Injectable Fertility Medications
When are gonadotropins used vs. clomiphene?
Gonadotropins are injectable hormones used to treat infertility. These medications, including Follistim, Menopur, Bravelle and Gonal-F, all contain an active form of the FSH, the main hormone responsible for producing mature eggs in the ovaries.
Gonadotropins are often capable of inducing ovulation in women who have not had success with other fertility medications such as clomiphene and letrozole. By prompting the release of multiple egg follicles during the menstrual cycle, gonadotropins significantly increase the likelihood of fertilization and pregnancy. Like clomiphene, gonadotropins also help to regulate the menstrual cycle, so that ovulation is gauged more precisely. This in turn enables more successful timing of such fertility procedures as intrauterine insemination (IUI)
How do gonadotropins work?
Gonadotropins are identical to human pituitary FSH, so injecting them into the body will lead to stimulation of ovarian follicle growth. The stimulation of multiple follicles (i.e. the creation of multiple eggs) is the primary way to enhance fertility.
Gonadotropin medications are given by injection subcutaneously (i.e. under the skin with a very small needle). These medications can't be taken orally, as these protein hormones would be destroyed by the digestive system. Gonadotropins come in a powder form that is mixed with sterile water, or as pre-mixed cartridge that fits into a self-injection device. Medication is taken daily until it is determined that a given number of mature eggs have developed in the ovarian follicles.
We know that for many patients, the thought of self injection can be daunting. Before and throughout our patient's treatment cycle, our nurses provide hands-on clinics and phone or in-person assistance and encouragement at any time. Additionally, instruction videos are available on this website and through the pharmaceutical companies' websites.
Patients receive regular ultrasound exams throughout the treatment cycle in order to determine the number and size of egg follicles in each ovary and to ensure that the ovaries are receiving the proper level of stimulation. When it is determined that follicles have achieved an adequate size and the eggs within should be mature, patients receive an injection of hCG (human chorionic gonadotropin) also known as Ovidrel. This hormone initiates the release of the egg (ovulation) and the development of the corpus luteum, which will help the body to produce progesterone. Ovulation usually occurs approximately 38-44 hours after the hCG injection.
Cancellation of a gonadotropin stimulation cycle
Occasionally, a gonadotropin treatment cycle will need to be cancelled. After one has committed to course of treatment, this can be an extremely frustrating experience.
Cancellation may occur for any of the following reasons:
- Excessive follicle growth (concern for the development of ovarian hyperstimulation syndrome or excessive risk for multiple gestation is high)
- Premature, spontaneous ovulation
In the event of an unsuccessful cycle, physicians will often advise skipping a cycle before resuming treatment. While it can be very difficult to wait, a pause is sometimes necessary to allow the ovaries to recover their optimal level of responsiveness. This period of time can also be used for additional testing and to design a more optimal treatment plan for the next cycle.
Every patient responds differently to fertility medications, and it is helpful to know in advance that it may take two or more cycles to arrive at the right stimulation protocol.
Complications resulting from gonadotropin treatment
The two significant potential complications resulting from the use of gonadotropin stimulation are multiple gestation (twins or greater) and ovarian hyperstimulation syndrome.
The release of multiple eggs significantly increases pregnancy chances for many couples. However, this ovarian stimulation can also result in multiple pregnancies. The occurrence of twins is about 20% - 25% of the achieved pregnancies, and triplets about 5% of gonadotropin pregnancies. A multiple gestation of quadruplets or more is extremely uncommon.
Multiple gestation may be considered risky for the mother as well as for the growing embryos. In this situation, doctor and patient may decide to pursue a selective reduction, in which one or more of the fetuses are terminated to reduce the number down to twins. Selective reduction can be performed at 12-13 weeks of pregnancy and involves an injection of potassium chloride into the sac of the fetus to be terminated. It is conducted under ultrasound guidance. The fetus or fetuses will then be slowly resorbed over the next several weeks. While the procedure is considered very safe, there is about a 5% risk of miscarrying the remaining embryos. Because of the psychological difficulties in terminating a desired fetus, we very much want to avoid triplet or higher order pregnancies. For this reason, we are very cautious about recommending gonadotropin treatment to younger patients, especially those with a good prognosis for success.
Because of the short and long term risks associated with multiple gestation, Pacific Fertility Center does not typically recommend gonadotropins as a first-line treatment for women less than 35 years of age. With patients 35 years and older, and with proper monitoring, the odds of achieving a triplet or higher multiple gestation are much lower and therefore may be an acceptable risk after careful discussion and consideration with a patient's RE physician.
Ovarian hyperstimulation syndrome
The second complication associated with gonadotropin treatment is the possibility of an exaggerated response known as ovarian hyperstimulation syndrome. This condition is marked by abdominal bloating, nausea and diarrhea, and in more severe cases, symptoms including shortness of breath, difficulty with urination and chest pain. Treatment can be adjusted for those who hyperstimulate, by shortening the treatment cycle and decreasing medication. In 1% of cases, severe hyperstimulation may require intervention with intravenous fluids or removal of abdominal fluid so that fertility treatment may continue.
The symptoms of hyperstimulation begin about a week after ovulation. Mild cases last about a week and usually respond to hydration and careful monitoring. In general, ovarian hyperstimulation is highly unlikely, given careful monitoring of follicle development.
While concerns have been raised about use of fertility drugs and ovarian cancer risks later in life, research does not show any connection. Current research indicates that risk from gonadotropin treatment is low to non-existent; and long term studies have failed to show any increased risks.