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Preservation of Fertility
                   Living Beyond Cancer




                            NYCIVF
                            Personal & Innovative Fertility Care
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.
10 9 8 7 6 5 4 3 2 1
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
iv   |   Preservation of Fertility




                                     NOTES
|   1




1                     Preservation of Fertility in Women

           Fertility is a key aspect for quality of life   a.        In 2009 about 700,000 women will be di-
for cancer patients of childbearing age. Preservation      agnosed with cancer, about 10% of them under the
of fertility is defined as the application of medi-        age of 45. Breast cancer is the most common cancer
cal, surgical and laboratory procedures to preserve        affecting women.
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
                                                           Proportion of cancer by site in women. (From American Cancer
States and recently diagnosed with cancer or
                                                           Society, 2009)
another condition that threatens your future ability
to mother or father children, this bulletin is writen
                                                           Each year bout 15,000 women will be diagnosed
with you in mind. The odds are you will beat your
                                                           with breast cancer before 45year
disease and survive for many years to come. Consid-
ering fertility-sparing before starting disease treat-     Women can also be diagnosed with leukemias, lym-
ment may greatly enhance your ability to conceive a        phomas, cancer of the colon, uterus, ovary, skin or
biological child after cure.                               thyroid gland. Treatment of all these cancers is as-
                                                           sociated with long term effects during the survivor-
Who needs to consider preser-                              ship period including decline in fertility. The effects
                                                           of cancer treatment go beyond the harm caused by
vation of Fertility?                                       the method of treatment itself to the time spent in
                                                           treatment and time needed for follow up. This delay
2   |   Preservation of Fertility




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

    b.        Women undergoing bone marrow trans-                Effects of Cancer Treatment
    plantation for treatment of cancer, anemias (e.g.
    Sickle cell disease) and other diseases. The use of          on Ovarian Function
    chemotherapy and radiation prior to transplantation
                                                                 In general the younger the woman, the more
    is usually associated with fertility loss in the vast
                                                                 oocytes she harbors in the ovary and the higher
    majority of patients.
                                                                 the likelihood that some oocytes will remain in the
    c.         Some women develop breast or ovarian              ovary after treatment.
    cancers due to abnormality in breast cancer gene
                                                                 A.        Chemotherapy and the Ovary. The use of
    (BRCA1 & 2). Reducing the risk of future cancer
                                                                 chemotherapy can lead to fast loss of oocytes (eggs).
    may require removal of both ovaries with loss of
                                                                 Oocytes carry the genetic material that women pass
    fertility.
                                                                 to their children after fertilization by a sperm. The
    d.        Women diagnosed with connective tissue             effect of these agents is variable depending on the
    disease (Systemic lupus, rheumatoid arthritis...) or         drug, dose, frequency of administration, and age of
    autoimmune disease may have severe disease af-               the woman at the time of treatment. Cyclophosph-
    fecting their organs (e.g. Kidney). Chemotherapy is          amide is the most harmful agent for future fertility.
    sometimes used to suppress their immunity which
                                                                 These medication appear to cause loss of eggs
    may lead to fertility decline. Moreover, the antibod-
                                                                 through damage of its DNA and inducing sponta-
    ies generated by the disease process may directly
                                                                 neous demise of the egg. There is no proven method
    affect ovarian function.
                                                                 that can prevent this loss.
    e.        Individuals exposed to accelerated loss
                                                                 B.        Pelvic Radiation and the Ovary. Expo-
    of eggs due to genetic disease (e.g. Mosaic Turner
                                                                 sure of the ovary to radiation can damage the eggs
    syndrome) can also benefit from preservation of
                                                                 and the remaining tissue of the ovary. The amount
    fertility
                                                                 of radiation that leads to complete loss of ovar-
    f.        Fertility extension. Women delaying preg-          ian function is dependent on the age. A dose of
    nancy for career or social reasons (no male partner          1500cGy will sterilize the majority of women at age
    at this time) can consider freezing their eggs or            30. Smaller doses will sterilize older women.
    embryos (using donor sperm). This option was not
                                                                 C.        Time factor. Cancer treatment usually re-
    studied in large population studies.
                                                                 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
        Cancer treatment (chemotherapy, radiation and            others oncologists recommend a period of observa-
        bone marrow transplantation) will not only dimin-        tion for 1 to 2 years. This will a woman’s plan to
        ish fertility by accelerating loss of oocytes but also   start a family to a later age when fewer oocytes
        by delaying attempts to become pregnant for years        remain in the ovary.
                                                                 Actually the effect of cancer treatment on the ovary
                                                                 appears to be similar. Continuous loss of eggs from
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.                  Women exposed to chemotherapy exhibit a much
                                                             lesser response to medications that stimulate egg
D.        Pelvic Radiation and the Uterus. Expo-
                                                             production in the ovary than women presenting
sure of the uterus to radiation increases the risk of
                                                             before exposure to chemotherapy, hence the impor-
miscarriage, preterm labor and abnormal pregnancy
                                                             tance of considering preservation of fertility early
outcome.
                                                             after cancer diagnosis.

