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NYC IVF Personal & Innovative Fertility Care Preservation of Fertility Living Beyond Cancer

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Page 1: Fertility Preservation; an e-Guide

NYCIVF Personal & Innovative Fertility Care

Preservation of FertilityLiving Beyond Cancer

Page 2: Fertility Preservation; an e-Guide

Preservation of Fertility

© 2010 Amr Azim, NYCIVF.

Preservation of fertility after the diagnosis of cancer and other allied conditions is a complex task requir-ing careful evaluation of risks and benefits. The information contained in this document is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images and information, contained in this document is for general information purposes only. Please consult with your physician about the risks and success of fertility preservation issues before pursuing or declining any option for preservation of fertility.

This work is available for download for educational purposes only by actual patients and their families. No part of this work should be copied for profit purposes, distribution or production in different format with-out writen permission from the author.

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Preservation of Fertility | iii

Table of Contents

1 Preservation of Fertility in Women 1

Who needs preservation of fertility 1

Effects of cancer treatment on future fertility 2

Ovarian function after exposure to chemotherapy & radiotherapy 3

Methods used for preservation of fertility 3

Genetic Perspective 7

Coordination of treatment and preservation of fertility 8

Real Cases 9

Pregnancy after breast cancer 9

2 Preservation of Fertility in Men 11

Who needs to consider preservation of fertility 11

Methods used for preservation of fertility 12

Page 4: Fertility Preservation; an e-Guide

NOTES

iv | Preservation of Fertility

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| 1

1 Preservation of Fertility in Women

Fertility is a key aspect for quality of life for cancer patients of childbearing age. Preservation of fertility is defined as the application of medi-cal, surgical and laboratory procedures to preserve the potential of genetic parenthood in adults and children at risk of sterility before the end of natural reproductive lifespan (Gosden 2009). Decrease or loss of fertility can take place due to exposure to medication (chemotherapy), radiation or surgery (e.g. Removal of the ovaries). The American Cancer Society estimates that cancer affects one in each 3 women living in the United States. Modern cancer treatment commonly involve exposure to chemo-therapy and sometimes pelvic radiation.

Cancer and its treatment though is not the only situation that affect fertility. Fertility can also be diminished by bone marrow transplantation and treatment of kidney disease usually due to lupus.

If you are a women or a man living in the United States and recently diagnosed with cancer or another condition that threatens your future ability to mother or father children, this bulletin is writen with you in mind. The odds are you will beat your disease and survive for many years to come. Consid-ering fertility-sparing before starting disease treat-ment may greatly enhance your ability to conceive a biological child after cure.

Who needs to consider preser-vation of Fertility?

a. In 2009 about 700,000 women will be di-agnosed with cancer, about 10% of them under the age of 45. Breast cancer is the most common cancer affecting women.

Proportion of cancer by site in women. (From American Cancer Society, 2009)

Each year bout 15,000 women will be diagnosed with breast cancer before 45year

Women can also be diagnosed with leukemias, lym-phomas, cancer of the colon, uterus, ovary, skin or thyroid gland. Treatment of all these cancers is as-sociated with long term effects during the survivor-ship period including decline in fertility. The effects of cancer treatment go beyond the harm caused by the method of treatment itself to the time spent in treatment and time needed for follow up. This delay

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2 | Preservation of Fertility

means women will probably attempt pregnancy several years later than they intended.

b. Women undergoing bone marrow trans-plantation for treatment of cancer, anemias (e.g. Sickle cell disease) and other diseases. The use of chemotherapy and radiation prior to transplantation is usually associated with fertility loss in the vast majority of patients.

c. Some women develop breast or ovarian cancers due to abnormality in breast cancer gene (BRCA1 & 2). Reducing the risk of future cancer may require removal of both ovaries with loss of fertility.

d. Women diagnosed with connective tissue disease (Systemic lupus, rheumatoid arthritis...) or autoimmune disease may have severe disease af-fecting their organs (e.g. Kidney). Chemotherapy is sometimes used to suppress their immunity which may lead to fertility decline. Moreover, the antibod-ies generated by the disease process may directly affect ovarian function.

e. Individuals exposed to accelerated loss of eggs due to genetic disease (e.g. Mosaic Turner syndrome) can also benefit from preservation of fertility

f. Fertility extension. Women delaying preg-nancy for career or social reasons (no male partner at this time) can consider freezing their eggs or embryos (using donor sperm). This option was not studied in large population studies.

