Medications Used Commonly in Fertility Treatments
Clomid
Clomiphene Citrate (Clomid) is a compound that is very similar in structure to estrogen. Because of this likeness, Clomid is able to bind to estrogen receptors in the hypothalamus (a part of the brain that regulates ovulation). This prevents the brain from seeing the negative signal from estrogen that is being released by the ovaries. As a result, the hypothalamus continues to stimulate the pituitary gland to make FSH and LH. These hormones stimulate follicular growth in the ovary.
Clomiphene citrate is administered orally in 50 mg increments (50, 100, 150) over 5 days. There are 2 common regimens for administration. Using the first day of menses as cycle day 1, Clomid is taken on days 3-7 or days 5-9. If follicular monitoring is used, an ultrasound is usually done on day 10 through day 12 of the cycle. The actual release of the follicle using HCG is timed when the follicles reach optimal size.
Pregnancy rates with Clomid range from 6-10% in most studies, however California IVF has experienced an average of 15 to 18% success with clomid and IUI. Pregnancy rates of 18-20% may be seen in certain populations of patients using IUI with donor sperm. Of the pregnancies that occur using Clomid, 85% will occur in 3 months. 99% will occur within 5 months. Treatment beyond 5 months is generally not seen as useful. There are various other medications that can be used with Clomiphene citrate. Among these are glucocorticoids like dexamethasone, estrogen, and metformin.
Letrozole is an aromatase inhibitor that can be used to affect the development of follicles within the ovary. The mechanism of action is different than that of clomid but can be very effective at causing multiple follicles to develop. Letrozole, or Femara, can be used in combination with intrauterine insemination (IUI) for higher rates of pregnancy.
Injectable Medications – gonadotropins
Gonadotropins are hormone medications to make the ovary produce extra follicles. Gonadotropins include follicle stimulating hormone (FSH) and luteinizing hormone (LH). There are several different brand names of medications available. Some of the more common ones include: Follistim, Menopur, and Gonal-F. These shots must be used under the supervision of a doctor to prevent harmful side effects such as ovarian hyperstimulation (OHSS). Detailed mixing and administration instructions are provided by the clinic. More information about injectable medications used for infertility treatments such as Follistim, Gonal-F, Menopur, Repronex, and Bravelle can be found here.
Lupron
Lupron (leuprolide acetate) is an injectable medication administered just below the skin (subcutaneously or SQ). It is a gonadotropin releasing hormone (GnRH) agonist which means it should stimulate the release of FSH and LH from the pituitary gland. What is seen, in actuality, is a paradoxical effect. After an initial stimulation of gonadotropin release, Lupron actually prevents release of FSH and LH. This is the desired clinical application of Lupron in an ovarian stimulation cycle. By preventing the pituitary gland from stimulating the ovaries with FSH, and preventing LH from triggering ovulation, the ovaries are effectively “turned off”. This allows your physician to control the amount of ovarian stimulation by the amount of medication you inject. Ovulation is also not likely without the surge of LH that is also blocked by Lupron. When the follicles are ready, ovulation can be triggered by giving HCG which has structural similarities to LH. After ovulation has been triggered there is no further need to continue Lupron.
A newer method of using Lupron instead of HCG to trigger ovulation has drastically reduced the risk of ovarian hyperstimulation (OHSS). Ovulation is prevented by using GnRH antagonists and Lupron is used to trigger ovulation and prepare for the egg retrieval procedure. While it is still possible to see OHSS, it is considered very rare. Measurements of AMH, or antimullerian hormone can be used to estimate the ovarian response to stimulation medications and gauge the risk of OHSS. Physicians use this information to strategize which methods of ovarian suppression is used.
Side effects you may experience while taking Lupron include hot flashes, vaginal dryness, and headaches. If these side effects occur, they will usually resolve after you start taking gonadotropins or estrogen.
Lupron is usually overlapped with birth control pills to help coordinate the treatment cycle and synchronize the growth of follicles. The usual starting dose for Lupron is 10 units (0.1cc). Once patients start gonadotropins, the dose of Lupron is reduced to 5 units (0.05cc). In a frozen embryo cycles, or egg donor recipient cycles, Lupron is used in combination with estrogen patches to prepare the lining of the uterus for the embryo transfer. There are other lupron protocols such as the lupron flare and micro-dose Lupron. Patients will have specific protocols assigned to them and outlined on their medication calendars. Be sure to follow your directions that are individually assigned to you.
