|
|
Oocyte Cryopreservation > Stopping
the Biological Clock
Oocyte Cryopreservation
For decades, sperm and embryos
(fertilized eggs) have been successfully frozen for the purposes
of fertility preservation and donation for men and couples.
Although both sperm and embryo cryopreservation have become
commonplace, oocyte preservation or the freezing of unfertilized
oocytes (or eggs) for similar applications in women has not
historically delivered the acceptable success rates necessary to
drive adoption across the board.
Unlike sperm and embryos, oocytes did not survive the
freeze/thaw aspects of the egg freezing process well primarily
because the egg is the largest cell in the human body and
comprised mostly of water. The water inside the cell forms ice
crystals that destroy the egg during the traditional egg
freezing process. Prior to 2002, the success rate of live births
from frozen eggs was 1-3% globally, with few babies born from
frozen eggs over decades of attempts. Fortunately, a number of
advances in our knowledge of oocyte preservation, oocyte
physiology and laboratory techniques are rapidly changing this
fertility extension dream into a reality.
Oocyte Preservation provides the ability to preserve
unfertilized oocytes, a profound development in the field of
reproductive medicine. Egg-freezing should appeal to a broad
range of women. Ultimately, the common factors that link all of
these women are the strong desire to have a family and the
willingness to take proactive steps to give themselves the best
odds possible.
1) While some couples are comfortable with the concept of
embryo freezing, many have moral
and ethical dilemmas regarding the freezing of embryos. For
those that believe that life is created at the moment of
conception, each frozen embryo represents a life and, if unused,
a life unfulfilled. Oocyte cryopreservation, like sperm
cryopreservation, presents us with the possible opportunity to
preserve one's fertility while avoiding these ethical dilemmas.
2) Oocyte cryopreservation provides young women facing
chemotherapy or irradiation for treatment of life-threatening
disease, such as cancer, the opportunity to preserve their
fertility. The importance of this can not be understated.
Treatment regimens for many of the malignancies faced by
adolescents and young adults result in the destruction of their
gametes (sperm or eggs). The advancements in cancer treatments
are also ensuring that many of these cancer survivors are living
long, productive lives. Thus, the opportunity to preserve their
ability to have children later in life is critical.
3) The professional and personal opportunities for women
have exploded over the past 30 years, encouraging many women to
postpone motherhood. Unfortunately, the biology of female eggs
hasn’t kept pace and women often face challenges starting their
families later in life. Women, who are born with a limited
supply of eggs, start to experience diminished fertility rates
in the late twenties and this rapidly accelerates as they reach
their mid-thirties. Childlessness is one of the biggest concerns
for professional women. Studies show that the majority of the
33% of high-achieving women that are childless at ages 41–55 did
not choose to be childless. In fact, more than a quarter of
high-achieving women in the 41–55 year old age group said they
would still like to have children. For women age 41-55, the
ability to preserve their eggs (and thus their future fertility)
through egg freezing, oocyte cryopreservation, and egg
harvesting gives them more flexibility as to when they can start
their families.
4) Oocyte cryopreservation will allow those who need to
resort to egg donation (the use of someone else's eggs due to
the diminished fertility potential of their own eggs) more
affordable female fertility treatment options. Today, when a
couple chooses to use donor eggs, they must bear the cost of the
donor's entire IVF cycle alone. The ability to use only the
limited number of eggs necessary while freezing the unused eggs
will allow couples using donor's eggs to cut their expenses
dramatically. This will allow individuals who were unable to
afford egg donation the opportunity to pursue having children.
Oocyte Cryopreservation Techniques
Given the magnitude of the need, clinicians around the world
have raced to develop a Oocyte cryopreservation technique for
successful egg-freezing, and, beginning in 2002, promising
results ranging from 20-40% successful pregnancy rate (on par
with a woman’s natural peak fertility rate) were published. The
key difference over previous techniques was the change in
cryoprotectants used to protect the egg during the egg freezing
process. Cryoprotectant acts as an “anti-freeze” to protect the
delicate eggs as the temperature drops. Before attempting to
understand how our ability to cryopreserve unfertilized eggs has
been achieved, it is important to understand how sperm and
embryo (fertilized oocytes) cryopreservation has long been
commonplace.
The major problem faced in freezing a cell is to minimize damage
to the membranes induced by ice crystal formation. Intracellular
ice formation is dangerous because it may rupture the cell
membranes causing cellular destruction. The smaller the cell,
the less likely ice crystal formation will occur. Sperm cells
are about 1/80th the size of a mature egg and thus can be easily
preserved. Embryos, which are eggs that have been fertilized,
are approximately the same size as mature eggs, but are much
more likely to survive the egg freezing/thawing cycles. This is
due to the fact that the eggs membranes undergo dramatic changes
during fertilization, making them more likely to tolerate the
stresses associated with oocyte cryopreservation and egg
freezing. The use of cyroprotectants and highly controlled egg
freezing/thawing rates have dramatically improved the survival
rates of frozen sperm and frozen embryos. In many ways, the
lessons learned from freezing sperm and embryos are being
applied to freezing oocytes. However, the unique nature of the
female egg has required additional study and technological
developments. A number of oocyte cryopreservation egg freezing
approaches have been taken in order to maximize the survival
rates of frozen oocytes.
