Endometriosis and Fertility: What the New Science Means for Your Chances

Endometriosis and fertility used to be explained in one tidy sentence: tissue like the womb lining growing where it shouldn’t. That sentence is why so many women were told their pain was “just bad periods”, why diagnosis still takes the best part of a decade, and why the fertility conversation so often ended with “let’s see what the laparoscopy shows”.

The science has moved on, mostly in the last five years. Endometriosis is now understood as a whole-body condition, driven by an immune system that feeds the disease, lesions that rewire their own metabolism, and a nervous system that learns pain. For anyone trying to conceive, that shift explains things the old story never could: why mild disease can matter as much as severe disease, why both egg quality and the womb lining are involved, why miscarriage is more common after natural conception but not after IVF, and why some long-standing treatments turned out not to help.

This is the guide every woman deserves before her first appointment. The short version is right here; the rest is the same thing, slowed down.

---

What is endometriosis? Types, stages and how it’s diagnosed now

What a pathologist actually sees. Under the microscope, endometriosis is tissue that looks like the womb lining (glands, the supporting cells around them called stroma, or both) growing outside the womb, almost always with inflammation around it. Since 2021 that has been the official international definition (Tomassetti et al., 2021). The words “looks like” are doing real work there. These are not simply normal cells in the wrong place: they are altered cells that have learned to survive where they shouldn’t, as the next sections explain.

It comes in three forms, and they may be three different diseases. Superficial spots on the pelvic lining; ovarian “chocolate cysts” (endometriomas); and deep nodules, often involving the bowel. They look different, behave differently, and the genetic signal is strongest for the ovarian form.

Your “stage” describes anatomy, not how much it hurts or how fertile you are. The I–IV system scores what a surgeon sees. In over a thousand women, the link between stage and pain was “marginal and inconsistent” (Vercellini et al., 2007). Stage I is not trivial. Stage IV is not a verdict.

You no longer need keyhole surgery to be diagnosed. The 2022 European guideline says plainly that “laparoscopy is no longer the diagnostic gold standard” and puts ultrasound or MRI first (Becker et al., 2022). NICE followed in 2024. The caveat is real: a normal scan does not exclude superficial disease. A saliva test validated in 2025 is being trialled in NHS primary care, but its accuracy outside specialist clinics is unknown. Even now, the average wait for a diagnosis in the UK is over nine years (Endometriosis UK, 2026). If your symptoms have been dismissed, that is a system failure, not proof that nothing is wrong. (For the tests that belong in a first fertility work-up, see when to start fertility testing.)

---

Why does endometriosis happen? A century of theories in five minutes

In 1927 John Sampson proposed that period blood flows backwards through the fallopian tubes and seeds the pelvis with living cells (Sampson, 1927). A hundred years on, “retrograde menstruation” is still the starting point, and still what patients are told. It has a problem, though. When surgeons looked into the pelvis during periods, they found blood in 90% of women with open tubes, whether or not they had endometriosis (Halme et al., 1984). Backwards periods are common. Endometriosis affects one in ten. Something else decides who develops it.

Other theories came and went: pelvic lining cells transforming, embryonic remnants, stem cells from the bone marrow. Each explains a corner of the picture. By 2020 the field had settled on a more honest answer. Endometriosis is multifactorial: a seeding event, plus inherited susceptibility, plus an immune system that fails to clear the cells, plus a hormonal environment that lets them thrive (Zondervan et al., 2020).

Three findings pushed the story from “plumbing” to “biology”:

• It runs in families. Twin studies put the inherited share of risk at 47% (Saha et al., 2015). A 2026 study of 1.4 million women found 80 risk regions, many acting on nerve growth and pain, and shared with migraine, chronic pain and asthma (Koller et al., 2026). That is why so many women with endometriosis also have migraine: the genes overlap.
• Lesions carry “cancer-type” mutations without being cancer. Sequencing found them in 79% of deep lesions (Anglesio et al., 2017). The reassuring part: normal womb lining carries the same mutations. They help lesions survive and invade, not turn malignant.
• It affects the whole body. The 2021 Lancet review is titled “Endometriosis is a chronic systemic disease”, with altered metabolism in the liver and fat tissue, body-wide inflammation and changed gene expression in the brain (Taylor et al., 2021). The label is no longer controversial.

Twenty years ago the interesting question was where the cells come from. Today it is why the pelvis nourishes what it should clear. That question has two answers: immune and metabolic.

---

Endometriosis risk factors: what matters, what doesn’t

This question carries so much guilt that it deserves a plain answer: nothing you ate, drank or did is proven to cause endometriosis, and nothing is proven to prevent it. Much of the risk is set long before you make a single lifestyle choice.

Genes carry about half of it. There is still no useful genetic test, so if you have daughters, tell them your history: their pain deserves to be taken seriously sooner.

Your cycle leaves clues. Short cycles and an early first period mean more menstrual flow over a lifetime, and modestly higher risk (Wei et al., 2016; Lu et al., 2023). Severe period pain as a teenager is an early sign, not a cause.

Pregnancy and breastfeeding are linked to lower risk (Missmer et al., 2004; Youseflu et al., 2022), though part of that link runs backwards: hidden endometriosis makes pregnancy harder.

