Clearly Reproductive Medicine changed forever after the birth of Louise Brown in 1978. The first US IVF baby did not arrive until 1980 with the birth of Elizabeth Carr. I was up on Capitol Hill a few years ago on a committee promoting insurance coverage for fertility care and Elizabeth was on the panel with me. I asked her why her Mom had remained in the hospital in Virginia for the entire pregnancy and why they had come down from Massachusetts. She explained that IVF was not available in Massachusetts at the time and may have even been illegal. Wow, how times have changed given that Massachusetts has mandated statewide fertility benefits now….But why not go home after the pregnancy was established? She told me that there were so many death threats against her parents that for their safety they stayed in the hospital under an assumed name. Hard to believe. I only rarely use an assumed name and usually it is while I am cruising websites to see how badly I am being bashed in cyberspace. Hey, in Hollywood people read their own reviews don’t they???
Over the next few blog posts let’s review IVF and discuss some hot topics. First we will start at the beginning with the basics. I will break this into 3 posts so those with short-attention spans will not be distracted like Dori in Finding Nemo. So as our book slowly rises in the Amazon.com ratings here is the Question of the Day from 100 Questions and Answers about Infertility…
50. What is IVF and how is it performed?
In vitro fertilization (IVF) was first successfully performed in Oldham, England, in 1978, resulting in the birth of Louise Brown. Since then, more than 1 million children have been born using IVF. The introduction of this technique completely changed—and greatly improved—our ability to treat even the most difficult cases of infertility, many of which were previously untreatable. Although it is clearly not a “cure-all” for infertility, IVF has revolutionized our approach to, and understanding of, the disease called infertility. IVF literally means “the fertilization of eggs with sperm in the laboratory.” An IVF cycle consists of several discrete phases, as detailed in the sections that follow.
PHASE 1: OVARIAN STIMULATION A woman’s ovaries contain thousands of fluid-filled sacs called follicles. Inside each follicle is an egg (or ovum). In a normal reproductive cycle, only a single follicle (and egg) reaches maturity. Although Louise Brown (the world’s first IVF baby) was produced in a natural cycle from a single follicle, this form of IVF is less efficient because it often leads to cancelled cycles as a result of premature ovulation prior to the egg collection or the failure to retrieve the single egg that is produced. The introduction of injectable gonadotropin drugs enabled physicians to increase the efficiency of IVF through the production of multiple mature follicles. Two forms of these medications are used: (1) drugs containing equal parts of the pituitary hormones follicle-stimulating hormone (FSH) or luteinizing hormone (LH) [Menopur] or (2) drugs containing only FSH (Bravelle, Gonal-F, Follistim). Both kinds of medications induce the growth of multiple ovarian follicles, so it is important to monitor the woman’s response to them carefully with ultrasound and blood hormone testing.
Estrogen is produced within each of the developing follicles and induces the growth of the lining of the uterus (endometrium). Unfortunately, the rise in estrogen can also induce the pituitary gland to prematurely trigger ovulation, resulting in the cancellation of an IVF cycle. Two other classes of drugs are used to reduce the chance of this problem occurring during an IVF stimulation: (1) GnRH agonists (such as Lupron and Synarel) and (2) GnRH antagonists (such as Centrotide and Antagon) . Lupron (or Synarel) is usually started 1 week prior to the woman’s anticipated next menstrual cycle. Given that a patient may have spontaneously conceived during this cycle, all women beginning Lupron are recommended to use a barrier form of contraception. Approximately 1 week after starting Lupron, the woman should experience a normal menstrual period. An ultrasound exam is performed at the start of this menstrual cycle to examine the ovaries and measure any existing cysts. In some cases, empty follicles from a previous cycle will persist and may influence the response to FSH. If the baseline ultrasound and blood tests are normal, then the patient receives instructions that afternoon as to when and what dose of medication she should take and when she should report back to the office for repeat ultrasound and blood tests.
Patients remain on Lupron to prevent the premature release of the eggs until the end of the stimulation phase. During a typical treatment cycle, they take daily injections for 9 to 12 days before the follicles reach maturity based on their ultra- sound results and blood hormone levels. Once the follicles reach a 20- to 24-mm diameter, the woman receives a final injection of human chorionic gonadotropin (HCG; Pregnyl, Profasi) at a precise time. This hormone serves as a trigger to incite the final maturation and release of the egg (ovulation). Ovulation typically occurs about 40 hours after this shot, so the egg collection procedure is scheduled for 34–36 hours after the HCG injection.
Cycles using GnRH antagonists are somewhat different. GnRH antagonists are started several days following the start of ovarian stimulation with gonadotropins. Most clinics add the GnRH antagonist once the largest follicle reaches a diameter of 14 mm. This medication effectively prevents the release of LH from the pituitary within hours of administration. Although many clinics have used GnRH antagonists successfully as part of their IVF stimulation protocols, some studies have demonstrated a trend towards decreased implantation rates in IVF cycles using this class of medications.