Evaluation of Ovarian Func-
                                                          Methods used for Fertility
tion after Cancer Treatment
Although many think that resumption of men-
                                                          Preservation
struation after cancer treatment indicates that the       Methods used to preserve fertility in women are
woman retains the ability to conceive, this is not        generally divided into three categories:
true. Some women have regular menses with near
                                                          Modification of cancer treatment plan to reduce damage
exhaustion of the eggs in the ovaries. Thus, men-
                                                          to the ovaries and uterus:
struation is not a reliable indicator of the ability to
conceive.                                                 1. Preserving one ovary in women affected with
                                                             early ovarian cancer.
The function of the ovary before after cancer treat-
ment can be evaluated using hormone tests and             2. Preservation of the body of the uterus with
ultrasound.                                                  removal of the cervix in early cervical cancer.

♦   Cycle day 2 or 3 FSH (normal is less than             3. Use of progesterone treatment instead of re-
    12mIU/mL)                                                moval of the uterus in endometrial cancer.

♦   Inhibin                                               Protection of the ovaries from the damage caused by
                                                          cancer treatment:
♦   Antimullerian hormone (AMH). This is a new
    and promising marker and appear to be more            1 Ovarian transposition is a surgical procedure to
    accurate than the other markers.                      move the ovaries upwards, away from radiation field
                                                          before pelvic radiation. Results are variable as some
♦   Vaginal ultrasound to evaluate the number of
                                                          scattered radiation still reaches the ovaries.
    small follicles visible in the ovary.
                                                          2. Protection of the ovaries from the effect of
Although these markers are more accurate than
                                                          chemotherapy. GnRH agonists are a group of
menstrual history, normal markers after treatment
                                                          medications that suppress the master gland in the
does not mean that ovarian function is completely
                                                          brain, preventing the release of the hormones that
preserved after exposure to treatment.
                                                          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.
4   |   Preservation of Fertility




                                                             special attention. The use of fertility medication is
                                                             usually associated with considerable rise in estrogen
                                                             levels. One potential risk of estrogen rise, though
    Low Temperature Storage of Embryos, Oocytes or Ovarian   not proven, is increase in activity of cancer cells.
    Tissue:                                                  This is addressed during stimulation by adding a
    a.         Embryo Freezing. This is considered the       medicine (letrozole) that blocks the enzyme that
    standard method for preservation of fertility. Its       makes estrogen in the ovaries, so that stimulation
    suitable for women with a male partner or ac-            with gonadotropins can progress without increase in
    cepting the use of donor sperm and when cancer           estrogen. When the follicles (the bag that contain
    treatment does not need to be started immediately.       the eggs) reach adequate size, final maturation is
    This method entails stimulation of the ovary with        triggered using another hormone, hCG. This is fol-
    medications and frequent monitoring of response          lowed by egg harvest.
    using ultrasound and blood work. This stimulation        The safety of this method for stimulation of the ovary
    usually requires 12 to 14 days. The eggs are then        was studied. We compared women presenting for
    removed from the ovary by an outpatient procedure        ovarian stimulation after the diagnosis of breast
    under sedation. Egg retrieval requires passing a         cancer with women diagnosed with breast cancer and
    needle through the vagina into the ovary. Eggs are       declined ovarian stimulation. The follow up period was
    then fertilized in the lab and the resulting embryos     approximately 2 years. There was no increase in breast
    are frozen 2 to 6 days later and stored for later use.   cancer recurrence between both groups (Azim et al ,
    Cancer treatment can start immediately after egg         Journal of Clinical Oncology 2008). Although further
    retrieval. After cure, women can request to use their    follow up is required, results so far are reassuring that
    embryos, that are placed back into the uterus after      this method is probably safe.
    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




                                                                      hCG


                                                GnRH antagonist


                                         FSH/hMG


                                    Letrozole                                             Letrozole
Women   |   5




                                                                  egg at thawing. The egg is placed in a solution that
                                                                  prevents damage caused by ice crystals (cryopro-
Protocol for stimulation of the ovaries in women diagnosed with   tectant) and then stored in liquid nitrogen at -170.
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                   Three oocytes frozen in a small film of fluid.
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                Mature oocyte.
earlier.
The human egg is unique. Its the largest cell in the              The success rate for egg freezing based in all pub-
body with high water contents. The membrane sur-                  lished reports in the world are given below.
rounding the cell is not very permeable. Moreover,                In general 2/3 of eggs frozen using slow freezing
its the only cell in the body where chromosomes are               method survive compared to about 90% of oocytes
spread on flimsy structure called the spindle, rather             frozen by vitrification method. After thaw, the eggs
than being enclosed inside the nucleus of the cell.               need to be fertilized using intracytoplasmic sperm
The egg requires special expertise to freeze. Two                 injection (ICSI). About 70 to 90% fertilization rate
techniques are used; slow freezing or vitrification               is expected. Embryos are cultured to day 3 stage or
(rapid freezing). The newer vitrification method has              blastocysts before transfer. Each thawed egg yield
the advantage of avoiding the formation of ice crys-              about 2-3% pregnancy rate after slow freezing and
tals inside the egg and yields better survival of the             about 8 to 10% when vitrification was used. Transfer
6   |   Preservation of Fertility




