Normally ovulating women mature only one egg each month. In order to obtain multiple eggs for In Vitro Fertilization, women are given a series of fertility medications to stimulate more eggs to mature. In egg donation cycles, it is also important to synchronize the egg maturity with the maturing of the recipient's endometrial (uterine) lining.
Egg donors are given the same fertility medications as those undergoing ovarian stimulation for IVF. The sequence, dosage and schedule for each donor will be carefully planned by the physician and nurse coordinator, and a specific calendar will be set up to guide the donor throughout this process.
In order to produce multiple eggs, donors are given a series of medications. The fertility medications serve to first ready the body for ovarian stimulation, and then prompt the ovaries to produce multiple eggs for donation. A single dosage of a final medication will trigger actual ovulation so that eggs can be retrieved.
Birth control pills
Use of birth control pills is one of the major ways we synchronize the egg maturation in egg donors with the uterine lining maturation of the recipient. The donor will start birth control pills, usually on Day 3 of her menstrual cycle and may take them for 21 to 35 days total, depending on where the recipient is at in her cycle. Of course, the donor will be initially evaluated to make sure she has no medical reasons why she cannot take birth control pills and will be advised of minor side effects such as spotting, breast tenderness, or headaches.
Approximately 14-21 days after beginning birth control medication, donors will begin to take a medication called Lupron (Leuprolide acetate). Lupron is a known as a gonadotropin releasing hormone (GnRH) agonist. This means that the medication acts similarly to the body's natural GnRH hormone produced in the brain.
In a normal menstrual cycle, the body's GnRH stimulates the brain's pituitary gland to produce two gonadotropin hormones. These are: luteinizing hormone (LH) and follicular stimulating hormone (FSH). FSH is responsible for the development of mature, egg-containing follicles in the ovaries, and for the production of estrogen, the hormone necessary to build the uterine lining. Luteinizing hormone (LH) normally triggers the release of the egg during ovulation and releases other hormones necessary for pregnancy.
How Lupron works
Lupron serves to 'turn off' the pituitary gland's production of LH and FSH. The purpose of this is to make sure that the body's own LH is not activated too quickly, leading to premature ovulation that would interfere with the stimulation and egg recovery process. Approximately 7-10 days after starting Lupron, there will be a drop in the body's estrogen level. This will in turn lead to 'withdrawal bleeding' (vaginal bleeding). The birth control pills will be discontinued at this point but the donor will stay on Lupron until two days prior to the egg retrieval procedure.
How Lupron is taken
Lupron is an injection given daily, for a period of three weeks. It is given under the skin (subcutaneously) with a very small needle.
During the time that the donor is taking Lupron, we will closely monitor her treatment and evaluate her response to the medication.
Lupron side effects
There are virtually no significant side effects to Lupron. Occasionally there may be a gap of several days between the time that birth control pills are completed and stimulation medications are started, and during this time the donor may experience a mild headache, which can be treated with Tylenol. Other far less common side effects include temporary fluctuations in mood, hot flashes or nausea.
A recent alternative to Lupron is being used in many donor cycles, particularly if a donor has shown a tendency to develop Ovarian Hyperstimulation in the past. In this protocol, a medication called Ganirelix (a GnRH antagonist) is used in place of Lupron. Ganirelix produces the same desired effect as Lupron: stopping premature ovulation. The avoidance of Lupron in these cycles allows us to use Lupron later in the cycle along with a much smaller dose of hCG (see below) to trigger final maturation of the eggs. This lowers the risk of development of Ovarian Hyperstimulation Syndrome.
In conjunction with Lupron, donors will begin taking a type of medication called Gonadotropins, which will serve to stimulate the egg follicles to produce multiple eggs. These medications, which include Follistim, Menopur and Gonal-F, all contain an active form of the FSH, the main hormone responsible for producing mature eggs in the ovaries.
How Gonadotropins work
Gonadotropins are identical to human pituitary FSH, so raising these levels in the bloodstream by taking daily injections will overcome the ovary's natural feedback processes and lead to the maturing of extra eggs along with the one egg that would have naturally been matured. These eggs come from a pool of resting eggs that would have naturally undergone programmed cell death (atresia) during that cycle.
How Gonadotropins are taken
As with Lupron, Gonadotropin medications are given by injection under the skin (subcutaneously) with a very small needle. Medication is taken daily for nine or more days until ultrasound and blood testing determine that a given number of mature eggs have developed in the ovarian follicles.
Gonadotropin side effects
Patients commonly experience a mild version of a condition called Ovarian Hyperstimulation Syndrome (OHSS), marked by abdominal bloating and/or pain. This generally stops in a few days. In order to minimize OHSS symptoms, we try to use the lowest dose of Gonadotropins possible.
Severe Ovarian Hyperstimulation Syndrome, affecting approximately 1-2% of IVF stimulation patients, is characterized by more significant ovarian enlargement accompanied by abdominal fluid, possible shortness of breath and possible decreased urination. These symptoms can be treated with pain medications, IV fluids and bed rest. In some cases, an outpatient procedure may be performed to remove excess intra-abdominal fluid. In very rare cases, treatment may require hospitalization.
Other unwanted effects for donors could include pregnancy, including multiple births. Donors are therefore advised to not be sexually active during a treatment cycle, from one week prior to retrieval procedure to the beginning of the menstrual period.
Human Chorionic Gonadotropin (hCG)
Throughout the Gonadotropin treatment, donors will be monitored by ultrasound and blood testing to assess egg follicle growth. When monitoring indicates that follicles have developed sufficiently, an egg retrieval procedure will be scheduled and donors will receive one injection of a medication called Human Chorionic Gonadotropin (hCG). This is a hormone produced by the placenta, the human organ responsible for nourishing the fetus.
How hCG works
This hormone serves to fully mature the eggs so that they are ready for retrieval. hCG triggers the release of the egg (ovulation). Because ovulation usually occurs 34-42 hours after hCG injection, patients are instructed to receive the injection exactly 36 hours prior to the scheduled egg retrieval.
hCG side effects
Side effects from hCG are generally very uncommon but may include headache, irritability, fatigue, swelling and pain at the site of injection. These side effects may last one to seven days but virtually always go away on their own.