| In Vitro Fertilization (IVF) |
IVF involves collecting eggs and sperm from a couple and placing them together in a laboratory dish to fertilize outside the body, or in vitro. The fertilized eggs are then transferred several days later into the woman's uterus, or womb, where implantation and embryo development will hopefully occur just as in a normal pregnancy.
In vitro fertilization (IVF) is a four-stage procedure:
Your physician will want to maximize your chances for fertilization with each IVF attempt. To do so, ovarian stimulation will be used to produce multiple mature follicles, rather than the single egg normally developed each month. By having several mature eggs available for fertilization and transfer, it is hoped that at least one will result in pregnancy.
Various hormonal medications are used to stimulate the ovaries to develop as many ovarian follicles as possible. Follicles are fluid-filled sacs in which eggs grow to maturity. In addition to multiple follicle development, these medications are also used to control the timing of ovulation for egg recovery. Your physician may refer to this part of treatment as controlled ovarian hyperstimulation or superovulation.
Ovarian stimulation involves the use of follicle-stimulating hormone (FSH), the hormone necessary for multiple oocyte development. FSH is available in the form of Metrodin® (urofollitropin for injection), which was introduced in the United States in 1986. Metrodin® is known as a single-agent drug (containing only FSH) and belongs to a class of injectable drugs called gonadotropins. A gonadotropin is a hormon capable of stimulating the ovaries to produce eggs. One of the uses of Metrodin® is stimulating the development of multiple follicles in normally ovulating women undergoing assisted reproductive technologies.
Metrodin® is given by daily injection, and a response is generally evident after 5 to 7 days. The number of days and the dose will vary depending of follicle development. Your physician will monitor the ovarian response and time the administration of a second product, Profasi® (chorionic gonadotropin for injection, USP). Profasi® is comprised of a hormone called human chorionic gonadotropin (hCG), which causes the release of the egg in a woman in the same way that luteinizing hormone (LH) does in a normal cycle. It is usually administered after the last dose of Metrodin® to stimulate ovulation.
When discussing ovarian stimulation and ART with your physician, you may also hear the term pituitary desensitization. This is a medically induced condition that basically shuts down the pituitary gland. A desensitized pituitary gland minimizes the chance of a premature LH surge. Such a surge usually results in a cancelled ART cycle because the eggs necessary to continue the procedure cannot be retrieved.
Monitoring Ovarian Stimulation
Your physician will carefully monitor your response to Metrodin® by one or both of the following methods:
Ultrasound
Ultrasound is a technology that turns sound waves into pictures. Your physician will use a series of ultrasound scans to obtain an actual image of the ovaries and to regularly monitor follicle growth in the ovary beginning on or before Day 8 of the cycle. As follicles mature, they grow larger. Through ultrasound, your physician can observe follicle growth, number and size, and can determine follicle maturity and prepare for Profasi® administration.
Ultrasound may be performed abdominally or vaginally. The sound waves cannot be felt and the procedure is painless. There have been no reported harmful effects on developing eggs or on an early pregnancy.
Blood Tests
Another way your physician can monitor the response to Metrodin® is through the use of blood tests. Developing follicles secrete increasing amounts of the estrogen hormone, particularly estradiol (E2). Along with ultrasound, E2 levels are used to determine the optimal timing for the administration of Profasi®, which acts as an ovulatory trigger and is the final step leading to egg recovery. Your E2 level will be monitored by a blood test, usually every other day, starting on or before Day 8 of the cycle.
The next stage of therapy is called egg recovery or retrieval. Once Profasi® is administered, your physician will try to retrieve as many mature eggs as possible. Not all of the eggs retrieved will be used in the current IVF cycle.
There are two procedures commonly used for egg retrieval:
Laparoscopy
Laparoscopy is a surgical procedure that usually requires general anesthesia. Through the use of a laparoscope, a tube with a tiny camera on the end of it, your physician can view the pelvic structures, in particular the ovaries and fallopian tubes.
While the physician looks through the laparoscope, an aspiration system (which uses light suction to retrieve the egg from the follicle) is guided to the ovarian follicles, and their contents are removed and placed in a sterile test tube. The result is immediately examined under a special microscope. If an egg has not been retrieved, the process is repeated until an egg is recognized and until all the mature follicles have been aspirated.
