What are progesterone in oil injections, and how do surrogates manage them?

Why is progesterone needed in a surrogate's transfer cycle?

Progesterone is the hormone that turns a thick uterine lining into one that can accept an embryo and sustain an early pregnancy. In a natural cycle, the ovary makes it after ovulation.

In a medicated frozen embryo transfer cycle, the surrogate does not ovulate. Estrogen builds her lining, and often Lupron first suppresses her own cycle, so her ovaries are not making progesterone. The clinic has to supply all of it, from a set number of days before transfer until the placenta can take over. Without it, the lining cannot support implantation, and an early pregnancy cannot continue.

That is why progesterone in oil, or PIO, is the medication surrogates talk about most. It is a daily intramuscular injection: progesterone dissolved in sesame oil, olive oil or ethyl oleate, injected deep into a large muscle. The oil holds the progesterone in the muscle and releases it steadily over the day.

The full cycle, from estrogen to transfer to the pregnancy test, is laid out on the frozen embryo transfer protocol page.

What is the typical dose and schedule?

The clinic sets the dose and schedule. A typical pattern:

• Start: 5 days before a day 5 blastocyst transfer. The timing matches the embryo's age, so the lining and the embryo are at the same stage on transfer day.
• Frequency: once a day, at about the same time each day.
• Dose: set by the clinic. A common dose is 50 milligrams, which is 1 milliliter, once a day.
• Duration: if the pregnancy test is positive, injections usually continue until about 10 weeks of pregnancy.

Some clinics check blood progesterone levels and adjust the dose. Others combine PIO with vaginal progesterone. Your clinic's calendar is the one to follow.

How do you give a PIO injection, step by step?

Clinic nurses teach the technique before the first dose, and PLS surrogates learn it from them. The steps below are a general guide. Follow your clinic's instructions where they differ.

1. Gather supplies. The vial, a syringe, a larger drawing needle, a smaller injecting needle, alcohol pads, gauze, a bandage and a sharps container.
2. Warm the oil. Hold the vial in your hand or under your arm for a few minutes. Warm oil flows more easily and stings less.
3. Wash your hands and clean the top of the vial with an alcohol pad.
4. Draw the dose. Attach the larger needle. Pull back air equal to the dose, inject the air into the vial, turn the vial upside down and draw the prescribed amount. Tap out any air bubbles.
5. Switch needles. Replace the drawing needle with the injecting needle.
6. Find the site. Picture the buttock divided into four quarters. The injection goes into the upper outer quarter, away from the sciatic nerve. Clean it with alcohol and let it dry.
7. Inject. Relax the muscle by putting your weight on the opposite leg, or have the surrogate lie face down. Insert the needle straight in, at 90 degrees, with a quick, steady motion. Follow your clinic's guidance on whether to draw back first. Push the plunger slowly.
8. Withdraw and press. Pull the needle straight out and press gauze on the site.
9. Massage and warm. Massage the site briefly, then apply a heating pad.
10. Dispose and record. Put the needle and syringe in the sharps container and note the time and side on a calendar.

Many surrogates have their partner give the injection, since the site is hard to reach. Some learn to self-inject using a mirror.

What reduces pain, lumps and bruising?

The oil absorbs slowly, and small hard knots under the skin are common. A few habits make a real difference:

• Warm the vial before drawing, and use heat on the site afterward.
• Inject slowly. A thick oil pushed fast is more painful.
• Alternate sides every day, and move the exact spot slightly each time.
• Relax the muscle during the injection. A tense muscle hurts more.
• Massage the site after each injection to spread the oil.
• Keep moving. A walk after the injection helps the oil disperse.
• Ice before, heat after, if the clinic allows. A brief cold pack numbs the skin.

Some bruising is normal and fades. If lumps become large, red or very painful, tell the clinic.

What side effects are normal, and which need a call to the clinic?

Normal and expected:

• Soreness at the injection site, sometimes lasting a day or two.
• Small lumps or knots under the skin.
• Bruising.
• Fatigue, bloating, breast tenderness and mood changes, which are effects of progesterone itself and overlap with early pregnancy symptoms.

Call the clinic the same day for:

• A missed or late dose. Call immediately. A late dose is usually given as soon as you remember, but the clinic decides. In a medicated cycle, missing doses risks the pregnancy.
• Signs of infection: redness that spreads, heat at the site, pus or fever.
• Bleeding or severe cramping.

Call 911 for signs of a serious allergic reaction: hives, swelling of the face or throat, or difficulty breathing. Tell the clinic before the first dose about any allergies. If you have a sesame allergy, PIO is also prepared in olive oil or ethyl oleate.

A full list across all transfer medications is on the medication side effects page.

What are the alternatives: vaginal progesterone and combination protocols?

PIO is not the only way to give progesterone. Clinics also use:

• Vaginal progesterone, as a suppository, gel or insert, used one or more times a day. It avoids injections. It can cause discharge and local irritation.
• Combination protocols, which pair vaginal progesterone with less frequent PIO injections, for example every few days instead of daily.

Which approach to use is the clinic's decision. Studies comparing them have reached different conclusions, and clinics have their own preferences and experience. Surrogates often prefer fewer injections, and it is reasonable to ask whether a combination protocol is an option.

When does PIO stop, and what happens to the pregnancy?

If the pregnancy test is negative, the clinic tells the surrogate to stop progesterone and estrogen, and her period follows within days.

If the beta hCG test is positive, injections continue through the first weeks of pregnancy. Most clinics continue until about 10 weeks, when the placenta makes enough progesterone on its own. The clinic then tapers the dose over days or a couple of weeks, on its own schedule. Stopping on the clinic's schedule does not harm the pregnancy, because by then the placenta has taken over.

For surrogates, the injections are a real commitment: daily, for weeks. PLS surrogates receive a $500 medication start fee from escrow when injections begin. Case managers Natalie Gaudio-Fricano and Jenni Symons, who carry the active matches, have both been surrogates themselves.

If you are considering surrogacy and want to know what the medical part involves, see becoming a surrogate.

This page gives general information. It is not medical advice. Follow your clinic's instructions for every dose.

Sources

• ASRM (American Society for Reproductive Medicine), guidance on luteal phase support in IVF and frozen embryo transfer. https://www.asrm.org/
• SART (Society for Assisted Reproductive Technology), patient information on IVF medications. https://www.sart.org/
• ACOG (American College of Obstetricians and Gynecologists), patient information on early pregnancy. https://www.acog.org/