Agents: Vincristine Methotrexate Fluorouracil Radioactive Iodine 131 RISK TREATMENT Unknown New Chemotherapy or Antibody Agents : Taxanes (Paclitaxel-Taxol, Docetaxel-Taxotere) Oxaliplatin (Eloxatin) Irinotecan (Camptosar) Bevacizumab (Avastin) Cetuximab (Erbitux) Trastuzumab (Herceptin) Erlotinib (Tarceva) Imatinib (Gleevec) A. Before Treatment Starts : FERTILITY PRESERVATION OPTIONS 1. Ovarian Stimulation, Egg Retrieval, In Vitro Fertilization and Embryo Freezing Most commonly used fertility preservation option Standard technique used for more than 30 years Requires 4-6 weeks for ovarian stimulation, egg retrieval, egg fertilization and embryo freezing Elevated estrogen/progesterone levels may impact cancer prognosis in patients with hormone sensitive cancers Pregnancy rates per embryo transfer range from 10% to 40%, depending on the patient s age Frozen embryos stored successfully up to 15 years Costs: About $10,000 plus fertility medications (~ $5,000) and about $400/year fee for long term storage of frozen embryos Page 7 of 16

8 Patients who are not covered by medical insurance should be aware that the UIC IVF program offers a complete IVF cycle for under $10,000. Certain tests and procedures are excluded and medications are not included in this package. Please contact Sandy Young at for more information. 2. Unstimulated Egg Retrieval with In Vitro Maturation, In Vitro Fertilization and Embryo Freezing Investigational (research) technique which requires Institutional Review Board approval Requires 1-2 weeks for egg retrieval, in vitro maturation, fertilization and embryo freezing No fertility drugs required There is no rise in estrogen or progesterone hormone levels Pregnancy rate per embryo transfer in women <35 years is 40% There are 1,000 live births reported Costs: $10,000 plus $250/year fee for long term storage of frozen embryos 3. Ovarian Stimulation, Egg Retrieval and Egg Freezing Investigational (research) technique which requires Institutional Review Board approval Requires 4-6 weeks for ovarian stimulation, egg retrieval and egg freezing Approximately 2-5% live birth rate per thawed oocyte (>200 live births reported) Pregnancy rate per embryo transfer varies according to freezing technique: o Computerized slow egg freezing 1-10% o Immediate egg vitrification 20-40% Costs: About $10,000 plus fertility medications (~$5,000) and about $250/year fee for long term storage of frozen eggs 4. Unstimulated Egg Retrieval with In Vitro Maturation and Egg Freezing Investigational (research) technique which requires Institutional Review Board approval Requires 1-2 weeks for egg retrieval, in vitro maturation and egg freezing No fertility drugs required No rise in estrogen or progesterone hormone levels Page 8 of 16

9 Pregnancy rate per embryo transfer in women <35 years is 20% Approximately 2% live birth rate per thawed egg (>200 live births reported) Costs: $10,000 plus $250/year fee for long term storage of frozen eggs 5. Ovarian Tissue Freezing Investigational (research) technique which requires Institutional Review Board (IRB) approval UIC is part of the Oncofertility Consortium and we have received IRB approval to obtain ovarian tissue from patients who are at risk of losing future fertility to study the best ways to freeze and then thaw frozen ovarian tissue and eggs Outpatient laparoscopic removal of one ovary Tissue divided into small strips and frozen in the laboratory Costs: About $13,000-15,000 for outpatient surgery and about $250/year fee for long term storage of frozen ovary 6. Surgical Transposition of the Ovaries Standard surgical technique used to reposition the ovaries away from the pelvis in patients who are scheduled to undergo pelvic radiation therapy Must be done before pelvic radiation begins if no chemotherapy is administered Laparoscopy outpatient surgery can be done to shield the ovaries behind the uterus or high in the abdomen, away from the field of radiation Ovarian function after treatment may be compromised up to 50% of the time due to decreased blood supply to the ovaries or radiation scatter Costs: About $13,000-15,000 for outpatient surgery 7. Radical Surgical Removal of the Cervix (Trachelectomy) Standard surgical technique to remove the cervix in patients with invasive cancer (stages Ia and Ib) in order to preserve the uterus and ovaries for future fertility Involves inpatient surgery It does not increase the risk of cancer recurrence in appropriately selected patients (cervical cancer stages Ia and Ib) Costs included in the treatment for cervical cancer B. During Treatment: Page 9 of 16