    The only caveat to vitrification is that this method   c.        Ovarian Tissue Freezing. This is an ex-
    has not been around long enough to ascertain its       perimental method for preservation of fertility. In
    safety.                                                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
    Cleavage stage (day 3) embryo.                         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
    Blastocyst stage (day 5-6) embryo.                        freezing. It yields outcome comparable to embryo
                                                              freezing.
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                    Vitrification
                                                     (38 studies)         (EG 2.7M+DMSO 2.1M+sucrose 0.5M)


                  Oocytes thawed                     11937                            1346
                  Oocytes 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 Perspective
Genetic 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.
8   |   Preservation of Fertility




    Some Genetic syndromes with increased susceptibility to cancer
Women          |   9




                                                            Questions to       Questions            Things to do
                                                               ask
                                                            Oncologist     *Type of cancer          Ask for a
                                                                                                        referral
                                                                           *Stage                       letter
                                                                           *Treatment plan          Obtain
                                                                                                        medical
                                                                               1. Surgery               records;
   Women interested in preservation of fertility                               2. Chemo-            Surgery
   should be counseled about the availability of                               therapy                  records
   genetic screening pertaining to their cancer and if                         3. Bone mar-         Pathology
                                                                               row transplant           records
   carriers about PGD to avoid transmission to future                          4. Radiothera-       Other tests;
   children.                                                                   py                       ER, PR,
                                                                                                        her2/neu,
                                                                               5. Hormonal              BRCA
                                                                               treatment
                                                                                                    General medi-
                                                                               *Is Preservation         cal tests
                                                                               of fertility suit-
                                                                               able for me?

Coordination of Cancer Treat-                               Reproduc-      *How is cancer and       Blood work;
ment and Preservation of
                                                               tive             cancer treat-           FSH,
                                                                                ment expected to        estradiol,
                                                            Endocrinol-         impact future my        AMH
                                                               ogist            fertility?
Fertility                                                                  *What are the suit-
                                                                                able options for
                                                                                preservation of
                                                                                                    Ultrasound
                                                                                                    Semen analy-
                                                                                                        sis
Multiple studies in the US surveying patients or                                fertility?
                                                                                                    Other gen-
oncologists found that discussion and referral for                         Embryo freezing              eral tests
                                                                                                        required
preservation of fertility takes place in less than 50%                     Oocyte freezing              for IVF
                                                                                                        and cell
of patients. Referral was more likely when patients                        Ovarian tissue freez-        and tissue
                                                                                ing                     freezing
inquire about fertility issues.                                            Others                   Referral for
                                                                                                        genetic
This underlines the importance of educating women                          Combination                  counsel-
                                                                                                        ing
about fertility issues and the diagnosis of cancer                         *Is it safe?
                                                                                                    Coordinate
and other allied diseases. Empowering women to                             *What to do with the         fertility
                                                                                                        preserva-
ask questions appears to one of the most important                         frozen embryos, eggs         tion plan
                                                                                                        with the
initial steps to receive appropriate information about                     or tissue after cure         oncologist
and possibly pursue preservation of fertility.                             *What is the success
                                                                                rate for my op-
                                                                                tions
Collecting information and coordination of care
between providers concerned with cancer treatment
                                                            Psychologist How to deal with           Make an ap-
and those that deal with preservation of fertil-                            stresses of treat-         pointment
                                                                            ment
ity can be a demanding task, especially at difficult
and busy times. The table below aims at organizing          Support        Help with referral       E.g. fertile-
your thoughts and collecting information about the             group                                     hope.org
                                                                           Help with medica-
feasibility of preservation of fertility after diagnosis,                      tions                livestrong.org
before making a decision to pursue these options                                                    youngsurvival.
                                                                                                         org
or to bypass them and proceed directly to disease                                                   lbbc.org
treatment.
Women         | 10




