Fertility on Ice

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 nycivf@nycivf.org
Fax: 800•780•6167 www.twitter.com/nycivf
©2010 AmrAzim, 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 )

Worldwide, 240,000 women
are diagnosed with breast cancer
each year are under the age of
45 years
(Globocan 2002)

Breast Cancer Treatment…
Surgery
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
Chemotherapy
Radiation
Hormonanal treatment
Other treatments

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)

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

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)

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.

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)

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.

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

Embryo Cryopreservation
This method requires
Ovarian stimulation with fertility medication
Time; 2-3 weeks
Sperm source (partner or donor)
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

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 cycle days

There 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 oocytescryopreserved per patient

Timeline
Consultation with a fertility preservation specialist
Ovarian stimulation and egg retrieval
Embryo or oocyte freezing

Pregnancy after Breast Cancer Treatment
Embryos can be replaced in a gestational carrier.
If embryos are placed in a breast cancer survivor, pregnancy does not increase the odds for breast cancer recurrence.
A waiting period after treatment of 6 months to 2 years is advised

Pregnancy after Breast Cancer Treatment
When 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)

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

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!

Slow Freezing Vitrification
The 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.

Egg Freezing; Facts

Egg Freezing; Facts
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.
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.

Ovarian Tissue Cryopreservation

This method requires
No ovarian stimulation needed
Require a day surgery for harvesting ovarian tissue
Require only few hours to accomplish
This is an experimental method for
fertility preservation.
Potential risk:
transmission of malignant cells after
transplantation

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).

Yes You Can
You can have your biological child after you were diagnosed with breast cancer.
Even if you have no male partner
Even if you have no time
Even if you do not or cannot get pregnant yourself

Yes just need to..
Get timely information about risks and benefits early after your diagnosis, before starting treatment
Information is available
You are, however, less likely to get the information unless you ask
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Fertility on Ice

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