Infertility Medications
Clomid
Clomiphene Citrate (Clomid) is a compound that is very similar in structure to estrogen. Clomid binds to estrogen receptors in the hypothalamus/pituitary, the part(s) of the brain that regulates ovulation. As a result, the brain releases follicle stimulating hormone (FSH) and luteinizing hormone (LH) hormones. These hormones stimulate follicular growth and egg maturation in the ovaries.
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Clomiphene citrate is administered orally in 50 mg increments (50, 100, 150) over five days.
The growth of the follicles is monitored using transvaginal ultrasound. Follicular monitoring is done on day 10 through day 13 of the menstrual cycle. The addition of an ovulation trigger may be used with Clomid when the follicles reach an optimal size. Patients are usually recommended to do timed intercourse or intrauterine insemination (IUI) after Clomid.
Pregnancy rates with Clomid range from 6-10% in most studies. Adding in IUIs in some cases may increase those pregnancy rates to 12-15%. An estimated pregnancy rate of 18-20% has been reported for certain patient populations using IUI with donor sperm. Of the pregnancies that result using Clomid, 85% will occur in 3 months.
Various other medications can be used with Clomiphene citrate. Among these are metformin, estrogen, and gonadotropins (injections).
Femara (Letrozole)
Letrozole is an aromatase inhibitor (blocks the peripheral conversion of androgens to estrogens), thus decreasing peripheral estrogen production. This decrease leads to the brain increasing its FSH stimulation to the ovary. It affects the development of follicles within the ovary. The mechanism of action is different from that of Clomid but can be very effective at causing 1-2 follicles to develop.
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Just like Clomid, Letrozole (also known as Femara) can be used in combination with intrauterine insemination (IUI) for higher pregnancy rates.
Letrozole is given in a dose increment of 2.5mg (2.5mg, 5 mg, 7.5mg) over 5 days. A midcycle follicular ultrasound assesses the follicle growth on days 10-13. The addition of an ovulation trigger may be used with Letrozole when the follicles reach an optimal size to ensure ovulation. Patients are usually encouraged to try timed intercourse or intrauterine inseminations. Other medications may also be used with Letrozole, such as metformin, estrogens, and gonadotropins (injections).
Pregnancy rates are similar to Clomid rates in timed intercourse cycles, IUI cycles, and donor sperm IUI cycles. However, Letrozole is being used more and more in our polycystic ovarian syndrome (PCOS) population to decrease the risk of ovarian hyperstimulation in a subset of patients.
Gonadotropins
Gonadotropins are hormone medications to stimulate the ovary to produce extra follicles and hence more eggs. Gonadotropins include follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones are the same hormones our brain sends to stimulate the ovary but are given in higher doses to encourage multi-follicular development.
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These injections must be used under the supervision of a doctor to prevent harmful side effects such as ovarian hyperstimulation (OHSS). The clinic provides detailed mixing and administration instructions.
Lupron
Lupron (leuprolide acetate) is an injectable medication administered daily just below the skin (subcutaneously or SQ) in the cycle before the controlled ovulation stimulation (COS) cycle and throughout the COS cycle. Lupron initially causes the release of LH from the pituitary gland in the brain. The LH is essentially emptied from the pituitary gland so that during the COS cycle, the higher levels of estrogen from the multiple growing follicles will not cause an LH surge and premature ovulation.
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In other words, Lupron prevents the LH surge and premature ovulation. When the follicles have reached an optimal size, and the estrogen levels are appropriate, you will be instructed to administer an ovulation-trigger injection called hCG. After ovulation is triggered, there is no further need to continue Lupron.
Side effects while taking Lupron include hot flashes, vaginal dryness, and headaches. If these side effects occur, they will usually resolve after it is discontinued.
GnRH Antagonists
These medications directly block the release of LH from the pituitary gland.
Like Lupron, these medications prevent the LH surge and premature ovulation. However, GnRH antagonists are taken for fewer days. They are administered daily when follicles reach a certain size or when estradiol reaches a certain level. Common antagonist medications are Cetrotide and Ganirelix.