Real Cases                                                Colon Cancer
                                                          A 34 year old presented with her husband after a
                                                          recent diagnosis of colon cancer. Her planned treat-
Breast Cancer                                             ment was chemotherapy, pelvic radiation followed
1. A 28 year old Caucasian system analyst present-        by surgery. She wanted to preserve the ability to
ed with her partner shortly after the diagnosis of        have biological children.
duct carcinoma of the breast. The tumor was stage II      She was counseled that
after lumpectomy and axillary lymph node sampling         1. Chemotherapy used for colon cancer has mild or
and was estrogen receptor positive. Her treatment         no long term effects on future ovarian function
plan per her oncologist was 4 cycles of cyclophos-        2. Pelvic radiation at the planned dose, however will
phamide, adriamycin and taxol followed five years of      very likely result is complete cessation of ovarian
tamoxifen.                                                function
She was counseled to the effect of chemotherapy on        3. Pelvic irradiation will likely damage the tissue of
ovarian function. The risk for ovarian failure is about   the uterus so that pregnancy would not be safe.
30%. Time factor also should be considered (she           She was offered a combined approach to preserve
will be 35 by the time she could attempt pregnancy).      her fertility
The possibility of underlying genetic factor was also     1. Ovarian stimulation and egg retrieval and embryo
discussed and breast cancer gene testing was offered      freezing
(she turns out to be BRCA1 and 2 negative).               2. Laparoscopic surgery to move one ovary upwards
As she had a steady partner, she was offered ovar-        away from radiation field
ian stimulation using letrozole and gonadotropins         3. Harvest of the other ovary during the same sur-
followed by oocyte retrieval and embryo cryopreser-       gery and freezing it for later transplantation.
vation. The risks and benefits of this approach was
discussed in details. She accepted this option and so     She accepted only ovary stimulation and embryo
did her oncologist. After retrieval, 6 blastocysts were   freezing. This was performed after consulting with
frozen within 18 days. She completed cancer treat-        her oncologist and 20 blastocysts were frozen.
ment and her period stopped after chemotherapy            After radiation, her menses stopped.
and did resume yet.                                       She came back with her to use the embryos. One
                                                          embryo was transferred to the uterus of her sister
2. A 37 year old mathematician presented shortly          resulting in pregnancy and delivery of healthy baby.
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,
                                                          Pregnancy after Breast Cancer
                                                          Is it safe to get pregnant after treatment for breast
recommended 5 years of tamoxifen.                         cancer? It is the general consensus that pregnancy
This delay in attempting pregnancy (she would be          after treatment and a follow up period of 6 months
42 at the end of treatment) and because she de-           to two years is not associated with increase in the
clined the use of donor sperm, she was offered egg        odds for breast cancer recurrence. Most oncologists
freezing. With the approval of her oncologist, she        advise their patients to wait for a variable period
underwent two cycles of egg freezing and 10 eggs          after treatment before attempting pregnancy. Recent
were cryopreserved after each cycle by vitrification.     evidence from multiple studies including a large
She is in good health so far.                             Danish study indicated that there is no evidence
11 |   Preservation of Fertility                            Women   | 11




   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 Reading
   1. 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
12 |    Preservation of Fertility




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    Sperm count sometimes recover to a variable extent
less invasive compared to women. 50–70% of men            years after cancer treatment. This depends on the
diagnosed with cancer wanted children in the future.      type of cancer and treatment used. For example
Only 24% of young cancer patients banked sperm,           90% of men diagnosed with Hodgkin’s lymphoma,
including 37% of childless men. The most com-             treated with MOPP chemotherapy regimen, do not
mon reason for failing to bank sperm was a lack of        have any sperm in the ejaculate after one year.
information.                                              b.       Bone marrow transplantation for cancer of
                                                          nonmalignant diseases usually require prior irradia-
Who needs to consider preser-                             tion and chemotherapy. This is associated with high
                                                          risk (85%) of complete failure of sperm production.
vation of Fertility?                                      c.       Connective tissue / autoimmune diseases
a.        The American Cancer Society estimates           as lupus and rheumatoid arthritis requiring treat-
that 760,000 men will be diagnosed with cancer in         ment with chemotherapy.
2009. Cancer itself (before treatment) is known to
be associated with less sperm production in men.          d.       Genetic abnormalities associated with
This is specially the case in Hodgkin’s lymphoma,         rapid loss of male germ cells e.g. Kleinefelter syn-
testicular cancer, leukemias and colon cancer.            drome, Y chromosome microdeletion (AZFc).

