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Embryo Transfer
Embryo transfer typically occurs 3 to 5 days
after egg
retrieval. The procedure usually takes just 10 to 15 minutes, with an
additional 30-minute rest period. Sedation is not required but the patient is
required to have a mildly full bladder so the physician can visualize the
uterus using an abdominal sonogram.
The physician prepares the patient by
inserting a speculum to widen the cervix, and swabbing it with a non-toxic
solution. The embryologist loads the selected embryo(s) into a specially
designed embryo transfer catheter, a very soft, flexible plastic tube. When
the patient is appropriately prepared, the embryologist delivers the catheter
containing the embryos to the procedure room.
During the procedure, the physician gently
threads the catheter through the cervix and into the uterine cavity. Once
complete, the embryologist examines the catheter to confirm that all embryos
were deposited into the uterus. Patients are required to rest for
approximately 30 minutes before being discharged. A small amount of watery
discharge is likely post-transfer; this is the fluid that was used to clean
the cervix, and is not the culture medium that was transferred with the
embryos.
Blastocyst Culture and Transfer
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A human blastocyst on day five of
development (in vitro) |
The first human pregnancy after in
vitro fertilization (IVF), reported in 1976 by Robert Edwards and Patrick
Steptoe, was achieved after replacement of a single blastocyst
in the uterus. Although that pregnancy was ectopic (occurring outside the
uterus) and was not delivered, it demonstrated the feasibility of extended
embryo culture and replacement at the blastocyst stage.
In the years that followed, blastocyst transfer was virtually abandoned
because it was very difficult to obtain blastocysts in culture using the
available technology. It was also argued that reducing the time spent in
culture to a minimum may be beneficial to the embryo and improve pregnancy
results. However, in 1985, IRMS Scientific Director Dr. Jacques Cohen and his
colleagues at Bourn Hall Clinic in England reported the first successful
pregnancies after replacement of frozen-thawed blastocysts; this generated
renewed interest in blastocyst culture and replacement. The recent
re-emergence of this technology is a result of major advances in culture
techniques and media preparations that more consistently support the
development of early human embryos for five to six days.
At the blastocyst stage, an embryo contains approximately 100 cells. It has
developed to the point at which, following hatching from the zona pellucida,
its implantation is imminent. The cells on the outer layer of the blastocyst
eventually form the placenta, the sac that protects and nurtures the
developing fetus during pregnancy, while the fluid-filled inner core of the
blastocyst contains cells that will form the fetus. Blastocysts are easily
recognizable, allowing for relatively easy selection by the embryologist. By
contrast, embryo selection during earlier cleavage stages is more difficult
and requires more experience.
IRMS and many other IVF programs reserve blastocyst transfer for patients
who are under the age of 40, produce 10 or more eggs and are at risk for high
order multiple pregnancy. The eggs must be fertilized normally and exhibit
good development during the first three days in culture. It is becoming
increasingly evident that many patients and embryos do not benefit from this
treatment modality. For instance, patients with poor embryo morphology are
encouraged to have replacement of day 3 embryos with assisted
hatching and fragment
removal, since these embryos do not tolerate extended periods in culture.
Those over 40 years of age may be more likely to achieve an ongoing pregnancy
after preimplantation
genetic diagnosis pgd, and replacement of embryos that appear free of genetic
abnormalities that can affect implantation and miscarriage rates.
Studies at IRMS and elsewhere indicate that pregnancy rates for blastocyst
transfer are similar to those resulting from day 3 embryos. However,
implantation rates may be higher. Also, since replacement is limited to two
blastocysts, high order multiple pregnancies with three or more fetuses are
largely avoidable – as they are when day 3 replacements are limited to two
embryos in patients with very good pregnancy prognosis.
Articles with additional information on
Blastocyst Culture can be found in our research
articles page.
Disadvantages of Blastocyst Transfer
While nearly 80% of fertilized eggs survive
through the third day in culture, even under ideal circumstances, only about
30%-40% become well-structured blastocysts by the fifth day. Although embryos
are carefully examined on day 3 and selected for extended culture, there are
no guarantees that they will continue to develop. As a result, a couple with
viable embryos on day three could end up with no blastocysts for replacement.
Moreover, there may be fewer embryos available for cryopreservation and the
freeze/thaw process is less successful for blastocysts than those frozen at
earlier stages of development.
There is also concern regarding the sex ratio among children born after
blastocyst transfer. At least one large study suggests that more males than
females are born. Another possible risk of this treatment is the apparent
increase in the incidence of monozygotic (identical) twinning, and the
associated obstetric complications of such pregnancies.
Transfer Guidelines
The transfer of more than one embryo
increases the likelihood of establishing a pregnancy. However, the risk of
multiple pregnancy increases as more embryos are replaced. Factors affecting
the likelihood of pregnancy (and multiple pregnancy) include the patient’s
age, embryo quality, the specific cause(s) of infertility and a couple’s
reproductive history.
Couples have an opportunity to discuss their personal preferences related to
embryo transfer with their physician prior to the start of the IVF cycle. At
the time of the embryo transfer, the physician will discuss the quality of the
embryos and the probability of pregnancy and multiple pregnancy. When embryo
quality is high, and in the absence of other considerations, we typically
transfer two embryos to patients under age 36, three embryos to patients
36-39, and four embryos to patients older than 39.
High quality embryos that are not transferred may be cryopreserved.
Approximately 25% of all IVF patients have embryos available for cryopreservation.
However, the success rates for cryopreservation are greater for younger
patients; therefore, IRMS rarely freezes embryos for patients age 40 and
older.
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