Two beliefs worth correcting. The pill masks pain and delays diagnosis; it has never been shown to prevent endometriosis (Vercellini et al., 2011). And being slim did not cause it: genetic studies find no causal effect of body weight (Venkatesh et al., 2022).

Lifestyle and environment: links, not causes. An umbrella review of 40 environmental factors in over five million women found none with convincing evidence (Zhang and Ma, 2021). A healthy eating pattern was linked to 13% lower risk and a “Western” one to 27% higher (Dougan et al., 2024); smoking shows no link (Bravi et al., 2014). One finding deserves a gentle mention: physical or sexual abuse in childhood is linked to higher risk (Harris, Wieser et al., 2018), possibly through the way the nervous system learns pain. If that is part of your story, you deserve care that understands it.

---

Endometriosis and the immune system: a pelvis that feeds what it should clear

If backwards periods are near-universal, the immune system’s job is to mop them up. In endometriosis it doesn’t. Worse, it helps.

Macrophages are the gardeners. The most common immune cells in lesions, they feed lesion growth, grow blood vessels and wire in new nerve fibres, and oestrogen keeps that conversation going. Which ones arrive matters: those carried in with the shed lining promote disease, fresh ones from the blood suppress it (Hogg et al., 2021). The goal is shifting from suppressing the immune system to re-programming it.

Natural killer cells are switched off. These cells should destroy stray endometrial cells. In endometriosis they carry more “off” receptors and fewer “on” receptors. Their numbers in pelvic fluid are normal; their function fails (Adamyan et al., 2026). It is a won’t, not a can’t.

The pelvic fluid is hostile. It carries more inflammatory messengers and reactive oxygen, and it bathes the ovaries and the open ends of the tubes. At ovulation the egg is released into this fluid before the tube catches it, and some of the fluid seeps into the tube where egg and sperm meet. In the laboratory, this fluid disrupts the scaffold that sorts chromosomes in the egg. That may be one reason natural conception is less efficient with endometriosis, while IVF, where egg and sperm meet in the lab, bypasses it.

And the nerves? Because lesions grow their own nerves and the nervous system learns the pain, pain can persist after every visible lesion has been removed. It is not “in your head”. It is, quite literally, in your nervous system.

---

Endometriosis as a metabolic condition: sugar-burning lesions, iron and progesterone resistance

This is the part of the science that has changed most, and the part patients hear least about.

Lesions run a cancer-like metabolism. They burn glucose without oxygen, the way tumours do, which fuels invasion and blood-vessel growth. A cheap, repurposed drug, dichloroacetate, reversed this in the dish and shrank lesions in mice (Horne et al., 2019). The honest status: a 30-woman feasibility study in 2025, some temporary nerve side effects, and no placebo-controlled trial yet (Whitaker et al., 2025). Nobody should be buying it online, but a non-hormonal, metabolic treatment is finally being tested properly.

Endometriomas are iron-saturated. Free iron inside a chocolate cyst runs at more than a thousand times the level in other ovarian cysts, and the oxidative stress it creates harms the cells that nurse the egg (Ni et al., 2022). That is why women with endometriomas produce fewer eggs that mature less reliably. It does not make embryos more often chromosomally abnormal (more on that below).

The tissue makes its own oestrogen and ignores progesterone. Lesions contain the enzyme that manufactures oestrogen locally, even when blood levels are normal, and they lack the progesterone receptor that should switch it off (Bulun et al., 2019). This “progesterone resistance” is the molecular heart of the disease. It also spills into the womb lining itself, which becomes a little less receptive to an embryo. Not unreceptive. A little less. We’ll put a number on that shortly.

The heart. In a Danish registry of 60,000 women, heart-attack risk was about a third higher over 16 years, though overall mortality was actually lower (Havers-Borgersen et al., 2024). The absolute risk at reproductive age is low. This is a reason for ordinary heart-health habits across your life, not alarm. And the gut? We cover the gut–endometriosis connection separately: the mouse evidence is compelling, the human evidence still small and inconsistent.

---

Can you get pregnant naturally with endometriosis?

Very often, yes. The figures usually quoted are that endometriosis is found in 25–50% of women investigated for infertility, that 30–50% of women with endometriosis struggle to conceive, and that the monthly chance of pregnancy is around 2–10% against 15–20% in unaffected couples (ASRM, 2012). Those are old, cross-sectional estimates. The best prospective data come from the Nurses’ Health Study, which followed 58,000 women. Confirmed endometriosis roughly doubled the risk of later infertility, but only in women under 35. After 35, age itself dominated. And the most reassuring statistic: 83% of women with endometriosis had a child by 40 (Prescott et al., 2016).

How does it interfere? Not in one place, but at four checkpoints on the way to a baby. That map also shows where treatment can help.