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.
men     | 13




Methods used for Fertility                                modern reproductive medicine can handle the
                                                          majority of compromised specimens yielding excel-
Preservation                                              lent pregnancy rates, similar to those of fresh sperm.
                                                          b.                 Testicular Sperm Extraction
Methods used to preserve fertility in men are gener-
                                                          (TESE). This surgical procedure retrieves sperm
ally divided into two categories:
                                                          from inside the testes if no sperm was found in the
Protection of the testes from damage caused by cancer     ejaculate. If this procedure is used before cancer
treatment:                                                treatment, sperm are retrieved in over 50% of cases.
                                                          Sperm or testicular biopsies are frozen for later use.
1. Shielding the testes from radiation field.
                                                          ICSI is used for fertilization. In case of testicular
2. Protection of the testes from the effect of chemo-
                                                          cancer, sperm retrieval can be performed at the same
therapy. GnRH agonists are a group of medications
                                                          time of surgery for cancer.
that suppress the master gland in the brain, pre-
venting the release of the hormones that stimulate        c.                       Testicular Tissue or Germ
sperm production in the testes. Although suggested,       Cell Freezing. This is an experimental technique.
there is no proof that they actually increase the odds    Immature germ cells or testicular pieces are frozen
for pregnancy after the use of chemotherapy.              for later transplantation. No pregnancy was achieved
There is no effective protective medication               using this method so far.
available for use in humans.
                                                          In conclusion, fertility-sparing strategy is readily
Low Temperature Storage of Sperm and Testicular Tissue:   available to the majority of men at risk for dimin-
a                       Sperm Cryopreservation.           ished fertility through sperm cryopreservation. Men
This is the standard method for preservation of           interested in fathering children in the future should
fertility in men. A sperm sample is obtained by           be counseled about this option.
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,
NYCIVF, 400 East 56 Street. New York, NY 10022 ¤ 800•853•7595 www.nycivf.org, preservationoffertility.rg




        NYCIVF
         Personal & Innovative Fertility Care

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Fertility Preservation; an e-Guide

