IVF Medications

What are IVF medications used for?

Your IVF stimulation cycle begins on the first day of your menstrual cycle (the day you get your period). From there, you will typically have baseline tests, including an ultrasound and blood tests, completed on the third day of your cycle. On this day, you will begin administering your IVF stimulation medications leading up to your egg retrieval.

IVF medications have 2 main functions:

Cause multiple eggs to mature
Control when ovulation occurs

Here are the most common types of IVF medications:

Gonadotropins (Follistim, Gonal-F, Menopur)

These are synthetic forms of the reproductive hormones FSH and/or LH that hyper-stimulate the ovaries so multiple follicles (with eggs inside of them) grow.

Note: Menopur is the only gonadotropin that contains both FSH and LH. Follistim and Gonal-F only contain FSH.

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Review: During the first half of a menstrual cycle, the brain naturally releases the hormones FSH and LH. FSH (and LH, to a lesser extent) cause multiple follicles (with eggs inside) to grow in the ovaries, but only one follicle ends up becoming the dominant follicle. The dominant follicle contains the egg that will be ovulated that cycle. The other follicles that started to grow will all degenerate as the FSH levels decrease and ovulation approaches.

But... you want there to be multiple eggs retrieved for your IVF cycle so you have a higher chance of getting at least one healthy embryo from the cycle. Gonadotropins supply your body with a steady supply of FSH and/or LH, which in turn causes multiple follicles (eggs) to grow and not degenerate. Thus, there will be multiple mature eggs available for our IVF cycle instead of just one.

Gonadotropins are typically administered through a subcutaneous (under the skin) injection with a pre-filled pen at the start of IVF stimulation. The dosage can be adjusted depending on how your body is responding to the medications.

Side effects of gonadotropins may include headaches, hot flashes, breast tenderness, bloating, nausea, fatigue, and irritation/infection of the injection side.

GnRH Antagonists (Cetrotide, Ganirelix)

These injectable medications block GnRH activity in the brain to prevent premature ovulation.

Review: During a normal menstrual cycle, one part of the brain releases the hormone GnRH, which in turn causes another part of the brain to release the hormone LH (luteinizing hormone). A surge of LH released by the brain triggers ovulation to occur.

So, if GnRH is not being released, then LH is also not being released. No LH surge means no ovulation. This is helpful during an IVF cycle because it prevents ovulation from occurring too early (if ovulation occurs too early, the eggs cannot be retrieved). In a sense, GnRH antagonists put the body into a brief menopausal state in order to control when ovulation occurs.

GnRH antagonists are administered via a subcutaneous (below the skin) injection either between the belly button and the bikini line, or at the top of the thigh. The medication will come in a pre-filled pen with a dial on the side. You can adjust the dosage by changing the dial on the pen (per your doctor's instructions). GnRH antagonists are normally administered for a few days in a row during IVF stimulation as the follicles begin to grow.

Side effects of GnRH antagonists can include hot flashes, mood swings, headaches, nausea, abdominal pain/tenderness, and injection site pain.

Ovulation trigger medications (Ovidrel, Novarel, Lupron, Pregnyl, hCG)

These injectable medications cause the eggs in the ovaries to finish maturing and trigger ovulation to occur.

Review: During the first half of a menstrual cycle, a surge of LH is released by the brain to trigger ovulation.

Administering an ovulation trigger medication mimics the LH surge which, in turn, triggers ovulation to occur.

Egg retrievals are scheduled for 35-36 hours after the trigger is administered so that the eggs have time to finish maturing, but ovulation has not yet occurred. If ovulation occurs prior to an egg retrieval, the eggs cannot be retrieved. Thus, the timing of the trigger administration is essential in order to have a successful egg retrieval.

Most ovulation trigger medications are given via an intramuscular (into the muscle) injection, though Ovidrel is given subcutaneously (under the skin) with a pre-filled syringe.

Side effects of ovulation trigger medications can include headaches, bloating, pelvic/abdominal pain, dizziness, injection site pain/tenderness, and OHSS.