Surgery: helpful, but not the way it used to be sold

In the landmark trial, keyhole treatment of mild disease roughly doubled the monthly pregnancy rate, from 2.4 to 4.7 per 100 months (Marcoux et al., 1997). Cochrane pools this with later trials into a 1.9-fold improvement in viable pregnancy, with no trial ever reporting live birth (Bafort et al., 2020). In the UK, NICE recommends offering keyhole surgery to remove or destroy endometriosis and free adhesions when the bowel, bladder and ureters aren’t involved, because it improves the chance of natural pregnancy. Deep disease involving those organs is a case-by-case decision, weighing benefits and risks together (NICE, 2024). What guidelines no longer recommend is a laparoscopy just to look.

After surgery, ask for your Endometriosis Fertility Index (EFI). It scores your age, how long you’ve been trying, previous pregnancies, and how well your tubes and ovaries work at the end of the operation. It genuinely predicts natural pregnancy: around 60–70% within three years with a score of 9–10, versus 10–18% with a score of 0–4, where IVF sooner is wiser.

Endometriomas need care. The cyst itself already lowers AMH, and AMH falls 26% in six months with an untreated endometrioma versus 7% in healthy women (Kasapoglu et al., 2018). Stripping the cyst removes healthy ovary too, dropping AMH by about a further 1.1 ng/mL. NICE recommends offering surgery for endometriomas when you’re hoping to conceive naturally, either removing the cyst wall or draining and ablating it, but only after weighing the effect on egg reserve; drainage and ablation may protect reserve better (NICE, 2024). So removing a cyst isn’t automatic. Before IVF, the European guideline advises against routine cyst surgery: operate for pain, size, diagnostic doubt or access at egg collection. Not to improve IVF, which it doesn’t.

Two things that don’t improve natural fertility

Hormonal suppression. The pill, progestogens such as dienogest, and GnRH analogues control pain and slow progression. They do not improve your chance of conceiving afterwards, and there is no “washout bonus”. Both ESHRE and NICE say so in strong terms. Think of them as a bridge while you plan, not a fertility treatment.

Waiting too long. In mild disease, expectant management gives about 2–3% a month. Ovarian stimulation with insemination lifted the live-birth rate per cycle from 2% to 11% in the only randomised trial (Tummon et al., 1997). Under 35 with endometriosis and six to twelve months of trying, or over 35 and six months: ask for an assessment now.

---

Endometriosis and IVF success rates: what the numbers say

What consistently differs is egg numbers: on average one to two fewer eggs with ovarian disease. Fertilisation and embryo quality are only modestly affected. (New to IVF? Start with how IVF works.)

Is it the egg or the womb? What donor eggs tell us

Egg donation is the clever way to separate the two. In early studies, women with endometriosis who received donor eggs conceived as well as anyone, while eggs from donors with endometriosis implanted less well, pointing at the egg (Simón et al., 1994). Then the story got more nuanced. In 13,600 UK cycles, switching to donor eggs did not improve live birth for women with endometriosis, and registry data show a small, real reduction in live birth among recipients with the disease, about 10% (Paffoni et al., 2024). The synthesis: both contribute. The egg is the larger factor, the lining the smaller one.

And the reassuring part: embryos from women with endometriosis are not more often chromosomally abnormal. In 1,880 tested embryos, abnormality rates matched women of the same age without the disease (Juneau et al., 2017). After transfer of a chromosomally normal embryo, pregnancy, loss and live-birth rates were no different (Bishop et al., 2021).

What helps before IVF, and what we’ve stopped doing

• Freeze-all. Transferring frozen embryos in a later, calmer cycle is linked to about 30% higher live-birth odds in endometriosis (Han et al., 2025). Observational, but widely and reasonably used.
• Don’t remove an endometrioma just for IVF. It didn’t improve live birth and it costs ovarian reserve. ESHRE’s recommendation against it is a strong one.
• Months of “down-regulation” are out. The 2019 Cochrane update found the old evidence very weak and, in the one trial reporting it, live birth was lower (Georgiou et al., 2019). Dienogest pre-treatment fares no better.
• ICSI adds nothing unless there’s a sperm problem. (See IUI, IVF and ICSI explained.)
• Protect egg numbers. Adequate stimulation and, where reserve is low, banking eggs or embryos over more than one cycle. If endometrioma surgery is unavoidable, freezing eggs first is worth discussing.

---

Endometriosis, implantation and miscarriage risk

Counter-intuitively, mild disease is not “safer”: in a Swiss study the miscarriage rate was highest in mild, superficial disease (Kohl Schwartz et al., 2017), which points at inflammation rather than anatomy. Ectopic pregnancy risk roughly doubles, so an early scan to confirm the pregnancy is in the womb is sensible, not paranoid.

After IVF, the extra risk largely disappears. Across 39 studies, miscarriage odds were 1.8 times higher after natural conception but no different after IVF (Huang et al., 2020). Two findings explain why. The embryos are not the problem: when miscarried tissue was tested, chromosomal abnormality rates were the same as in other women, so endometriosis-related losses are mostly of normal embryos, an environment effect (Kong et al., 2025). And after transfer of a chromosomally normal embryo, loss rates were no higher. The remaining risk after IVF sits mainly with women who also have adenomyosis.

