Is Endometriosis the Only Reason IVF Keeps Failing?

Is endometriosis the full explanation when IVF keeps failing despite good embryos?

Sometimes, but often not completely. Deep infiltrating endometriosis — disease that grows beneath the peritoneal surface rather than sitting on top of it — is genuinely associated with lower implantation and pregnancy odds in IVF. But the receptivity research is more mixed than most patients are told: when a high-quality or chromosomally normal embryo is transferred into a well-prepared uterus, several studies find outcomes close to those of women without endometriosis. A diagnosis that is real and a diagnosis that explains every failed transfer are two different things, and the gap between them is where a lot of unanswered questions live.

Why "endometriosis" isn't one uniform category

Two people can carry the same one-word diagnosis and face very different fertility implications. Superficial peritoneal lesions, ovarian endometriomas, and deep infiltrating endometriosis (DIE) — disease involving structures like the uterosacral ligaments, the posterior cul-de-sac, or the bowel — behave differently, and the location, depth, and extent of the disease all matter.

This is why comparing outcomes with someone else in a patient group is rarely informative. Her stage II superficial disease and your stage IV DIE with bowel involvement are not the same condition in any way that predicts a transfer result, even though the internet treats them as interchangeable.

Does severity actually change IVF outcomes?

It does in some datasets and not in others, and that inconsistency is worth knowing about rather than smoothing over.

The systematic review most often cited here (Harb and colleagues, BJOG 2013) found lower implantation and clinical pregnancy rates in women with stage III/IV disease compared with women without endometriosis — a relative risk of about 0.79 for both. A separate meta-analysis the following year (Barbosa and colleagues, Ultrasound in Obstetrics & Gynecology 2014) compared stage III/IV directly against stage I/II and found no statistically significant difference in live birth or clinical pregnancy. More recently, a French cohort (Morcel and colleagues, Reproductive Health 2024) found that women with endometriosis as a group did not have significantly different ongoing pregnancy rates than women without it, while cumulative rates within the endometriosis group were markedly lower for advanced-stage disease than for early-stage disease.

Put together: advanced and deeply infiltrating disease carries a real signal, but "DIE significantly lowers IVF success" is stronger than the evidence supports as a blanket statement. It is a risk factor with wide confidence intervals, not a verdict on your cycle.

One more piece belongs in this conversation: whether surgery before IVF changes anything. A systematic review of deep infiltrating disease found better clinical pregnancy odds in women operated on before IVF compared with those who went straight to treatment, with the strongest signal in disease involving the bowel (Journal of Minimally Invasive Gynecology, 2021). The evidence is not strong enough to make surgery routine, and it comes with its own risks to ovarian reserve when endometriomas are involved — but if you have deep disease that has never been surgically addressed and transfers keep failing, it is a legitimate question for your surgeon, not a closed one. Our piece on severe endometriosis without pain is worth reading if you have never had significant symptoms and assumed that ruled deep disease out.

If receptivity looks normal in the research, why do transfers still fail?

This is the part that complicates the tidy version of the story, and it deserves saying plainly.

A matched-pair case-control study from the University of Milan group (Casalechi, Vercellini and colleagues, Reproductive BioMedicine Online 2023) looked specifically at women with moderate or severe endometriosis undergoing frozen transfers and found live birth rates of 50% versus 58% in matched controls — a difference that was not statistically significant, with similar predicted success across four transferred embryos. Work in euploid transfers points the same direction: when the embryo has already been screened as chromosomally normal, endometriosis has not consistently reduced live birth rates.

That does not make endometriosis irrelevant. It does mean that if you have had good embryos, an addressed endometriosis diagnosis, and repeated failure anyway, "it's the endo" is an incomplete answer — and it is entirely reasonable to keep looking. Our piece on why implantation keeps failing walks through the factors that get skipped in that exact situation.

What is progesterone resistance, and how is it different from low progesterone?

Progesterone resistance means the endometrium does not respond normally to progesterone's signal even when progesterone itself is present at adequate levels — whether your body made it or a pharmacy supplied it. The problem is not the amount in the bloodstream; it is what the tissue does with the message.

Mechanistically it is well described in the endometriosis literature: reduced progesterone receptor B expression in endometrial tissue, altered HOXA10 signaling, and chromatin-level changes affecting steroid hormone response (reviewed in International Journal of Molecular Sciences 2023 and Acta Obstetricia et Gynecologica Scandinavica). It sits alongside implantation failure and early pregnancy loss as its own disturbance in endometriosis-associated infertility.

The practical consequence matters: adding more progesterone solves a supply problem. It does nothing for a responsiveness problem. If your levels have always been adequate and supplementation has never changed anything, that pattern is at least consistent with a signaling issue rather than a dosing one. Our piece on whether low progesterone affects implantation covers the supply-side question this contrasts with.

Can you get tested for progesterone resistance?

Not in the way most people hope, and this is worth being straight about before you take it to your appointment.

