In Vitro Fertilization (IVF) and Related Procedures
Blastocyst Transfer and Culture
A blastocyst is an embryo that has developed two different cell types and also contains a central fluid-filled cavity. The outer cells, called the trophectoderm, will become the placenta, and the inner cells will become the fetus. Blastocyst formation in the human usually occurs on the 5th day after fertilization. By the end of the sixth day, the blastocyst should hatch from its outer shell (the zona pellucida), and within another 24 hours the hatched blastocyst begins to implant in the lining of the mother's uterus.
Over the first two decades of experience with in vitro fertilization (IVF), embryos were routinely cultured for two to three days in the laboratory, and then transferred to the uterus. This is quite different than when embryos normally enter the uterus from the fallopian tube (day 5 or 6). During a natural cycle, 2-3 days after conception, embryos are typically found in the fallopian tubes and may not be ready to enter the uterus. Recently, laboratory culture conditions have been improved so that embryos resulting from an in vitro fertilization cycle can develop to the blastocyst stage in the laboratory, and therefore be replaced into the uterus at the more "natural" time, Day 5 or 6 after fertilization.
The additional benefit of waiting longer to transfer embryos is reducing the number of embryos needing to be transferred to result in a viable pregnancy. While extended culture of embryos will not improve the quality of an abnormal or poor quality embryo, by culturing embryos to the blastocyst stage there is more opportunity to choose the healthiest ones for transfer, thereby reducing the number transferred with the result of limiting the risk of a multiple gestation pregnancy.
Electroejaculation
Electroejaculation is a procedure that is performed when a medical or psychological condition prevents a male from ejaculating. During an electroejaculation procedure, the doctor inserts an electrical stimulation probe into the rectum. The doctor controls the amount of electrical stimulation delivered so that an ejaculation occurs. This can be done either in the office or in the operating room with anesthesia, depending on the sensory status of the patient. Alternative methods of sperm retrieval, including testicular sperm extraction, are recommended when penile vibratory stimulation and rectal probe ejaculation are unsuccessful or unavailable.
Embryo Cryopreservation
Also known as “embryo freezing,” embryo cryopreservation is a method used to preserve embryos where they are stored at very low temperatures. Embryo cryopreservation allows the use of a woman’s own embryos for subsequent treatment cycles. A frozen embryo transfer cycle does not require use of follicle stimulating hormones and egg retrieval is not needed, thereby significant reducing the cost and invasive care as compared to an in vitro fertilization cycle using newly created embryos. Embryos may be stored indefinitely and there appears to be no increase risk of birth defects from cryopreserved embryos. However, embryo cryopreservation is not without risks, as almost 40 percent of cryopreserved embryos do not survive the freezing and thawing process. The pregnancy rates associated with frozen embryo transfer cycles are slightly lower than with fresh transfer. This may be caused by additional stress placed on the embryo during the cryopreservation and thawing process or simply by the selection of the most promising embryos for fresh transfer. See also Vitrification for a description of the laboratory technique involved in cyropreservation.
In Vitro Fertilization
In vitro fertilization (IVF) is the process of retrieving eggs and sperm and manually fertilizing them in a laboratory dish outside the womb. Healthy embryos are then transferred back into the uterus with the goal of implantation and further embryo development. IVF is performed by physicians who specialize in reproductive medicine and have received additional education and training in the evaluation and treatment of male-factor and female-factor infertility.
IVF was originally developed in the early 1970’s to treat infertility caused by blocked or damaged fallopian tubes. Louise Brown, born in the United Kingdom in 1978, was the first baby conceived with the help of IVF. She made headlines again in 2006 when she went on to naturally conceive a healthy baby of her own. The technology of IVF and advanced reproductive technologies has improved markedly since then; and over 3 million babies have been born since Louise Brown with the help of IVF.
IVF involves four steps:
Stage I: Ovarian Stimulation and Monitoring - In order to maximize the patient's chances for successful fertilization, a patient undergoing IVF usually take hormones in the form of injections to increase the number of eggs produced in a given month. Frequent monitoring is performed to continuously follow a woman's ovarian response, allowing the physician to adjust and time medication dosage appropriately.
Stage II: Egg (Ovum) Retrieval - Under sedation, the reproductive specialist extracts mature eggs via ultrasound guidance. Egg retrieval is a minimally invasive procedure that normally takes less than 15 minutes. Patients typically can resume normal activity within the next day.
Stage III: Culture and Fertilization - Embryologists use high-power microscopes and steady precision to fertilize the eggs with sperm in the embryology laboratory. At times, the sperm are released on top of the oocyte to fertilize it. In other cases, especially when there are less than one million living sperm, intracytoplasmic sperm injection (ICSI) is used where a single sperm is microinjected directly into the cytoplasm of the ovum.