Recurrent miscarriage (three or more) is somewhat more common. Endometriosis surgery has never been shown to prevent further losses; the ESHRE recurrent-loss guideline suggests looking for adenomyosis instead. Later in pregnancy, there are small increases in low-lying placenta (roughly 0.5% to 1.5%), preterm birth and caesarean. ESHRE’s view is that these do not justify extra monitoring or discourage pregnancy, but do tell your maternity team.

What does not (yet) have evidence: endometrial receptivity (ERA) testing, which failed its definitive trial; aspirin, heparin or immune therapies, never tested in endometriosis; and progesterone in early pregnancy, which helps only women with bleeding and previous miscarriages (Coomarasamy et al., 2019).

---

Diet, supplements and lifestyle: the short version

No diet, supplement or lifestyle change has been shown to improve your chance of pregnancy with endometriosis (Becker et al., 2022). But safe changes, such as Mediterranean-style eating, movement, sleep and stress care, can ease pain, calm the gut and help you cope while you plan treatment. For every popular tip fact-checked, and what actually helps, read Endometriosis Diet and Lifestyle Tips: What Works and What’s Hype, or grab the free endometriosis cheat sheet. If you’re heading for IVF, our 90-day preparation plan has the practical version. Our evidence-graded guide to supplements for endometriosis is coming next.

---

Endometriosis and fertility treatment: the options, ranked

Pulling it together for the woman who wants a baby, here is how the endometriosis and fertility options rank, and what each is actually for.

---

The bottom line

Endometriosis and fertility, in seven lines:

• Endometriosis is a whole-body immune and metabolic condition that shows up in the pelvis. Not “tissue in the wrong place”, and nothing you caused.
• Stage is anatomy, not prognosis. Mild disease can matter as much for fertility and miscarriage as severe disease.
• Natural fertility is roughly halved, mainly under 35, and most women with endometriosis still have children.
• IVF is effective: fewer eggs, slightly lower implantation, comparable live births. Don’t strip an endometrioma or spend months on down-regulation just for IVF.
• Miscarriage and ectopic risk are higher after natural conception and largely normalise after IVF, unless adenomyosis is present. So scan for it.
• Hormonal treatment is a bridge, not a fertility treatment. Lifestyle is scaffolding, not a cure.
• Genuinely new, non-hormonal treatments are in trials for the first time, built on exactly the immune and metabolic science above.

---

When personalised guidance makes the difference

If you’ve been told “it’s endometriosis, try IVF” without anyone explaining which endometriosis, whether adenomyosis is there too, what your reserve looks like, or whether a few months of trying with the right help is still sensible at your age, you deserve a proper conversation. These are the results that should shape it:

---

Common questions about endometriosis and fertility

+

Real questions from patients, answered directly, without the vagueness.

Can I get pregnant naturally with endometriosis?+

Very often, yes. Endometriosis roughly halves natural fertility, mainly in women under 35, but in a large prospective study 83% of women with endometriosis had a child by 40. Mild disease with open tubes and normal sperm can be given time or helped with stimulation and insemination. More severe disease, low ovarian reserve or age over 35 usually mean IVF sooner is wiser.

Does endometriosis lower IVF success rates?+

A little, not a lot. Women with endometriosis produce fewer eggs and implantation per embryo is somewhat lower, mainly in stage III/IV disease, but pooled live-birth rates are close to those of other diagnoses. In a Swedish cohort, cumulative live birth over three cycles was 53% versus 69%. Freeze-all and protecting egg numbers help; endometrioma surgery and months of down-regulation before IVF do not.

Does endometriosis increase the risk of miscarriage?+

After natural conception, yes: about 1.4 to 1.8 times the background rate, roughly 15% of pregnancies versus 10%, with the highest rates in mild disease. After IVF the extra risk largely disappears, particularly after transfer of a chromosomally normal embryo, because the embryos themselves are not more often abnormal. Adenomyosis is the exception: it roughly doubles miscarriage risk even after IVF.

Should I have surgery before IVF?+

Usually not for the sake of IVF. Removing an endometrioma before IVF does not improve live birth and lowers ovarian reserve, so guidelines recommend against it routinely. Surgery is reserved for pain, very large cysts, diagnostic doubt or cysts that block access to follicles. If surgery is unavoidable, ask about egg freezing first and about drainage and ablation rather than stripping.

Should I take hormonal treatment before trying to conceive?+

Not to improve fertility. The pill, progestogens such as dienogest and GnRH analogues control pain and slow progression but do not increase spontaneous pregnancy rates, and there is no “washout” benefit. Prolonged GnRH-agonist treatment before IVF is no longer recommended either. Hormonal treatment is a bridge between attempts, not a fertility treatment.

Is endometriosis an autoimmune disease?+

No. It is immune-dysregulated: natural killer cells fail to clear stray cells, macrophages feed the lesions, and the pelvic fluid is inflammatory. But there is no causal antibody and it does not respond to immunosuppression. Women with endometriosis are modestly more likely to be diagnosed with autoimmune conditions such as lupus, rheumatoid arthritis, Sjögren’s or coeliac disease, so new joint, dryness, thyroid or gut symptoms deserve proper investigation.