Low-dose or diluted hCG

hCG is the hormone that the embryo secretes when it implants into the uterine lining, but it turns out that hCG and LH are actually very similar (except that hCG lasts longer in your body). So, administering a low-dose hCG medication is just like supplying your body with LH, which works with FSH to help your follicles grow as the eggs inside of them mature.

Note: low-dose hCG only needs to be administered with Follistim or Gonal-F since they do not contain LH. If you are taking Menopur, you will not need to take low-dose hCG since Menopur contains both FSH and LH.

Low-dose hCG is typically administered subcutaneously (under the skin) with a cold, pre-mixed solution that is drawn from a vial. This solution needs to be kept cold to be effective. Low-dose hCG is administered at the beginning of the IVF stimulation alongside the Follistim or Gonal-F.

Side effects of low-dose hCG may include headaches, fatigue, mood swings, and injection site pain/tenderness.

GnRH Agonists (Lupron, Synarel, Zoladex)

These injectable medications stimulate the brain to briefly release a lot of hormones, but then cause the hormone levels to fall rapidly.

Review: When the female brain discovers that a pregnancy has not occurred, a new menstrual cycle begins. The brain begins to release GnRH, which in turn causes the release of FSH and LH. FSH stimulates egg growth in the ovaries, while LH triggers ovulation. The brain can also adjust how much of these hormones are released.

GnRH agonists stimulate the brain to produce a lot of FSH and LH, so there will be a higher level of these hormones than normal. The brain quickly detects these high levels of FSH and LH in the body and stops releasing them, so the levels of these hormones will rapidly decline.

For these reasons reason, GnRH agonists can be given at 3 times:

Before an IVF stimulation begins. GnRH agonists can suppress ovarian function and wipe out the FSH and LH levels in the body right before IVF stimulation begins. This helps control the hormone levels at the start of an IVF stimulation and prevents premature ovulation from occurring. This is known as down regulation.
During an IVF stimulation. A GnRH agonist initially provides a surge of FSH, which can help stimulate multiple follicles (and their eggs) in the ovaries to grow. It also helps prevent premature ovulation because the hormone levels begin to decline when there would naturally be an LH surge.
As an ovulation trigger. The surge in FSH allows the eggs to finish maturing, while the surge in LH mimics the body's natural LH surge, which triggers ovulation.

While Lupron is given as an intramuscular (in the muscle) shot, other GnRH agonists are now available as nasal sprays or implants.

Side effects of GnRH agonists can include hot flashes, headaches, nausea, mood swings, and body aches.

Progesterone (Crinone, PIO)

If you are opting to do a fresh embryo transfer (a transfer 5 days after your egg retrieval), you will likely need to take progesterone leading up to your transfer.

Review: in the second half of the menstrual cycle, the corpus luteum (which was the dominant follicle prior to ovulation) secretes progesterone to help the endometrium (uterine lining) thicken in preparation for embryo implantation. The corpus luteum secretes progesterone until the placenta takes over a few weeks after embryo implantation.

Progesterone can be taken as an injection, pill, or a vaginal suppository/gel to help prepare the endometrium for implantation. It is typically administered before the egg retrieval and is continued for 8-12 weeks if a pregnancy occurs (until the placenta takes over progesterone secretion).

Note: Progesterone is also administered prior to a frozen embryo transfer in order to prepare the uterine lining for embryo implantation and to help sustain the pregnancy after the embryo has been transferred.

Side effects of progesterone can include headaches, breast tenderness, injection site pain/tenderness, nausea, and mood swings.

Birth Control Pills (OCPs)

Birth control pills are typically prescribed to patients in the weeks or months prior to an IVF cycle in order to prepare the body for an upcoming IVF stimulation.

Birth control pills have two main goals when it comes to IVF stimulation:

Suppress the menstrual cycle (prevent ovulation) in order to "prime" the body for an upcoming IVF cycle.
Regulate the menstrual cycle to ensure that the timing of the IVF stimulation is accurate. This also prevents premature ovulation from occurring.

The side effects of birth control pills are minimal but may include headaches, nausea/dizziness, or mood swings.