  • 1. Preservation of Fertility Living Beyond Cancer NYCIVF Personal & Innovative Fertility Care
  • 2. 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. 10 9 8 7 6 5 4 3 2 1
  • 3. 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
  • 4. iv | Preservation of Fertility NOTES
  • 5. | 1 1 Preservation of Fertility in Women Fertility is a key aspect for quality of life a. In 2009 about 700,000 women will be di- for cancer patients of childbearing age. Preservation agnosed with cancer, about 10% of them under the of fertility is defined as the application of medi- age of 45. Breast cancer is the most common cancer cal, surgical and laboratory procedures to preserve affecting women. 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 Proportion of cancer by site in women. (From American Cancer States and recently diagnosed with cancer or Society, 2009) another condition that threatens your future ability to mother or father children, this bulletin is writen Each year bout 15,000 women will be diagnosed with you in mind. The odds are you will beat your with breast cancer before 45year disease and survive for many years to come. Consid- ering fertility-sparing before starting disease treat- Women can also be diagnosed with leukemias, lym- ment may greatly enhance your ability to conceive a phomas, cancer of the colon, uterus, ovary, skin or biological child after cure. thyroid gland. Treatment of all these cancers is as- sociated with long term effects during the survivor- Who needs to consider preser- ship period including decline in fertility. The effects of cancer treatment go beyond the harm caused by vation of Fertility? the method of treatment itself to the time spent in treatment and time needed for follow up. This delay
  • 6. 2 | Preservation of Fertility means women will probably attempt pregnancy several years later than they intended. b. Women undergoing bone marrow trans- Effects of Cancer Treatment plantation for treatment of cancer, anemias (e.g. Sickle cell disease) and other diseases. The use of on Ovarian Function chemotherapy and radiation prior to transplantation In general the younger the woman, the more is usually associated with fertility loss in the vast oocytes she harbors in the ovary and the higher majority of patients. the likelihood that some oocytes will remain in the c. Some women develop breast or ovarian ovary after treatment. cancers due to abnormality in breast cancer gene A. Chemotherapy and the Ovary. The use of (BRCA1 & 2). Reducing the risk of future cancer chemotherapy can lead to fast loss of oocytes (eggs). may require removal of both ovaries with loss of Oocytes carry the genetic material that women pass fertility. to their children after fertilization by a sperm. The d. Women diagnosed with connective tissue effect of these agents is variable depending on the disease (Systemic lupus, rheumatoid arthritis...) or drug, dose, frequency of administration, and age of autoimmune disease may have severe disease af- the woman at the time of treatment. Cyclophosph- fecting their organs (e.g. Kidney). Chemotherapy is amide is the most harmful agent for future fertility. sometimes used to suppress their immunity which These medication appear to cause loss of eggs may lead to fertility decline. Moreover, the antibod- through damage of its DNA and inducing sponta- ies generated by the disease process may directly neous demise of the egg. There is no proven method affect ovarian function. that can prevent this loss. e. Individuals exposed to accelerated loss B. Pelvic Radiation and the Ovary. Expo- of eggs due to genetic disease (e.g. Mosaic Turner sure of the ovary to radiation can damage the eggs syndrome) can also benefit from preservation of and the remaining tissue of the ovary. The amount fertility of radiation that leads to complete loss of ovar- f. Fertility extension. Women delaying preg- ian function is dependent on the age. A dose of nancy for career or social reasons (no male partner 1500cGy will sterilize the majority of women at age at this time) can consider freezing their eggs or 30. Smaller doses will sterilize older women. embryos (using donor sperm). This option was not C. Time factor. Cancer treatment usually re- studied in large population studies. 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 Cancer treatment (chemotherapy, radiation and others oncologists recommend a period of observa- bone marrow transplantation) will not only dimin- tion for 1 to 2 years. This will a woman’s plan to ish fertility by accelerating loss of oocytes but also start a family to a later age when fewer oocytes by delaying attempts to become pregnant for years remain in the ovary. Actually the effect of cancer treatment on the ovary appears to be similar. Continuous loss of eggs from
  • 7. 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. Women exposed to chemotherapy exhibit a much lesser response to medications that stimulate egg D. Pelvic Radiation and the Uterus. Expo- production in the ovary than women presenting sure of the uterus to radiation increases the risk of before exposure to chemotherapy, hence the impor- miscarriage, preterm labor and abnormal pregnancy tance of considering preservation of fertility early outcome. after cancer diagnosis. Evaluation of Ovarian Func- Methods used for Fertility tion after Cancer Treatment Although many think that resumption of men- Preservation struation after cancer treatment indicates that the Methods used to preserve fertility in women are woman retains the ability to conceive, this is not generally divided into three categories: true. Some women have regular menses with near Modification of cancer treatment plan to reduce damage exhaustion of the eggs in the ovaries. Thus, men- to the ovaries and uterus: struation is not a reliable indicator of the ability to conceive. 1. Preserving one ovary in women affected with early ovarian cancer. The function of the ovary before after cancer treat- ment can be evaluated using hormone tests and 2. Preservation of the body of the uterus with ultrasound. removal of the cervix in early cervical cancer. ♦ Cycle day 2 or 3 FSH (normal is less than 3. Use of progesterone treatment instead of re- 12mIU/mL) moval of the uterus in endometrial cancer. ♦ Inhibin Protection of the ovaries from the damage caused by cancer treatment: ♦ Antimullerian hormone (AMH). This is a new and promising marker and appear to be more 1 Ovarian transposition is a surgical procedure to accurate than the other markers. move the ovaries upwards, away from radiation field before pelvic radiation. Results are variable as some ♦ Vaginal ultrasound to evaluate the number of scattered radiation still reaches the ovaries. small follicles visible in the ovary. 2. Protection of the ovaries from the effect of Although these markers are more accurate than chemotherapy. GnRH agonists are a group of menstrual history, normal markers after treatment medications that suppress the master gland in the does not mean that ovarian function is completely brain, preventing the release of the hormones that preserved after exposure to treatment. 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.