Can diet or supplements treat endometriosis or improve my chances?+

No diet or supplement has been shown in a randomised trial to improve pregnancy or live birth in endometriosis, and both ESHRE and NICE say so. Safe changes can still ease pain and bloating: see our guide to endometriosis diet and lifestyle tips. A full supplements guide is coming next.

How is endometriosis diagnosed now?+

By expert transvaginal ultrasound or MRI first; laparoscopy is no longer the diagnostic gold standard and is reserved for negative imaging or treatment failure. A normal scan does not rule out superficial disease. A saliva test validated in 2025 is being trialled in NHS primary care but is not yet routine. Diagnosis still takes over nine years on average in the UK, so push if your symptoms are dismissed.

Dr Helena Cepparo Consultant Gynaecologist & Fertility Specialist · AFMCP Functional Medicine Over 20 years of experience in reproductive medicine and IVF, with international training across Italy, Canada, Japan and the UK. Dr Cepparo takes a root-cause approach to fertility — integrating evidence-based medicine with functional medicine to create personalised plans. She founded MyFertilityPod to make clear, evidence-based fertility information accessible to everyone. She practises at a private fertility clinic in Central London.

References & Scientific Sources

+

87 sources, with links to the original papers.

1. World Health Organization. Endometriosis — fact sheet. Updated 15 October 2025. who.int
2. Zondervan KT, Becker CM, Missmer SA. Endometriosis. New England Journal of Medicine. 2020;382(13):1244–1256. doi:10.1056/NEJMra1810764
3. Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet. 2021;397(10276):839–852. doi:10.1016/S0140-6736(21)00389-5
4. Saunders PTK, Horne AW. Endometriosis: etiology, pathobiology, and therapeutic prospects. Cell. 2021;184(11):2807–2824. doi:10.1016/j.cell.2021.04.041
5. Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;379:e070750. doi:10.1136/bmj-2022-070750
6. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. American Journal of Obstetrics and Gynecology. 1927;14(4):422–469. doi:10.1016/S0002-9378(15)30003-X
7. Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstetrics & Gynecology. 1984;64(2):151–154. PubMed 6234483
8. Viganò P, Caprara F, Giola F, et al. Is retrograde menstruation a universal, recurrent, physiological phenomenon? A systematic review of the evidence in humans and non-human primates. Human Reproduction Open. 2024;2024(3):hoae045. doi:10.1093/hropen/hoae045
9. Saha R, Pettersson HJ, Svedberg P, et al. Heritability of endometriosis. Fertility and Sterility. 2015;104(4):947–952. doi:10.1016/j.fertnstert.2015.06.035
10. Rahmioglu N, Mortlock S, Ghiasi M, et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nature Genetics. 2023;55(3):423–436. doi:10.1038/s41588-023-01323-z
11. Koller D, He J, Løkhammer S, et al. Multi-ancestry genome-wide association and integrated multi-omics analyses of endometriosis and its clinical manifestations. Nature Genetics. 2026;58(5):1051–1061. doi:10.1038/s41588-026-02582-2
12. Anglesio MS, Papadopoulos N, Ayhan A, et al. Cancer-associated mutations in endometriosis without cancer. New England Journal of Medicine. 2017;376(19):1835–1848. doi:10.1056/NEJMoa1614814
13. Becker CM, Bokor A, Heikinheimo O, et al; ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Human Reproduction Open. 2022;2022(2):hoac009. doi:10.1093/hropen/hoac009
14. National Institute for Health and Care Excellence. Endometriosis: diagnosis and management. NICE guideline NG73. 2017, updated November 2024. nice.org.uk/guidance/ng73
15. De Corte P, Klinghardt M, von Stockum S, et al. Time to diagnose endometriosis: current status, challenges and regional characteristics — a systematic literature review. BJOG. 2025;132(2):118–130. doi:10.1111/1471-0528.17973
16. Endometriosis UK. The State of Endometriosis Care in the UK: a roadmap for driving down diagnosis times and improving access to care. March 2026. endometriosis-uk.org
17. Bendifallah S, Roman H, Suisse S, et al. Validation of a saliva micro-RNA signature for endometriosis. NEJM Evidence. 2025;4(11):EVIDoa2400195. doi:10.1056/EVIDoa2400195
18. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Human Reproduction. 2007;22(1):266–271. doi:10.1093/humrep/del339
19. Greaves E, Temp J, Esnal-Zufiurre A, Mechsner S, Horne AW, Saunders PTK. Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis. American Journal of Pathology. 2015;185(8):2286–2297. doi:10.1016/j.ajpath.2015.04.012
20. Forster R, Sarginson A, Velichkova A, et al. Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis. FASEB Journal. 2019;33(10):11210–11222. doi:10.1096/fj.201900797R
