What Are the Side Effects of Progesterone With IVF?

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If you undergo in vitro fertilization (IVF), your doctor typically gives you the hormone progesterone to help create a favorable environment for the embryo to implant and to help support the pregnancy in its early stages. Progesterone can be given in several different ways. Two common routes are as a suppository or gel inserted into the vagina or as an injection into a muscle, typically in one of the buttocks. Like all medical treatment, progesterone may produce side effects, some of which depend on the route of administration.

PMS-like Symptoms

Most women experience only mild side effects while taking progesterone as part of IVF treatment because they use it for a relatively short time. Progesterone use with IVF is stopped immediately if the pregnancy test is negative. If the pregnancy test is positive, progesterone is continued for the first 9 to 12 weeks of pregnancy until the placenta makes enough progesterone by itself to support the pregnancy.

The most common side effects from progesterone administered by any route are symptoms that mimic premenstrual syndrome (PMS). These may include headaches, bloating, irritability, breast tenderness, sleepiness, depression or mood swings. Although these symptoms may also be due to an oncoming period, women are encouraged to keep taking progesterone until their pregnancy test indicates whether they are pregnant.

Muscle Injection Side Effects

When progesterone is manufactured as a liquid for intramuscular injections, it is mixed with an oil. Although intramuscular progesterone is not approved by the US Food and Drug Administration for use in IVF, some physicians still prefer giving progesterone in this traditional form because it produces higher progesterone levels in the blood than other administration methods. But many women find these injections painful, and the need for daily injections inconvenient. Some women develop a reaction to the oil that appears as hives, a rash or painful lumps at the site of injection.

Vaginal Side Effects

Vaginal progesterone has fewer side effects than intramuscular administration. But it also produces lower progesterone levels in the blood, providing less reassurance that progesterone levels in the uterus will be high enough to support a pregnancy. When progesterone is given as a vaginal suppository or gel, irritation of the vagina may occur. Some women find the suppositories and gels messy and unpleasant to use. Vaginal dryness and yeast infections are other possible side effects of vaginal progesterone.

Blood Clots

Rarely, women may experience serious side effects from progesterone related to the formation of blood clots. If a blood clot occurs, it often develops in a lower leg vein as a deep vein thrombosis (DVT). This can produce pain, swelling, warmth and redness of the calf. If part of the DVT breaks free, it can travel through the bloodstream to the lungs, causing a pulmonary embolus. This may produce shortness of breath, chest pain or coughing up blood.

If a clot occurs in an artery supplying the brain, it may cause stroke symptoms. These may include sudden onset of weakness in the limbs or speech problems, a headache, vomiting, dizziness or fainting. A clot may also occur in a blood vessel of the eye, leading to sudden partial or complete loss of vision.

Warnings and Precautions

Before beginning progesterone, tell your doctor if you have any allergies, including food allergies. Intramuscular progesterone preparations contain various types of oils, such as sesame, peanut or olive oil. Do not use any other vaginal products when receiving treatment with vaginal progesterone, as they may interfere with the absorption of progesterone.

Contact your doctor if you have any symptoms that may be due to the progesterone treatment. Seek immediate medical care if you notice any symptoms of a possible blood clot.

Reviewed by Mary D. Daley, MD.