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

| Reviewed By Kimberly Langdon, M.D.

If you have recently begun your IVF journey, you have likely been prescribed daily progesterone in oil or PIO injections to help supplement your body’s own production of the hormone.

With so much at stake, you are likely wondering how important the timing of these shots is in regard to your treatment.

It is highly recommended that PIO shots are given at the same time each day as this can lessen your chance of experiencing side effects and helps the medication work. Consistent injections essentially help to align with your natural cycles, increasing the likelihood of successful fertility treatment.

Which part of the day you take these injections (morning, afternoon, or evening) is not important as everyone has their preference, and a missed dose is not a huge cause for concern.

What matters is finding a suitable time and routine and staying consistent with it.

In the following, we’ll discuss the timing of PIO shots, what happens if a dose is late, tips on making injections easier, and answers to some of your most pressing concerns.

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.

Life happens though, and your doctor will appreciate that there may be schedule changes along the way.

Let’s look at the importance of PIO timing and answer some common questions.

Why It Matters

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 and usually at the same time every 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.”

Mayo Clinic

Founder and medical director of the Houston Fertility Center Sonja Kristiansen, MD echoes 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

Massachusetts General Hospital states that progesterone shots “may be given in the morning, afternoon, or evening at approximately the same time each day.”

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.

Sharing her experience of PIO shots with the What To Expect community, one patient found that morning shots left her a lot less sore than evening shots as she had all day to move her muscles rather than lie in bed to focus on the pain!

What if I’m Late Taking the 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.”

For further reference, one mother on The Bump discussion forum shared that her healthcare provider suggested taking a late dose “within an hour of the normal time” when asked about dose variation.

Be sure to consult your own healthcare professional if in doubt.

Can PIO Shot Schedule Be Adjusted?

Yes, it’s 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 Do You Take Progesterone Shots After IVF Transfer?

According to the Fertility & Reproductive Medicine Center of Washington University Physicians, “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 below that, in the case of a blastocyst transfer, progesterone shots should continue for a further 6-7 weeks.

What Happens 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

Rarer more severe side effects that should be reported asap to your healthcare provider include:

  • A blood clot (sudden breathlessness, chest pain, redness, and warmth in your leg or arm)
  • Stroke
  • Allergic reactions (skin rash, 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 Progesterone in Oil Injections Easier

The timing of your PIO shots may be crucial, but it’s important not to rush the actual injection. Here are a few tips for making each injection go as smoothly as possible:

  1. Prep the syringe plunger – 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.
  3. Get someone else’s help – If you can ask your partner or a trusted friend to help administer the shot, then do it! Many find this can take away a lot of the anxiety around these shots.
  4. 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.
  5. 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.

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 once daily but can be painful.

Progesterone and IVF

Most but not all women undergoing IVF will be given progesterone following the retrieval of their eggs. This is to make sure that the lining of the uterus is prepared for the implantation of the fertilized eggs.

During an IVF cycle, certain medications are used to prevent premature ovulation. These can blunt your ovary’s ability to produce progesterone.

The role of a progesterone supplement in IVF, therefore, is to make up for your body’s lower levels of this hormone.

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), then treatment of progesterone is then recommended to “continue until 16 weeks of pregnancy.”

It is unclear whether this would take the form of suppositories or injections though.

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

According to the non-profit pregnancy educator March of Dimes, progesterone shots may be offered to you during pregnancy if you had “a previous spontaneous premature birth” while vaginal progesterone may be offered to help reduce the risk of preterm birth if you have a short cervix.

Progesterone shots in this case are usually offered between weeks 16 and 24 of your pregnancy, but the specific timing for the shots is not known.

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 can be at 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.

Stopping at 12 weeks pregnant appears to be a common time for IVF patients as demonstrated in this Mumsnet forum.

Related Questions:

What Helps Pain After Progesterone Injection?

Pain and tenderness following a PIO shot can be alleviated by massaging the injection site for 5 to 10 minutes or applying a warm compress such as a cloth or towel run under hot water.

This can help to break up the progesterone so pain and swelling are reduced at the site of injection.

Do Progesterone Shots Make You Tired?

Yes, progesterone shots can cause fatigue just as the natural increase in progesterone levels during a healthy pregnancy can cause women to feel tired.

Fatigue is caused not only by the altered hormone levels as a result of PIO shots but also by the stress that comes with undergoing IVF treatment.

Closing Thoughts

To sum up, the most important aspect of your PIO shots is that they are taken at the same time (or as close to the same time) each day for the best possible chance of the medication working and reducing the possibility of side effects.

If you are finding it difficult to stick to your current shot schedule, please speak to your doctor about adjusting it to a routine that suits you best.

Staying on top of your injections is hard in an already fraught and emotional time, but with support and determination, you can keep to a consistent plan.