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 [email protected] Fax: 800•780•6167 www.twitter.com/nycivf

©2010 Amr Azim, NYCIVF. www.nycivf.org

http://www.nycivf.org/

http://www.preservationoffertility.org/

mailto:[email protected]

http://www.twitter.com/nycivf

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…

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


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

Oocyte Cryopreservation

In Vitro Maturation of Oocytes

Ovarian Tissue Freezing


EMBRYO CRYOPRESERVATION


Embryo Cryopreservation

This method requires

1. Ovarian stimulation with fertility medication

2. Time; 2-3 weeks

3. 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



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



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)


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 (%

)


TIMELINE

Consultation with a fertility preservation specialistOvarian stimulation and egg retrievalEmbryo or oocyte freezing


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


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)


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 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.


Egg Freezing; Facts


Egg Freezing; Facts


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


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


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).


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


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


Documents

Fertility on Ice