GnRH Antagonists
These medications directly block the effect of brain’s stimulation of the pituitary gland. These medications are used to block ovulation and can act similar to Lupron. They can usually be taken for a shorter duration than Lupron. Great care must be taken to avoid accidental ovulation and timing of the medication is crucial. When used properly, these medications can provide equal prevention of ovulation as Lupron. Pregnancy rates are fairly equivalent for between the agonists and antagonists. Common antagonist medications are Cetrotide and Ganirelix.
Human Chorionic Gonadotropin (hCG)
HCG has a chemical structure that is very similar to LH (luteinizing hormone) which triggers ovulation. HCG is also the hormone produced by pregnancies from the chorionic villi and placenta. A pregnancy test is essentially a test for the presence of HCG. HCG can be used to trigger ovulation at the appropriate time when your follicles are ready. Patients are provided individualized instructions on the dose and timing of HCG. Using HCG to time treatments is often referred to as the “trigger” or “release” as it refers to the release of the egg from the wall of the follicle and sets up the timeline for fertility treatments such as IUI or IVF. Once HCG is given there will be no further Lupron or gonadotropin injections. Brand names include Novarel and Pregnyl, and Ovidrel. The generic hCG may be labeled as “Chorionic Gonadotropin”.
Progesterone
Progesterone is produced by the corpus luteum in the ovary after ovulation. During the retrieval process some of the hormone producing cells are removed from the inside of the follicles. As an attempt to support the lining of the uterus and prepare for implantation, supplemental HCG or progesterone is usually used. This supplemental HCG can further stimulate hormone production in the ovary and worsen the symptoms of ovarian hyperstimulation. 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. Progesterone in oil injections is the most common method for administering progesterone. The oil that holds the progesterone can make the shots uncomfortable. There are several tips that may help with your progesterone injections. Click for more information. There are various types of progesterone supplementation. 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 has been associated with many diseases including PCOS and insulin resistance. Metformin use has been associated with improved ovulation, weight loss, and decreased pregnancy losses. Common side effects include nausea, bloating, and diarrhea. Metformin is much more effective when combined with a diet aimed at reducing insulin stimulation and a regular exercise program. Dr. Zeringue specializes in working with insulin resistance and metformin. This experience is passed on to individual patients through education sessions designed to help people understand the underlying disorder. [More Information]
Supplements
Vitamin supplementation has long been recommended in women attempting to conceive. You may use over the counter vitamins or prenatal vitamins as long as they contain 1mg of folic acid. If you eat a well balanced diet you may prefer to take only the folic acid which is available in 1mg amounts. Some women may need to take 4mg of folic acid based on certain risk factors. Consult your physician to find out which dose is right for you. Proper supplementation can significantly reduce the risk of neural tube defects.
Supplements to Help Sperm
Many products are being advertised with the promise of helping sperm and improving pregnancy. Unfortunately, most of these claims are not back up by reputable data. There is a trend towards improvement with some of the anti-oxidant treatments but it is still too early to draw any firm conclusions. Some clinics are starting to use “Fertility Blend” more frequently. Caution should be used with all supplements as they are not regulated by the FDA and may contain ingredients which can actually hinder your efforts!
Herbal Supplements
Any substance labeled as “Dietary Supplement” is not regulated by the FDA. These supplements can contain all types of ingredients and do not have to have any proven effect. Unfortunately, the herbal industry is supported by billions of dollars and the advertising can be quite convincing. While there are likely some legitimate herbal supplements available, we encourage you to refrain from using them at this time. Some of these supplements may actually interfere with your fertility efforts. As more evidence is accumulated, fertility clinics will certainly embrace the help of anything that has a proven benefit. Many current medications are derived from herbs and natural compounds. After years of research they become labeled as medications and receive FDA approval. Your safety and success may be at stake.
Acupuncture and Chinese Herbal Medications
When used by a trained specialist, acupuncture and herbal medications prescribed by a specialist in Traditional Chinese Medicine specialist may have some benefit. California IVF works with acupuncturists with experience in treating fertility patients. Herbal supplements are often taken during the preparation phase of fertility treatments and discontinued at the time of the embryo transfer.
Additional information:
- Common fertility medications
- Pharmacies
- Injectable fertility medications
- Metformin
- Acupuncture and Herbal Supplements
More advanced forms of infertility treatments will rely on injectable medications. Most of these medications are given through subcutaneous injections. Subcutaneous injections use very tiny needles like diabetics use for their insulin. Many women are scared of the injections at first. Once the injections start, they are usually very easy to manage and most women will learn to self administer the injections. We provide a teaching session with our staff for the purpose of specifically reviewing the medications, injections, and your detailed treatment calendar. This page provides you with information about the various medications used during treatments.