Cancer treatment (chemotherapy, radiation and bone marrow transplantation) will not only dimin-ish fertility by accelerating loss of oocytes but also by delaying attempts to become pregnant for years

Effects of Cancer Treatment on Ovarian FunctionIn general the younger the woman, the more oocytes she harbors in the ovary and the higher the likelihood that some oocytes will remain in the ovary after treatment.

A. Chemotherapy and the Ovary. The use of chemotherapy can lead to fast loss of oocytes (eggs). Oocytes carry the genetic material that women pass to their children after fertilization by a sperm. The effect of these agents is variable depending on the drug, dose, frequency of administration, and age of the woman at the time of treatment. Cyclophosph-amide is the most harmful agent for future fertility.

These medication appear to cause loss of eggs through damage of its DNA and inducing sponta-neous demise of the egg. There is no proven method that can prevent this loss.

B. Pelvic Radiation and the Ovary. Expo-sure of the ovary to radiation can damage the eggs and the remaining tissue of the ovary. The amount of radiation that leads to complete loss of ovar-ian function is dependent on the age. A dose of 1500cGy will sterilize the majority of women at age 30. Smaller doses will sterilize older women.

C. Time factor. Cancer treatment usually re-quires several months. For some cancers (e.g. Breast cancer) medical treatment (tamoxifen) is required for 2 to 5 years after surgery and chemotherapy. For others oncologists recommend a period of observa-tion for 1 to 2 years. This will a woman’s plan to start a family to a later age when fewer oocytes remain in the ovary.

Actually the effect of cancer treatment on the ovary appears to be similar. Continuous loss of eggs from

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Women | 3

the ovary takes place in all women. Cancer treat-ment accelerates this loss so that the number of eggs in the ovary would correspond to older age.

D. Pelvic Radiation and the Uterus. Expo-sure of the uterus to radiation increases the risk of miscarriage, preterm labor and abnormal pregnancy outcome.

Evaluation of Ovarian Func-tion after Cancer Treatment Although many think that resumption of men-struation after cancer treatment indicates that the woman retains the ability to conceive, this is not true. Some women have regular menses with near exhaustion of the eggs in the ovaries. Thus, men-struation is not a reliable indicator of the ability to conceive.

The function of the ovary before after cancer treat-ment can be evaluated using hormone tests and ultrasound.

Cycle day 2 or 3 FSH (normal is less than ♦12mIU/mL)

Inhibin ♦

Antimullerian hormone (AMH). This is a new ♦and promising marker and appear to be more accurate than the other markers.

Vaginal ultrasound to evaluate the number of ♦small follicles visible in the ovary.

Although these markers are more accurate than menstrual history, normal markers after treatment does not mean that ovarian function is completely preserved after exposure to treatment.

Women exposed to chemotherapy exhibit a much lesser response to medications that stimulate egg production in the ovary than women presenting before exposure to chemotherapy, hence the impor-tance of considering preservation of fertility early after cancer diagnosis.

Methods used for Fertility PreservationMethods used to preserve fertility in women are generally divided into three categories:

Modification of cancer treatment plan to reduce damage to the ovaries and uterus:

Preserving one ovary in women affected with 1. early ovarian cancer.

Preservation of the body of the uterus with 2. removal of the cervix in early cervical cancer.

Use of progesterone treatment instead of re-3. moval of the uterus in endometrial cancer.

Protection of the ovaries from the damage caused by cancer treatment:

1 Ovarian transposition is a surgical procedure to move the ovaries upwards, away from radiation field before pelvic radiation. Results are variable as some scattered radiation still reaches the ovaries.

2. Protection of the ovaries from the effect of chemotherapy. GnRH agonists are a group of medications that suppress the master gland in the brain, preventing the release of the hormones that stimulate development of follicles in the ovaries. Although suggested, there is no proof that they actually protect the ovaries and improve the chance of pregnancy after the use of chemotherapy.

