Progesterone in Oil (PIO) Injection Timing – Why It Matters

| Reviewed By Kimberly Langdon, M.D.

For the best results, we recommend giving PIO shots at the same time every day to coincide with your body’s natural cycles. This may improve the effectiveness of fertility treatment.

Which part of the day you take these injections (morning, afternoon, or evening) is not as important as establishing a routine and staying consistent with it.

Mayo Clinic states that progestin medications for infertility procedures must be taken as your doctor directs, which is typically one to two times a day. 

“Try to take the medicine at the same time each day to reduce the possibility of side effects and to allow it to work better.”

Health experts advise that a late dose should be taken as soon as possible but that patients should never double the dose after a missed injection.

PIO Shot Timing

As progesterone supplements are given to mimic your body’s natural processes in the lead-up to conception, it’s important to be consistent with the timing of your PIO injections.

Why It Matters

Founder and medical director of the Houston Fertility Center Dr. Sonja Kristiansen confirms the critical timing of fertility medication sharing that:

“Each phase of IVF treatment aligns with the woman’s menstrual cycle so that viable eggs can be released and collected for fertilization and embryo transfer at the right time.”

Progesterone in Oil Morning or Night

According to Gynecology & Fertility Clinic, there is currently no research to suggest that taking stimulation injections (such as PIO shots) demonstrates a “difference in pregnancy rates when injections are taken in the morning or evening.”

It is ultimately up to you to decide on the most convenient time.

One thing to consider is that morning shots may result in less muscle soreness compared to evening shots.

Many patients claim that having time throughout the day to move their muscles prevents them from having as much soreness compared to when they take their shots at night and then lie in bed and focus on the pain. 

What To Do if You’re Late Taking Your PIO Shot

The Mayo Clinic advises taking a late PIO dose as soon as possible.

However, if you’re late to the point that it is almost time for your next PIO shot, then “skip the missed dose and go back to your regular dosing schedule. Do not double dose.”

The best way to avoid missing a shot is to set a timer on your phone each day when it is time for your injection. 

Adjusting Your PIO Shot Schedule

It is possible to adjust your PIO shot schedule to fit injections around a time that is more convenient for you.

Taking your shot at the same time every day is the most important thing, so if you need to move your shot times to earlier or later in the day, please discuss this change with your doctor.

How Long Progesterone Shots Are Continued After IVF Transfer

According to the Fertility & Reproductive Medicine Center, “most IVF clinics in the US recommend progesterone supplementation for 8-10 weeks after egg retrieval/FET” (frozen embryo transfer).

How long you take progesterone after a transfer will vary depending on your specific situation though, so speak to your healthcare provider about how long this will be.

For example, fertility expert Dr. Randy Morris explains in the video below that, in the case of a blastocyst transfer, progesterone shots should continue for a further 6-7 weeks.

When You Stop Taking Progesterone After IVF

In a normal pregnancy, the placenta takes over from progesterone production at around 12 weeks or after the first trimester.

In the case of IVF treatment, however, progesterone supplementation needs to carry on for at least 9-12 weeks as stopping progesterone any earlier than this can increase the chances of a miscarriage.

This continuation of 9 to 12 weeks is recommended as by this time, the placenta should be producing enough progesterone to safely sustain the pregnancy.

Progesterone in Oil Side Effects

Some side effects of taking PIO shots include:

  • Breast pain
  • Water retention
  • Appetite changes
  • Headaches
  • Nausea
  • Pain at the injection site
  • General weakness/fatigue
  • Abdominal pain
  • Irregular periods or spotting
  • Mood swings
  • Drowsiness
  • Dizziness
  • Fatigue

Other rare side effects should be reported to your healthcare provider immediately:

  • A blood clot (sudden breathlessness, chest pain, redness, and warmth in your leg or arm)
  • Stroke
  • Allergic reactions (skin rash or swelling in face, lips, throat)
  • Jaundice
  • Liver inflammation
  • Depression
  • High blood pressure
  • Pneumonia

Here’s a full list of the side effects from PIO ranked by severity.

Tips for Making PIO Injections Easier & Less Painful

A large needle with thick oil being injected into your behind is not the most comfortable experience.

Most women experience varying degrees of pain during and after the injection.  

Here are a few tips for making each injection go as smoothly and painlessly as possible:

1. Prep the Syringe Plunger

Always use a clean syringe and needle.

The syringe may be quite stiff on first use, so prime the plunger a few times back and forth while it’s empty for a smoother time drawing and injecting the medication.

2. Warm Up the Vial

When the oil in the medication is cold, it tends to be more viscous, which can mean it takes longer to inject.

Warm up the vial of PIO by running it under warm water or cupping it in your hands/armpit/elbow for a few minutes.

Do not use a hot water bath or a microwave to heat up the vial as this can potentially damage the medicine or cause burns during the injection. 

3. Get Someone Else’s Help

While you can do it on your own, it will be much easier and less painful if you have someone to help you.

If you can, ask your partner or a trusted friend to help administer the shot. Many find this can take away a lot of the anxiety around these shots.

