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Amr A Azim, MD, MSc, DSc, FACOG
Diplomate, American Board of Obstetrics & Gynecology Board Certified in Reproductive Endocrinology & Infertility
400 East 56 Street, Suite #1 www.nycivf.org New York, NY 10022 www.preservationoffertility.org Tel: 800•853•7595 [email protected] Fax: 800•780•6167 www.twitter.com/nycivf
©2010 Amr Azim, NYCIVF. www.nycivf.org
How Many Women are diagnosed…
Invasive breast cancer will affect 207,000 women in the US in 2010,
10% (1:80; 18,000 to 21,000 cases)
are under the age of 45 (ACS, 2010 )
2.9 breast cancer survivors by 2010
65% survive >5y
Will increase 30% by 2015(DeAngelis 2009 )
©2010 Amr Azim, NYCIVF. www.nycivf.org
Worldwide, 240,000 women
are diagnosed with breast cancer
each year are under the age of
45 years (Globocan 2002)
©2010 Amr Azim, NYCIVF. www.nycivf.org
Breast Cancer Treatment…
1. Excision of the tumor
2. Healing period (4-6 weeks)
3. Combination of three drugs
(4-6 months)
4. Radiation of the axilla
5. Tamoxifen for 5 years for hormone receptor positive cancer
Hormonanal treatment
Radiation
Other treatments
Surgery
Chemotherapy
©2010 Amr Azim, NYCIVF. www.nycivf.org
Chemotherapy for Breast Cancer
Use of these drugs especially cyclophosphamide (C) markedly reduce the number of eggs remaining in the ovary. The effect is unpredictable but its related to age, dose and type of drug used.(Petrek 2006, Lee 2006)
©2010 Amr Azim, NYCIVF. www.nycivf.org
Even if menstrual cycle resumes…When we attempted to stimulate the ovaries of women that were exposed to chemotherapy and regained menstrual cycles after chemotherapy and has normal markers of ovarian function, they still exhibited reduced ability to produce eggs compared to women that sought preservation of fertility before chemotherapy. (Azim
2006)
11.7
4.9 oocytes retrieved
©2010 Amr Azim, NYCIVF. www.nycivf.org
Age is also an important factor…After treatment women are commonly asked to take tamoxifen and other agents for 2-5 years.
Oncologists also advice a period of observation of two years before attempting pregnancy. The natural loss of eggs during these periods compounds the effect of chemotherapy (Broekmans 2007)
©2010 Amr Azim, NYCIVF. www.nycivf.org
Nobody told you all that…
You and more that 50% of women in their reproductive ages were not told all that, according to national surveys (Quinn 2009)
survey of 613 oncologists practicing in the US regarding knowledge, practice behavior and attitudes concerning preservation of fertility in cancer patients indicated
• 47 % of respondents routinely refer cancer patients of childbearing age to a reproductive endocrinologist.
• Referrals were more likely among female physicians.
• Referrals were more likely when patients routinely ask about preservation of fertility.
©2010 Amr Azim, NYCIVF. www.nycivf.org
Age is also an important factor…After treatment women are commonly asked to take tamoxifen and other agents for 2-5 years.
Oncologists also advice a period of observation of two years before attempting pregnancy. The natural loss of eggs during these periods compounds the effect of chemotherapy (Broekmans 2007)
©2010 Amr Azim, NYCIVF. www.nycivf.org
Protection
So far, no convincing evidence that the effect of chemotherapy can be prevented or mitigated.
The benefit of medications that suppresses the ovary (leuprolide, zoladex) is unproven.
5; primordial follicles
Chemotherapy mainly damage the very small follicles. These are not responsive to hormones in the blood.
©2010 Amr Azim, NYCIVF. www.nycivf.org
Preservation of Fertility
Freezing of eggs and embryos (fertilized eggs) is the most practical method to preserve fertility.
Those can be later thawed and transferred to the uterus (own or carrier)
Eggs can also be frozen within the ovary (ovarian tissue freezing)
Embryo Cryopreservation
Oocyte Cryopreservation
In Vitro Maturation of Oocytes
Ovarian Tissue Freezing
©2010 Amr Azim, NYCIVF. www.nycivf.org
EMBRYO CRYOPRESERVATION
©2010 Amr Azim, NYCIVF. www.nycivf.org
Embryo Cryopreservation
This method requires
1. Ovarian stimulation with fertility medication
2. Time; 2-3 weeks
3. Sperm source (partner or donor)
©2010 Amr Azim, NYCIVF. www.nycivf.org
A special method of ovarian stimulation is used for safer stimulation in women diagnosed with breast cancer.
OVARIAN STIMULATION IN ESTROGEN SENSITIVE CANCERS
Ovarian Stimulation & Breast Cancer
Ovarian stimulation causes marked increase in estrogen levels.
