IN VITRO FERTILIZATION IVF is the treatment of choice in cases of tubal disease, pelvic adhesions, severe male factor, and advanced endometriosis. IVF is also the last option when other therapies have failed. The word "in vitro" means "outside of the body". In vitro fertilization means fertilizing the egg outside of the body. In this method, the ovaries are stimulated with injectable medications to produce multiple eggs. Once they reach maturity, the eggs are aspirated through the vagina under ultrasound guidance and IV sedation. The eggs are then inseminated or injected with the sperm, and the resulting embryos are typically cultured for 5 days, the length of time it normally takes an embryo to travel from the tube into the uterus. Finally, two embryos (blastocysts) are transferred into the uterus via a soft catheter. The remaining embryos can be frozen for future use. For more detail of the most popular IVF protocols please read on: THE LUPRON PROTOCOL The classic IVF protocol involves the use of Lupron to suppress the pituitary before starting ovarian stimulation. Pituitary suppression is important for recruitment of multiple follicles. By desensitizing the pituitary to signals from the brain, Lupron blocks the natural tendency of the brain to allow only one dominant follicle to grow in each cycle. The Lupron IVF protocol spans about 2 months and can be illustrated by the following diagram: Menses Menses HCG Retrieval Transfer |
 Menstruation starts. Baseline labs such as FSH can be drawn on day 3. Birth control pill is used to suppress the pituitary and to resolve any residual ovarian cyst from previous cycles. The pill also allows flexibility in IVF scheduling. Women who start menses at different times can have their cycles synchronized by the pill in order to start IVF treatment as a group. A trial transfer is performed during the pill cycle to detect any potential difficulty during transfer. A soft transfer catheter is threaded into the uterine cavity to map the cervix and the uterus to ensure a smooth embryo transfer at the end of the IVF cycle. Lupron, an injectable medication, is started near the end of the pill cycle to further suppress the pituitary. The pill is eventually discontinued while Lupron is continued into the next phase to maintain pituitary suppression. Ovarian stimulation is initiated once there is sufficient suppression of the pituitary, as evident by a low estradiol level and quiet ovaries on the sonogram. The injectable medications used to stimulate the ovaries (Bravelle, Follistim, Gonal-f, Repronex) are actually LH and FSH, the same hormones normally produced by the pituitary. Close monitoring of the ovaries with blood works and sonograms is essential during this period to ensure optimal egg development and avoid complications. Human Chorionic Gonadotropin (HCG) injection is given when the follicles reach mature sizes. HCG induces the eggs to undergo the final maturation. It also causes the eggs to be detached from the wall of the follicles to facilitate their removal. Egg retrieval is performed about 36 hours after the HCG injection. The procedure takes 20 minutes and is conducted under IV anesthesia. A long needle is introduced into the pelvic space through the vagina under ultrasound guidance. After their aspiration, the eggs are inseminated or injected with the sperm in the same day. Embryo culture typically takes 5 days after the day of retrieval, the same duration an embryo takes to travel from the tube into the uterus under natural condition. Embryo transfer usually takes place on the fifth day of culture. Two best blastocysts are transferred into the uterus using a soft catheter. The procedure is similar to an IUI and requires no anesthesia. The remaining embryos can be frozen for future use. Endometrial support with progesterone and estrogen supplements is important to prepare the uterine lining for implantation. Progesterone is started on the day after the retrieval. Progesterone transforms the endometrium into a rich environment to prepare for embryo implantation. Progesterone is usually administered in oil form by deep muscular injection into the buttocks. Our patients use progesterone vaginally instead of by injections. Our decision to use vaginal progesterone is based on numerous scientific researches that showed the superiority of the vaginal route over the intramuscular or oral route in endometrial maturation. Estrogen is added back to maintain hormonal balance within the endometrium. The estrogen level usually drops after egg retrieval since many estrogen producing cells are also removed along with the eggs. Estrogen can be used as a patch or as tablets. Pregnancy test can be performed 12 days after embryo transfer. Once the test is positive, progesterone and estrogen are continued until the 11th week. A vaginal sonogram is performed at the 7th week to confirm the pregnancy.
Back to Beginning THE ANTAGONIST PROTOCOL The antagonists belong to a new class of medications that can be used for pituitary suppression in an IVF cycle. Unlike Lupron which takes at least 10 days for adequate pituitary suppression, these medications (Cetrotide, Ganirelix) take only 1 day for the same effect. One advantage of the antagonist protocol is fewer injections. Another advantage is that it may give better ovarian response in patients with low ovarian reserve (ie. women of age ≥ 38) due to absence of pituitary suppression prior to ovarian stimulation. A potential disadvantage of the antagonist protocol is the fact that some studies had found a slightly lower pregnancy rate than that of the Lupron protocol. In our experience, both protocols are equally effective. Every patient needs to be evaluated carefully to find the protocol best suited to her situation. Like the Lupron protocol, the antagonist protocol takes place over 2 months and is consisted of the following events: Menses Menses HCG Retrieval Transfer |
 Menstruation begins. Birth control pill is used to suppress the pituitary. A trial transfer is performed during this interval. Ovarian stimulation is initiated at the end of the pill cycle. Close monitoring is required. An antagonist (Cetrotide or Ganirelix) is started after 4-5 days of ovarian stimulation and is continued everyday afterward until the day of HCG. Pituitary suppression occurs 24 hours after the injection of the antagonist. Egg retrieval takes place about 36 hours after the injection of HCG. Eggs are inseminated or injected with sperm approximately 4 hours after retrieval. Embryo culture for 5 days. Embryo transfer of 2 blastocysts. Endometrial support using vaginal progesterone and topical estrogen. Pregnancy test 12 days after embryo transfer.
Back to Beginning THE MICRODOSE LUPRON FLARE PROTOCOL The microdose Lupron flare protocol is one of the most potent IVF protocols available. It has helped many women with poor ovarian reserves to conceive, and in our opinion, is the last resort before donor egg IVF. The protocol takes advantage of a special property of Lupron. When used in tiny amounts, Lupron stimulates the release of natural FSH from the pituitary for several days before exerting its suppressive effect. During this 'flare' period, the ovaries are stimulated by natural FSH. The subsequent addition of high doses of FSH from medications gives the ovaries maximum stimulation. The flare protocol can be summarized as below: Menses Flare effect HCG Retrieval Transfer |
 Menstruation begins. Birth control pill is used to suppress the pituitary for 10 to 14 days. Low dose types are preferable. A trial transfer is performed during this period. Minidoses of Lupron are started 3 days after the last pill to stimulate the pituitary to release its own store of FSH (the flare effect). After 5 days, Lupron begins to suppress the pituitary to prevent premature ovulation. Lupron is continued until the day of HCG. Ovarian stimulation is initiated 5 days after the last pill using the highest dose of FSH. The combination of natural FSH and medicated FSH gives the ovaries maximum stimulation. Close monitoring is required. HCG injection is used to mature the eggs. Egg retrieval takes place about 36 hours after HCG injection. Embryo culture for 5 days. Embryo transfer of 2 blastocysts. Endometrial support using vaginal progesterone and topical estrogen. Pregnancy test 12 days after transfer.
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