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4 | Preservation of Fertility

Low Temperature Storage of Embryos, Oocytes or Ovarian Tissue: a. Embryo Freezing. This is considered the standard method for preservation of fertility. Its suitable for women with a male partner or ac-cepting the use of donor sperm and when cancer treatment does not need to be started immediately. This method entails stimulation of the ovary with medications and frequent monitoring of response using ultrasound and blood work. This stimulation usually requires 12 to 14 days. The eggs are then removed from the ovary by an outpatient procedure under sedation. Egg retrieval requires passing a needle through the vagina into the ovary. Eggs are then fertilized in the lab and the resulting embryos are frozen 2 to 6 days later and stored for later use. Cancer treatment can start immediately after egg retrieval. After cure, women can request to use their embryos, that are placed back into the uterus after simple preparation of the lining of the uterus. The transfer of two embryos into the uterus yields a pregnancy rate of about 30%.

Women diagnosed with an estrogen sensitive tumors (e.g. Breast cancer, uterine cancer) require

special attention. The use of fertility medication is usually associated with considerable rise in estrogen levels. One potential risk of estrogen rise, though not proven, is increase in activity of cancer cells. This is addressed during stimulation by adding a medicine (letrozole) that blocks the enzyme that makes estrogen in the ovaries, so that stimulation with gonadotropins can progress without increase in estrogen. When the follicles (the bag that contain the eggs) reach adequate size, final maturation is triggered using another hormone, hCG. This is fol-lowed by egg harvest.

The safety of this method for stimulation of the ovary was studied. We compared women presenting for ovarian stimulation after the diagnosis of breast cancer with women diagnosed with breast cancer and declined ovarian stimulation. The follow up period was approximately 2 years. There was no increase in breast cancer recurrence between both groups (Azim et al , Journal of Clinical Oncology 2008). Although further follow up is required, results so far are reassuring that this method is probably safe.

Letrozole

FSH/hMG

GnRH antagonist

hCG

Letrozole

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Women | 5

egg at thawing. The egg is placed in a solution that prevents damage caused by ice crystals (cryopro-tectant) and then stored in liquid nitrogen at -170.

Three oocytes frozen in a small film of fluid.

Mature oocyte.

The success rate for egg freezing based in all pub-lished reports in the world are given below.

In general 2/3 of eggs frozen using slow freezing method survive compared to about 90% of oocytes frozen by vitrification method. After thaw, the eggs need to be fertilized using intracytoplasmic sperm injection (ICSI). About 70 to 90% fertilization rate is expected. Embryos are cultured to day 3 stage or blastocysts before transfer. Each thawed egg yield about 2-3% pregnancy rate after slow freezing and about 8 to 10% when vitrification was used. Transfer

Protocol for stimulation of the ovaries in women diagnosed with breast or endometrial cancer.

Embryo freezing is the standard method for preser-vation of fertility in women with male partner (or using a donor sperm) and when cancer treatment does not need to be started immediately.

For women not diagnosed with estrogen sensitive cancer (e.g. Lymphoma) or those at risk for decline of fertility due to non-cancer conditions, standard methods for ovarian stimulation are used. The ultimate success of this option is dependant on the number and quality of embryos produced which is related to woman’s age and ovarian function at the time of stimulation. Cancer diagnosis in itself does not appear to affect success provided stimulation is started before cancer treatment.

After cure some women transfer the embryos to their own uterus or to a gestational carrier.

b. Oocyte Cryopreservation (egg freezing). It is considered for women with no male partner and declining the use of donor sperm. It requires stimu-lation of the ovaries and egg harvest as described earlier.

The human egg is unique. Its the largest cell in the body with high water contents. The membrane sur-rounding the cell is not very permeable. Moreover, its the only cell in the body where chromosomes are spread on flimsy structure called the spindle, rather than being enclosed inside the nucleus of the cell.

The egg requires special expertise to freeze. Two techniques are used; slow freezing or vitrification (rapid freezing). The newer vitrification method has the advantage of avoiding the formation of ice crys-tals inside the egg and yields better survival of the

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6 | Preservation of Fertility

c. Ovarian Tissue Freezing. This is an ex-perimental method for preservation of fertility. In this method one ovary is removed, processed and frozen. After cure, the ovary is transplanted back in the pelvis (orthotopic) or under the skin (hetero-topic). Processing of the ovary means that the outer 2-3mm (this is the part that contains the eggs-the cortex) is shelled out and cut into thin strips. So far the ovary cannot be frozen as a whole organ because its too thick for cryoprotectants (the substance that protects the tissue from damage caused by freez-ing) to diffuse into it before freezing. Removal of the ovary is performed using laparoscopy (minimal access surgery) or at the time of surgery for other indication. The inner part of the ovary (does not contain eggs) is sent for tissue examination to make sure it does not contain any malignant cells.

