In-Vitro Fertilization (IVF) is an amazing advance in medical technology. The idea of human reproduction which occurs partly outside of a woman’s body is the stuff that science fiction writers dream about. Today this is our reality, and the procedure has helped countless couples who would otherwise be infertile become parents. It is not a simple course of action, however, as the science behind this methodology is both remarkable and complicated.
There are a few concepts and terms which are important to be aware of in order to understand how IVF medications work. The choice of medication, protocol, and the particular preferences of each reproductive endocrinologist are unique to each IVF cycle. This is why one woman’s experience at a fertility clinic may be completely different from another woman’s experience. Even if they are the same woman, and even if they are at the same fertility clinic.
Hypothalamus – Pituitary – Ovarian Axis (H-P-O Axis), or “How Babies are Made in Nature”
To understand how IVF suppression and stimulation medications work, we first need to see how a woman’s reproductive cycle functions without medical intervention. An organ found in the brain, called the hypothalamus, releases a hormone called Gonadotropin Releasing Hormone (GnRH). This GnRH stimulates the pituitary gland (also in the brain) to release other hormones called Gonadotropins (i.e. follicle stimulating hormone (FSH) and Luteinizing Hormone (LH)). These pituitary hormones travel through the blood stream and stimulate the ovaries to generate egg-containing follicles, which produce increasing amounts of estrogen. As estrogen levels rise, they first signal the pituitary to stop the release of Gonadotropins. But once estrogen levels rise to a certain level, the pituitary is triggered to release more Gonadotropins again. This results in ovulation. The now empty follicle becomes the corpus luteum, and begins to produce progesterone. Progesterone acts to nourish the uterine lining and prevent its breakdown. If an embryo, derived from a fertilized egg, implants into the uterine lining it will begin to produce the hormone Human Chorionic Gonadotropin (HCG), which maintains the integrity of the uterine lining and allows the pregnancy to continue. If there is no implanted embryo, all hormone levels begin to drop until the uterine lining is finally shed, marking the beginning of the next menstrual cycle.
In-Vitro Fertilization – overriding the reproductive hormone system in order to maximize ovarian response
The purpose of the medications involved in an IVF cycle is to encourage the ovaries to produce many more follicles than during a normal menstrual cycle. Lots of follicles mean lots of eggs which can be harvested, and for reproductive endocrinologists this is important to help improve the odds for a successful pregnancy. By using medications which mimic the effects of the naturally occurring hormones, the response of the ovaries can be influenced. There are 2 main protocols that are used in IVF – the “long protocol” and the “short protocol”.
The long protocol – downregulation / suppression
In some IVF protocols, the H-P-O Axis is disrupted completely in order to fully control the response of the ovaries. In the “long IVF protocol”, the response of the pituitary gland is blocked from functioning by GnRH agonists, like Lupron (injection) or Synarel (nose spray). This serves to “down-regulate”, or “suppress” the pituitary gland from its normal job of stimulating the ovaries. GnRH agonists are usually started in the menstrual cycle before the IVF cycle, and prevent the pituitary gland from interfering with the intended effects of the ovarian stimulation medications. GnRH agonists also prevent ovulation from happening before the time is right.
Some reproductive endocrinologists choose to have their patients take oral contraceptive pills (OCP) for a month or a few months before their IVF cycle begins. This is thought to help prevent Ovarian Hyperstimulation Syndrome (OHSS), a potentially life threatening complication to IVF where too many follicles are generated too quickly. Birth control pills are also used to help prevent ovarian cysts or a dominant follicle from forming, which can disrupt the IVF cycle.
After a menstrual bleed and the confirmation of pituitary suppression (which is confirmed with ultra-sounds and blood tests), the stimulation phase of the IVF cycle begins. Daily injections of medications which imitate the effects of Follicle Stimulating Hormone (called “FSH analogues”, such as Gonal-F, Puregon, Repronex, or Follistim) stimulate egg-containing ovarian follicles to grow en masse. Throughout the stimulation period, the growth and progress of the follicles is continuously monitored with ultrasound, and hormone levels are checked with blood tests. Most woman are stimulated for approximately 2 weeks until their follicles grow to a size where the eggs are mature and are ready to be retrieved from the ovaries.
The short protocol – The flare protocol
The short IVF protocol seeks to maximize the response of the ovaries without suppressing the function of the pituitary gland for weeks or months before the IVF cycle begins. In this protocol, medication to stimulate the growth of ovarian follicles (usually an FSH analogue) is administered at the beginning of a new menstrual cycle. To prevent a spontaneous ovulation, pituitary suppression medications are also administered at the beginning (GnRH agonists) or at the end (GnRH antagonists) of this ovarian stimulation phase. This protocol is also called the “flare protocol” because the initial dosage of GnRH agonist causes the pituitary to release an initial “flare” of FSH and LH, which “jump-starts” the ovarian stimulation. Ultrasound and blood tests monitor the growth and size of the follicles; once they reach maturity they are ready to be harvested from the ovaries.
IVF, Acupuncture and Chinese Medicine
Over the last few years, research has shown that acupuncture can help increase the success rates of an IVF cycle. Reasons for this may include increased blood circulation to the organs of reproduction, a sensitization of the body to IVF medications, and a reduction in stress. Please click here for more information about IVF acupuncture.
Because there hasn’t been very much hard research done to explore any interaction between herbal medicine and either GnRH agonists or FSH analogues, most reproductive endocrinologists prefer that women undergoing an IVF cycle do not take Chinese herbs (or, any herbal medicine) at the same time as medications. Since this is an extremely precise process, reproductive endocrinologists want to be able to eliminate as many variables as possible, and Chinese herbs (while perhaps being helpful) may interfere with the desired effects of the medications. However, Chinese herbal medicine can be used in the weeks and months before IVF medications begin, as part of pre-conception care and preparing your body for the IVF cycle. But in almost all cases in Vancouver, your fertility doctor will ask you to stop taking all herbal supplements before IVF medications begin.
