Hyperbaric oxygen increases follicular vascular endothelial growth factor secretion, stimulates capillary production around the follicular wall, promotes endometrial growth, increases endometrial thickness and facilitates the implantation of pregnant eggs. It has been shown in the literature that hyperbaric oxygen significantly improves the tolerance of the endometrium. Hyperbaric oxygen can play an important role in the treatment of infertility patients and it is recommended that couples work together to improve their success rate!
Infertility is more or less a worldwide problem. Generally speaking, one in six couples has a related problem and needs medical help. One of the causes of infertility in women is the problem of endometrial tolerance. Many of the drugs used to vasodilate and increase the blood supply, i.e. to provide blood volume to the endometrium, are only effective if there are sufficient endothelial cells and the effect remains short-term and negligible.
Endometrial ultrasound and colour Doppler can be used to predict the occurrence of natural or resting cycle pregnancies. This literature is about using transvaginal colour
Doppler to evaluate changes in the endometrium after hyperbaric oxygen therapy and to measure the effectiveness of hyperbaric oxygen therapy by endometrial thickness and reflectivity, subendometrial layer, endometrial and uterine perfusion.
Conclusion: The application of hyperbaric oxygen has provided the first two factors for endometrial tolerance, i.e. optimal quality of the endometrium and adequate subendometrial vascularisation and oxygenation. If endometrial tolerance is regulated by adequate vascularisation and oxygenation, then hyperbaric oxygen therapy is the treatment of choice.
References: Mitrović A, Nikolić B, Dragojević S, et al. Hyperbaric oxygenation is a possible therapy of choice for infertility treatment. Bosn J Basic Med Sci. 2006 May;6(2):21-24.
Patients profile
Thirty-two women aged from 24 to 34 years and excluded to exclude male infertility. The study included patients with no history of early assisted reproductive technology (ART) and patients who used only moderate ovulation stimulants during normal sexual intercourse.
All patients underwent a complete diagnostic procedure and analysis.
Treatment in groups
01 Hyperbaric oxygen therapy
Hyperbaric oxygen therapy, starting on day 5 of the menstrual cycle, 2.3 ATA, once a day for 70 minutes for 7 days.
02 Control group treatment
The same treatment and analysis were performed on 10 patients, at 1 ATA pressure.
03 Observations
The effectiveness of hyperbaric oxygen therapy was evaluated using transvaginal
color Doppler ultrasound continuously from day 8 of the menstrual cycle.
The London Centre for Gynaecology and Fertility criteria were used to evaluate the quality of the endometrium: grade A – best, grade B – moderate, and grade C poor.
Uterine artery blood flow was monitored and pulsatility index (pulsatility index), resistance index (resistance index), systolic/diastolic ratio, and sub-endometrial capillary bed markers were measured.
Pre-treatment status
The majority of patients were graded: 91.2% as grade C and about 8% as grade B.
The desired endometrial ultrasound image could not be shown even at ovulation.
The endometrial thickness of the pre-treatment cycle was 7.7 mm ± 1.6 and the prognosis was also poor.
These findings of transvaginal ultrasound correlated significantly with the low probability of pregnancy.
Hyperbaric oxygen group
After hyperbaric oxygen treatment, the endometrium responded well in 82.9%-84.8% of patients, with optimal quality in the pre-ovulatory and ovulatory periods.
In addition, the endometrial thickness at ovulation was 11.1 mm ± 2.6 when observed alone (pre-treatment endometrial thickness was 7.7 mm ± 1.6), which can be described as having a good prognosis.
The quality of the endometrium in the hyperbaric oxygen treatment cycle was good and significantly better than in the control group (p<0.001).
In addition, endometrial fluctuations were observed in only 2% of patients, while optimal early endometrial morphology was found to be independent of follicle size in 1.9% of patients.
Control group
Patients treated with 1ATA as a control group had no increase in endometrial thickness at ovulation and no expected endometrial ultrasound presentation, p>0.05. Infertility is more or less a worldwide problem. Generally speaking, one in six couples has a problem and needs the help of a qualified person.
One of the causes of infertility in women is of course the problem of endometrial tolerance, i.e. the quality of the uterine mucosa in which the future embryo is implanted. Considering that in vitro fertilisation programmes produce a high percentage of high-quality embryos which are implanted in the uterus by embryo transfer, it is expected that they will implant in the endometrium and achieve the desired pregnancy. However, for unknown reasons, a large number of embryos fail to implant and bleeding is not a sign of an expected pregnancy, but of a failed menstrual cycle and implantation. Many factors influence the quality of this dynamic tissue: the anatomy of the cavity and the uterus, the optimal hormonal status and the absence of endometrial fluctuations are among the most important factors.
Many drugs used to vasodilate and increase the blood supply, i.e. to provide blood volume to the endometrium, are only effective if the endothelium is adequate and the effect remains short-term and negligible.
Only an adequately developed endometrium is capable of blastocyst implantation and gestational development. Considering that this concept is influenced by many factors, it is extremely important to look at each one individually. The most powerful means of making a non-invasive diagnosis of endometrial quality is by vaginal colour Doppler ultrasound. Thanks to most modern ultrasound instruments, we are able to
analyze different ultrasound parameters to assess the quality of the endometrium and monitor blood flow throughout the uterus, all the way down to the subendometrial spiral arteries and capillaries. We realized that one of the most important predictors of endometrial quality has long been its thickness alone, so a thickness of less than 7 mm at ovulation is almost incompatible with pregnancy.
In addition, the texture and reflectivity of the endometrium were analyzed, so that inadequate endometrial appearance (grade C) was incompatible with pregnancy. The introduction of colour Doppler procedures showed that changes in uterine arterial resistance during ovulation and the lack of an adequate capillary network under the endometrium were incompatible with pregnancy. Today, it is quite possible to assess the quality of the endometrium – endometrial tolerance – by transvaginal colour Doppler ultrasound and hormonal status analysis.
