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Fertility and the womb lining

A thin womb lining is one reason embryo transfers fail. A 2023 study matched 41 women with a persistently thin lining who had hyperbaric oxygen against similar women who did not, and found a thicker lining and a higher pregnancy rate with blastocyst transfer in the treated group. An earlier small randomised study in unexplained infertility reported better lining thickness and blood flow. Both are small and neither is a large randomised trial, so we treat this as an area to watch rather than a promise.

Evidence so far
Early
Reading timeAbout 12 minutes

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Why this is being studied

For an embryo to implant, the lining of the womb needs to grow thick enough each month and develop a rich supply of small blood vessels; doctors call the combination of thickness, structure and blood flow 'receptivity'. On the male side, sperm are easily damaged by oxidative stress. Because oxygen delivery underlies both lining growth and antioxidant defence, researchers have begun testing hyperbaric oxygen in thin-lining IVF cycles, in unexplained infertility and in male-factor infertility. The studies are small and mostly not randomised, and none of them should be read as a promise about pregnancy.

Where the evidence stands

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The mechanism

What is going on, and why this might help

What is going on in the body

A successful pregnancy needs a receptive endometrium: a lining that is thick enough, well vascularised and hormonally prepared to accept an embryo. A thin lining, defined in many clinics as under 7 mm, is associated with lower implantation rates in IVF, and is often linked to poor uterine blood flow, scarring from previous procedures or infection, or reduced responsiveness to oestrogen. On the male side, sperm quality is affected by oxidative stress and testicular blood flow. In the ovary, egg quality declines with age partly through mitochondrial dysfunction in the oocyte, and the follicular environment can be relatively hypoxic in poor responders.

Where oxygen comes in

The clearest rationale concerns the endometrium. Hyperbaric oxygen improves tissue oxygenation in poorly perfused tissue and induces angiogenesis via VEGF and HIF-1α signalling, mechanisms directly relevant to a thin, under-vascularised lining. A small human study reported increased endometrial thickness and improved uterine artery Doppler flow after a course of sessions in women with thin lining. Stem-cell mobilisation (Thom 2006) has been proposed as a route to endometrial regeneration in scarred uteri. For oocyte and sperm quality, effects on mitochondrial function are the main theoretical link, though hyperoxia also increases reactive oxygen species, so the balance between improved mitochondrial function and oxidative stress on gametes is not established. Anti-inflammatory effects are relevant in chronic endometritis and endometriosis-related infertility.

How solid is this

Largely theoretical with small uncontrolled human studies. There are no randomised trials showing improved live birth rates. The endometrial thickness and blood flow findings come from very small series (for example Mitrović et al. 2006), and the angiogenic mechanism is well established elsewhere, but effects on egg or sperm quality are speculative. Key references: Mitrović et al. 2006; Thom 2006 (stem-cell mobilisation).

Explainer illustration

The studies

Every study is laid out the same way: what the researchers wanted to find out, who took part, what they actually did, what they found, why it might work and where the limits are. No jargon, and a link to the original if you want to read it yourself.

Each study is laid out the same way: what the researchers asked, who took part, what they did, what they found, why it might work, and where the limits are. The clinician layer at the end of each one carries the numbers.

Paper 1

Hyperbaric oxygen therapy: a possible choice for patients with resistant thin endometrium during frozen embryo transfer treatments

Li et al. · Reproductive Biology and Endocrinology · 2023 · propensity-matched cohort, 41 matched pairs

Read the paper

What they asked

For an embryo to implant, the lining of the womb (the endometrium) needs to be thick enough and well enough supplied with blood. In IVF, a lining under about 7 millimetres on the day of embryo transfer is often treated as too thin, and some women's linings stay thin despite every standard remedy. Li and colleagues in Changsha, China, asked whether a course of hyperbaric oxygen could thicken a persistently thin lining and whether embryo transfers then went ahead.