21. Hogg C, Panir K, Dhami P, et al. Macrophages inhibit and enhance endometriosis depending on their origin. Proceedings of the National Academy of Sciences. 2021;118(6):e2013776118. doi:10.1073/pnas.2013776118
22. Henlon Y, Panir K, McIntyre I, et al. Single-cell analysis identifies distinct macrophage phenotypes associated with prodisease and proresolving functions in the endometriotic niche. Proceedings of the National Academy of Sciences. 2024;121(38):e2405474121. doi:10.1073/pnas.2405474121
23. Reis JL, Rosa NN, Ângelo-Dias M, Martins C, Borrego LM, Lima J. Natural killer cell receptors and endometriosis: a systematic review. International Journal of Molecular Sciences. 2022;24(1):331. doi:10.3390/ijms24010331
24. Adamyan L, Pivazyan L, Kurbatova K, Barsegyan S, Mailova K, Stepanian A. Alterations in cellular immunity in patients with endometriosis: systematic review and meta-analysis. American Journal of Reproductive Immunology. 2026;96(2):e70296. doi:10.1111/aji.70296
25. Shigesi N, Kvaskoff M, Kirtley S, et al. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Human Reproduction Update. 2019;25(4):486–503. doi:10.1093/humupd/dmz014
26. Aziz M, Beaton MA, Aziz MA, Opoku-Anane J, Elhadad N. Endometriosis and autoimmunity: a large-scale case-control study of endometriosis and 10 distinct autoimmune diseases. npj Women’s Health. 2025;3(1):36. doi:10.1038/s44294-025-00086-8
27. Young VJ, Brown JK, Maybin J, Saunders PTK, Duncan WC, Horne AW. Transforming growth factor-β induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis. Journal of Clinical Endocrinology & Metabolism. 2014;99(9):3450–3459. doi:10.1210/jc.2014-1026
28. Horne AW, Ahmad SF, Carter R, et al. Repurposing dichloroacetate for the treatment of women with endometriosis. Proceedings of the National Academy of Sciences. 2019;116(51):25389–25391. doi:10.1073/pnas.1916144116
29. Whitaker LHR, Williams LJ, Koscielniak M, et al. Dichloroacetate for the treatment of endometriosis-associated pain (EPiC1): a single-arm feasibility study. The Lancet Obstetrics, Gynaecology & Women’s Health. 2025;1(3):e189–e197. doi:10.1016/j.lanogw.2025.100028
30. Yamaguchi K, Mandai M, Toyokuni S, et al. Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clinical Cancer Research. 2008;14(1):32–40. doi:10.1158/1078-0432.CCR-07-1614
31. Ni Z, Li Y, Song D, et al. Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity. Cell Death & Disease. 2022;13(7):579. doi:10.1038/s41419-022-05037-8
32. Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis. Endocrine Reviews. 2019;40(4):1048–1079. doi:10.1210/er.2018-00242
33. Lessey BA, Kim JJ. Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why. Fertility and Sterility. 2017;108(1):19–27. doi:10.1016/j.fertnstert.2017.05.031
34. Shah DK, Correia KF, Vitonis AF, Missmer SA. Body size and endometriosis: results from 20 years of follow-up within the Nurses’ Health Study II prospective cohort. Human Reproduction. 2013;28(7):1783–1792. doi:10.1093/humrep/det120
35. Venkatesh SS, Ferreira T, Benonisdottir S, et al. Obesity and risk of female reproductive conditions: a Mendelian randomisation study. PLOS Medicine. 2022;19(2):e1003679. doi:10.1371/journal.pmed.1003679
36. Havers-Borgersen E, Hartwell D, Ekelund C, et al. Endometriosis and long-term cardiovascular risk: a nationwide Danish study. European Heart Journal. 2024;45(44):4734–4743. doi:10.1093/eurheartj/ehae563
37. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertility and Sterility. 2012;98(3):591–598. doi:10.1016/j.fertnstert.2012.05.031
38. Prescott J, Farland LV, Tobias DK, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Human Reproduction. 2016;31(7):1475–1482. doi:10.1093/humrep/dew085
39. Marcoux S, Maheux R, Bérubé S; Canadian Collaborative Group on Endometriosis. Laparoscopic surgery in infertile women with minimal or mild endometriosis. New England Journal of Medicine. 1997;337(4):217–222. doi:10.1056/NEJM199707243370401
40. Bafort C, Beebeejaun Y, Tomassetti C, Bosteels J, Duffy JMN. Laparoscopic surgery for endometriosis. Cochrane Database of Systematic Reviews. 2020;10:CD011031. doi:10.1002/14651858.CD011031.pub3
41. Adamson GD, Pasta DJ. Endometriosis fertility index: the new, validated endometriosis staging system. Fertility and Sterility. 2010;94(5):1609–1615. doi:10.1016/j.fertnstert.2009.09.035
42. Vesali S, Razavi M, Rezaeinejad M, Maleki-Hajiagha A, Maroufizadeh S, Sepidarkish M. Endometriosis fertility index for predicting non-assisted reproductive technology pregnancy after endometriosis surgery: a systematic review and meta-analysis. BJOG. 2020;127(7):800–809. doi:10.1111/1471-0528.16107