Since ovarian harvest can be accomplished in 1 to 2 hours, this method is used when there is no time to complete ovarian stimulation (2 to 3 weeks) or when stimulation of the ovary is not possible as in girls before puberty. Because of the experimental nature of the procedure, its offered to women with very high risk for ovarian failure after treatment.

The main risk for transplantation is transferring cancer cells in the graft leading to recurrence of can-cer. Although possible, no such case was reported thus far.

Worldwide, several hundred women froze their ovaries. So far much smaller number came back for transplantation. There were eight babies born after transplantation. (Belgium 1, Israel 1, Spain 1, Den-mark 5) All the ovaries resulting in live births were transplanted in the pelvis.

Vitrification is a very promising method for egg freezing. It yields outcome comparable to embryo freezing.

The only caveat to vitrification is that this method has not been around long enough to ascertain its safety.

Cleavage stage (day 3) embryo.

Blastocyst stage (day 5-6) embryo.

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Women | 7

of two to three embryos can yield a pregnancy rate similar to that obtained after embryo thawing.

Oocyte cryopreservation; World Experience

Slow freezing (38 studies)

Vitrification(EG 2.7M+DMSO 2.1M+sucrose 0.5M)

Oocytes thawed 11937 1346Oocytes survived 7610 (63.8%) 1233 (91.6%)

Oocytes injected with a sperm 6871 1123

Oocytes fertilized 5029 (73.2%) 964 (91%)Clinical Pregnancy per oocyte thawed 275 (2.3%) 157 (8.8%)

Miscarriage rate 21.8% 16.8%

Amr Azim, MD, FACOG

d. In Vitro Maturation of Oocytes. In this method a very short ovarian stimulation for 3 to 5 days is performed followed by retrieval of immature eggs. Eggs are then matured in the lab, fertilized and the resulting embryos are frozen for later use. The efficiency of this method is lower than retrieving fully mature oocytes. About 50% of follicles punctured yield an egg. Approximately 70% of the eggs reach maturity in the lab and about 70% of those fertilize with ICSI. This method is suitable for women demonstrating high response to stimulation to fertility medication.

Genetic PerspectiveGenetic susceptibility to cancer is now recognized for a number of malignancies. The most famous is breast cancer susceptibility genes BRCA1 &2. Women diagnosed with cancer that associated with mutation of one of the known genes are at risk for passing this gene to her future children. If a woman is a carrier of one of these known genes, the effort to preserve her fertility can be combined with testing of oocytes or embryos to prevent the transmission of the gene to her children. Pre-implantation genetic diagnosis (PGD) is a techniques where one or few cells from an embryo can be analyzed for specific genetic information. The majority of cancer susceptibility genes can be detected in the embryo, so that affected embryos can be excluded from transfer back to the uterus. Not all women though accept screening or embryo testing.

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8 | Preservation of Fertility

Some Genetic syndromes with increased susceptibility to cancer

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Women | 9

Women interested in preservation of fertility should be counseled about the availability of genetic screening pertaining to their cancer and if carriers about PGD to avoid transmission to future children.

Coordination of Cancer Treat-ment and Preservation of FertilityMultiple studies in the US surveying patients or oncologists found that discussion and referral for preservation of fertility takes place in less than 50% of patients. Referral was more likely when patients inquire about fertility issues.

This underlines the importance of educating women about fertility issues and the diagnosis of cancer and other allied diseases. Empowering women to ask questions appears to one of the most important initial steps to receive appropriate information about and possibly pursue preservation of fertility.

Collecting information and coordination of care between providers concerned with cancer treatment and those that deal with preservation of fertil-ity can be a demanding task, especially at difficult and busy times. The table below aims at organizing your thoughts and collecting information about the feasibility of preservation of fertility after diagnosis, before making a decision to pursue these options or to bypass them and proceed directly to disease treatment.

Questions to ask

Questions Things to do

Oncologist *Type of cancer *Stage *Treatment plan 1. Surgery 2. Chemo-

therapy 3. Bone mar-

row transplant 4. Radiothera-

py 5. Hormonal

treatment *Is Preservation

of fertility suit-able for me?