  • 8. 4 | Preservation of Fertility special attention. The use of fertility medication is usually associated with considerable rise in estrogen levels. One potential risk of estrogen rise, though Low Temperature Storage of Embryos, Oocytes or Ovarian not proven, is increase in activity of cancer cells. Tissue: This is addressed during stimulation by adding a a. Embryo Freezing. This is considered the medicine (letrozole) that blocks the enzyme that standard method for preservation of fertility. Its makes estrogen in the ovaries, so that stimulation suitable for women with a male partner or ac- with gonadotropins can progress without increase in cepting the use of donor sperm and when cancer estrogen. When the follicles (the bag that contain treatment does not need to be started immediately. the eggs) reach adequate size, final maturation is This method entails stimulation of the ovary with triggered using another hormone, hCG. This is fol- medications and frequent monitoring of response lowed by egg harvest. using ultrasound and blood work. This stimulation The safety of this method for stimulation of the ovary usually requires 12 to 14 days. The eggs are then was studied. We compared women presenting for removed from the ovary by an outpatient procedure ovarian stimulation after the diagnosis of breast under sedation. Egg retrieval requires passing a cancer with women diagnosed with breast cancer and needle through the vagina into the ovary. Eggs are declined ovarian stimulation. The follow up period was then fertilized in the lab and the resulting embryos approximately 2 years. There was no increase in breast are frozen 2 to 6 days later and stored for later use. cancer recurrence between both groups (Azim et al , Cancer treatment can start immediately after egg Journal of Clinical Oncology 2008). Although further retrieval. After cure, women can request to use their follow up is required, results so far are reassuring that embryos, that are placed back into the uterus after this method is probably safe. 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 hCG GnRH antagonist FSH/hMG Letrozole Letrozole
  • 9. Women | 5 egg at thawing. The egg is placed in a solution that prevents damage caused by ice crystals (cryopro- Protocol for stimulation of the ovaries in women diagnosed with tectant) and then stored in liquid nitrogen at -170. 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 Three oocytes frozen in a small film of fluid. 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 Mature oocyte. earlier. The human egg is unique. Its the largest cell in the The success rate for egg freezing based in all pub- body with high water contents. The membrane sur- lished reports in the world are given below. rounding the cell is not very permeable. Moreover, In general 2/3 of eggs frozen using slow freezing its the only cell in the body where chromosomes are method survive compared to about 90% of oocytes spread on flimsy structure called the spindle, rather frozen by vitrification method. After thaw, the eggs than being enclosed inside the nucleus of the cell. need to be fertilized using intracytoplasmic sperm The egg requires special expertise to freeze. Two injection (ICSI). About 70 to 90% fertilization rate techniques are used; slow freezing or vitrification is expected. Embryos are cultured to day 3 stage or (rapid freezing). The newer vitrification method has blastocysts before transfer. Each thawed egg yield the advantage of avoiding the formation of ice crys- about 2-3% pregnancy rate after slow freezing and tals inside the egg and yields better survival of the about 8 to 10% when vitrification was used. Transfer
  • 10. 6 | Preservation of Fertility The only caveat to vitrification is that this method c. Ovarian Tissue Freezing. This is an ex- has not been around long enough to ascertain its perimental method for preservation of fertility. In safety. 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 Cleavage stage (day 3) embryo. 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 Blastocyst stage (day 5-6) embryo. freezing. It yields outcome comparable to embryo freezing.
  • 11. 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 Vitrification (38 studies) (EG 2.7M+DMSO 2.1M+sucrose 0.5M) Oocytes thawed 11937 1346 Oocytes 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 Perspective Genetic 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.
  • 12. 8 | Preservation of Fertility Some Genetic syndromes with increased susceptibility to cancer
  • 13. Women | 9 Questions to Questions Things to do ask Oncologist *Type of cancer Ask for a referral *Stage letter *Treatment plan Obtain medical 1. Surgery records; Women interested in preservation of fertility 2. Chemo- Surgery should be counseled about the availability of therapy records genetic screening pertaining to their cancer and if 3. Bone mar- Pathology row transplant records carriers about PGD to avoid transmission to future 4. Radiothera- Other tests; children. py ER, PR, her2/neu, 5. Hormonal BRCA treatment General medi- *Is Preservation cal tests of fertility suit- able for me? Coordination of Cancer Treat- Reproduc- *How is cancer and Blood work; ment and Preservation of tive cancer treat- FSH, ment expected to estradiol, Endocrinol- impact future my AMH ogist fertility? Fertility *What are the suit- able options for preservation of Ultrasound Semen analy- sis Multiple studies in the US surveying patients or fertility? Other gen- oncologists found that discussion and referral for Embryo freezing eral tests required preservation of fertility takes place in less than 50% Oocyte freezing for IVF and cell of patients. Referral was more likely when patients Ovarian tissue freez- and tissue ing freezing inquire about fertility issues. Others Referral for genetic This underlines the importance of educating women Combination counsel- ing about fertility issues and the diagnosis of cancer *Is it safe? Coordinate and other allied diseases. Empowering women to *What to do with the fertility preserva- ask questions appears to one of the most important frozen embryos, eggs tion plan with the initial steps to receive appropriate information about or tissue after cure oncologist and possibly pursue preservation of fertility. *What is the success rate for my op- tions Collecting information and coordination of care between providers concerned with cancer treatment Psychologist How to deal with Make an ap- and those that deal with preservation of fertil- stresses of treat- pointment ment ity can be a demanding task, especially at difficult and busy times. The table below aims at organizing Support Help with referral E.g. fertile- your thoughts and collecting information about the group hope.org Help with medica- feasibility of preservation of fertility after diagnosis, tions livestrong.org before making a decision to pursue these options youngsurvival. org or to bypass them and proceed directly to disease lbbc.org treatment.
