Progesterone and recurrent pregnancy loss – what a fertility consultant wants you to know

Pregnancy loss is something many of us quietly move through. It’s emotionally difficult, confusing and often isolating, especially when it keeps happening and you’re trying to work out what’s going on, and what to do next.

You may have heard about a progesterone recurrent pregnancy loss link, or read about progesterone treatment as an option – the latter being something which is particularly close to our hearts, here at TRB HQ. Following two losses back to back early on in her fertility journey, Senior Editor Jessie Day had progesterone treatment multiple times. “Looking back, calm, clear, accessible guidance is just so important when you’re in that place,” she shares.

For exactly this, we asked the brilliant Dr. Shirin Khanjani, Consultant Gynaecologist and accredited subspecialist in reproductive medicine, and Medical Director at Fitzrovia Fertility, our go-to in London for bespoke, evidence-based fertility care.

Read on for her answers to the following:

• The progesterone recurrent pregnancy loss link
• What the latest research tells us
• When and why treatment with progesterone may be recommended
• The progesterone dose for recurrent miscarriage
• Progesterone pessaries vs other treatment methods and protocols
• How recurrent miscarriage care is personalised to you at Fitzrovia Fertility

Over to Dr. Khanjani.

What role does progesterone play in early pregnancy?

Progesterone supports early pregnancy from the very beginning. After ovulation, progesterone helps to prepare the uterine lining for implantation. The lining becomes thicker, richer and more supportive, helping an embryo attach and grow.

Progesterone also helps calm uterine activity and influences your immune system, so that the pregnancy can establish safely.

What is the progesterone recurrent pregnancy loss connection?

Sometimes, progesterone levels during the luteal phase or early pregnancy are low. In some cases, this is because the pregnancy is not developing as expected.

Low progesterone may contribute to pregnancy loss by:

• failing to support the uterine lining, which can shed too early
• disrupting the immune system’s shift into a more pregnancy-friendly state

In some women, the issue isn’t progesterone levels but how the uterine lining responds to it. This is known as progesterone resistance.

Studies have shown reduced progesterone receptor expression in some women with recurrent miscarriage. This is why I’d recommend a really personalised approach to progesterone replacement for those who have experienced recurrent pregnancy loss in particular.

What does the research show about progesterone for recurrent miscarriage?

Two major UK trials provide the clearest guidance:

• The PROMISE trial – Looked at progesterone in women with unexplained recurrent miscarriage. It did not show increased live birth when progesterone was used routinely.
• The PRISM trial – Looked at women with early pregnancy bleeding. In the subgroup of women who had bleeding and at least one previous miscarriage, progesterone did increase live birth rates. The benefit was greatest in women with three or more prior miscarriages.

What is the typical progesterone dose for recurrent miscarriage?

These trial findings form the basis of the current NICE guidance, which recommends vaginal micronised progesterone 400 mg twice daily in women who:

• are experiencing bleeding in early pregnancy and
• have had one or more previous miscarriages

It’s worth noting that higher doses have not been shown to improve outcomes.

In what situations do you usually recommend progesterone?

In line with the current NICE guidance, I’ll recommend progesterone when:

• there is bleeding in early pregnancy and
• there has been one or more previous miscarriages and
• an intrauterine pregnancy is confirmed by scan

Outside this scenario, I’d look to discuss the evidence, uncertainties and personal factors with each patient individually.

Note – It’s important to separate this from the use of progesterone priming in an IVF context, where it is a standard part of luteal-phase support. Read our collab piece on short and long protocols for IVF to learn more about how this works.

When should progesterone treatment start, and when does it stop?

This varies slightly depending on the situation:

• Spontaneous conception with early pregnancy bleeding and previous miscarriage – Start once an intrauterine pregnancy is confirmed. Continue until 16 weeks, when placenta reliably produces progesterone.
• IVF or assisted conception – Start on the day of egg collection or a few days before embryo transfer. Continue until around 10–12 weeks.
• Suspected luteal phase insufficiency – Sometimes started immediately after ovulation, before pregnancy test confirmation, on a case-by-case basis.

What is the typical progesterone for recurrent miscarriage protocol?

At Fitzrovia Fertility, most women with early pregnancy bleeding and previous loss follow the PRISM-based protocol, as follows:

• Confirm intrauterine pregnancy by scan
• Start vaginal micronised progesterone 400 mg twice daily
• Continue until 16 weeks
• Regular early pregnancy scans for reassurance and monitoring

For women with recurrent miscarriage or suspected luteal phase deficiency, I sometimes take a more proactive approach and begin progesterone immediately after ovulation, rather than waiting for a positive pregnancy test.

This strategy is supported by smaller studies, and extensive experience in reproductive medicine. I would then review and adjust as the pregnancy develops.

Progesterone pessaries for recurrent miscarriage

Progesterone pessaries are small inserts placed into the vagina. They deliver progesterone directly to the uterus, with fewer body-wide side effects.

Typical use:

• 400 mg pessaries, twice daily, until the treatment stopping point in the second trimester

Other forms of progesterone

There are several forms or routes for progesterone, each with pros and cons. Here’s a quick overview:

• Vaginal micronised progesterone (pessary or capsule): Best evidence for recurrent miscarriage, high local absorption.
• Oral micronised progesterone: Easy to take, but absorption varies. Can cause drowsiness.
• Vaginal gel: Convenient, once daily. Evidence for recurrent miscarriage is more limited.
• Progesterone injections: Useful for fertility treatment or where other forms aren’t tolerated, but can cause soreness.

At Fitzrovia Fertility, the route and formulation will always be chosen collaboratively. While I start with the evidence-based standard, I always take into account your comfort, cultural preferences, previous experiences, and ability to use the medication consistently.

Are there any side effects or risks?

Most people using progesterone experience only mild, manageable effects, like:

• vaginal discharge
• local irritation
• breast tenderness
• sleepiness

Research from large studies hasn’t shown an increase in birth defects or serious health problems for the mother at the usual doses.

Recurrent pregnancy loss needs a truly tailored approach

But progesterone can play an important role, particularly where early bleeding and previous miscarriage are part of the picture.

The research now offers clearer guidance than ever before, and thoughtful tailoring can help ensure you receive the right approach for your body and circumstances.

At Fitzrovia Fertility, I’ll review your:

• previous pregnancies and miscarriages
• cycle regularity and luteal phase timing
• hormone levels
• your personal preferences and comfort

Your care will then be shaped around both the evidence and your lived experience, with the aim of steady, clear support through what can be a really anxious and sensitive time.