IVF or in-vitro fertilization was first performed in 1978 in UK, resulting in the birth of a healthy baby boy, since then more than one million babies have been born using this technique. Over the years, IVF is improved and increasingly able to deal with more serious infertility problems, many of which were once thought untreatable. Although IVF is not a “cure-all” solution, it revolutionizes our approach in treating infertility. In-vitro fertilization literally means “eggs fertilization with sperm outside the mother’s body (in laboratory)”. These are five phases of IVF:
Phase 1: Ovarian Stimulation
Women has thousands of follicles (fluid-filled sacs) in their ovaries, inside each follicle is an ovum (egg). When everything is normal, a follicle (and an ovum) will reach maturity. The first IVF method relied on the natural cycle of follicles, which was inefficient due to the fact that premature ovulation can happen before the ovum is collected, sometimes the doctor also fail to retrieve a healthy egg. Later method involves the use gonadotropin drugs, which allow doctors to improve the IVF efficiency by inducing the production of multiple mature follicles. There are two types of drugs used:
• Drugs with equal parts of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
• Drugs that is consisted of only FSH
These drugs can trigger the growth of many mature ovarian follicles and the doctor will observe the women’s development with blood hormone testing and ultrasound. Each developing follicle produces estrogen and the hormone induces the endometrium growth (uterus lining). However, the high level of estrogen can force the pituitary gland to trigger ovulation prematurely, resulting in higher rate of IVF cycle cancellation. Doctors often use these drugs to reduce the probability of cancellation:
• GnRH antagonists (such as Antagon and Centroride).
• GnRH agonists (such as Synarel and Lupron).
GnRH agonists are used one week before the menstrual period. Because women may conceive spontaneously at this phase, women with Lupron are recommended to use contraception.
About one week after the patient is given Lupron, she may experience a regular menstrual period. The presence of cysts and the condition of ovaries can be known at this stage with an ultrasound examination. In a few cases, there are still empty follicles from the previous menstrual cycle and they may influence how a woman respond to FSH. If blood tests and baseline ultrasound are normal, then she will be given an instruction on what dose of medication she should take and when she should return for another exam.
Patients will be given Lupron continuously to prevent the eggs from released prematurely before the stimulation phase ends. In a normal treatment, they may get daily injection for almost two weeks before the follicles are mature. The final injection of chorionic gonadotropin is given once the follicles are more than 20 mm in diameter. The injection will trigger the final maturation, which results in ovulation (the release of egg). Ovulation often happens in less than two days after the injection. If the doctor chooses to use GnRH antagonists, the cycles are quite different. It is given a few days after the injection of gonadotropins and many doctors also use GnRH antagonists when some follicles have reached 15 mm in diameter. GnRH anatagonists can prevent the pituitary from releasing LH, hours after the administration. Although the medication is proven to be effective in IVF procedures, statistics show that implantation rate in IVF cycles is lower when women are given this medication.
Phase 2: Oocyte Retrieval
IVF is often performed in doctor’s office. Some IVF programs are performed exclusively in hospitals. IVF performed in doctor’s office can be beneficial, because the physician and the nurse can become more familiar with the patient. Often the more relaxed atmosphere in a doctor’s office encourages better communication between patient, doctor, embryology staff and the nurse. However, people who also have significant medical issues (such as severe pulmonary disease and cardiac disease) should undergo IVF in the hospital, which can reduce the risk of complications.
Many women are slightly more nervous before the oocyte retrieval procedure, however it is often thought to be more bearable than tests leading up to IVF. Patients will be in light conscious intravenous sedation condition when the egg is collected using the needle guide adapter, which is assisted with vaginal ultrasound probe. The embryologist will inspect the fluid containing the eggs with a microscope. Both the ovum and the sperm will be mixed in a small plastic dish and incubated for about 4 days.
Phase 3: Embryo Culture
One day after the eggs are collected, patients can learn about the amount of viable eggs, mature eggs usually have a diameter of more than 17 mm. Generally, about 75% of mature eggs can be fertilized, however when we consider the attrition rate in each IVF phase, the figure is actually much lower than that. Three days after the eggs are collected, embryos will form and some of them will be selected for transfer. If a blastocyst transfer is planned, the step may be performed after five days.
The embryologist will make a recommendation on the number of embryos that should be transferred. Although some embryos are not transferred, they actually of excellent quality and they could be preserved in liquid nitrogen for future uses. So when the selected embryos fail to develop, the patient doesn’t need to undergo the whole IVF process. Poor-quality embryos are discarded as they won’t survive the preservation process anyway.
Phase 4: Embryo Transfer
This is among the most critical phases, healthy embryos are transferred using a method that is similar to IUI. If it is performed in doctor’s office, the transfer can be assisted with abdominal ultrasound to allow the embryos to be placed accurately on the uterus. Patient is also asked to drink a lot of water and keep a full bladder during the actual procedure. It will allow doctor to see the transfer more clearly.
Phase 5: Pregnancy
Supplemental progesterone (suppositories and shots) are given two weeks after the transfer. If low level of estrogen is detected, estrogen supplement may also be given as well. It is also the time for blood pregnancy test, if the result is positive, the test will be repeated every two days until high HCG level is observed. After a few months, ultrasound exam is performed to detect the presence of cardiac activity. The positive result confirms the successful outcome of the entire IVF procedure and the patient is referred to a gynecologist for prenatal care.