Who took part

Women undergoing frozen embryo transfer whose previous cycles had been cancelled because the lining stayed under 7 millimetres despite standard and add-on treatments. From 398 women screened, 55 agreed to hyperbaric oxygen. Using statistical matching on factors such as age and lining history, 41 treated women were paired with 41 similar women who did not have the treatment. This is a matched cohort study, not a randomised trial.

What they did

Treated women attended daily sessions at 2.5 ATA, each lasting about 100 minutes in total (20 minutes pressurising, 60 minutes at pressure, 20 minutes depressurising), breathing 100 per cent oxygen for 70 minutes of that time. Sessions ran through the first half of the cycle, when the lining is building, and stopped on the day progesterone was started. The minimum course was 10 sessions; the average was about 28, with a wide spread. Lining thickness was measured by ultrasound before and after, and the team recorded whether the cycle was cancelled, whether embryos implanted, and pregnancy rates.

What they found

Average lining thickness rose from about 5.8 to 6.6 millimetres, a change of under one millimetre but statistically significant (p = 0.002). The proportion of cycles cancelled fell from 62 per cent to 19 per cent. In the matched comparison, the embryo implantation rate was 33 per cent in the treated group against 11 per cent in controls (p = 0.008). For women transferring blastocysts (day-5 embryos), clinical pregnancy was 54 per cent versus 18 per cent (p = 0.017); for earlier-stage embryos there was no difference. Live birth rates were not the focus and should not be inferred from these figures.

Why it might work

The endometrium regrows every cycle from a thin base layer, and that growth depends on the spiral arteries bringing blood and oxygen up through the tissue. A thin, poorly supplied lining is thought to be a relatively low-oxygen environment. Raising dissolved oxygen may support the growth of new capillaries and the proliferation of the lining cells, and may improve receptivity, the short window in which the lining can accept an embryo. The study did not measure blood flow directly, so this remains the proposed rather than the demonstrated mechanism.

Limits

Women chose whether to have treatment, so those who did may have differed in motivation or other unmeasured ways; matching reduces but does not remove that bias. Forty-one pairs is a small group and the pregnancy sub-analyses are smaller still. The number of sessions varied enormously. Doppler blood-flow measurements were not taken, and the authors note the timing of lining preparation was not uniform. The gain in thickness was small in absolute terms. No funding source was clearly stated in the version we read. A randomised trial is needed before any firm conclusion, and nothing here promises a pregnancy to any individual.

Paper 2

Hyperbaric oxygenation as a possible therapy of choice for infertility treatment

Mitrović et al. · Bosnian Journal of Basic Medical Sciences · 2006 · small randomised study, n=32

Read the paper

What they asked

Unexplained infertility is the label used when standard tests find no reason a couple has not conceived. One suspicion is that the womb lining is not developing as well as it looks. Mitrović and colleagues in Belgrade asked whether a short course of hyperbaric oxygen changed the structure and blood supply of the endometrium in women with unexplained infertility, as seen on ultrasound.

Who took part

Thirty-two women with unexplained infertility. The published abstract describes the design as randomised, but the comparison group and how it was formed are not clearly described in what we were able to access. This is a small, early study from 2006 and should be read as exploratory.

What they did

Women had seven consecutive daily sessions at 2.3 ATA, each lasting 70 minutes, in a multi-person chamber, starting on day 5 of the menstrual cycle, that is during the phase when the lining is regrowing. Transvaginal colour Doppler ultrasound, which measures both lining thickness and the resistance to blood flow in the vessels supplying it, was performed from cycle day 8 through to ovulation in three cycles: the month before treatment, the treatment cycle, and the month after.

What they found

In the treated cycles the lining reached an average thickness of about 11 millimetres at ovulation, which is comfortably within the range usually considered favourable. Doppler showed a dense network of small vessels within the lining with low resistance to flow (a resistance index below 0.45), which is the pattern associated with good perfusion. Interestingly, resistance in the main uterine arteries was slightly higher, suggesting the change was in the fine vessels of the lining itself rather than the bulk supply. The authors report that overall endometrial quality improved significantly during treatment cycles (p below 0.001). Pregnancy rates were not reported.