Other Medications

Doxycycline or Zithromax: These antibiotics may be prescribed after an egg retrieval to decrease the risk of developing any infections after the procedure. They can also be prescribed to males before they submit a semen sample in order to decrease the amounts of bacteria in their semen samples. These medications are only taken for a few days. Side effects may include sensitivity to sunlight and GI distress/diarrhea.
Dexamethasone: This steroid may increase a woman's response to certain IVF medications by decreasing the amounts of male hormones that her body releases. This is typically only used for women with poor responses to IVF medications or for women with a low number of eggs. This pill is taken once a day and side effects may include increased urination, headache, nausea, and fatigue.
Prenatal Vitamins: After an embryo transfer, many providers recommend taking a prenatal vitamin. In addition to a number of important vitamins and minerals, these contain folic acid, which may decrease the incidence of some serious birth defects. These should be continued throughout a pregnancy.
Medrol (methylprednisolone) This is an oral anti-inflammatory steroid that aids in embryo implantation. Medrol also slightly weakens a woman's immune system so that her body does not attack the embryo as it tries to implant (sometimes a woman's body will do this). One pill is taken after an egg retrieval for 4 days leading up to the fresh embryo transfer (or leading up to a frozen embryo transfer). There are typically no significant side effects from Medrol, but some side effects can include blurred vision, shortness of breath, mood swings, or unusual bruising.
Bromocriptine (Parlodel) or Dostinex (Cabergoline): These medications decrease the amount of prolactin that the brain releases. In some cases of female infertility, ovulation does not occur correctly because the brain is producing too much prolactin. These medications can be administered either orally or vaginally over the course of a few weeks, at which time the prolactin release should be normalized. Side effects can include nausea, vomiting, nasal congestion, headache, and fluctuations in blood pressure.
Provera (Medroxyprogesterone): This medication is a progestin (a derivative of progesterone) which induces menstruation (a period) to occur. Provera may be used to trigger menstruation for women who have abnormal menstrual cycles. This, in turn, regulates the timing of IVF stimulation and ovulation. Provera is a pill that is taken daily for around 5 days. Side effects may include spotting, vaginal irritation, headache, dizziness, breast tenderness, bloating, nausea, and vision changes.
Methotrexate: This injectable chemotherapy medication treats ectopic pregnancies (pregnancies that occur in the Fallopian tube rather than the uterus). Ectopic pregnancies are life-threatening and unfortunately must be terminated. Methotrexate causes the embryo tissue to degenerate and be reabsorbed by the body. Typically, only one intramuscular (into the muscle) injection is required, though sometimes 2 or even 3 injections may be needed. Methotrexate has not been shown to affect a woman's egg count or future chances of getting pregnant, but women should wait a few months before attempting to get pregnant after administering methotrexate since it can remain in the body for some time. Side effects may include fever, nausea, sensitivity to light, and mouth sores.
Estrace: This medication mimics a form of estrogen, which helps the uterine lining thicken prior to a frozen embryo transfer. Recall that estrogen levels are high in the first half of the menstrual cycle, which causes the endometrium to thicken. Estrace is administered both orally and vaginally every day until the uterine lining appears thick enough on an ultrasound for an embryo transfer, and then it is continued until the transfer occurs. Side effects can include headaches, vaginal irritation and discharge, body aches, and diarrhea.
Clomid (Clomiphene citrate or Serophene) and Femara (Letrozole): These medications are typically not used for IVF, but they are worth mentioning. They are administered to women with PCOS, unexplained infertility, and abnormal menstrual cycles with irregular ovulation. Clomid and Femara stimulate the development of multiple follicles (and eggs) and induce ovulation by increasing the amount of FSH and LH released by the brain. A couple will undergo timed intercourse (or an IUI will be performed) shortly before ovulation is expected to occur in hopes of natural fertilization occurring in the Fallopian tube. Clomid and Femara are pills that are typically taken daily for 5 days leading up to ovulation. Side effects of Clomid and Femara can include hot flashes, breast tenderness, mood swings, nausea, and visual disturbances, headaches, fatigue, and dizziness.