  • 14. Women | 10 Real Cases Colon Cancer A 34 year old presented with her husband after a recent diagnosis of colon cancer. Her planned treat- Breast Cancer ment was chemotherapy, pelvic radiation followed 1. A 28 year old Caucasian system analyst present- by surgery. She wanted to preserve the ability to ed with her partner shortly after the diagnosis of have biological children. duct carcinoma of the breast. The tumor was stage II She was counseled that after lumpectomy and axillary lymph node sampling 1. Chemotherapy used for colon cancer has mild or and was estrogen receptor positive. Her treatment no long term effects on future ovarian function plan per her oncologist was 4 cycles of cyclophos- 2. Pelvic radiation at the planned dose, however will phamide, adriamycin and taxol followed five years of very likely result is complete cessation of ovarian tamoxifen. function She was counseled to the effect of chemotherapy on 3. Pelvic irradiation will likely damage the tissue of ovarian function. The risk for ovarian failure is about the uterus so that pregnancy would not be safe. 30%. Time factor also should be considered (she She was offered a combined approach to preserve will be 35 by the time she could attempt pregnancy). her fertility The possibility of underlying genetic factor was also 1. Ovarian stimulation and egg retrieval and embryo discussed and breast cancer gene testing was offered freezing (she turns out to be BRCA1 and 2 negative). 2. Laparoscopic surgery to move one ovary upwards As she had a steady partner, she was offered ovar- away from radiation field ian stimulation using letrozole and gonadotropins 3. Harvest of the other ovary during the same sur- followed by oocyte retrieval and embryo cryopreser- gery and freezing it for later transplantation. vation. The risks and benefits of this approach was discussed in details. She accepted this option and so She accepted only ovary stimulation and embryo did her oncologist. After retrieval, 6 blastocysts were freezing. This was performed after consulting with frozen within 18 days. She completed cancer treat- her oncologist and 20 blastocysts were frozen. ment and her period stopped after chemotherapy After radiation, her menses stopped. and did resume yet. She came back with her to use the embryos. One embryo was transferred to the uterus of her sister 2. A 37 year old mathematician presented shortly resulting in pregnancy and delivery of healthy baby. 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, Pregnancy after Breast Cancer Is it safe to get pregnant after treatment for breast recommended 5 years of tamoxifen. cancer? It is the general consensus that pregnancy This delay in attempting pregnancy (she would be after treatment and a follow up period of 6 months 42 at the end of treatment) and because she de- to two years is not associated with increase in the clined the use of donor sperm, she was offered egg odds for breast cancer recurrence. Most oncologists freezing. With the approval of her oncologist, she advise their patients to wait for a variable period underwent two cycles of egg freezing and 10 eggs after treatment before attempting pregnancy. Recent were cryopreserved after each cycle by vitrification. evidence from multiple studies including a large She is in good health so far. Danish study indicated that there is no evidence
  • 15. 11 | Preservation of Fertility Women | 11 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 Reading 1. 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
  • 16. 12 | Preservation of Fertility 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 Sperm count sometimes recover to a variable extent less invasive compared to women. 50–70% of men years after cancer treatment. This depends on the diagnosed with cancer wanted children in the future. type of cancer and treatment used. For example Only 24% of young cancer patients banked sperm, 90% of men diagnosed with Hodgkin’s lymphoma, including 37% of childless men. The most com- treated with MOPP chemotherapy regimen, do not mon reason for failing to bank sperm was a lack of have any sperm in the ejaculate after one year. information. b. Bone marrow transplantation for cancer of nonmalignant diseases usually require prior irradia- Who needs to consider preser- tion and chemotherapy. This is associated with high risk (85%) of complete failure of sperm production. vation of Fertility? c. Connective tissue / autoimmune diseases a. The American Cancer Society estimates as lupus and rheumatoid arthritis requiring treat- that 760,000 men will be diagnosed with cancer in ment with chemotherapy. 2009. Cancer itself (before treatment) is known to be associated with less sperm production in men. d. Genetic abnormalities associated with This is specially the case in Hodgkin’s lymphoma, rapid loss of male germ cells e.g. Kleinefelter syn- testicular cancer, leukemias and colon cancer. drome, Y chromosome microdeletion (AZFc). 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.
  • 17. men | 13 Methods used for Fertility modern reproductive medicine can handle the majority of compromised specimens yielding excel- Preservation lent pregnancy rates, similar to those of fresh sperm. b. Testicular Sperm Extraction Methods used to preserve fertility in men are gener- (TESE). This surgical procedure retrieves sperm ally divided into two categories: from inside the testes if no sperm was found in the Protection of the testes from damage caused by cancer ejaculate. If this procedure is used before cancer treatment: treatment, sperm are retrieved in over 50% of cases. Sperm or testicular biopsies are frozen for later use. 1. Shielding the testes from radiation field. ICSI is used for fertilization. In case of testicular 2. Protection of the testes from the effect of chemo- cancer, sperm retrieval can be performed at the same therapy. GnRH agonists are a group of medications time of surgery for cancer. that suppress the master gland in the brain, pre- venting the release of the hormones that stimulate c. Testicular Tissue or Germ sperm production in the testes. Although suggested, Cell Freezing. This is an experimental technique. there is no proof that they actually increase the odds Immature germ cells or testicular pieces are frozen for pregnancy after the use of chemotherapy. for later transplantation. No pregnancy was achieved There is no effective protective medication using this method so far. available for use in humans. In conclusion, fertility-sparing strategy is readily Low Temperature Storage of Sperm and Testicular Tissue: available to the majority of men at risk for dimin- a Sperm Cryopreservation. ished fertility through sperm cryopreservation. Men This is the standard method for preservation of interested in fathering children in the future should fertility in men. A sperm sample is obtained by be counseled about this option. 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,
  • 18. NYCIVF, 400 East 56 Street. New York, NY 10022 ¤ 800•853•7595 www.nycivf.org, preservationoffertility.rg NYCIVF Personal & Innovative Fertility Care