By Manju Dawkins, MD — Dermatologist, co-founder of Thimble and mom of 2. Last reviewed July 2026.
Among all of the injections people go through during IVF, progesterone in oil (PIO) is the one I hear about most often. Patients describe it as the shot they dread, not because the needle is especially large, but because it's repeated night after night, delivered into muscle, and often leaves lingering soreness.
PIO discomfort comes from several sources: the needle passing through the skin, the medication being delivered into the muscle, and the thick oil creating pressure as it's injected. Afterwards, the muscle itself may remain sore while the oil is gradually absorbed.
Because the pain has more than one cause, no single strategy solves everything. The goal is to make each part of the experience a little easier: reduce the pain of the needle, improve comfort during the injection, and care for the muscle afterward. Together, those small changes can make a meaningful difference over weeks of treatment.
Here's what actually helps.
How to make PIO shots hurt less
Warm the medication first
Progesterone in oil is thicker than many injectable medications. Warming the medication reduces its viscosity, allowing it to flow more easily through the needle and into the muscle. Many patients find this makes the injection noticeably more comfortable.
Take the medication out ahead of time and allow it to come to room temperature, or gently warm the filled syringe between your hands for a minute or two. Never use a microwave or direct heat, and always follow your fertility clinic's instructions for storing and handling your medication.
Numb the skin before the injection
One source of PIO pain is the needle passing through the skin. Applying topical numbing beforehand addresses that part of the experience. Research on needle procedures consistently shows that topical anesthetics reduce pain from needle insertion, and many people undergoing IVF find this makes nightly injections much more manageable.
Apply topical numbing to the injection site before your injection so it's working when you're ready. A numbing patch keeps the process simple when you're already managing medications, appointments, and everything else that comes with IVF.
Rotate injection sites
Repeated injections into the same area can lead to increasing soreness and areas of firmness over time. Alternating sides each night allows the tissue time to recover between injections.
Keeping a simple note in your phone or on a calendar can help you remember which side you used last.
Care for the area afterward
The soreness that follows PIO injections is real, and over weeks of treatment it can become just as challenging as the injection itself.
Many fertility clinics recommend applying gentle warmth after the injection to help relax the muscle and improve comfort. Some also recommend gentle massage, while others have different protocols, so it's best to follow your clinic's instructions.
Recover was designed to support comfort after needle procedures. If you're experiencing recurring soreness over weeks of injections, caring for the area afterward can be just as important as preparing beforehand.
Have your partner give the injection, if possible
PIO is one of the most difficult injections to give yourself because of where it's administered. Having a partner or support person give the injection, after they've been taught the proper technique by your fertility team, often allows for better positioning and a more relaxed muscle.
For many couples, it also transforms the injection from something you have to face alone into something you do together.
Create a predictable routine
One thing I've learned from caring for people with needle fear is that the experience doesn't begin when the needle goes in, and it doesn't end when it comes out. Preparing beforehand, making the injection itself more comfortable, and caring for the area afterward all shape how you feel about tomorrow night's injection.
Injecting at roughly the same time each evening, preparing your supplies ahead of time, and following the same routine each night can reduce anticipatory anxiety. Many people find it helpful to listen to music, practice slow breathing, or simply pause for a few deep breaths before the injection.
A long, slow exhale as the needle goes in activates the parasympathetic nervous system, helping your body relax. It won't eliminate the discomfort, but it often makes the experience feel more manageable.
Be gentle with yourself
Many people going through IVF describe progesterone in oil injections as one of the hardest parts of the entire process. Not because you're doing anything wrong, but because it's physically and emotionally demanding to face the same injection night after night for something that matters so deeply.
Acknowledging that it's hard isn't complaining. It's honest. And while the soreness is temporary, you don't have to simply grit your teeth through it. There are evidence-based ways to make the experience more comfortable, and those small improvements add up over the course of treatment.
Manju Dawkins, MD is a board-certified dermatologist, mom of two, and the co-founder of Thimble. She created the Thimble Needle Care System after experiencing her daughter's first shots.
FAQ
How can I make PIO shots less painful?
Warm the medication before injecting, numb the skin beforehand, rotate injection sites, and follow your fertility clinic's recommendations for caring for the area afterward. Addressing both the pain of the needle and the muscle soreness that follows can make nightly injections much more manageable.
Why do PIO shots hurt so much?
PIO discomfort comes from several sources. The needle passes through the skin, the medication is injected into the muscle, and the thick oil creates pressure as it's delivered. Repeated injections into the same areas can also lead to soreness and areas of firmness over time, which is why rotating sites and caring for the area afterward are important.
Where do you inject PIO, and why does it ache there?
PIO is typically injected into the upper outer buttock (gluteal muscle). Because it's an intramuscular injection that's repeated over many days or weeks, the area can become sore and develop areas of firmness during treatment. Rotating injection sites and warming the medication beforehand can help improve comfort.
Can I numb the area before a PIO shot?
Yes. Applying topical numbing to the injection site before your injection can reduce the pain of needle insertion. Research consistently shows that topical anesthetics reduce pain from needle procedures, and many people undergoing IVF find this makes nightly injections easier to manage.
What helps with PIO knots and soreness?
Some soreness and areas of firmness are common with repeated PIO injections. Rotating injection sites, following your fertility clinic's recommendations regarding warmth or massage after the injection, and caring for the area afterward can help reduce discomfort and prevent soreness from building over time.