Although brief, this may increase the growth of cancer
We have developed and tested a protocol for ovarian stimulation that prevents increase in estrogen during stimulation
(Azim 2008)
Letrozole is a medication that prevents the ovary from making estrogen. Its approved by FDA for treatment of breast cancer
©2010 Amr Azim, NYCIVF. www.nycivf.org
Ovarian Stimulation & Breast Cancer
Letrozole
FSH/hMG
GnRH antagonist
hCG
Letrozole
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 cycle days
©2010 Amr Azim, NYCIVF. www.nycivf.org
Ovarian Stimulation & Breast Cancer
79 completed protocol1. Surgery
2. COS+IVF+cryo3. Chemo ± hormonal therapy
136 declined COS79 consented to COS
215 patients
136 breast cancer treatment only
1. Surgery2. Chemo ± hormonal therapy
Outcomes known 79Lost to follow up 0
Outcomes known 102Lost to follow up 34; considered
NED
79 analysed0 excluded from analysis
136 analysed0 excluded from analysis
Breast cancer events (n=11):Distant recurrence (n=9)
Locoregional recurrence (n=1)Contralateral breast cancer (n=1)
Breast cancer events (n=3):Distant recurrence (n=2)
Locoregional recurrence (n=1)Contralateral breast cancer (n=0)
©2010 Amr Azim, NYCIVF. www.nycivf.org
Ovarian Stimulation & Breast CancerThere was no difference in breast cancer recurrence between women stimulated to preserve their eggs or embryos and those who declined stimulation (median follow up 2 years)
Length of stimulation was 9.87 days. Peak E2 levels 405.94 pg/mL
An average of 10.3 oocytes were retrieved, and 5.97 embryos or oocytes cryopreserved per patient
Number of patients at riskL 79 74 37 18 7 5C 136 81 56 38 26 19
0 12 24 36 48 60 7240
50
60
70
80
90
100
Letrozole goup (L)
Control group (C)p=0.36, HR=0.56
Time (months)
Rel
apse
free
sur
viva
l (%
)
©2010 Amr Azim, NYCIVF. www.nycivf.org
TIMELINE
Consultation with a fertility preservation specialistOvarian stimulation and egg retrievalEmbryo or oocyte freezing
©2010 Amr Azim, NYCIVF. www.nycivf.org
Pregnancy after Breast Cancer Treatment
a. Embryos can be replaced in a gestational carrier.
b. If embryos are placed in a breast cancer survivor, pregnancy does not increase the odds for breast cancer recurrence.
c. A waiting period after treatment of 6 months to 2 years is advised
©2010 Amr Azim, NYCIVF. www.nycivf.org
Pregnancy after Breast Cancer TreatmentWhen all studies related to pregnancy after breast cancer
were compiled (20,000 women and 1,400 pregnancies), those who became pregnant after treatment had a much lower risk of death due to breast cancer (Azim 2010)
©2010 Amr Azim, NYCIVF. www.nycivf.org
Low Estrogen Ovarian Stimulation
We have also reported the use of this procedure in women diagnosed with endometrial cancer and other estrogen sensitive cancers e.g thyroid cancer
OOCYTE CRYOPRESERVATION
©2010 Amr Azim, NYCIVF. www.nycivf.org
The Egg is a Unique Cell
It’s the largest cell in the body
It has a lot of water
Its cell membrane does not allow water to pass easily
Chromosomes are spread on a spindle
A special expertise is required to freeze an egg!
©2010 Amr Azim, NYCIVF. www.nycivf.org
Slow FreezingVitrificationThe temperature is dropped very slowly.
Low concentration of cryoprotectant (a chemical added to the freezing conctail to reduce ice crystal formation during freezing).
The temperature is dropped very fast.
High concentration of cryoprotectant is used.
©2010 Amr Azim, NYCIVF. www.nycivf.org
Egg Freezing; Facts
©2010 Amr Azim, NYCIVF. www.nycivf.org
Egg Freezing; Facts
©2010 Amr Azim, NYCIVF. www.nycivf.org
More recent reports on vitrification report better results, with each thawed egg yielding a pregnancy rate of 10%. The transfer of 2 or 3 embryos can result in a reasonable chance for pregnancy and delivery.
Caveats
Experience with vitrification is still small. Few babies were borne worldwide and long term outcomes are not known yet. It is still considered experimental.
OVARIAN TISSUE CRYOPRESERVATION
©2010 Amr Azim, NYCIVF. www.nycivf.org
Ovarian Tissue Cryopreservation
This method requires
1. No ovarian stimulation needed
2. Require a day surgery for harvesting ovarian tissue
3. Require only few hours to accomplish
©2010 Amr Azim, NYCIVF. www.nycivf.org
This is an experimental method for fertility preservation.Potential risk: transmission of malignant cells after transplantation
Ovarian Tissue Cryopreservation
One ovary is removed using laparoscopy (minimally access surgery ). The ovary then is cut into thin slices and frozen.
After cancer cure the strips are thawed and transplanted in the abdominal cavity (orthotopic) or under the skin (heterotopic).
©2010 Amr Azim, NYCIVF. www.nycivf.org
Yes You CanYou can have your biological child after you were diagnosed with breast cancer.
Even if you have no male partnerEven if you have no time
Even if you do not or cannot get pregnant yourself
©2010 Amr Azim, NYCIVF. www.nycivf.org
Yes just need to..
Get timely information about risks and benefits early after your diagnosis, before starting treatment
Information is availableYou are, however, less likely to get the
information unless you ask
Preservationoffertility.org
©2010 Amr Azim, NYCIVF. www.nycivf.org