There is no validated, routinely available clinical test for endometrial progesterone resistance. It is measured in research settings — receptor expression on endometrial tissue, methylation and gene-expression patterns — not through a blood draw your reproductive endocrinologist can order and act on. Asking "has my progesterone resistance been evaluated?" will usually get a puzzled answer, because there is no standard evaluation to have run.

The useful version of the question is different: my progesterone levels have been adequate on every check and supplementation hasn't changed the outcome — what does that pattern tell you about whether this is an endometrial response problem, and does it change anything in the protocol? That is a question a reproductive endocrinologist can actually engage with.

Does a repeating pattern of very early losses mean something?

It can. Losses that consistently land at a similar, very early point — often right around when a period would have been due — across multiple attempts, whether from natural conception or embryo transfer, look different from random, embryo-driven chance. Random loss scatters. A pattern that repeats at the same point suggests something recurring in implantation or early placentation.

Raise it as a pattern, not as a list of separate events. Bring the dates, how far along each one was, and whether each followed a transfer or a natural cycle. Clinics respond to patterns; individual reports of "another chemical" tend to get filed as bad luck.

If chronic endometritis was treated, was it confirmed cured?

This is one of the most concrete gaps we see, and it is fixable. Treatment is not the same as resolution. In the published series, a repeat biopsy after antibiotics shows persistent chronic endometritis in a meaningful minority — resolution rates rose to roughly three-quarters after a second biopsy-and-treatment round and closer to 90% after a third. Women whose chronic endometritis was confirmed resolved before transfer have had better live birth rates than those whose inflammation persisted.

So if you were treated once and moved straight to transfer, the honest status of that finding is unknown, not resolved. A repeat biopsy before the next transfer is a reasonable ask.

What's worth asking when endometriosis alone doesn't explain repeated failure

Four questions carry weight in this specific situation:

• Given that my levels have been adequate, could this be an endometrial response problem rather than a progesterone dosing problem — and would that change the protocol?
• If chronic endometritis was found and treated, was a repeat biopsy done to confirm resolution before the next transfer?
• Has the specific extent and location of my endometriosis been considered — superficial, endometrioma, deep infiltrating — rather than treated as one uniform diagnosis?
• Do my losses form a pattern at a consistent point, and does that pattern change what we investigate next?

Our piece on laparoscopy after recurrent pregnancy loss covers how these anatomic findings get diagnosed and interpreted in practice.

How we approach this at East to West

At our Huntington clinic we spend most of our time with patients whose diagnosis is real and whose picture still doesn't add up — good embryos, a treated diagnosis, repeated failure. The work is layered: metabolic and immune contributors, inflammation, thyroid and iron status, sleep and stress physiology, and the timeline of what has actually been ruled out versus assumed. None of that replaces your reproductive endocrinologist. It sits alongside the IVF cycle, and it is why patients travel to us from across Long Island and New York City rather than repeating the same protocol with a different clinic. You can read more about our fertility care for endometriosis and PCOS.

The bottom line

Deep infiltrating endometriosis is a real and meaningfully more severe category than mild disease, and it is a legitimate contributor to lower IVF success. It also may not be the whole story, particularly when good embryos keep failing to implant. Progesterone resistance is a distinct mechanism worth understanding — even though it is not something you can currently have tested — and a consistent pattern of very early losses is a clue worth naming out loud. A real diagnosis is not always the complete explanation.

This article is for general educational purposes and isn't a substitute for individualized guidance from your reproductive endocrinologist. Evaluation of recurrent implantation failure and its underlying mechanisms should be pursued directly with your care team.

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East to West Fertility is a metabolic and immune-focused fertility clinic in Huntington, Long Island, serving patients across Long Island, NYC, and beyond. Learn more about our Metabolic & Immune Fertility Evaluation or call 631-416-4940.

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References

• Harb HM, Gallos ID, Chu J, Harb M, Coomarasamy A. "The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis." BJOG, 2013;120(11):1308-1320.
• Barbosa MA, Teixeira DM, Navarro PA, et al. "Impact of endometriosis and its staging on assisted reproduction outcome: systematic review and meta-analysis." Ultrasound in Obstetrics & Gynecology, 2014.
• Morcel K, et al. "What is the impact of endometriosis and the AFS stage on cumulative pregnancy rates in IVF programs?" Reproductive Health, 2024.
• Casalechi M, Vercellini P, et al. "Is endometrial receptivity affected in women with endometriosis? Results from a matched pair case-control study of assisted reproductive technology treatments." Reproductive BioMedicine Online, 2023.
• Zhang P, Wang G. "Progesterone resistance in endometriosis: current evidence and putative mechanisms." International Journal of Molecular Sciences, 2023.
• Patel BG, et al. "Progesterone resistance in endometriosis: origins, consequences and interventions." Acta Obstetricia et Gynecologica Scandinavica, 2017.
• Cicinelli E, et al. "Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure." American Journal of Reproductive Immunology, 2018.
• Bafort C, et al. "Impact of surgery for deep infiltrative endometriosis before in vitro fertilization: a systematic review and meta-analysis." Journal of Minimally Invasive Gynecology, 2021.