COH cycles involve the use of injectable medications to guide the ovaries into making multiple follicles which contain eggs. Gonadotropins include follicle stimulating hormone (FSH) and lutenizing hormone (LH). There are several different brand names of medications available. Some of the more common ones include: Follistim, Repronex, Bravelle, Menopur, and Gonal-F. These shots must be used under the supervision of a doctor to prevent harmful side effects such as ovarian hyperstimulation (OHSS). Once the eggs have been grown to the appropriate size, ovulation can be triggered with HCG or Ovidrel. Intercourse or intrauterine insemination can be timed based on the time the medication was given to cause ovulation.
IVF uses the same medications as above, gonadotropins. Usually slightly higher doses of the medications will be used to produce more eggs. The medications are administered on a daily basis for about 10-14 days. Another medication must be used to block ovulation. Lupron, Cetrotide, and Antagon are common medications used to block ovulation. When the eggs are ready for collection, or retrieval, HCG or Ovidrel is used to make the final changes necessary in the ovaries and the egg collection is scheduled at a specific time. Progesterone is then administered to make certain the pregnancy receives enough progesterone. Progesterone can be administered by an injection or suppository. Injectable progesterone will be discussed below.
These medications are dispensed in several formats. Follistim and Gonal-F are available in multidose pens which offer the convenience of dialing a dose, pulling back on the plunger, and injecting the dose of medication. Gonal-F is also available in multidose vials that will allow several doses to be taken from one vial. Repronex, Menopur, and Bravelle are mixed from individual vials before dispensing. Then you will receive instructions on your dose and steps involved in the medication preparation process.
These medications are usually given as subcutaneous injections. These injections can be given anywhere on the body but the abdomen is the most common site used due to comfort and convenience. The injection site is usually cleaned with an alcohol wipe or cotton ball moistened with rubbing alcohol. The needle used for these injections is very small – usually about 1/2″ in length. The injections are placed just below the skin and are best given by pinching a roll of skin until it becomes uncomfortable. You will then inject the syringe into the skin you are holding. While keeping the skin pinched, inject the medication. Remove the needle and release the skin. Small bruises may form and some of the medications cause redness around the area of the injection site.
Lupron (leuprolide acetate) is an injectable medication administered just below the skin (subcutaneously or SQ). It is a gonadotropin releasing hormone (GnRH) agonist which means it should stimulate the release of FSH and LH from the pituitary gland. What is seen, in actuality, is a paradoxical effect. After an initial stimulation of gonadotropin release, Lupron actually prevents release of FSH and LH. This is the desired clinical application of Lupron in an ovarian stimulation cycle. By preventing the pituitary gland from stimulating the ovaries with FSH, and preventing LH from triggering ovulation, the ovaries are effectively “turned off”. This allows your physician to control the amount of ovarian stimulation by the amount of medication you inject. Ovulation is also not likely without the surge of LH that is also blocked by Lupron. When the follicles are ready, ovulation can be triggered by giving HCG which has structural similarities to LH. After ovulation has been triggered there is no further need to continue Lupron.
Side effects you may experience while taking Lupron include hot flashes, vaginal dryness, and headaches. If these side effects occur they will usually resolve after you start taking gonadotropins.
Lupron is usually overlapped with birth control pills to help coordinate the treatment cycle and synchronize the growth of follicles. The usual starting dose for Lupron is 10 units (0.1cc). Once you start your gonadotropins, you will decrease your lupron dose to 5 units (0.05cc). There are other lupron protocols such as the lupron flare so be sure to follow your directions that are individually assigned to you.
Lupron is usually given as a subcutaneous injection. These injections can be given anywhere on the body but the abdomen is the most common site used due to comfort and convenience. The injection site is usually cleaned with an alcohol wipe or cotton ball moistened with rubbing alcohol. The needle used for the injection is very small – usually about 1/2″ in length (27 gauge). The injections are placed just below the skin and are best given by pinching a roll of skin until it becomes uncomfortable. You will then inject the syringe into the skin you are holding. While keeping the skin pinched, inject the medication. Remove the needle and release the skin. Small bruises may form and the medication may cause redness around the area of the injection site.