Ask for a referral letter

Obtain medical records;

Surgery records

Pathology records

Other tests; ER, PR, her2/neu, BRCA

General medi-cal tests

Reproduc-tive

Endocrinol-ogist

*How is cancer and cancer treat-ment expected to impact future my fertility?

*What are the suit-able options for preservation of fertility?

Embryo freezingOocyte freezingOvarian tissue freez-

ingOthersCombination *Is it safe? *What to do with the frozen embryos, eggs or tissue after cure *What is the success

rate for my op-tions

Blood work; FSH, estradiol, AMH

UltrasoundSemen analy-

sisOther gen-

eral tests required for IVF and cell and tissue freezing

Referral for genetic counsel-ing

Coordinate fertility preserva-tion plan with the oncologist

Psychologist How to deal with stresses of treat-ment

Make an ap-pointment

Support group

Help with referralHelp with medica-

tions

E.g. fertile-hope.org

livestrong.org youngsurvival.

orglbbc.org

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Women | 10

Real Cases

Breast Cancer 1. A 28 year old Caucasian system analyst present-ed with her partner shortly after the diagnosis of duct carcinoma of the breast. The tumor was stage II after lumpectomy and axillary lymph node sampling and was estrogen receptor positive. Her treatment plan per her oncologist was 4 cycles of cyclophos-phamide, adriamycin and taxol followed five years of tamoxifen. She was counseled to the effect of chemotherapy on ovarian function. The risk for ovarian failure is about 30%. Time factor also should be considered (she will be 35 by the time she could attempt pregnancy). The possibility of underlying genetic factor was also discussed and breast cancer gene testing was offered (she turns out to be BRCA1 and 2 negative).As she had a steady partner, she was offered ovar-ian stimulation using letrozole and gonadotropins followed by oocyte retrieval and embryo cryopreser-vation. The risks and benefits of this approach was discussed in details. She accepted this option and so did her oncologist. After retrieval, 6 blastocysts were frozen within 18 days. She completed cancer treat-ment and her period stopped after chemotherapy and did resume yet.

2. A 37 year old mathematician presented shortly after the diagnosis of stage I, estrogen receptor positive breast cancer. She does not have a partner. The size of the tumor was small that her oncologist did not recommend chemotherapy. She, however, recommended 5 years of tamoxifen.This delay in attempting pregnancy (she would be 42 at the end of treatment) and because she de-clined the use of donor sperm, she was offered egg freezing. With the approval of her oncologist, she underwent two cycles of egg freezing and 10 eggs were cryopreserved after each cycle by vitrification. She is in good health so far.

Colon CancerA 34 year old presented with her husband after a recent diagnosis of colon cancer. Her planned treat-ment was chemotherapy, pelvic radiation followed by surgery. She wanted to preserve the ability to have biological children.She was counseled that1. Chemotherapy used for colon cancer has mild or no long term effects on future ovarian function2. Pelvic radiation at the planned dose, however will very likely result is complete cessation of ovarian function3. Pelvic irradiation will likely damage the tissue of the uterus so that pregnancy would not be safe.She was offered a combined approach to preserve her fertility1. Ovarian stimulation and egg retrieval and embryo freezing2. Laparoscopic surgery to move one ovary upwards away from radiation field3. Harvest of the other ovary during the same sur-gery and freezing it for later transplantation.

She accepted only ovary stimulation and embryo freezing. This was performed after consulting with her oncologist and 20 blastocysts were frozen.After radiation, her menses stopped.She came back with her to use the embryos. One embryo was transferred to the uterus of her sister resulting in pregnancy and delivery of healthy baby.

Pregnancy after Breast CancerIs it safe to get pregnant after treatment for breast cancer? It is the general consensus that pregnancy after treatment and a follow up period of 6 months to two years is not associated with increase in the odds for breast cancer recurrence. Most oncologists advise their patients to wait for a variable period after treatment before attempting pregnancy. Recent evidence from multiple studies including a large Danish study indicated that there is no evidence

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Women | 1111 | Preservation of Fertility

that pregnancy after breast cancer diagnosis in-creases the risk of poorer outcome.

Remember that the use of a gestational carrier is always an option for women that do not want to or cannot get pregnant in their own uterus.

The vast majority of young cancer survivors view themselves as potential parents. Inquiring about survivorship issues including fertility increases the odds that you will referred for counseling and subsequently become informed about your options.

