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In vitro fertilization (IVF), sometimes called "test tube baby," is
a process that was first successful in England in 1978. Initially IVF was used
to treat only infertility caused by blocked falllopian tubes. Today, IVF has
evolved to being an effective treatment for all causes of infertility for which
simpler treatments have not been successful or are not an option. In fact, IVF
success rates of 50 percent or more can be seen in women under 35 years old.
The IVF procedure
In natural conception, an egg is released from the ovary into the fallopian
tube in the middle of a menstrual cycle. The egg is fertilized in the fallopian
tube. The fertilized egg then begins to divide in the fallopian tube, thus
becoming an early embryo. After being in the fallopian tube for several days the
embryo enters the uterus where it will implant.
IVF can be thought of as a bypass of the fallopian tubes. The IVF process
involves stimulating the ovaries with "fertility shots" to make
multiple eggs. Development of the eggs is monitored with blood tests and vaginal
ultrasound examinations. Once the eggs are "mature," they are removed
from the ovary through the vagina with a very minor procedure for which the
woman receives a mild anaesthetic. After the eggs are retrieved, they are put
into a petri dish and exposed to the man's sperm. By the next day, the eggs can
be examined to see if they have been successfully fertilized by the sperm. The
fertilized eggs are left in the petri dish for several days during which time
they begin to divide and become early embryos (as occurs in the fallopian tubes
during natural conception). After several days in the petri dish, embryos are
placed in the woman's uterus with a simple procedure that is generally no more
uncomfortable than a Pap test. If there are extra embryos that are viable, they
can be cryopreserved (frozen) for future use.
IVF laboratory procedures
Several types of IVF laboratory procedures are performed at the Cleveland
Clinic. The full spectrum of laboratory procedures includes:
- Fertilization with intracytoplasmic sperm injection (ICSI). ICSI is
used when insufficient sperm are available, sperm parameters are
compromised, or when previous fertilization methods have failed. Through
ICSI, even the most severe cases of male infertility -- very low numbers of
sperm or even no sperm in the ejaculate -- can be successfully treated with
IVF. In these cases, sperm often can be obtained from the testes or
epididymis by a minor surgical procedure.
- Assisted hatching. In order for an embryo to implant in the uterus
it must break through the zona pellucida, a thin "shell"
surrounding the embryo. The process of the embryo breaking through the zona
pellucida is called "hatching." Hatching can be aided by making a
tiny opening in the zona pellucida just prior to transferring the embryo to
the uterus. In the Cleveland Clinic IVF program, assisted hatching is
routinely performed on all embryos before they are transferred to the
uterus. The procedure seems to be particularly helpful for older women and
patients who have had previous IVF cycles in which the embryos failed to
implant.
- Embryo freezing. Surplus embryos not transferred to the patient's
uterus may be able to be frozen ("cryopreserved") for future use
by the couple. In the Cleveland Clinic IVF program, cryopreservation of
embryos is carried out either on the third day after egg retrieval when the
embryo is between 6 and 8 cells in size or on the fifth or sixth day after
egg retrieval (the "blastocyst" stage). Only embryos of good
morphology are cryopreserved since only they have potential to become
successful pregnancies in the future.
- Co-culture. Following fertilization the embryo and the endometrium
(lining of the uterus) are advancing each day getting ready for the
implantation process. The embryo has to keep up with the developing
endometrium in order to implant and create a viable pregnancy. Embryos from
some patients need extra help growing in the culture dish. For these
patients, embryos are grown on a layer of special cells, to further mimic
the normal environment in the fallopian tube. The growth factors secreted by
these cells can help embryos continue to divide and activate their genetic
material, hopefully enhancing the embryos' chance of successfully implanting
in the uterus. This treatment option technique has been used quite
successfully at the Cleveland Clinic IVF laboratory for improving clinical
outcomes in patients with repeated IVF failures, for patients of advanced
age, and for patients with poor quality embryos.
- Preimplantation genetic diagnosis (PGD). In 2002, the Cleveland
Clinic IVF program launched its PGD program and is one of the only clinics
in the region offering this technology. PGD involves removing a single cell
from a developing embryo at the eight-cell stage. The cell is then analyzed
and embryos with normal chromosome content are selected for transfer to the
woman's uterus. For patients with sex-linked diseases or single gene
disorders, genetic screening at the preimplantation embryo stage is a
powerful technique. In these patients, IVF coupled with embryo screening can
greatly reduce the risk of offspring being affected by the disease.
