In Vitro Fertilization, IVF Clinic Bellevue, Seattle Washington
IVF is a “first line” treatment for many of the conditions that cause infertility. It is an accepted medical procedure and thousands of healthy babies have been born as a result of in vitro fertilization. Before IVF came into routine clinical use, many couples, especially those with male factor infertility or tubal disease, had no hope of creating a genetically related child.
IVF is divided into several steps, which are discussed below:
and monitoring the development of ovarian follicles
(each follicle contains one egg).
To control the timing of egg maturation, and to increase the chance of collecting more than one egg, fertility drugs are commonly used in in vitro fertilization cycles. The use of fertility drugs is not mandatory as techniques are available to collect only one or two eggs from a natural cycle (no medications). However, it is known that with increased numbers of eggs being collected, there is a greater chance of ultimate success. Natural cycles typically produce lower pregnancy rates than stimulated cycles. The major benefit of natural cycles is reduced cost.
Fertility drugs used in In Vitro Fertilization
The fertility drugs commonly used for the in vitro fertilization process include one or more of the following:
- Lupron (leuprolide acetate)- Lupron is a GnRH agonist that works in the hypothalamus to suppress pituitary and ovarian function. In one protocol, the drug is typically administered late in the cycle before ovarian stimulation, and continues until the eggs are mature. Lupron shuts down the patient's reproductive hormone system and eliminates a potential premature LH surge. When the LH surge occurs in a natural non-stimulated cycle, it initiates ovulation. Lupron prevents the LH surge in stimulated cycles thus preventing ovulation before the eggs are retrieved. In select cases, Lupron is administered in dilute form early in the cycle, known as the mircroflare protocol, to assist in the production of eggs. There is a characteristic "spike" in FSH levels when Lupron therapy first begins.
- Ganirelix, Cetrotide-These drugs are GnRH Ganirelixists and, like Lupron, prevent premature ovulation. Lupron is a GnRH agonist and works at the hypothalamus while Ganirelix and Cetrotide are GnRH Ganirelixists, which block the action of GnRH on the pituitary gland. They cause a "more complete and quicker" suppression of reproductive hormones and for this reason are administered for a shorter period of time. It is sometimes necessary to use more FSH in Ganirelix/Cetrotide cycles.
- Pure Gonadotropins, Follicle Stimulating Hormone- Follistim, and Gonal-F are common fertility drugs that are administered for approximately 10 days commencing on day two or three of the patient's cycle. The particular drug and dosage varies between patients depending on the patient's age, weight, and previous response to fertility drugs. Other gonadotropins containing both FSH and LH include Repronex, Bravelle, and Menopur. These may also be used to promote egg development.
- The administration of FSH in ART cycles is termed controlled ovarian hyperstimulation. This process causes the production of several eggs that will be harvested for the in vitro fertilization process. Ultrasound and estradiol measurements are used to monitor the development of the follicles. Patients must come to our office several times during their stimulation for these tests. When the follicles measure 18 mm in mean diameter, and the estradiol levels are appropriate, ovulation is triggered by the use of recombinant Ovidrel (recombinant LH) or hCG.
- Recombinant LH (Ganirelix)- Ganirelix may be used with FSH to induce ovulation.
- hCG, (Pregnyl, Novarel) –hCG is commonly utilized to trigger ovulation after the administration of gonadotropins or in patients with severe hormone deficiencies. This medication induces ovulation 36 hours after its administration in a “properly primed” follicle. Because of this phenomenon, egg retrieval usually occurs between 34-35 hours after the administration of LH.
- Ovidrel is a genetically engineered pure form of hCG, which is also used to induce ovulation.
- Progesterone- Progesterone is administered to support the development of the endometrium, which must thicken and become more vascular to support the developing embryo and fetus.
- Estrogen- Estrogen may be administered late in the IVF cycle, usually by skin patches, in order to support the development of the embryo and stabilize the uterine lining.
- Aspirin- Aspirin is prescribed to all patients after egg retrieval. It acts as a blood thinner, increasing the blood supply to the lining of the uterus where implantation is to occur.
- Acupuncture- Acupuncture has been shown to increase the blood supply to the ovary and endometrium, and may be prescribed in difficult cases. Increased blood supply to the ovary means increased delivery of fertility drugs and theoretically a better ovulation induction. With increased blood supply to the endometrium, the chance of implantation of embryos is increased.
eggs from the ovary
After successful super ovulation, and the administration of hCG, the eggs are collected from the ovaries using a procedure called ultrasound-guided transvaginal oocyte retrieval. This is performed in the operating room of the Washington Center for Reproductive Medicine IVF Center infertility clinic under conscious sedation. The anesthesiologist starts an IV line and pain medication is administered to make the patient comfortable.
