Fertility
HBOT as an Adjunct Therapy to Improve Fertility
Summary
Hyperbaric Oxygen Therapy (HBOT) is a safe and tolerable complementary therapy option for infertility.
HBOT improved ovarian reserve function and ovarian stimulation through enhancing angiogenesis.
HBOT sessions improved erectile function in men who suffered from non-surgical erectile dysfunction, and in men who suffered from erectile dysfunction post injury/ post-surgery (e.g. post post-urethral surgery, bladder surgery, vasectomy etc.)
As a complementary therapy, HBOT decreased cycle cancellation due to endometrium receptivity.
HBOT is a complementary therapy for fertility treatments, and decisions have to be taken according to infertility causes and the overall health status of the patients.
Introduction
Hyperbaric Oxygenation (HBO) is a form of therapy directed to significantly increase the partial pressure of oxygen in the blood and in the tissues of the patients to the levels significantly exceeding those achieved in normobaric conditions. This therapy is a promising adjunctive treatment for infertility, whereas other conventional therapies have limited success. HBOT enhances tissue oxygenation, modulates inflammation, and supports cellular repair mechanisms. Recent research highlights its potential to improve reproductive outcomes, such as ovarian stimulation, erectile dysfunction and endometrium receptivity.
Mechanisms of Action of HBOT
HBOT involves inhaling 100% oxygen within a pressurized chamber, significantly increasing the amount of oxygen dissolved in blood plasma. This elevated oxygen availability improves tissue perfusion and cellular function, which is vital for reproductive health.
Promote angiogenesis: HBOT stimulates angiogenesis, improving oxygenation to the ovaries, testes, and endometrium(Bosco et al., 2024). This mild oxygenation improves vascularisation, which increases cell metabolism. Vascular Endothelial Growth Factor (VEGF) and vascular Permeability Factor (VPF) are mitogens for vascular development and function. FSH and LH induce their expression and production in the ovary. They are related to the ovarian follicle cycle and corpus luteum development and maintenance, mediating ovarian angiogenesis during women’s reproductive life (Geva and Jaffe, 2000; Ishihara, 2019). In testes, this activation is essential for spermatogenesis(Ishihara, 2019). In the endometrium, blood flow and vascularisation contribute to increased thickness and receptivity, increasing implantation rates (Chen et al., 2023).
Reduce oxidative stress: HBOT enhances oxygen supply to reproductive tissue, reducing inflammation and reactive oxygen species (ROS), reducing oxidative stress (Bosco et al., 2024). This reduction potentially reduces DNA damage on gametes, improving sperm and oocyte quality (Liu et al., 2023; Ma et al., 2023).
Mitochondrial activity and energy production: Mitochondrial dysfunction—caused by oxidative stress, ageing, or environmental factors—can impair gamete quality and reduce fertility. Long-term HBOT sessions may help restore mitochondrial function and support oocyte maturation, sperm motility, fertilization, and early embryo development, enhancing oxygen delivery and stimulating mitochondrial activity without altering the redox balance (Cecchino et al., 2018; Schottlender et al., 2021; Vahedi Raad et al., 2024).
Enhance tissue regeneration: HBOT promotes tissue regeneration by modulating gene expression linked to apoptosis, stem cell mobilization and development, angiogenesis, and cell-to-cell communication, among other mechanisms (Bosco et al., 2024). These regenerative effects of HBOT are valuable in reproductive tissues. HBOT support follicular development in the ovaries by repairing hypoxic or damaged stromal tissue (Ma et al., 2023). In the testes, it may aid in the regeneration of seminiferous tubules and support spermatogenic recovery (Zhang et al., 2013). HBOT promotes angiogenesis and cell-to-cell communication, which are crucial for enhancing implantation and embryo development (Chen et al., 2023).
Benefits of HBOT for Patients Who Suffer from Infertility
HBOT is a well-tolerated therapy with a low incidence of side effects associated (Zhang et al., 2023). The implementation of this therapy as complementary –based on health tenets– to fertility treatments demonstrated benefits through a holistic assessment of infertility.
In Women
Improved Ovarian Reserve and Response: HBOT has been shown to benefit women with diminished ovarian reserve or poor response to stimulation protocols by improving follicle development and oocyte maturation. Defects in ovary angiogenesis may contribute to ovulatory disorders, pregnancy loss, ovarian hyperstimulation syndrome, and ovarian neoplasms. For women undergoing laparoscopic ovarian cystectomy, the adjuvant hyperbaric oxygen therapy could significantly improve the postoperative ovarian reserve function with remarkable effects(Yu et al., 2022).