4. Use Numbing Cream

Using lidocaine-based patches and gels may be helpful in decreasing the pain at the injection site. 

5. Relax Your Glute

It is important to relax the muscle before the injection in order to reduce soreness.

Try lying down, or if you are standing, bend your knee on the side you are injecting to help relax the gluteal muscle.

Slightly lifting the leg on the injection side will also help to take unnecessary weight off of the muscle and keep it relaxed. 

6. Apply a Warm Compress Afterward

Be ready with a moist hot towel or microwaveable heat pad to place on your freshly injected area.

This helps to spread the medication and feels quite soothing

7. Massage

Gently massaging the injection site for 3-5 minutes after the injection helps to prevent knots from forming and encourages absorption. 

8. Movement

Moving around after the injection helps to prevent or reduce soreness.

Go for a walk, or try to stay active after your shot to keep your muscles from getting too stiff. 

9. Rotate Your Injection Sites

Be sure not to inject into the same spot twice as this can cause extra pain and swelling in the form of small lumps/knots under the skin where excess oil has accumulated. Rotate sites daily. 

Progesterone and IVF

During an IVF cycle, certain medications may be used to prevent premature ovulation.

By doing so, they blunt your ovary’s ability to produce progesterone, a critical hormone that aids in conception by preparing the uterus for implantation.

In such cases of medicated cycles, progesterone supplements are used to make up for the body’s lower levels of this hormone. 

Most women undergoing IVF will be given progesterone following the retrieval of their eggs to make sure that the lining of the uterus is prepared for the implantation of the fertilized eggs.

Progesterone Injections vs. Suppositories

Progesterone supplements can also be taken in the form of vaginal gel and pill suppositories.

Suppositories are viewed as an effective method as progesterone has the chance to be absorbed directly into the uterus.

According to BabyMed, both methods of progesterone supplement are equally effective, so it comes down to personal choice.

Suppositories are simple and comfortable to insert, but these need to be taken 3-4 times a day and can create a great deal of discharge.

PIO injections, meanwhile, are often used once daily but can be painful.

Progesterone Injections During Pregnancy

Progesterone injections may be used during pregnancy for several reasons, including:

  • History of Recurrent Pregnancy Loss (RPL): Progesterone plays a crucial role in maintaining the uterine lining and supporting early pregnancy. Some women who have a history of recurrent miscarriages may be prescribed progesterone injections to help support the pregnancy.
  • Assisted Reproductive Technologies (ART): Procedures like IVF, intrauterine insemination (IUI), or frozen embryo transfer (FET) may also involve the use of progesterone injections to support the uterine lining and embryo implantation.
  • Threatened or Recurrent Miscarriage: In some cases, when a woman experiences bleeding or other signs of a threatened miscarriage or has a history of recurrent miscarriages, progesterone supplementation may be recommended to support the pregnancy.
  • Luteal Phase Deficiency: Some women may have a condition known as luteal phase deficiency, which means that the phase of the menstrual cycle after ovulation is shorter than normal. In such cases, progesterone supplementation can help support the uterine lining and the early stages of pregnancy.
  • Preterm Labor Prevention: In certain situations, especially if a woman has a history of preterm labor or has certain risk factors, progesterone supplementation may be used to help prevent preterm birth.
  • Assisted Hatching: In some cases during assisted reproductive procedures, the outer shell of the embryo may be artificially weakened to facilitate its implantation in the uterus. Progesterone may be given to support this process.
  • Gestational Surrogacy: In cases of gestational surrogacy, progesterone injections may be used to support the pregnancy until the placenta is capable of producing sufficient progesterone on its own.
  • Certain Medical Conditions: In some cases, women with specific medical conditions or hormonal imbalances may benefit from progesterone supplementation during pregnancy.

Progesterone Injections During Pregnancy To Prevent Miscarriage

Some small-scale studies have suggested that the risk of miscarriage may be reduced in women who experienced bleeding in early pregnancy if vaginal pessaries are used (a removable silicone device containing micronized progesterone).

In 2021, The Guardian reported that if “a fetal heartbeat is confirmed” (after use of micronized progesterone twice daily), treatment of progesterone is recommended to “continue until 16 weeks of pregnancy.”

As for the timing of progesterone injections or suppositories to prevent miscarriage, fertility expert Dr. Randy Morris explains that:

“In order to prevent a miscarriage, progesterone must be present after the embryo implants.”

Progesterone To Prevent Preterm Birth

If you’ve had a premature baby previously, progesterone shots may be offered to you during your pregnancy to prevent early labor.

Healthcare providers give the shots in the back of the arm, hip, or thigh area. 

In this case, PIO shots are usually offered between weeks 16 and 24 of your pregnancy.

Depending on your situation, your healthcare provider can discuss the best time to take these injections.

When To Stop Taking Progesterone During Pregnancy

Essentially, progesterone supplementation can be stopped when it is agreed upon by your doctor that your placenta is adequately producing progesterone, taking on the role of your ovaries.

This is usually around 12-14 weeks.

However, depending on your situation and history (e.g., pregnant with twins on IVF or having suffered a previous miscarriage), your time frame may differ.