Hyperbaric Oxygen Therapy and Female Infertility: A Systematic Review of Human Clinical Evidence
5 affiliations
- 1Divers and Special Forces Group “Teseo Tesei”, Italian Navy, 19025 Portovenere, Italy
- 2Ravenna Hyperbaric Center, 48124 Ravenna, Italy
- 3Interdisciplinary Research Center “Health Science”, Scuola Superiore Sant’Anna, 56127 Pisa, Italy
- 4Institute of Clinical Physiology, IFC, National Research Council of Italy—CNR, Via G. Moruzzi, 1, 56124 Pisa, Italy
- 5Institute of Nanoscience, National Research Council of Italy—CNR, Via G. Moruzzi, 1, 56124 Pisa, Italy
Abstract
Background/Objectives: Female infertility represents a major global health issue, and effective treatment remains challenging in several infertility-related conditions. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential adjunctive intervention in reproductive medicine, although human clinical evidence remains limited. This systematic review aimed to evaluate the available human evidence regarding the association between HBOT and reproductive outcomes in women with infertility or infertility-related conditions. Potential biological mechanisms, including the hypothetical involvement of sirtuin-related signaling in adaptive responses to intermittent hyperoxia, were also considered. Methods: A systematic literature search of PubMed/MEDLINE, Scopus, LILACS and the Cochrane Library was updated through 10 May 2026. The search was restricted to studies published from 1 January 2016 to 10 May 2026, reflecting the review’s prespecified focus on approximately the preceding decade of human clinical evidence. Original human studies investigating HBOT in women with infertility or infertility-related conditions and reporting reproductive outcomes were eligible. Study selection was conducted according to predefined eligibility criteria and reported in accordance with the PRISMA 2020 statement. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and the certainty of evidence for the main outcomes was evaluated using the GRADE approach. Owing to substantial clinical and methodological heterogeneity and the absence of sufficiently comparable outcomes across studies, a pooled meta-analysis was not performed. Results: Seventy-six records were identified through electronic database searches, and 11 reports underwent full-text eligibility assessment. Two original human studies involving women with resistant thin endometrium or poor ovarian response met the eligibility criteria. In women with resistant thin endometrium undergoing frozen embryo transfer, endometrial thickness increased after HBOT (6.57 ± 1.23 vs. 5.76 ± 1.66 mm before HBOT; p = 0.002). Compared with propensity-score-matched concurrent controls, women receiving HBOT had a higher implantation rate (RR, 3.00; 95% CI, 1.26–7.14) and a higher intrauterine pregnancy rate after blastocyst transfer (RR, 2.96; 95% CI, 1.14–7.70). In women with poor ovarian response undergoing IVF/ICSI, fully adjusted analyses showed that HBOT was associated with a higher number of retrieved oocytes (β = 1.51; 95% CI, 0.92–2.10), available embryo rate (β = 24.29 percentage points; 95% CI, 7.27–41.31), and normal fertilization rate (β = 17.23 percentage points; 95% CI, 2.35–32.11). Clinical pregnancy occurred in 1 of 10 pre-HBOT cycles (10.0%) and 1 of 19 post-HBOT cycles (5.3%); one live birth was reported following HBOT. This single event does not provide a comparative estimate of live-birth rates. Certainty of evidence was very low for all outcomes assessed using GRADE: endometrial thickness, implantation, intrauterine pregnancy, number of oocytes retrieved, available embryo rate, and normal fertilization rate. Conclusions: Available human evidence reports associations between HBOT and selected reproductive outcomes in women with resistant thin endometrium or poor ovarian response. However, the evidence is based on only two small, non-randomized studies addressing different clinical populations and outcomes, and the certainty of evidence was very low for all outcomes assessed using GRADE. Current evidence is therefore insufficient to establish a causal therapeutic effect, support the routine use of HBOT for female infertility or define an optimal treatment protocol. Further well-designed prospective controlled studies are required.