Further Reading1. Azim et al. Safety of Fertility Preservation by Ovarian Stimulation With Letrozole and Gonado-tropins in Patients With Breast Cancer: A Prospec-tive Controlled Study. Journal of Clinical Oncology 2008, 28(18):2630-5.2. Gook & Edgar. Human oocyte cryopreservation. Human Reproduction 2007,13(6):591-605.3. Lee et al. American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients. Journal of Clinical Oncology 2006.4. http://ulmanfund.org/Portals/0/files/Educa-tion/NoWay.pdf

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2 Preservation of Fertility in men

Like women, men are also diagnosed with diseases that directly or by virtue of their treatments impair future fertility. Recognition of these diseases enables timely counseling and effort to preserve male germ cells. This is specially important since the interven-tion to preserve future fertility in men is easier and less invasive compared to women. 50–70% of men diagnosed with cancer wanted children in the future. Only 24% of young cancer patients banked sperm, including 37% of childless men. The most com-mon reason for failing to bank sperm was a lack of information.

Who needs to consider preser-vation of Fertility?a. The American Cancer Society estimates that 760,000 men will be diagnosed with cancer in 2009. Cancer itself (before treatment) is known to be associated with less sperm production in men. This is specially the case in Hodgkin’s lymphoma, testicular cancer, leukemias and colon cancer.

Cancer treatment (chemotherapy and radiation) also significantly impair sperm production. The effect of chemotherapy depends on age, drug used, dose and duration. Cyclophosphamide appears to be the most harmful agent. Radiation also impairs sperm production especially at doses of 1200cGy or more.

Sperm count sometimes recover to a variable extent years after cancer treatment. This depends on the type of cancer and treatment used. For example 90% of men diagnosed with Hodgkin’s lymphoma, treated with MOPP chemotherapy regimen, do not have any sperm in the ejaculate after one year.

b. Bone marrow transplantation for cancer of nonmalignant diseases usually require prior irradia-tion and chemotherapy. This is associated with high risk (85%) of complete failure of sperm production.

c. Connective tissue / autoimmune diseases as lupus and rheumatoid arthritis requiring treat-ment with chemotherapy.

d. Genetic abnormalities associated with rapid loss of male germ cells e.g. Kleinefelter syn-drome, Y chromosome microdeletion (AZFc).

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men | 13

Methods used for Fertility PreservationMethods used to preserve fertility in men are gener-ally divided into two categories:

Protection of the testes from damage caused by cancer treatment: 1. Shielding the testes from radiation field. 2. Protection of the testes from the effect of chemo-therapy. GnRH agonists are a group of medications that suppress the master gland in the brain, pre-venting the release of the hormones that stimulate sperm production in the testes. Although suggested, there is no proof that they actually increase the odds for pregnancy after the use of chemotherapy.There is no effective protective medication available for use in humans.

Low Temperature Storage of Sperm and Testicular Tissue:

a Sperm Cryopreservation. This is the standard method for preservation of fertility in men. A sperm sample is obtained by masturbation and frozen for later use. If feasible multiple samples are obtained. In the future sperm sample are used for intrauterine insemination or IVF / intracytoplasmic sperm injection (ICSI). Banking sperm was found to offer not only a chance to father children in the future but also encourage-ment and improved morale during disease treat-ment especially if it was initiated by the patient own initiative.

Lack of information and counseling is the most important reason why men diagnosed with cancer do not bank thier sperm.

Although freezing may reduce the quality of sperm especially if it was not optimal before freezing,

modern reproductive medicine can handle the majority of compromised specimens yielding excel-lent pregnancy rates, similar to those of fresh sperm.

b. Testicular Sperm Extraction (TESE). This surgical procedure retrieves sperm from inside the testes if no sperm was found in the ejaculate. If this procedure is used before cancer treatment, sperm are retrieved in over 50% of cases. Sperm or testicular biopsies are frozen for later use. ICSI is used for fertilization. In case of testicular cancer, sperm retrieval can be performed at the same time of surgery for cancer.

c. Testicular Tissue or Germ Cell Freezing. This is an experimental technique. Immature germ cells or testicular pieces are frozen for later transplantation. No pregnancy was achieved using this method so far.

In conclusion, fertility-sparing strategy is readily available to the majority of men at risk for dimin-ished fertility through sperm cryopreservation. Men interested in fathering children in the future should be counseled about this option.

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NYCIVF Personal & Innovative Fertility Care