Why it might work

The endometrium is one of the few adult tissues that grows a whole new blood supply every month. That growth is driven partly by low-oxygen signalling early in the cycle, but the maturing lining then needs generous perfusion to become receptive. The hypothesis here is that additional dissolved oxygen during the growth phase supports the sprouting of new capillaries and the proliferation of glandular tissue, producing a thicker lining with lower vascular resistance. Doppler findings are consistent with that but cannot prove it.

Limits

Thirty-two women is small, and the lack of a clearly described control group means before-and-after changes could reflect normal cycle-to-cycle variation. Ultrasound measurements are operator-dependent and it is not stated whether the sonographer was blinded. The outcome is an imaging appearance, not a pregnancy or a birth. Seven sessions is a very short course. The study is nearly twenty years old and, to our knowledge, has not been replicated with a randomised design. It shows that lining appearance can change over a treatment cycle; it does not show that this helps anyone conceive.

Paper 3

Hyperbaric oxygen therapy for male infertility: a systematic review and meta-analysis on improving sperm quality and fertility outcomes

Medical Gas Research · 2025 · systematic review and meta-analysis

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What they asked

Roughly half of couples' fertility problems involve a male factor, most often low sperm count, poor motility, abnormal shape or fragmented sperm DNA. Oxidative stress, an imbalance between damaging reactive molecules and the body's antioxidant defences, is implicated in much of this. This 2025 systematic review and meta-analysis in Medical Gas Research pooled the available studies to ask whether hyperbaric oxygen improves semen quality or fertility outcomes in men. We were only able to read the abstract, and could not verify the author list, so this summary is deliberately cautious about detail.

Who took part

Men with infertility enrolled in the small number of published clinical studies of hyperbaric oxygen, mostly from Russia, Eastern Europe and Asia. The abstract indicates that the included studies were few and small, with a mix of designs and, in several cases, no control group. Exact numbers of studies and participants were not available to us.

What they did

The authors searched the major databases for studies in which infertile men received hyperbaric oxygen and semen parameters or pregnancy outcomes were measured before and after, or against a comparison group. Reported protocols in this literature typically range from about 1.5 to 2.5 ATA for 40 to 90 minutes, over 10 to 20 sessions, but the abstract does not give a pooled protocol. Standard meta-analytic methods were used to combine results, with heterogeneity assessed.

What they found

The abstract reports that hyperbaric oxygen was associated with improvements in one or more semen parameters, with motility and DNA fragmentation the outcomes most consistently reported as improving, and describes fertility outcomes such as pregnancy as encouraging in the small subset of studies that reported them. The authors frame these findings as preliminary and low in certainty because of the small number of studies, their size, and their design. We were unable to confirm the pooled effect sizes or confidence intervals, so we deliberately do not quote figures here.

Why it might work

Sperm are unusually vulnerable to oxidative damage because their membranes are rich in unsaturated fats and they carry little repair machinery. It might seem paradoxical that breathing more oxygen could reduce oxidative stress, but intermittent exposure to high oxygen appears to trigger an adaptive rise in the body's own antioxidant enzymes, and improved testicular blood flow and oxygenation may support the cells that nurture developing sperm. This is a plausible chain of reasoning drawn mostly from laboratory work; the human data are thin.

Limits

Meta-analysis cannot manufacture quality from weak inputs. Few studies, small samples, uncontrolled designs, varied protocols and variable outcome reporting all limit confidence, and publication bias is likely in a field where negative results are rarely written up. Semen parameters are surrogate measures; the outcome that matters is a healthy birth, and the evidence for that is minimal. We also had only the abstract. This paper should be read as a map of where research is needed rather than a verdict on effectiveness.