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Why should Fertility Preservation be of concern for newly diagnosed cancer patients?
- Because annually, approximately 150,000 men and women during their child-bearing years are newly diagnosed with cancer and at risk for permanent infertility.*
- Because the prognosis of the average oncology patient has improved dramatically over the past twenty years.
- Because of the advancements in reproductive medicine over the past twenty years.
*fertileHOPE 2006-2007 Cancer and Fertility Resource Guide
Why is Fertility at Risk from Treatment?
- As you may have learned already, the cytotoxicity of chemotherapy is not limited to the cancer cells, many other cells in the body are also effected, some of these cell types include hair, mucosal membranes, and germ cells (eggs and sperm producing cells)
- Germ cell toxicity can be broken down by general chemo class
- Definitely cause infertility
- Likely to Cause infertility
- Not likely to cause infertility
- Radiation Treatment
- Fertility Risk
- Typically, decreased fertility or infertility is temporary in men when only radiation treatment is used, however, every case is different, discuss with your physician(s).
- Infertility risk in females is less understood, however direct exposure of the ovaries to high amounts of radiation has been shown to cause long term fertility loss.
- Fertility Risk
- Should I be concerned with possible DNA damage?
- Although chemotherapy and ionizing radiation cause significant DNA injury, the potential for transmitting genomic defects to offspring is remote.
- No significant increase in major or minor genetic defects has been observed in the offspring of parents who have had cancer or undergone cancer therapy.
- Abnormalities in sperm DNA prevent the introduction of damaged DNA into the oocyte. It is reasonable to recommend, however, that men delay attempting to father children for 6 months after completing chemotherapy or radiation therapy, to allow regeneration of developing spermatozoa.
Cancer and Male Factor Infertility, Constabile, RA, Spevak, M, Oncology, Vol 12, No 4 (April 1998)
When should a patient, caregiver or clinician consider Fertility Preservation?
- At diagnosis
- Always think about what course the treatment may take. There are multiple cases of treatment plans moving from an “unlikely to cause infertility” chemotherapy to a “definite to cause infertility” chemotherapy due to adjustments in the treatment dictated by the responsiveness of the cancer to a certain drug.
- The window to preserve fertility may only be now.
How is fertility preserved?
The most common method is by utilizing cryopreservation.
What is cryopreservation?
- The ultra-low temperature storage of cells or groups of cells.
- The principles of which require the cessation of cellular activity through the removal of water and the addition of cryoprotectants.
How long has cryopreservation been used in reproduction?
- Sperm was first cryopreserved in the 1950’s. Since then, millions of animals have been born through the use of cryopreserved (frozen) sperm. The use of cryopreserved human sperm has been in widespread use since the 1980’s.
- Embryo cryopreservation was first used in various farm animals in the 1970’s and is a very common procedure today in human infertility treatment.
- Egg cryopreservation is still relatively new (past 10 years).
How long can cryopreserved tissues be stored?
- We really can only rely on some complicated calculations which estimate the answer to be 2,000 to 4,000 years.
- Storage periods of more than 40 years for sperm and 20 years for embryos prior to pregnancies established have been documented, but these records will be broken.
Sperm Banking for Men
"The technology of assisted reproductive techniques (ART) in recent years has progressed at a tremendous pace. Today, cryopreservation of sperm with subsequent ART can provide most post-therapy infertile cancer patients an opportunity to father children. Men who once had little or no chance of producing a pregnancy through assisted techniques due to “poor" semen quality now have fertility rates approaching that of couples undergoing standard IVF when there is no male infertility involved. As a result, cryopreservation of sperm should be attempted before therapy by all men who may want to father children in the future."
Reprinted from CANCER, November 1, 1999/volume 86/number 9
Sperm Banking for Men - How are specimens collected?
- Specimens are collected by masturbation, either on-site at the reproductive laboratory or off-site and transported to the facility.
- Alternative collection processes include:
- TESE (Testicular Epidymal Sperm Extraction) This is essentially a needle biopsy
- Testicular Biopsy (open biopsy)
Sperm Banking for Men - What are the costs of sperm banking?
- The total cost will be dependent on the number of specimens banked as well as the facility which you use. The number of specimens required really is dependent on the sperm quality, number and functionality. Generally, one to three specimens are sufficient.
- Costs ~$100 for testing, $100 to $250 per specimen for processing and $275/yr for storage. Shipping fees may apply.
What are the procedures, success rates and costs associated with the use of cryopreserved sperm?
- IUI (Intra Uterine Insemination)
- Involves the monitoring (timing) of ovulation in the female, and then insemination into the uterus using a catheter.
- Pregnancy rates (13-23%, age dependant)
- Costs ($1,000 non-medicated)
- IVF (In Vitro Fertilization)
- Involves the ovarian stimulation of the female followed by the retrieval of eggs and subsequent fertilization of the eggs in the laboratory prior to the transfer of the fertilized eggs (embryos) back to the female.