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BibTeX
@article{moccia2026hyperbaric,
title = {{Hyperbaric Oxygen Therapy and Female Infertility: A Systematic Review of Human Clinical Evidence}},
author = {Enrico Moccia and Pasquale Longobardi and Vincenzo Lionetti and Sabrina Molinaro and Fabiola Troisi and Marco Scalese},
journal = {Journal of Clinical Medicine},
year = {2026},
month = nov,
doi = {10.3390/jcm15218713},
url = {https://www.mdpi.com/2077-0383/15/21/8713},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hyperbaric Oxygen Therapy and Female Infertility: A Systematic Review of Human Clinical Evidence
AU - Enrico Moccia
AU - Pasquale Longobardi
AU - Vincenzo Lionetti
AU - Sabrina Molinaro
AU - Fabiola Troisi
AU - Marco Scalese
PY - 2026
DA - 2026/11/08
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218713
UR - https://www.mdpi.com/2077-0383/15/21/8713
AB - Background/Objectives: Female infertility represents a major global health issue, and effective treatment remains challenging in several infertility-related conditions. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential adjunctive intervention in reproductive medicine, although human clinical evidence remains limited. This systematic review aimed to evaluate the available human evidence regarding the association between HBOT and reproductive outcomes in women with infertility or infertility-related conditions. Potential biological mechanisms, including the hypothetical involvement of sirtuin-related signaling in adaptive responses to intermittent hyperoxia, were also considered. Methods: A systematic literature search of PubMed/MEDLINE, Scopus, LILACS and the Cochrane Library was updated through 10 May 2026. The search was restricted to studies published from 1 January 2016 to 10 May 2026, reflecting the review’s prespecified focus on approximately the preceding decade of human clinical evidence. Original human studies investigating HBOT in women with infertility or infertility-related conditions and reporting reproductive outcomes were eligible. Study selection was conducted according to predefined eligibility criteria and reported in accordance with the PRISMA 2020 statement. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and the certainty of evidence for the main outcomes was evaluated using the GRADE approach. Owing to substantial clinical and methodological heterogeneity and the absence of sufficiently comparable outcomes across studies, a pooled meta-analysis was not performed. Results: Seventy-six records were identified through electronic database searches, and 11 reports underwent full-text eligibility assessment. Two original human studies involving women with resistant thin endometrium or poor ovarian response met the eligibility criteria. In women with resistant thin endometrium undergoing frozen embryo transfer, endometrial thickness increased after HBOT (6.57 ± 1.23 vs. 5.76 ± 1.66 mm before HBOT; p = 0.002). Compared with propensity-score-matched concurrent controls, women receiving HBOT had a higher implantation rate (RR, 3.00; 95% CI, 1.26–7.14) and a higher intrauterine pregnancy rate after blastocyst transfer (RR, 2.96; 95% CI, 1.14–7.70). In women with poor ovarian response undergoing IVF/ICSI, fully adjusted analyses showed that HBOT was associated with a higher number of retrieved oocytes (β = 1.51; 95% CI, 0.92–2.10), available embryo rate (β = 24.29 percentage points; 95% CI, 7.27–41.31), and normal fertilization rate (β = 17.23 percentage points; 95% CI, 2.35–32.11). Clinical pregnancy occurred in 1 of 10 pre-HBOT cycles (10.0%) and 1 of 19 post-HBOT cycles (5.3%); one live birth was reported following HBOT. This single event does not provide a comparative estimate of live-birth rates. Certainty of evidence was very low for all outcomes assessed using GRADE: endometrial thickness, implantation, intrauterine pregnancy, number of oocytes retrieved, available embryo rate, and normal fertilization rate. Conclusions: Available human evidence reports associations between HBOT and selected reproductive outcomes in women with resistant thin endometrium or poor ovarian response. However, the evidence is based on only two small, non-randomized studies addressing different clinical populations and outcomes, and the certainty of evidence was very low for all outcomes assessed using GRADE. Current evidence is therefore insufficient to establish a causal therapeutic effect, support the routine use of HBOT for female infertility or define an optimal treatment protocol. Further well-designed prospective controlled studies are required.
SN - 2077-0383
ER -