Progesterone is a hormone that is released by the ovaries and is important for menstrual function and pregnancy.  During the menstrual cycle, progesterone is important for the preparation of the endometrium (uterine lining) for implantation (attachment) of a fertilized egg (embryo).  Progesterone is a key player in pregnancy especially in the first eight weeks of pregnancy and even beyond. 

Why do I need progesterone supplementation during assisted reproductive technology?

Women undergoing Assisted Reproductive Technology procedures, such as in vitro fertilization or IVF, usually need progesterone supplementation after the eggs (oocytes) are removed during an oocyte retrieval procedure.  Women need more progesterone supplementation after retrieval procedures, secondary to the medications used in an IVF cycle, which may decrease proper progesterone formation as well as due to the retrieval process itself, which can deplete progesterone producing cells. 

When do I need progesterone supplementation?

Some IVF programs wait until after the embryo transfer, while others begin as early as the day after the oocyte retrieval to start progesterone supplementation. The duration of progesterone supplementation also varies.  Some physicians choose to continue supplementation until eight to ten weeks of pregnancy, while others choose to stop progesterone when they detect a heartbeat in the uterus, generally at six to seven weeks.  However, several studies have shown that progesterone supplementation can be discontinued at the time of the first pregnancy test without affecting the outcome o f the pregnancy.

How is progesterone administered?

The most studied formulation is intramuscular Progesterone.  This method usually involves an injection in the buttocks (the gluteus muscle) by using a syringe and needle.  The injections produce high levels of circulating progesterone in the bloodstream.  The injections are usually done once per day. 

The vaginal progesterone formulations can involve a gel, a tablet or a suppository which are inserted into the vagina anywhere from one to three times per day.  The vaginal administration has the benefit of causing no pain, but may require more frequent use and causes frequent vaginal discharge.

Vaginal progesterone is available in several formulations as described here:

VAGINAL GEL

The vaginal gel, which comes in pre-filled applicators, works by coating the vaginal walls for a controlled, steady release of progesterone, and is used once a day for progesterone supplementation in IVF.
• Approved by the Food and Drug Administration (FDA) for ART and for up to 12 weeks of pregnancy. 
• Approved for replacement in donor egg recipients and frozen embryo transfers, and is used twice a day for these procedures.

VAGINAL SUPPOSITORIES

Specialized fertility pharmacies often produce vaginal progesterone suppositories. They are placed into the vagina two or three times per day and dissolve over time. 
• They are considered safe and effective, but are not FDA approved for infertility treatment.

VAGINAL INSERTS OR TABLETS

These tablets come with a disposable applicator to help insert the tablet into the vagina two to three times per day. 
• Approved by the FDA for women needing progesterone supplementation. 

PROGESTERONE CAPSULES, USED VAGINALLY

Progesterone capsules, designed to be taken by mouth, can sometimes be prescribed for vaginal use. This helps avoid the side effects seen with oral administration and may increase absorption.
• The FDA has not approved the use of oral progesterone capsules for vaginal administration, nor for use during infertility treatment.

PROGESTERONE CAPSULES, TAKEN BY MOUTH

Orally administered progesterone is processed by the liver, which can break down most of the progesterone. Oral supplementation is thought to be less effective than other routes of progesterone administration in women undergoing ART procedures; side effects of oral progesterone include nausea, bloating, drowsiness and irritability.
PROGESTERONE INJECTIONS OR PROGESTERONE IN OIL

Progesterone in an oil-based solution is injected directly into a muscle, usually in the buttocks, once a day. Secondary to the need of injecting a thicker oily solution, the progesterone injections require a longer, thicker needle to help penetrate the layers of skin and fat to the muscle.  This is the original and oldest method for progesterone delivery during infertility treatment. The efficacy of this approach is well established and beneficial for IVF. This method usually requires a second person to perform the injection although some patients can do the injection themselves.  Side effects from this method of administration have been reported: 

• allergic reactions
• soreness and inflammation
• difficulty in sitting or walking

What are the side effects of all progesterone?

All types of progesterone can result in the following:

• bloating
• mood changes
• breast tenderness
• fatigue
• nausea & vomiting

Which progesterone is right for you?

Progesterone is an important part of infertility treatment because it supports implantation and early pregnancy. Your healthcare provider and you should decide on which progesterone formulation is suitable for your lifestyle and situation. 

Are there any alternatives to progesterone?

Luteal phase supplementation with human chorionic gonadotropin (hCG) has been shown to give ART success rates equivalent to progesterone. However, luteal phase hCG may increase the risk of ovarian hyper-stimulation and cause a false-positive pregnancy test, so it is seldom used for luteal supplementation.

This fact sheet has been underwritten by an unrestricted educational grant from Columbia Laboratories Inc., makers of Crinone 8% (progesterone gel).  http://www.crinoneusa.com, toll free support line 1-888-PROGEL8 (888.776.4358)