These medications directly block the effect of brain’s stimulation of the pituitary gland. They can usually be taken for a shorter duration than Lupron. Great care must be taken to avoid accidental ovulation and timing of the medication is crucial. When used properly, these medications can provide equal prevention of ovulation as Lupron. Pregnancy rates are fairly equivalent for between the agonists and antagonists. These medications usually come packaged with everything you need. Cetrotide (cetrorelix acetate) will require that you mix all of the liquid in the syringe with the vial of powder that comes in the box. This mixing process requires that you change the needle prior to injection. Antagon (ganirelix acetate) comes in a prefilled syringe that can be opened and injected without mixing.
HCG has a chemical structure that is very similar to LH (luteinizing hormone) which triggers ovulation. HCG is also the hormone produced by pregnancies from the chorionic villi and placenta. A pregnancy test is essentially a test for the presence of HCG. Ovidrel is a synthetic form of HCG that acts the same way. HCG can be used to trigger ovulation at the appropriate time when your follicles are ready. You will be instructed on a time to take HCG. This is often referred to as “release” as it refers to the release of the egg from the wall of the follicle. The type of cycle and day of the procedure (oocyte retrieval or insemination) will determine what time the HCG injection will be given. Once HCG is given there will be no further Lupron or gonadotropin injections.
Ovidrel comes in prefilled syringes that can be injected without any mixing. HCG will require mixing based on the desired dose that your doctor has recommended. You will use a large needle (usually an 18 gauge needle) to inject 1 or 2 mL of liquid into the vial containing 10,000 units of HCG powder. You then pull up the prescribed amount into the syringe and change needles to the smaller needle. A 25 gauge 1 1/2 inch needle is commonly used for intramuscular injections while a 1/2 inch 25 gauge needle is used for subcutaneous injections. You will receive printed directions on how to mix and administer HCG.
The timing of the HCG injection (or Ovidrel) is very important as this initiates the preparation of the eggs within the ovary. Your printed instructions should contain the time that you are supposed to take the HCG and this will be related to the timing of any procedures such as an egg retrieval (oocyte pick up), or intrauterine insemination (IUI). Contact the clinic staff if there is any problem with the timing of your injection as this can affect the success of your treatment.
Progesterone is produced by the corpus luteum in the ovary after ovulation. During the retrieval process some of the hormone producing cells are removed from the inside of the follicles. As an attempt to support the lining of the uterus and prepare for implantation, supplemental HCG or progesterone is usually used. This supplemental HCG can further stimulate hormone production in the ovary and worsen the symptoms of ovarian hyperstimulation. To avoid this undesired effect progesterone can be administered. There are several forms of progesterone available including vaginal suppositories, and injectable progesterone. Progesterone injections are usually continued until 10-12 weeks of pregnancy. The oil that holds the progesterone can make the shots uncomfortable.
Progesterone is given by intramuscular injection. The liquid is thicker (more viscous) than the other medications because it is in an oil solution (sesame oil, cotton seed oil, and ethyl oleate are common carriers for the progesterone). A large needle is used to pull the recommended dose into the needle. 1 mL is the most common dose when the progesterone is 50 mg/mL but you should verify the recommended dose with the clinic or by reviewing your printed information. Progesterone in oil must be given intramuscularly.
To administer the progesterone in oil injection, an 18 gauge needle (large needle) is used to pull the medication into the syringe. The needle is changed to a 1 1/2 inch 22 gauge needle for injection. The injection site is cleaned with alcohol like with the medications described above. Instead of pinching the skin you will push down and out with your fingers in an effort to flatten the skin as best as possible. The needle is then inserted into the muscle. Draw back on the plunger to make sure you do not see blood. If you do, you will need to change locations for the injection site. Once the progesterone is injected, hold the needle in place for a few seconds then withdraw the needle. Hold pressure over the site briefly. Bruising, discomfort at the injection site, itching and numbness at the injection site are all common problems encountered with progesterone. Many people complain of lumps forming at the site of the progesterone injection. This will usually go away within several days but they have been known to last several weeks.
Using ice packs on the injection site has been very helpful to people. After the injection, a hot compress may help. Many people have reported massaging injection area helps relieve the pain and diminish the occurrence of lumps. Other additional tips may be available to you at the time of your shot teaching.
Delestrogen is an injectable form of estrogen that is occasionally used for fertility treatments. It is oil based and must be injected intramuscularly like progesterone described above. The injection is usually not given every day. Your medication schedule and injection instructions will direct you on when to administer the medication as well as the prescribed dose. Delestrogen is usually better tolerated than the progesterone in oil injections.