Ultrasound-Guided Aspiration
Egg recovery may also be accomplished by ultrasound-directed procedures, which can be performed under local anesthesia. The ultrasound image allows for more accurate aspiration of the egg as the physician can guide a needle into each follicle and withdraw its contents. After egg recovery, the eggs are transferred to a sterile container to await fertilization.
About 2 hours before the eggs are retrieved, a semen sample is collected from the male partner and processed using various laboratory techniques. The goal is to obtain the strongest, most active sperm from the ejaculate. This process is called sperm washing.
Once mature eggs have been retrieved, the sperm and egg are placed together in the laboratory and incubated at a temperature identical to that of the woman's body. After about 48 hours, if the eggs have been successfully fertilized and are growing normally, they are ready to be transferred to the uterus. This is called embryo transfer.
Embryo transfer is not a complicated procedure and can be performed without anesthesia. The embryos are placed in a catheter (a tubular instrument ) and transferred into the uterus. Any embryos that have not been transferred can be frozen (or cryopreserved) and stored for future use.
Although your physician will try to fertilize all available eggs, not every resulting embryo will be transferred immediately. Each ART center will determine the "optimal" number of embryos for transfer for each patient. If there are any remaining embryros, they can be frozen through a process known as cryopreservation. Frozen embryos can be "thawed" and used at a later time. Once embryos are frozen and stored, most will remain unchanged for long periods of time. About two-thirds of embryos will survive the process of freezing and thawing.
An advantage of cryopreservation is that the likelihood of pregnancy may be improved. This is because the future transfer can be performed during a normal ovulatory cycle. The possible future transfer of cryopreserved embryos adds to the success rates of IVF and may lower the cost, as well. This is because the first few steps in ART therapy (ovarian stimulation, egg recovery and fertilization) don't have to be repeated.
IVF offers hope for many couples. Because it was the first assisted reproductive technology, it has the most experience behind it - about 15 years. The most recent reports indicate that the success rates (in terms of deliveries per retrieval) have risen from 16.9% in 1992 to 18.8% in 1993. This means there are more than 18 deliveries for every 100 patients who undergo egg retrieval. Some IVF programs have now achieved a 30% success rate in terms of deliveries per IVF cycle. Keep in mind the chance for a normal fertile couple to achieve pregnancy in any given month is about 25%.
One of the major benefits of IVF is the ability to know before transfer takes place if the male's sperm has actually fertilized the eggs. If fertilization fails to take place (as may happen in some cases of male infertility), changes can be made in the semen processing or fertilization conditions during a future attempt to create an embryo.
Another benefit of IVF is embryo transfer to the uterus. Because fertilized eggs are placed directly in the uterus, the woman doesn't need to have functioning fallopian tubes.
It has been shown that women under 40 years of age undergoing IVF have a substantially higher success rate than women over age 40. Therefore, one of the limitations of IVF is a low success rate in women over age 40. This is believed to be due to the quality of oocytes in older women.
Oocyte Donation
An encouraging alternative for older infertile women or those lacking ovarian function is the use of donor oocytes. This procedure involves using the eggs of a donor after stimulation of the donor's ovaries. The eggs are fertilized with sperm from the recipient's male partner and the embryos are transferred to the uterus of the recipient.
A couple may also choose to use oocyte donation if the female partner has a genetic disorder that might be passed on. Additionally, those with congenital abnormalities or those previously treated for certain types of cancer are also candidates.
Who Are the Donors?
Oocyte donation programs may use two types of donors:
Patients who have produced a large number of follicles for an ART procedure may be asked if they are willing to donate unused oocytes. Alternative sources of donor oocytes are close friends or relatives who undergo ovarian stimulation in order to help the recipient or women who agree to become egg donors.
Success Rates With Oocyte Donation
No longer is age or ovarian status always a barrier when it comes to treating infertility. ART with oocyte donation is one of the most successful treatment programs for infertility. Pregnancy rates as high as 38.1% per retrieval have been reported. Some 2,776 ART procedures using donated oocytes were carried out in 1993, with 895 resulting pregnancies and 716 deliveries. The success rate in terms of deliveries per retrieval was 30.5%.
You should discuss with your physician any medical, ethical or legal issues that you may have concerning this procedure.