Human Chorionic Gonadotropin
hCG has a chemical structure that is very similar to LH, which triggers ovulation and egg maturation. hCG is also the hormone produced naturally from the chorionic villi and placenta during pregnancy. A pregnancy test is essentially a test for the presence of hCG. hCG triggers ovulation when your follicles are ready. hCG stimulates LH receptors in the ovarian follicles just like the LH surge does in a natural cycle. Patients are provided individualized instructions on the dose and timing of hCG.
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hCG is often referred to as the “trigger” shot. hCG causes the final maturation of the eggs in the follicles and will cause ovulation or “release” of the eggs from the follicles approximately 38 to 40 hours later. Brand names include Novarel, Pregnyl, and Ovidrel. The generic hCG may be labeled as “Chorionic Gonadotropin.”
Lupron can also be used as a trigger shot, especially during IVF cycles in which there is a higher chance of hyperstimulation. Lupron will cause a surge of LH from the brain if the patient has been on GnRH antagonists. The LH surge causes the final maturation of the eggs in the follicles and will result in ovulation or the “release” of the eggs approximately 38-40 hours later.
In intrauterine insemination (IUI) cycles, insemination is scheduled for around the time of ovulation. For in vitro fertilization (IVF) cycles, the egg retrieval procedure is scheduled 36 hours after the trigger shot so that the eggs can be retrieved before ovulation.
Progesterone
Progesterone is naturally produced by the corpus luteum in the ovary after ovulation. In a natural cycle, the corpus luteum forms from the dominant follicle that released the egg with ovulation.
Progesterone produced from the corpus luteum stabilizes the uterine (endometrial) lining and keeps it healthy for an embryo to implant.
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In some cases, there is concern that a healthy corpus luteum may not be forming, and thus, lower progesterone may be produced. In this case, you may be instructed to take progesterone or hCG for luteal phase support.
In IVF cycles, some of the hormone-producing cells are removed from the inside of the follicles during the egg retrieval procedure. When the emptied follicles grow into corpora lutea, progesterone production may be compromised. Supplemental progesterone is used to support the lining of the uterus and prepare for implantation.
Progesterone can be administered as a vaginal insert, injection, or vaginal gel. Progesterone support is usually continued until 10-12 weeks of pregnancy in IVF cycles. Brand names include Endometrin and the vaginal gel Crinone.
Metformin – Glucophage
Metformin is an insulin-sensitizing medication used to counteract the effect of high circulating insulin levels (hyperinsulinemia). This elevated insulin level is associated with many diseases, including PCOS and insulin resistance. Metformin use has been associated with improved ovulation, weight loss, and decreased pregnancy losses.
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Metformin is effective when combined with a diet aimed at reducing insulin stimulation and a regular exercise program. Generally, metformin is used in combination with Clomid, Letrozole, or gonadotropins for successful ovarian stimulation.
Supplements
Vitamin supplementation is recommended for women attempting to conceive. You may use over-the-counter vitamins or prenatal vitamins as long as they contain 4mg of folic acid (newer guidelines from CDC increased folic acid from 1 mg to 4mg for pre-pregnancy). If you eat a well-balanced diet, you may prefer to take only the folic acid available in 1mg amounts.
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Consult your physician to find out which dose is correct for you.
Proper supplementation can significantly reduce the risk of neural tube defects. In addition to folic acid, women may consider prenatal vitamins that have DHA in them. DHA is a type of omega-3 fatty acid that also helps with the baby’s growth and development.
Lastly, in patients with age-related fertility decline, such as diminished ovarian reserve, some studies have shown a benefit in the number of eggs that may be stimulated and retrieved with Co-Enzyme Q 10 (Also known as CoQ10). CoQ10 is a substance in all cells that helps support mitochondrial activity and nutrients. The dosing of this has been controversial, but most fertility specialists will recommend a dose of 100-300 mg daily.
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