10 1. Ovarian Medical Suppression Investigational (research) technique which requires Institutional Review Board approval Must be started before chemotherapy begins Requires 6 weeks for ovarian suppression and has to be administered throughout chemotherapy Severe menopausal side effects (hot flashes and vaginal dryness) Few randomized trials with mixed results No benefit in women undergoing high-dose chemotherapy with stem cell transplantation Costs: Each monthly injection costs about $1, Ovarian Radiation Shielding Standard technique which reduces the radiation exposure to the ovaries when patients are being treated with radiation away from the pelvis Involves shielding of the pelvis with a lead apron Does not protect against toxic effects of chemotherapy to the ovaries Costs are included with the radiation therapy C. After Treatment Completion: 1. Frozen Embryo Thawing and Transfer Standard technique for patients who were able to store embryos prior to undergoing treatment Must have a functioning uterus to carry the frozen/thawed embryo Patient must use estrogen and progesterone supplementation in order to prepare the lining of the uterus to accept and carry the embryo during the first few weeks of pregnancy Overall frozen embryo survival ranges from 50%-70% Pregnancy rates per frozen embryo transfer range from 10-40%, depending on the age of the patient at the time of her egg collection, fertilization and embryo freezing Costs: Frozen Embryo Transfer charges range from $2,000-$4,000 plus about $2,000-$3,000 for medications. Page 10 of 16

11 2. Frozen Egg Thawing, In Vitro Fertilization and Embryo Transfer Investigational (research) technique which requires Institutional Review Board approval This technique is for patients who, after informed consent, were able to freeze eggs prior to undergoing treatment Requires several steps: Thawing of the eggs, In Vitro Fertilization of the eggs with the partner s sperm or the sperm of an anonymous sperm donor, and Embryo transfer Must have a functioning uterus to carry the embryo Patient must use estrogen and progesterone supplementation in order to prepare the lining of the uterus to accept and carry the embryo during the first few weeks of pregnancy Approximately 2-5% live birth rate per thawed oocyte (>200 live births reported) Pregnancy rates per embryo transfer vary according to freezing technique: o Computerized slow egg freezing 1-10% o Immediate egg vitrification 20-40% o In Vitro Maturation and immediate egg vitrification 10-20% Costs: Egg thawing and In Vitro Fertilization charges range from $1,500- $2,000. In addition, Embryo Transfer charges range from $1,500-$2,000 plus about $2,000-$3,000 for medications 3. Egg Donation Standard technique for patients who have premature ovarian failure after treatment and desire to use donor eggs UIC has had an active egg donation program for more than 15 years Patient needs to recruit a known or an anonymous egg donor and the eggs can then be fertilized with either her partner s sperm or an anonymous donor s frozen sperm Patient will be able to carry the baby, but she will not have the same genetic relationship to her child The donor has to undergo ovarian stimulation with fertility drugs and egg retrieval Patient must have a functioning uterus to carry the baby Patient must use estrogen and progesterone supplementation in order to prepare the lining of the uterus to accept and carry the embryo during the first few weeks of pregnancy Pregnancy rates per donor embryo transfer range from 35-50%, depending on the age of the egg donor Counseling should be considered by couples considering egg donation due to the emotional stress involved Page 11 of 16

12 Costs: Anonymous egg donor charges range from $12,000-$15,000. In addition, charges for ovarian stimulation, egg retrieval and fertilization, and embryo transfer range from 15,000-20, Embryo Donation Standard technique for patients who develop premature ovarian failure after treatment and desire to use donor embryos. Frozen donor embryos are donated to help childless couples Patient and her partner will be able to have the baby, but neither of them will have the same genetic relationship to their child Must have a functioning uterus to carry the donated embryo Patient must use estrogen and progesterone supplementation in order to prepare the lining of the uterus to accept and carry the embryo during the first few weeks of pregnancy Pregnancy rates per frozen donor embryo transfer range from 10-40%, depending on the age of the embryo donor Counseling should be considered by couples considering embryo donation due to the emotional stress involved Costs: Frozen Donor Embryo charges range from $2,000-$7,000. In addition, the costs for frozen embryo transfer range from $2,000-$4,000 plus about $2,000-$3,000 for medications. 5. Gestational Surrogacy Standard technique for patients who are unable to carry a pregnancy A gestational surrogate is a woman who is willing to carry the pregnancy, but has no genetic relationship to the child The child has the same genetic makeup of the couple, but not of the surrogate Patients may also choose to use donor eggs and/or donor sperm in order to produce embryos, which can then be transferred to the gestational surrogate Pregnancy rates per embryo transfer range from 10-40%, depending on the age of the patient who is having the eggs retrieved Patients considering gestational surrogacy should contact a reproductive rights attorney in order to understand the surrogacy laws in their state Counseling should also be considered by couples considering gestational surrogacy due to the emotional stress involved Costs: Gestational Surrogacy charges range from $50,000-$100,000 Page 12 of 16

