Causes & Treatment

Endometriosis, progesterone resistance and fertility – 3 things the research tells us

Emma Harpham in partnership with ReceptivaDx™  |   22 Apr 2024

Progesterone is often referred to as the ‘pregnancy hormone’ due to its crucial role in supporting conception and early pregnancy.

However, progesterone resistance, a condition linked with endometriosis, is an all too infrequently discussed fertility roadblock – and one which often gets left out of testing during first-line (and even second-line) fertility work-ups. 

So, what do we mean by progesterone resistance? How exactly are endo, progesterone resistance and fertility connected? And what is the test to ask for, to move things forward?

We’re diving into the specifics with ReceptivaDx™ – a fab partner whose dedication to advocacy and understanding the causes and latest treatment around unexplained infertility, IVF failure, recurrent miscarriage and more led them to develop the ground-breaking ReceptivaDx™ BCL6 Test.

Their test is the only one out there that can identify leading causes of unexplained infertility (including endometriosis, progesterone resistance, and endometritis) in a single sample, by flagging the presence of the B-cell CLL/lymphoma 6 (BCL6) protein.

Before we get started, you can connect with ReceptivaDx™ to learn more and book your test – pop the code TRB23 on your request form for $75 off.

Now, let’s get into it.

What is progesterone resistance?

To get to the root of this question, understanding the biological role that progesterone plays in pregnancy is key.

Doctors may prescribe progesterone for a variety of reasons, including to stimulate ovulation. Importantly though, progesterone prepares the endometrium for implantation in pregnancy and stimulates it to secrete nutrients that support the healthy development of the newly implanted embryo. This crucial process is called decidualization

Progesterone resistance occurs when the body’s cells become less responsive to progesterone, causing the uterine environment to never progress to normal decidualization – despite all other indications suggesting a normal pregnancy. 

This can happen even when the hormone is present at normal or elevated levels in the blood. Low progesterone, in contrast, happens when there is insufficient progesterone circulating in the body. 

And although more research into the causes is needed, we do know that progesterone resistance is a pathologic condition of endometriosis (which can often be asymptomatic) as well as a contributing factor in pregnancy loss and IVF transfer failures.

Here’s a handy summary of the research and knowledge points, to help support you in conversations with your doctor. 


3 things to know about progesterone resistance and fertility

1. Progesterone resistance disproportionately affects women with endometriosis

You might not have been aware of an endometriosis progesterone connection – endometriosis is often talked about as being an estrogen-dependent condition, after all.

However, progesterone resistance appears to disproportionately affect women with endometriosis. This piece of clinical research found that one-third of patients with endometriosis did not respond to progesterone appropriately. That’s a lot.

As stated, more research is needed on the whys, but inflammation within the reproductive system interfering with progesterone signalling and function with gradual onset has proven to be a contributing factor.

The research supporting a link between BCL6, endometriosis and progesterone resistance is piling up, too, with this key study placing BCL6 at the center of the pathogenesis of both conditions.

If you’re currently trying to conceive and your medical team seems stumped, endometriosis – whether we’re talking symptomatic, silent endometriosis, or paired with progesterone resistance – is an important cause to rule out. 

2. The pregnancy implications of endometriosis and progesterone resistance can be wide-ranging

Studies on endometriosis have shown that the condition can cause unfavourable changes in the uterine lining environment like scarring and inflammation, as well as blocking progesterone from carrying out its vital role, when paired with progesterone resistance.

This piece of research points to the presence of lower endometrial progesterone in cases of recurrent miscarriage, disrupting the development and maintenance of early pregnancy due to increased inflammation in the womb lining.

In turn, this scientific review highlights progesterone resistance and its correlation with recurrent implantation failure in the context of IVF.

So if recurrent miscarriage or implantation failure are part of your story, and your doctor or medical team aren’t sure why, it’s worth looking into progesterone resistance caused by endometriosis as an underlying cause.

3. The conditions can add a layer of complexity to fertility tracking too

Stepping back into menstrual cycle 101 – progesterone plays a key role in supporting healthy periods, as well as being a key player in early pregnancy.

The research tells us that endometriosis in combination with progesterone resistance could lead to unpredictable periods, heavy bleeding, or even missed periods – making it challenging for us to track ovulation accurately.

Also, impaired progesterone signaling could disrupt the timing of ovulation, according to this study, as well as potentially interfere with egg maturation. 

So whilst these cycle-related symptoms don’t impact pregnancy outcomes in the same way as the two points above, they can add a further layer of complexity to the process, if you’re having difficulty conceiving.


So, how can we test for endometriosis and associated progesterone resistance?

The ReceptivaDx™ BCL6 test detects inflammation in the uterine lining often caused by endometriosis, as part of the bigger picture of eliminating possible causes of unexplained infertility, recurrent pregnancy loss and implantation failure.

Testing for BCL6 allows your doctor to get a complete analysis of your uterine lining. This involves a biopsy, where a small sample is taken and sent off for analysis to check for BCL6 levels. 

It’s a really straightforward process, and typically, your doctor can expect to receive results within four to five business days. 

Plus, it can really move the needle when it comes to your fertility journey – studies show that in women who test positive for BCL6, the probability of a successful pregnancy goes up to over 60%, once endometriosis is detected and treated, compared to 15 – 25% if left untreated.

When to ask your doctor about the ReceptivaDx™ test

If you’ve been trying to conceive for a while, have had multiple miscarriages, have failed IVF at least once, or have a history or symptoms of endometriosis – you’re a candidate for testing. 

Do lean on the research points we’ve mentioned above, and tell your doctor that you want the ReceptivaDx™ test. They should be open and willing to guide you through the process with care and support. 

Remember, this is your fertility journey, and advocacy for testing is so important in making steps forward, if you’re not getting answers from your team. We’ve been there, and we know how difficult that can feel.

Looking to rule out endometriosis, and associated progesterone resistance? The ReceptivaDx™ approach for 2024 is simple – learn, empower and advocate. Connect with them for answers to your questions, and to schedule a 20-minute free consultation.

TRB readers can get $75 off – just use code TRB23 on your test request form.

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