43. Muzii L, Di Tucci C, Di Feliciantonio M, et al. Antimüllerian hormone is reduced in the presence of ovarian endometriomas: a systematic review and meta-analysis. Fertility and Sterility. 2018;110(5):932–940.e1. doi:10.1016/j.fertnstert.2018.06.025
44. Kasapoglu I, Ata B, Uyaniklar O, et al. Endometrioma-related reduction in ovarian reserve (ERROR): a prospective longitudinal study. Fertility and Sterility. 2018;110(1):122–127. doi:10.1016/j.fertnstert.2018.03.015
45. Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism. 2012;97(9):3146–3154. doi:10.1210/jc.2012-1558
46. Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database of Systematic Reviews. 2007;(3):CD000155. doi:10.1002/14651858.CD000155.pub2
47. Tummon IS, Asher LJ, Martin JS, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertility and Sterility. 1997;68(1):8–12. doi:10.1016/s0015-0282(97)81467-7
48. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertility and Sterility. 2002;77(6):1148–1155. doi:10.1016/s0015-0282(02)03112-6
49. 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. doi:10.1111/1471-0528.12366
50. Mappa I, Page ZP, Di Mascio D, et al. The effect of endometriosis on in vitro fertilization outcomes: a systematic review and meta-analysis. Healthcare. 2024;12(23):2435. doi:10.3390/healthcare12232435
51. Senapati S, Sammel MD, Morse C, Barnhart KT. Impact of endometriosis on in vitro fertilization outcomes: an evaluation of the Society for Assisted Reproductive Technologies Database. Fertility and Sterility. 2016;106(1):164–171.e1. doi:10.1016/j.fertnstert.2016.03.037
52. Alson S, Stenqvist A, Sladkevicius P. Cumulative live birth rates under three consecutive IVF/ICSI treatment cycles are reduced in women with endometriosis and/or adenomyosis diagnosed by ultrasonography. Human Reproduction. 2025;40(12):2332–2341. doi:10.1093/humrep/deaf184
53. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Human Reproduction Update. 2019;25(5):592–632. doi:10.1093/humupd/dmz012
54. Simón C, Gutiérrez A, Vidal A, et al. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Human Reproduction. 1994;9(4):725–729. doi:10.1093/oxfordjournals.humrep.a138578
55. Kamath MS, Subramanian V, Antonisamy B, Sunkara SK. Endometriosis and oocyte quality: an analysis of 13 614 donor oocyte recipient and autologous IVF cycles. Human Reproduction Open. 2022;2022(3):hoac025. doi:10.1093/hropen/hoac025
56. Paffoni A, Casalechi M, De Ziegler D, et al. Live birth after oocyte donation in vitro fertilization cycles in women with endometriosis: a systematic review and meta-analysis. JAMA Network Open. 2024;7(1):e2354249. doi:10.1001/jamanetworkopen.2023.54249
57. Juneau C, Kraus E, Werner M, et al. Patients with endometriosis have aneuploidy rates equivalent to their age-matched peers in the in vitro fertilization population. Fertility and Sterility. 2017;108(2):284–288. doi:10.1016/j.fertnstert.2017.05.038
58. Bishop LA, Gunn J, Jahandideh S, Devine K, Decherney AH, Hill MJ. Endometriosis does not impact live-birth rates in frozen embryo transfers of euploid blastocysts. Fertility and Sterility. 2021;115(2):416–422. doi:10.1016/j.fertnstert.2020.07.050
59. Han Y, Liu C, Liu D, Wu L, Huang W. Pregnancy outcomes in freeze-all versus fresh embryo transfer cycles of women with adenomyosis and endometriosis: a systemic review and meta-analysis. Frontiers in Endocrinology. 2025;16:1507252. doi:10.3389/fendo.2025.1507252
60. Hamdan M, Dunselman G, Li TC, Cheong Y. The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis. Human Reproduction Update. 2015;21(6):809–825. doi:10.1093/humupd/dmv035
61. Georgiou EX, Melo P, Baker PE, et al. Long-term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis. Cochrane Database of Systematic Reviews. 2019;11:CD013240. doi:10.1002/14651858.CD013240.pub2
62. Cobo A, Giles J, Paolelli S, Pellicer A, Remohí J, García-Velasco JA. Oocyte vitrification for fertility preservation in women with endometriosis: an observational study. Fertility and Sterility. 2020;113(4):836–844. doi:10.1016/j.fertnstert.2019.11.017
63. Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, et al. Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: a systematic review and meta-analysis. Reproductive BioMedicine Online. 2021;42(1):185–206. doi:10.1016/j.rbmo.2020.09.023
64. Bourdon M, Mimouni A, Maignien C, et al. Reduced live birth rates following ART in adenomyosis patients: a matched control study. Human Reproduction. 2025;40(5):855–864. doi:10.1093/humrep/deaf052
65. Saraswat L, Ayansina DT, Cooper KG, et al. Pregnancy outcomes in women with endometriosis: a national record linkage study. BJOG. 2017;124(3):444–452. doi:10.1111/1471-0528.13920
66. Farland LV, Prescott J, Sasamoto N, et al. Endometriosis and risk of adverse pregnancy outcomes. Obstetrics & Gynecology. 2019;134(3):527–536. doi:10.1097/AOG.0000000000003410