A minor surgical procedure is performed where an ultrasound probe is inserted into the vagina and by the use of a needle the follicles are aspirated. The embryologist receives the eggs in the follicular fluid and identifies and separates the oocytes.
During the surgical portion of the procedure, we strive to make patients experiences as pleasant as possible. Usually patients leave the office within one to two hours following egg retrieval and are prescribed pain medicine to deal with the mild discomfort associated with the egg retrieval process. Postoperatively, we keep in telephone contact with patients to make sure they are doing well. Dr. Kustin is available by telephone on a 24-hour basis should patients need his advice postoperatively.
IVF- Collecting sperm
The male will be asked to abstain from ejaculation for two to three days before the egg retrieval so that we might obtain an optimal specimen. Before initiating an in vitro fertilization cycle, the sperm is thoroughly analyzed. Many tests of sperm function are performed to analyze the likelihood that the sperm will be able to fertilize eggs.
In cases where there is a question about the ability of the sperm to fertilize eggs (such as severe male infertility), we offer intracytoplasmic sperm injection (ICSI). By the use of this technique, one sperm is injected directly into the egg, providing normal embryonic development. (Please see the section on ICSI.) We have a very comfortable facility (the Marilyn Monroe Room) where the male provides a fresh specimen on the day of his partner's egg retrieval.
In conventional IVF, the eggs and sperm are placed together in a special culture fluid and kept incubated in our laboratory to allow fertilization to occur. We maintain an extremely rigorous quality assurance program in our laboratory so that the appropriate conditions to facilitate fertilization and cell division are always present. After cell division, the fertilized eggs are known as embryos. In cases of male infertility, one sperm may be injected directly into each egg (ICSI).
IVF Combining eggs and sperm in the laboratory
Embryology is an exacting science and we constantly strive to use state of the art techniques. Our IVF laboratory is classified as a "clean room". Advanced air filtration techniques are used so that air borne toxins such as automobile emissions and other fumes that inhibit the growth of the embryo are extracted. With circulating air of the highest quality we are able to ensure the highest success rates for our patients. We were the first clinic in the Northwest to invest in this technology and to offer it to our patients. We are committed to constantly strive to offer the latest developments.
We also understand that the latest technology is only as good as the people who work with it. A highly experienced embryologist, with many years experience in IVF and ICSI, runs our IVF laboratory. The staff is meticulous in their work and is committed to providing the best results possible for our patients. They realize that patients are concerned about the welfare of their embryos and, together with the clinical staff, will keep you abreast of day-to-day progress in the laboratory.
IVF- Transferring embryos to the uterus
After several days of culturing embryos
in the laboratory, normally developing embryos are
transferred into the uterus using a small catheter
inserted through the cervix. Embryos are usually transferred
on the third day after egg retrieval when they are
at approximately the 8-cell stage. In some cases,
the embryos are biopsied at this stage with removal
of one cell for analysis by preimplantation
genetic diagnosis (PGD). This enables the embryos
sex to be determined as well as the presence of certain
chromosomal or genetic problems.
In certain cases, if the embryo quality on the third day is excellent, we may recommend that the embryos be cultured for a further two to three days until they develop into a blastocyst. The benefits of blastocyst transfer has a higher pregnancy rate because only the best embryos survive to the blastocyst stage. Apart from the higher pregnancy rate, the benefits of blastocyst transfer lie in the fact that fewer embryos need to be transferred, therefore, diminishing the risk of multiple pregnancies.
Embryo transfer remains the most crucial part of the IVF process and it is Dr. Kustin's philosophy that this process must be undertaken with the utmost care. The patient is prescribed a mild sedative and is asked to attend the clinic with a full bladder so that an abdominal ultrasound can be used to visualize the correct placement of the embryos in the uterus, thus facilitating the highest pregnancy rate.
At the time of embryo transfer, it is usual to transfer up to four embryos (this depends upon several factors such as patient age and diagnosis), while saving other embryos for cryopreservation (freezing). Following embryo transfer, the patient is asked to rest in our comfortable recovery area for two hours and then asked to return home for three days of bed rest.
The number of cryopreserved IVF cycles that can be attempted in the future is determined by the number of embryos resulting from the stimulated cycle. The woman's "hormonal cycle" is synched to match the events that occur in a normal pregnancy cycle using medications, such as progesterone. This insures that the endometrium thickens and becomes more vascular enabling it to accept and support a developing embryo. In general, success rates using cryopreserved embryos are lower than when using "fresh" embryos.
Following embryo transfer, support of the initial growth of the embryos is paramount and hormonal treatment with progesterone, either by injection or vaginal cream, is mandatory. Estrogen may also be prescribed via a patch. Twelve days after embryo transfer, the patient is asked to attend the clinic for a pregnancy test.
Assisted Reproductive Technologies