13 6. Adoption Standard procedure to help couples who would otherwise not be able to have a baby For a domestic adoption a couple needs to decide between an independent (non-agency) adoption and an agency adoption. There are also not-forprofit and for-profit organizations For an international adoption a couple will be adopting a child from another country and will need to follow the laws of that country Clearly a couple considering adoption will need proper legal advice in order to undertake this process The adoption process takes between 1-5 years Counseling should be considered by couples considering adoption due to the emotional stress involved Resolve is a national infertility association which can offer practical guidance to couples seeking to pursue adoption. For more information please visit resolve.org The American Society for Reproductive Medicine ( also provides patient information and has a fact sheet on adoption which may be helpful to couples considering this process Costs: An agency or international adoption plus legal advice charges may range between $15,000-$25, Ovarian Tissue Thawing Investigational (research) technique for patients who were able to freeze and store strips of ovarian tissue prior to undergoing treatment There are several ways in which the thawed ovarian tissue can be used: o Reimplantation of a strip of ovarian tissue back into the pelvis followed by either natural conception or In Vitro Fertilization and Embryo Transfer o Insertion of a strip of ovarian tissue under the skin in the arm or in the abdomen followed by In Vitro Fertilization and Embryo Transfer o Retrieval of immature eggs from the thawed ovarian tissue and In Vitro Maturation in the laboratory followed by fertilization and embryo transfer There is a risk that the ovarian tissue that is being reimplanted after cancer treatment may contain some cancer cells and the cancer may recur Subsequent surgical placement back in the body after cancer treatment Ovarian transplant lifespan: 3 months to 3years As of 2007 six live births reported Costs: The surgery to reimplant the ovarian tissue in the pelvis is about $13,000-$15,000. In Vitro Maturation of the eggs, fertilization and embryo transfer charges are about $10,000. Page 13 of 16

14 FERTILITY AFTER CANCER TREATMENT 1. Women who have been treated for cancer or severe rheumatologic and autoimmune diseases should consider having ovarian reserve testing within 4-6 months after treatment. Current tests for ovarian reserve include: Hormone tests: o FSH and Estradiol at the beginning of the menstrual cycle o Anti-Mullerian Hormone any time during the menstrual cycle o Inhibin-B at the beginning of the menstrual cycle Ovarian Ultrasound o Antral Follicle Count at the beginning of the menstrual cycle 2. Patients who are interested in future fertility should be evaluated for lung, heart, kidney and liver damage due to chemotherapy or radiation therapy prior to pregnancy 3. Some patients may have a genetic condition in which the cancer actually runs in the family and can be transmitted from one generation to the next one. We have listed a partial list of some of the genetic syndromes which can lead to familial cancer: Hereditary Genetic Syndromes o Hereditary Breast/Ovarian Cancer (BRCA1 and BRCA2) o Familial adenomatous polyposis (Colon Cancer) o Hereditary Nonpolyposis Colorectal Cancer o Li-Fraumeni Syndrome (Bone, Breast, Brain, Adrenal or Soft-tissue Cancer) o Multiple Endocrine Neoplasia Type 2A (Thyroid or Adrenal Cancer) o Neurofibromatosis 1and 2 (Brain, Spinal, Nerve or Skin Cancer) o Retinoblastoma (Eye, Brain, Bone or Skin Cancer) o Tuberous Sclerosis (Kidney or Brain Cancer) o Von Hippel-Lindau Disease (Kidney, Adrenal or Pancreas Cancer) Patients with Hereditary Genetic Syndromes may benefit from pre-pregnancy genetic counseling and testing Patients with Hereditary Genetic Syndromes may want to consider In Vitro Fertilization (IVF) with Preimplantation Genetic Diagnosis (PGD) to find out if Page 14 of 16

15 they have embryos which are carriers for a particular cancer gene so that they may avoid transmission of that gene to their children. Costs: Charges for In Vitro Fertilization (IVF) are about $10,000 plus fertility medication (about $5,000), and Preimplantation Genetic Diagnosis (PGD) charges are about $6, Patients who are found to have Premature Ovarian Failure following treatment may want to consider the following options, which were discussed under Fertility Preservation Options: Oocyte donation Embryo donation Adoption 4. Patients who have conditions in which pregnancy is contraindicated may want to consider the following options, which were discussed under Fertility Preservation Options: Gestational surrogacy Adoption PREGNANCY OUTCOME IN CANCER SURVIVORS 1. The largest follow up of patients who were previously treated for cancer is the Childhood Cancer Survivor Study (CCSS) with up of 20,000 childhood Cancer Survivors. During this study, cancer survivors who conceived were followed during pregnancy and after childbirth. The main findings in this study for patients who were treated with chemotherapy were the following: Decreased live birth rates in cancer survivors compared to their siblings No increased risk of stillbirth during pregnancy No specific chemotherapy agent effect on adverse pregnancy outcomes No increased risk of major congenital abnormalities No increased risk in the offspring of developing subsequent cancer 2. Patients in the Childhood Cancer Survivors Study who were treated with radiation therapy to the pelvis and then conceived had the following findings: Two-fold increased risk of low birth weight in the babies delivered Increased risk of preterm birth Page 15 of 16

16 3. Current research indicates that pregnancy after cancer treatment does not negatively affect survival or trigger recurrence of the cancer in most patients, including those with breast cancer PATIENT RESOURCES University of Illinois Fertility Preservation Program: Oncofertility Consortium: Fertile Hope: Gilda s Club Chicago: Page 16 of 16