67. Gurney JM, Tuominen A, Saavalainen J, et al. Endometriosis and early pregnancy outcomes: a registry-based cohort study in Finland. American Journal of Obstetrics and Gynecology. 2026;234(6):1650–1661. doi:10.1016/j.ajog.2026.01.027
68. Kohl Schwartz AS, Wölfler MM, Mitter V, et al. Endometriosis, especially mild disease: a risk factor for miscarriages. Fertility and Sterility. 2017;108(5):806–814.e2. doi:10.1016/j.fertnstert.2017.08.025
69. Huang Y, Zhao X, Chen Y, Wang J, Zheng W, Cao L. Miscarriage on endometriosis and adenomyosis in women by assisted reproductive technology or with spontaneous conception: a systematic review and meta-analysis. BioMed Research International. 2020;2020:4381346. doi:10.1155/2020/4381346
70. Kong H, Fan W, Ye T, Du L. Endometriosis does not impact aneuploidy rates of products of conception in IVF population. Scientific Reports. 2025;15(1):2193. doi:10.1038/s41598-025-86656-x
71. Boje AD, Egerup P, Westergaard D, et al. Endometriosis is associated with pregnancy loss: a nationwide historical cohort study. Fertility and Sterility. 2023;119(5):826–835. doi:10.1016/j.fertnstert.2022.12.042
72. Breintoft K, Pinnerup R, Henriksen TB, et al. Endometriosis and risk of adverse pregnancy outcome: a systematic review and meta-analysis. Journal of Clinical Medicine. 2021;10(4):667. doi:10.3390/jcm10040667
73. Doyle N, Jahandideh S, Hill MJ, Widra EA, Levy M, Devine K. Effect of timing by endometrial receptivity testing vs standard timing of frozen embryo transfer on live birth in patients undergoing in vitro fertilization: a randomized clinical trial. JAMA. 2022;328(21):2117–2125. doi:10.1001/jama.2022.20438
74. Coomarasamy A, Devall AJ, Cheed V, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. New England Journal of Medicine. 2019;380(19):1815–1824. doi:10.1056/NEJMoa1813730
75. Wen X, Xiong Y, Qu X, et al. The risk of endometriosis after exposure to endocrine-disrupting chemicals: a meta-analysis of 30 epidemiology studies. Gynecological Endocrinology. 2019;35(8):645–650. doi:10.1080/09513590.2019.1590546
76. Zhang Y, Liu H, Feng C, Yang Y, Cui L. Prevalence of sleep disturbances in endometriosis patients: a systematic review and meta-analysis. Frontiers in Psychiatry. 2024;15:1405320. doi:10.3389/fpsyt.2024.1405320
77. Tomassetti C, Johnson NP, Petrozza J, et al; International Working Group of AAGL, ESGE, ESHRE and WES. An international terminology for endometriosis, 2021. Human Reproduction Open. 2021;2021(4):hoab029. doi:10.1093/hropen/hoab029
78. Wei M, Cheng Y, Bu H, Zhao Y, Zhao W. Length of menstrual cycle and risk of endometriosis: a meta-analysis of 11 case-control studies. Medicine (Baltimore). 2016;95(9):e2922. doi:10.1097/MD.0000000000002922
79. Lu MY, Niu JL, Liu B. The risk of endometriosis by early menarche is recently increased: a meta-analysis of literature published from 2000 to 2020. Archives of Gynecology and Obstetrics. 2023;307(1):59–69. doi:10.1007/s00404-022-06541-0
80. Missmer SA, Hankinson SE, Spiegelman D, et al. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. American Journal of Epidemiology. 2004;160(8):784–796. doi:10.1093/aje/kwh275
81. Youseflu S, Savabi-Esfahani M, Asghari-Jafarabadi M, Maleki A. The protective effect of breastfeeding and ingesting human breast milk on subsequent risk of endometriosis in mother and child: a systematic review and meta-analysis. Breastfeeding Medicine. 2022;17(10):805–816. doi:10.1089/bfm.2022.0126
82. Vercellini P, Eskenazi B, Consonni D, et al. Oral contraceptives and risk of endometriosis: a systematic review and meta-analysis. Human Reproduction Update. 2011;17(2):159–170. doi:10.1093/humupd/dmq042
83. Venkatesh SS, Ferreira T, Benonisdottir S, et al. Obesity and risk of female reproductive conditions: a Mendelian randomisation study. PLoS Medicine. 2022;19(2):e1003679. doi:10.1371/journal.pmed.1003679
84. Zhang Y, Ma NY. Environmental risk factors for endometriosis: an umbrella review of a meta-analysis of 354 observational studies with over 5 million populations. Frontiers in Medicine. 2021;8:680833. doi:10.3389/fmed.2021.680833
85. Dougan MM, Fest S, Cushing-Haugen K, et al. A prospective study of dietary patterns and the incidence of endometriosis diagnosis. American Journal of Obstetrics and Gynecology. 2024;231(4):443.e1–443.e10. doi:10.1016/j.ajog.2024.04.030
86. Bravi F, Parazzini F, Cipriani S, et al. Tobacco smoking and risk of endometriosis: a systematic review and meta-analysis. BMJ Open. 2014;4(12):e006325. doi:10.1136/bmjopen-2014-006325
87. Harris HR, Wieser F, Vitonis AF, et al. Early life abuse and risk of endometriosis. Human Reproduction. 2018;33(9):1657–1668. doi:10.1093/humrep/dey248