Enhanced Endometrial Receptivity: Implantation success depends on several factors, including endometrial receptivity. The regular anatomy of the uterus and its cavity, optimal hormone status, and synchronized vascularization and oxygenation are critical for endometrial development. A 2006 study demonstrated that HBOT significantly improves both endometrial thickness (post-treatment average: 11.0 ± 2.6 mm) and microvascular density, as evidenced by Doppler ultrasound, which shows low-resistance sub-endometrial capillary networks in a group of women with infertility of unknown aetiology (Mitrović et al., 2006). Subsequent research confirms these vascular improvements are accompanied by normalized oxidative stress markers and tissue remodelling(Chen et al., 2023; Mitrović et al., 2006).
For women with a resistant thin endometrium (<7 mm), intrauterine adhesions, or unexplained infertility, HBOT enhances oxygen delivery to the basal endometrium, which is critical for decidualization and implantation. This reduces cycle cancellation rates in ART cycles and improves clinical pregnancy outcomes(Chen et al., 2023; Mitrović et al., 2006). (Mitrović et al., 2006)
In Men
Better Sperm Quality: HBOT mitigates oxidative damage to sperm cells, improving motility, morphology, and DNA integrity (Kangal and Özgök, 2021). On the other hand, blood concentration of total testosterone –essential for sperm production and libido, as it stimulates the production of key hormones, including FSH and LH, which directly drive spermatogenesis– increases after several sessions of HBOT (Passavanti et al., 2010).
Support for Erectile Function: High oxygen pressure ensures testicular circulation and vascularisation, improving non-surgical erectile dysfunction. HBOT enhance blood flow and restores vascular function, improving sperm quality and enhancing the likelihood of natural conception or success with assisted reproduction (Hadanny et al., 2018).
Practical Considerations and Clinical Evidence of HBOT on Infertility
Patient Selection
HBOT is a complementary therapy for patients who face infertility, but it shows particular promise for select patient populations. Ideal candidates include women with poor ovarian response, diminished ovarian reserve, endometrial insufficiency, or those recovering from ovarian surgery (e.g., laparoscopic cystectomy). Studies have reported that these women experience improved ovarian reserve markers, enhanced oocyte maturation, and regulated hormone levels after HBOT (Chen et al., 2023; Mitrović et al., 2006; Van Voorhis et al., 2005; Yu et al., 2022). In men, candidates may include those with non-obstructive azoospermia or oxidative stress-related sperm dysfunction, especially when preparing for procedures like testicular sperm extraction (TESE) (Kangal and Özgök, 2021).
HBOT should be considered part of an individualized care plan following a thorough reproductive assessment.
Treatment Protocols
Scientific reports support HBOT protocols involving 2.0–2.5 ATA with 60–120-minute sessions, typically administered 5 days weekly over 2–12 weeks. However, variations in pressure and duration reflect tailored approaches to specific infertility aetiologies (Bosco et al., 2024).
While larger randomized trials are needed to standardize protocols, they must be requested by the fertility specialist and supervised by a trained hyperbaric medicine specialist to ensure safety and optimize outcomes.
Integration with Standard Care
HBOT is most effective when it coordinates with the timing of ovarian stimulation or endometrial preparation and may further optimize outcomes (Chen et al., 2023; Yu et al., 2022).
HBOT is generally well-tolerated when performed at therapeutic pressures and durations, and the incidence of adverse events is rare and generally not severe. Patients who suffer from COPD, asthma, insulin-dependent diabetes, and claustrophobia require individualized risk assessment. In addition, low-pressure protocols have demonstrated a favourable safety profile and are suitable for reproductive-aged patients with minimal risk (Bosco et al., 2024).
Conclusion
HBOT offers a safe and promising adjunct to conventional fertility care. Its benefits, including enhanced tissue oxygenation, angiogenesis, and mitochondrial function, may improve reproductive outcomes in appropriately selected patients.
While further clinical studies will help refine its application and optimize treatment protocols within reproductive medicine, successful integration of HBOT into fertility care requires interdisciplinary collaboration, informed consent, and continuous monitoring to ensure patient safety while maximizing therapeutic benefits.
References
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