Spectral analysis of left and right uterine artery flow showed slightly higher than expected uterine vascular resistance in the cycle prior to treatment, with a beat index = 3.1, a resistance index = 0.81 and a systolic/diastolic ratio = 3.7. During treatment, the resistance decreased but not significantly, with a mean beat index < 3, a resistance index = 0.85 and a systolic/diastolic ratio = 3.5.
Power color Doppler maps of the sub-endometrial vessels were particularly important in assessing adequate vascularisation of the endometrium. In cycles where the ultrasound presentation of the endometrium failed to achieve ideal quality (grade A) before and during treatment with 1ATA, sub-endometrial specimens could show an almost complete absence of capillary networks or the presence of individual capillaries with significant resistance Ri=0.65, leading us to conclude that the process of neoangiogenesis was absent or inadequate.
In the cycle treated with 2.3 ATA hyperbaric oxygen, the specimen measurements showed a dense endometrial capillary network with a low resistance index <0.45, the result of a strong neovascularisation process.
Analysis of the results obtained confirmed that insufficient endometrial thickness and appearance, i.e. poor quality, were associated with a high percentage of poor endometrial tolerance.
Endometrial tolerability, in addition to ultrasound features, is characterized by uterine vascularisation, particularly of the endometrium.
So far, this has been accomplished in spontaneous cycles without any treatment or during cycles during treatment and the patient has had timely sex with her partner who is behaving normally and has a high chance of pregnancy.
Cell division in the basal endometrium is stimulated by increasing the amount of dissolved oxygen in the circulation, i.e. hyperoxia, and the maximum hemoglobin saturation in the arterial and venous blood flow in the presence of elevated gas pressure. During the proliferative phase of the cycle, hormonal action and optimal angiogenesis and oxygenation lead to dynamic changes in the thickening and so-called maturation of the endometrium and prepare it for possible future implantation of fertilized blastocysts.
In patients undergoing hyperoxia treatment, treatment starts at the follicular phase of a cycle as a result of following a strictly defined protocol, but the exact date of treatment depends on the subjective characteristics of the patient herself. Treatment should start no later than the 5th day of the menstrual cycle, in a regular cycle, with the first 3 treatments being given one after the other and, if possible, all treatments should be given consecutively (at least 5 times). We insist on continuing treatment during the I phase of the cycle and the pre-ovulatory phase because we believe it is necessary to maintain a high level of dissolved oxygen and to provide support for the process of neoangiogenesis under the endometrium.
In addition, we believe that adequate uterine oxygenation is important to prevent the development of smooth contractions of the uterine muscle tissue and endometrial fluctuations that may interfere with the implantation and implantation process. The use of hyperbaric oxygen therapy is superior in every respect to the drugs used to date to improve angiogenesis. Essentially, this is a problem of healthy people having infertility problems, not a vascular problem.
Experience tells us that uterine microcirculatory problems are a common cause of non-pregnancy. Problems that may be related to endothelial cells or microvascular
lesions can affect infertility. The action of drugs is dependent on the quality of the endothelial cells and capillary system and the use of this approach outweighs the action of the drugs.
Conclusion
Endometrial tolerance is an important factor in determining a range of conditions for pregnancy. It is influenced by the regular anatomy of the uterus and its cavity, the optimal hormonal status, and the optimal vascularisation and oxygenation. So far, the application of hyperbaric oxygen has provided the first two factors, namely the optimal quality of the endometrium and adequate subendometrial vascularisation and oxygenation. If endometrial tolerance is regulated by adequate vascularisation and oxygenation, then hyperbaric oxygen therapy is the treatment of choice.
Endometrial tolerance refers to the ability of the endometrium to allow the blastocyst to position, adhere, penetrate, implant, and allow the embryo to settle and develop. Endometrial tolerance is closely related to embryo implantation and is one of the key factors in determining the success of assisted reproduction techniques. Ultrasonographic assessment of endometrial tolerance includes endometrial thickness, endometrial type, endometrial hemodynamic parameters such as resistance index, pulsatility index and endometrial vascular index, and blood flow index. Most studies so far have shown that the clinical pregnancy rate is significantly higher in type A endometrium than in type B and C endometrium.
2. It is further confirmed by this literature that hyperbaric oxygen improves endometrial tolerance, which is an important factor in determining a range of conditions for pregnancy. As the literature concludes: if endometrial tolerance is regulated by adequate vascularisation and oxygenation, then hyperbaric oxygen therapy is the treatment of choice.
3. In fact, hyperbaric oxygen therapy in infertility has been studied in the past for a long time, as in this literature in 2006, 17 years ago, but it seems that it has not been given much attention and application. I have also written several articles on infertility and hyperbaric oxygen, so check out the extended reading.
4. With the current demand for second-trimester babies and other reasons, more and
more clinical cases have been reported or hyperbaric oxygen science has been popularized, which again confirms the effectiveness of hyperbaric oxygen therapy. Although sometimes clinical cases are reported on a case-by-case basis, the person in the case took or tried a variety of methods and still failed or failed, but the successful pregnancy and conception of a baby after the application of hyperbaric oxygen therapy shows the value of the application of hyperbaric oxygen therapy in this area.
5. This literature discusses the treatment protocols and timing of hyperbaric oxygen therapy, and I believe that the timing of application can be taken as a reference. The treatment pressure does not need to be 2.3 ATA, but can be lowered such as the conventional 2.0 ATA, but the total number of treatments can be increased to reduce the discomfort of treatment and further increase and consolidate the efficacy.
