Medication


Several medications are commonly used during in vitro fertilization (IVF) and other infertility treatments. The following is an explanation of the most common ones, their uses, side affects, and risks:


Gonadotropins, or injectable "fertility drugs" (Follistim®, Gonal-F®, Bravelle®, Menopur®): These natural hormones stimulate the ovary in hopes of inducing the simultaneous growth of several oocytes (eggs) over the span of 8 or more days. All injectable fertility drugs have FSH (follicle stimulating hormone), a hormone that will stimulate the growth of your ovarian follicles (which contain the eggs). Some of them also contain LH (luteinizing hormone) or LH like activity. LH is a hormone that may work with FSH to increase the production of estrogen and growth of the follicles. Luveris®, recombinant LH, can also be given as a separate injection in addition to FSH or alternatively, low-dose hCG can be used. These medications are given by subcutaneous or intramuscular injection. Proper dosage of these drugs and the timing of egg recovery require monitoring of the ovarian response, usually by way of blood tests and ultrasound examinations during the ovarian stimulation.


As with all injectable medications, bruising, redness, swelling, or discomfort can occur at the injection site. Rarely, there can be an allergic reaction to these drugs. The intent of giving these medications is to mature multiple follicles, and many women experience some bloating and minor discomfort as the follicles grow and the ovaries become temporarily enlarged. Up to 2.0 % of women will develop Ovarian Hyperstimulation Syndrome (OHSS) [see full discussion of OHSS in the Risks to Women section which follows]. Other risks and side effects of gonadotropins include, but are not limited to, fatigue, headaches, weight gain, mood swings, nausea, and clots in blood vessels.


Even with pre-treatment attempts to assess response, and even more so with abnormal pre-treatment evaluations of ovarian reserve, the stimulation may result in very few follicles developing, the end result may be few or no eggs obtained at egg retrieval or even cancellation of the treatment cycle prior to egg retrieval.


Some research suggested that the risk of ovarian tumors may increase in women who take any fertility drugs over a long period of time. These studies had significant flaws which limited the strength of the conclusions. More recent studies have not confirmed this risk. A major risk factor for ovarian cancer is infertility per se, suggesting that early reports may have falsely attributed the risk resulting from infertility to the use of medications to overcome it. In these studies, conception lowered the risk of ovarian tumors to that of fertile women.


GnRH-agonists (Leuprolide acetate) (Lupron®): This medication is taken by injection. There are two forms of the medication: A short acting medication requiring daily injections and a long-acting preparation lasting for 1-3 months. The primary role of this medication is to prevent a premature LH surge, which could result in the release of eggs before they are ready to be retrieved. Since GnRH- agonists initially cause a release of FSH and LH from the pituitary, they can also be used to start the growth of the follicles or initiate the final stages of egg maturation. Though leuprolide acetate is an FDA (Federal Drug Administration) approved medication, it has not been approved for use in IVF, although it has routinely been used in this way for more than 20 years. Potential side effects usually experienced with long-term use include but are not limited to hot flashes, vaginal dryness, bone loss, nausea, vomiting, skin reactions at the injection site, fluid retention, muscle aches, headaches, and depression.


No long term or serious side effects are known. Since GnRH-a are oftentimes administered after ovulation, it is possible that they will be taken early in pregnancy. The safest course of action is to use a barrier method of contraception (condoms) the month you will be starting the GnRH-a. GnRH-a have not been associated with any fetal malformations however you should discontinue use of the GnRH-a as soon as pregnancy is confirmed.


GnRH-antagonists (Ganirelix Acetate or Cetrorelix Acetate) (Antagon®, Cetrotide®): These are another class of medications used to prevent premature ovulation. They tend to be used for short periods of time in the late stages of ovarian stimulation. The potential side effects include, but are not limited to, abdominal pain, headaches, skin reaction at the injection site, and nausea.


Human chorionic gonadotropin (hCG) (Profasi®, Novarel®, Pregnyl®, Ovidrel®): hCG is a natural hormone used in IVF to induce the eggs to become mature and fertilizable. The timing of this medication is critical to retrieve mature eggs. Potential side effects include, but are not limited to breast tenderness, bloating, and pelvic discomfort.


Progesterone, and in some cases, estradiol: Progesterone and estradiol are hormones normally produced by the ovaries after ovulation. After egg retrieval in some women, the ovaries will not produce adequate amounts of these hormones for long enough to fully support a pregnancy. Accordingly, supplemental progesterone, and in some cases estradiol, are given to ensure adequate hormonal support of the uterine lining.


Progesterone is usually given by injection or by the vaginal route (Endometrin®, Crinone®, Prochieve®, Prometrium®, or pharmacist-compounded suppositories) after egg retrieval. Progesterone is often continued for some weeks after a pregnancy has been confirmed. Progesterone has not been associated with an increase in fetal abnormalities.


Side effects of progesterone include depression, sleepiness, allergic reaction and if given by intra-muscular injection includes the additional risk of infection or pain at the application site. Estradiol, if given, can be by oral, trans-dermal, intramuscular, or vaginal administration. Side effects of estradiol include nausea, irritation at the injection site if given by the trans-dermal route and the risk of blood clots or stroke.


Oral contraceptive pills: Many treatment protocols include oral contraceptive pills to be taken for 2 to 4 weeks before gonadotropin injections are started in order to suppress hormone production or to schedule a cycle. Side effects include unscheduled bleeding, headache, breast tenderness, nausea, swelling and the risk of blood clots or stroke.


Other medications: Antibiotics may be given for a short time during the treatment cycle to reduce the risk of infection associated with egg retrieval or embryo transfer. Antibiotic use may be associated with causing a yeast infection, nausea, vomiting, diarrhea, rashes, sensitivity to the sun, and allergic reactions. Anti-anxiety medications or muscle relaxants may be recommended prior to the embryo transfer; the most common side effect is drowsiness. Other medications such as steroids, heparin, low molecular weight heparin or aspirin may also be included in the treatment protocol.


Purchasing


Medication can be purchased at most pharmacies, however, it is best to choose one that routinely supplies fertility products. There are wide variations in price and it is best to obtain quotes from several stores in your area or talk with your physician regarding the pharmacy(ies) he recommends. You must also be absolutely sure that the pharmacy you choose will carry a backup supply of all products you are taking. If the doctor decides to increase your dosage it is essential that you obtain the additional medication on the day needed.


It is also very important to purchase hCG (human chorionic gonadotropin) well in advance of when you will need it. We recommend that you keep an additional vial on hand in the event you break the first. The injection of hCG must be given at the precise time prescribed or your treatment could have to be cancelled.


Recently, there has been discussion about purchasing products from outside of the United States. While these products can be less expensive, they are not subject to the same rigorous quality control standards as US product. There is little control over their storage and distribution and quality can vary significantly from vial to vial. Radical changes in temperature can alter the pharmacology of fertility medications rendering them inactive. For these and other reasons, we strongly recommend US approved products.


The average cost of medication for an in vitro fertilization (IVF) cycle is generally between $2,000 and $3,000. Medication does vary by patient need and physician recommendation. You and your physician will work together to decide which medication best suits your particular situation and if you may have insurance benefits available to help offset some of the cost.