Other patients that could potentially benefit from this new technology are
patients with recurrent pregnancy loss and older patients undergoing in vitro
fertilization. Abnormal chromosome number ("aneuploidy") is a frequent
cause of loss and/or failure to achieve pregnancy after an in vitro
fertilization cycle. The age-related decline in female fertility has been
partially attributed to an increase in the rate of aneuploidy in embryos
generated by these women. The percentage of embryos with abnormal chromosome
number ranges from 25 percent to as high as 50 percent in women over 40 years
old. Application of PGD screening for aneuploidy for selected patients can,
therefore, potentially increase their chance for a successful pregnancy.
- Oocyte/ovarian tissue cryopreservation.
The Cleveland Clinic IVF laboratory is becoming increasingly active in the
area of freezing eggs and ovarian tissue. Work in this area is still very
preliminary and the potential for successful pregnancies resulting from frozen
eggs and/or ovarian tissue is very small at this time. As the success rate
increases in the future, these procedures will offer some very exciting
opportunities including:
--Freezing of ovarian tissue for women in their 30s who want to delay child
bearing.
--Freezing of ovarian tissue for women undergoing chemotherapy or radiation in
order to preserve their childbearing capabilities. This is being done for
selected patients currently.
--Freezing of extra eggs obtained during IVF cycles. Many couples feel more
comfortable with frozen eggs than with frozen embryos. This procedure is
currently being offered to selected couples who are going through the IVF
procedure but do not want all of the eggs fertilized.
Where do I go for the IVF procedure?
In January of 2000, the Cleveland Clinic opened a state-of-the-art
Infertility and IVF Center in the Cleveland Clinic's Beachwood facility. All IVF
procedures for the entire Cleveland Clinic Health System are now done in this
new suburban facility. This facility is designed to be extremely patient
friendly, while providing the highest level of patient care. In addition, the
center includes sophisticated laboratories for continuing IVF research.
To maximize patient convenience, the new Cleveland Clinic Infertility and IVF
Service is organized in a "hub and spoke" fashion. The Beachwood
Fertility Center, located off the Cedar Road exit of Interstate 271, serves as
the hub for Infertility and IVF Services. This center offers all fertility
services from initial consultation through in vitro fertilization. A major spoke
of the infertility/IVF service is located at the Cleveland Clinic downtown
campus. At this spoke, all infertility services are available except for the
actual IVF procedures of egg retrievals and embryo transfers. Initial
infertility consultations and some fertility testing can be arranged at smaller
hubs located at Fairview Hospital and the Cleveland Clinic Strongsville Family
Health and Surgery Center. In addition, arrangements have been made with
facilities in Canton, Ohio, Erie, Pennsylvania and several other cities to
provide convenient monitoring for patients who are undergoing treatment with
fertility shots and/or IVF.
Who are the physicians involved with the IVF program?
James Goldfarb MD was recruited to become Director of the in vitro program
starting in January 2000. Dr. Goldfarb has devoted his career to IVF; his
program was responsible for the first IVF birth in Ohio (1983) and the World's
first IVF/surrogate birth (1986). Dr. Goldfarb brought his entire physician team
with him. Each member of the team, Cynthia Austin, MD, Hanna Lisbona, MD, and
Barry Peskin, MD, has at least 10 years experience treating infertility and
performing IVF. This physician team see patients at the Beachwood Fertility
Center. Drs. Marjan Attaran, Tomasso Falcone, and Jeffrey Goldberg have all been
involved with IVF at the Cleveland Clinic for more than 6 years and see patients
at the other facilities. These three physicians perform IVF procedures for their
patients at the Beachwood Fertility Center.
Who is in charge of the IVF laboratory procedures?
The laboratory procedures described in this handout are performed by a staff
of skilled embryologists and andrologists. Nina Desai, PhD, serves as director
of the IVF Clinical and Research Laboratories. Dr. Desai is well known for her
work on co-culture, growth factors, embryo morphology, and the development of
successful clinical IVF laboratories.
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