The greatest success has been achieved with protocols that use
slow egg freezing/rapid thaw protocols. Critical to any egg
freezing protocol is the use of cyroprotectants. Cryoprotectants
act by a variety of means to reduce the amount of water that
crystallizes within the cell and protects the cell during the
egg freezing process. Common cyroprotectants include an alcohol
(1,2-propranediol), a carbohydrate (sucrose) and a solvent
(DMSO). The concentration and the duration of exposure to most
cryoprotectants (alcohols and solvents) are critical as exposure
to high concentrations or exposure for prolonged periods of time
can result in damage to the cell. We have found that increasing
the concentration of sucrose (a relatively safe cryoprotectant
that works by pulling water out of the cell) results in
significantly improved survival rates, fertilization rates and
pregnancy rates for frozen oocytes. We also have found that the
removal of the cryoprotectant with progressive dilution is a
critical step in the thawing process. If oocytes are placed
directly in a medium without cryoprotectant after thawing, they
can swell and burst.
The use of
nonpermiating molecules (molecules that do not enter in the
thawing cell) such as sucrose act to oppose the inflow of water
into the cell and thus prevent the membrane from bursting.
Others have recently undertaken investigations using a process
called vitrification; a process that utilizes ultra rapid egg
freezing techniques. While some pregnancies have been achieved
utilizing this technique, it has not been shown to be more
efficacious than slow freeze/rapid thaw protocols and is more
susceptible to human error. This process exposes the egg to
potentially damaging levels of cryoprotectant and direct
exposure to liquid nitrogen. Exposure to liquid nitrogen is a
critical factor in this age of concern over infectious agents.
The infectious agents, while rare, can result in
life-threatening illnesses. This is a critical concern as the
cryopreserved cells are stored in common tanks and a single tank
may contain thousands of cells. Regardless of the egg freezing
technique, the oocyte goes through a number of changes that make
it less likely to fertilize using standard co-incubation
techniques (the mixing of eggs and sperm together). The
understanding that the zona pellucida (an exoskeleton that
covers the outside of the egg) undergoes changes due to the
premature release of the cortical granules (these are normally
released at the time of fertilization and prevents multiple
sperm from fertilizing the egg) is an important factor that has
lead to improved success with frozen eggs. This has led to
changes in how frozen oocytes are fertilized. Changes in the
zona pellucida that blocks the ability of the sperm to fertilize
the egg. With the introduction of intracytoplasmic sperm
injection (ICSI), the results in terms of fertilization, embryo
development and the implantation rates (attachment of the embryo
to the uterus) are approaching those obtained with fresh
embryos.
Oocyte Cryopreservation Research Study
Conclusions:
To date, we are just reaching a time where it is becoming
feasible for mature oocyte cryopreservation. These are harvested
after taking fertility medications to induce the maturation of a
number of mature oocytes. Women of this generation want more
options and power when it comes making life decisions and plans.
This is an exciting next step in the long line of developments
in the field of women’s reproductive health – on par with the
introduction of the birth control pill.
Contributors:
Christy Jones is the CEO and founder of Extend Fertility in
Boston, Massachusetts MA (USA).
Phone: (800) 841-7197
Email:
info@extendfertility.com
Website:
http://www.extendfertility.com
Dr. Bradford Kolb is a reproductive endocrinologist and OB/GYN
at Huntington Reproductive Center in Pasadena, California CA
(USA).
REFERENCES:
U.S. Census Bureau. “Distribution of Women by Average Number of
Children Ever Born, by Race, Age, and Marital Status.” Fertility
of American Women Current Population Survey (June 2000).
National Parenting Association. “Groundbreaking Study Exposes A
Crisis Among Successful Women: The Survey Behind Sylvia Ann
Hewlett's ‘Creating a Life.’” National Parenting Association.
To request additional information on Mature Oocyte
Cryopreservation please:
Call Extend Fertility at: 800-841-7197 or email:
info@extendfertility.com
Extend Fertility, Inc.
329 Washington Street | Suite 200 | Woburn, Massachusetts MA
(USA) 01801
Phone: (800) 841-7197 | Outside U.S.: (617) 987-0506 |
Fax: (617) 987-2137
Home |
Site Map
| Email Us
|
 |
|
"I felt very
supported by the women at Extend. They were my partners
in this adventure and gave me the power to have more
choices in the future."
— Megan, Age 36
Extend Fertility Client
Seattle, WA
|
|
|