Stage IV: Embryo Transfer - A fertility specialist will transfer the minimum number of healthy and mature embryo(s) back into the uterus, with the goal of implantation in the uterine wall. This procedure usually does not involve any sedation. The physician will use ultrasound to guide a small catheter through the cervix and deposit the embryo(s) in the uterus. The embryo transfer procedure takes only a few minutes and recovery time is less than a day. Remaining viable embryos can be cryopreserved and used for subsequent transfer cycles. A pregnancy test is performed 11 days after the embryo transfer to evaluate whether implantation successfully occurred.
Intracytoplasmic Sperm Injection (ICSI)
Intracytoplasmic sperm injection (ICSI) is a type of in vitro fertilization procedure in which a single sperm is injected directly into the egg. It is a revolutionary technique that provides effective treatment options for situations where few sperm are available for treatment or there are concerns about fertilization. Because some male factor infertility issues may be caused by chromosomal abnormalities in the male partner, it is important for those diagnosed with male factor infertility to have a thorough examination with a reproductive endocrinologist or urologist specializing in infertility.
Oocyte Cryopreservation
Oocyte cryopreservation is a new and exciting experimental procedure that may help a woman preserve her reproductive potential. Women who may benefit from this procedure include
1) Those women who are at risk of becoming sterile due to chemotherapy, radiotherapy or removal of their ovaries;
2) Women who are choosing to delay reproduction, for personal or career reasons, while attempting to maintain their reproductive potential;
3) Women who have a family history of endometriosis, early menopause or premature ovarian failure
Oocyte cryopreservation involves the extraction of a woman’s unfertilized eggs from her uterus. The process is the same as stage I and II of an in vitro fertilization cycle whereby the patient takes injectable hormones to increase oocyte production in order to obtain a number of eggs during the retrieval phase [see also In Vitro Fertilization]. The retrieved oocytes are then slowly cooled to a freeze and stored at extremely low temperatures. When the woman becomes ready to attempt pregnancy, a fertility specialist team will thaw the stored oocytes, attempt to fertilize the eggs and transfer subsequent embryos. See also Vitrification for a description of the laboratory technique involved in cyropreservation.
Ovum Donation
More than 150,000 women in the United States are unable to conceive children because of ovarian problems. Many women do not produce eggs, or have had their ovaries removed, have had radiation therapy or chemotherapy for cancer that destroyed their ovarian function, or have dysfunctional ovaries, and are no longer producing high quality eggs. Other women have deferred pregnancy until their late thirties or forties. Since the ovaries age at such dramatically different rates in different women, while some conceive quickly, others are no longer able to conceive using their own eggs and require donated eggs to conceive. Egg donation is a treatment that involves receiving from an appropriate donor. The donated eggs are then fertilized using male partner sperm or donor sperm, and results in the embryos being then transferred into the female recipient’s uterus.
Egg donors are typically healthy women between ages 21 and 32 who have been thoroughly screened to ensure they are physically healthy and fully aware of the donation process. Egg donors take injectable hormones for eight to ten days to increase their egg production. The eggs are retrieved transvaginally, using an ultrasound to guide the procedure. The recipient of the donated eggs usually takes hormones to synchronize her cycle with the donor's cycle and to prepare her uterus to receive the embryos, and thus enhance the likelihood of implantation occurring. In some programs, more than half of women undergoing ovum donation conceive and deliver.
Preimplantation Genetic Diagnosis - (PGD)
Traditional methods used to identify genetic disease require prenatal diagnosis through chorionic villus sampling (CVS) or amniocentesis, followed by potential termination of the pregnancy if the fetus is found to be affected. Recent scientific advances now allow the diagnosis of some genetic disorders before pregnancy is established using a technique known as pre-implantation genetic diagnosis (PGD). PGD combines the technology of in-vitro fertilization (IVF) with new molecular biology techniques.
A single cell is removed from an eight cell embryo in a procedure called an "embryo biopsy." This single cell is sent to a lab that specializes in detecting genetic abnormalities. If the embryo is found not to contain the genetic disorder being tested for, the embryo may be considered for transfer.
It is important to speak to both a genetic counselor and the treating physician to fully understand the accuracy rate of PGD.
Vitrification
Vitrification is a specialized laboratory technique that is used to cryopreserve, or freeze, human eggs (oocytes) or embryos. This is a rapid freezing technique that prevents formation of water crystals during the freezing process. Water crystals are a major cause of cell damage during the cryopreservation process. Vitrification also minimizes chemical toxicity by exposing the eggs or embryos to the cryoprotectants for a much shorter duration than what has been known as a "slow freeze" technique.
While more IVF clinics are moving towards use of vitrification, it is important to note that any eggs or embryos frozen using a slow freeze technique can continue to be stored and thawed for future use.