- Pregnancy rates (Age dependent 35-50%)
- Costs ($8,000-$12,000) / cycle however, in some states there is insurance coverage and many clinics offer Shared Risk plans)
- ICSI (Intra Cytoplasmic Sperm Injection)
- First utilized in the US in 1994, just a little more than 10 years ago.
- Enables the use of extreme low numbers of sperm. In fact, pregnancies have been achieved with sperm numbers in the single digits.
- Allows the use of sperm retrieved by:
- Testicular Biopsy
- Pregnancy rates (same as IVF)
- Costs (adds about $1,000 to $1,750 to IVF cost)
Fertility Preservation Options for Females
- Embryo Freezing
- Provides excellent pregnancy rates
- A downside is the need for multiple days of ovarian stimulation, which obviously raises estrogen levels which can be harmful with estrogen dependent cancers as well as delaying treatment.
- Recent research shows that some breast cancer patients may be safely stimulated by tamoxifen or letrozole.
- In Vitro Maturation is another area being studied in an attempt to find methods of limited estrogen exposure.
- A second downside for the single patient is the simple fact that embryos are the result of the fertilization of an egg (oocyte) with sperm. A source for sperm must be found, often an anonymous donor, which means that when a patient does find “Mr. Right”, he won’t be biologically linked to the child.
- Oocyte (egg) freezing
- If possible to arrange, this provides the patient with the combination of the least invasive procedure and the most options in the future.
- Once again the downside is the need for multiple days of ovarian stimulation, which obviously raises estrogen levels.
- Oocyte freezing is really just now becoming a real viable option. Very few centers in the US have significant experience with this technology. Worldwide, only about 1000 births have been established, thus this procedure should only be conducted under the guidance of an Institutional Review Board.
- Ovarian tissue storage
This procedure involves:
- Laproscopic surgical removal of one ovary.
- Slicing of thin strips of the exterior of the ovary
- Cryopreservation of those strips
- Storage for future transplant back into the patient or invitro maturation of the ovarian tissue and oocytes
- Can be completed quickly
- Does not require ovarian stimulation
- Allows for use of a future partner’s sperm
- Can be performed on pre-pubescent girls
- May allow natural conception
- Normal hormone production
- May allow In Vitro Maturation of follicles
- Invasive procedure
- Limited success to date
- Slight but possible risk of transferring cancerous cells back to the patient if the tissue is transplanted to the patient
Picture of ovarian tissue transplant procedure
Picture of ovarian tissue transplant procedure.
Pregnancy after Transplantation of Cryopreserved Ovarian Tissue in a Patient with Ovarian Failure after Chemotherapy, Meirow, et.al, New England Journal of Medicine, June 27, 2005 Online Content
Additional Options for Females not involving cryopreservation.
- Ovarian transposition – Surgical procedure
- GNRH agonist treatment during chemotherapy
Fertility Preservation Options for females - Approximate Costs
- Oocyte (egg) freezing
- Pregnancy rates (New technology, no general estimates available)
- Costs ($7,000-$10,000)
- Storage $275/year
- $5,000 estimated lab & clinical services at thaw
- Embryo Freezing
- Pregnancy rates (20-30% per cycle)
- Costs ($10,000- $13,000)
- Storage $400/year
- $1,700-$2,500 estimated lab & clinical services at thaw
- Ovarian tissue storage
- Pregnancy rates (Limited cases, no general estimates available)
- Costs ($6,000 to $8,000, after subsidization by hospital and/or surgeon)
- Storage $275/year
ReproTech urges every patient to have a consultation with an Infertility Specialist for a personalized review of their options prior to treatment.
This information has been provided to give you an overview and hopefully to assist you in your search for your options for Fertility Preservation.
- American Association of Tissue Banks
- American Society of Reproductive Medicine
- Oncofertility Consortium
Articles, papers, and references
- AmericanSociety of Clinical Oncology Fertility Preservation Guidelines
- ASRM Ethics Committee Report
- Efficacy of IVF after Chemotherapy
- Experiences with Sperm Banking and Infertility Issues Related to Cancer Treatment
- Fertility after cancer: a prospective review assisted reproductive outcome with banked semen specimens
- Fertility Preservation using Embryo Cryopreservation prior to Chemotherapy
- Leukemia & Lymphoma Society's Fertility Fact Sheet
- Long Term Effects of Cryopreservation on Human Spermatazoa
- Ovarian Function Preservation
- Ovarian Tissue and Oocyte Cryopreservation
- Patient's Fact Sheet
- Pregnancy after Transplantation of Cryopreserved Ovarian Tissue
- Semen Parameters of Cancer Patients at Diagnosis
- Sexuality and Fertility after Cancer
- Sperm Banking for Adolescent Cancer Patients
- Sperm Cryopreservation in Oncological Patients: A 14 Year Follow UpStudy
- Successful Pregnancies using ICSI with Cryopreserved Sperm
- Successful Pregnancy and Birth following 28 Years of Cryostorage