Ozone sauna therapy and pulsed electromagnetic field therapy could potentially improve outcome in women with diminished ovarian reserve undergoing assisted reproductive technology.

There are limited treatment options for women with severely diminished ovarian reserve (DOR) who experience repeatedly failed in vitro fertilization (IVF) cycles and with persistently thin endometrial lining thickness (EMT) during frozen embryo transfer cycles. Therefore, a large majority of patients resort to using donor oocytes and gestational carriers. Data from existing animal and human studies suggest that ozone sauna therapy (OST) and pulsed electromagnetic field therapy (PEMF) are emerging as potential therapeutic adjuncts for female reproduction. This study was conducted to assess the fertility outcome of OST + PEMF in vivo in patients undergoing IVF/frozen embryo transfe and the effects of OST in vitro on human granulosa cell (GC) function. Forty-four women with DOR underwent their 1st IVF cycle (Cycle 1), and then were administered transdermal and intravaginal OST + PEMF, twice a week for 3 weeks, followed by a 2nd IVF cycle (Cycle 2) using the same protocol as in Cycle 1. GCs collected from another six women who underwent egg retrieval were equally split and cultured with OST (test) or placed in room temperature (control) outside the OST chamber in the same room. The results demonstrated that Cycles 1 and 2 had no significant difference in the number of days of stimulation, baseline hormones measured, number of oocytes retrieved or peak estradiol levels. However, the number of embryos formed after OST + PEMF in Cycle 2 was significantly higher than the Cycle 1. Furthermore, EMT measured in Cycle 2 demonstrated a significant increase compared to Cycle 1 and all patients reached a satisfactory EMT of approximately 7 mm. In vitro studies demonstrated that OST led to a 5-fold significant increase in the aromatase enzyme while a significant 50% reduction was noted in the side-chain cleavage enzyme in GCs. Both OST + PEMF are known for their vasodilatory, anti-inflammatory, and antioxidant actions, which could enhance endometrial receptivity and increase the number of formed embryos without increasing the number of oocytes retrieved, suggesting an improvement in oocyte quality. Finally, ozone can alter genes involved in steroidogenesis suggesting that it could improve ovarian function.

Ozone Sauna Therapy (OST) and Pulsed Electromagnetic Field Therapy (PEMF) delivered via the HOCATT machine could improve endometriosis pain along with lowering serum inflammatory markers.

PROBLEM: Endometriosis, a common and challenging condition, is a pelvic inflammatory condition that causes chronic pelvic pain (CPP) and infertility. Even though standard medical therapies and surgeries can help CPP, a large percentage of women remain symptomatic following the conventional treatments. Thus, there is a need to study new non-traditional therapeutic adjuncts in this patient population to improve their quality of life. One non-traditional therapeutic agent is Ozone Sauna Therapy (OST) which has been shown to have an anti-inflammatory action, but no studies have been performed to assess the efficacy of OST in women with endometriosis suffering with CPP. Another non-traditional therapeutic agent is Pulsed Electromagnetic Field Therapy (PEMF) where one small pilot study has shown that PEMF exposure to women with endometriosis and pelvic pain showed dramatic relief in symptoms. METHOD OF STUDY: The HOCATT machine, by delivering a combination of both OST and PEMF in one machine, has been shown to improve fertility treatment outcome via in vitro fertilization (IVF) in older women by potentially improving oocyte quality. This study was conducted to assess the effect of the HOCATT machine use on the pain scale in patients struggling with CPP due to endometriosis. In the first study, eight women with endometriosis were administered transdermal and intravaginal OST + PEMF, twice a week for 3 weeks (total of 6 sessions). Once a week, the participants were asked to fill a pain scale. In the second study, 10 women were recruited in order to evaluate the changes in serum inflammatory markers following OST + PEMF exposure after 3-week period using the HOCATT machine twice a week (total of 6 sessions). RESULTS: The participants had a mean age of 39.7 ± 1.1 years. The results showed a significant improvement in pain scale following the fourth session (p < .05) and a significant drop in serum levels of the inflammatory markers CRP (p = .0438) and IL-1ß (p = .0031) and a significant increase in serum levels of IL-8 (p = .033). CONCLUSIONS: This pilot study suggests that a combination of OST and PEMF using the HOCATT machine could potentially represent potential therapeutic adjuncts for women with inflammatory disorders such as endometriosis. There is a definite need for larger cohort studies and even randomized trials in order to better assess the efficacy of OST and PEMF in women with other inflammatory disorders.

Ozone and pulsed electro-magnetic field therapies improve endometrial lining thickness in frozen embryo transfer cycles: Three case reports.

RATIONALE: In assisted reproductive technology, a persistently thin endometrial lining represents a huge challenge during frozen embryo transfer (FET) cycles. PATIENT CONCERNS: Three patients who had a persistently thin endometrial lining despite the use of several medical agents known to improve endometrial lining thickness. DIAGNOSES: Infertility undergoing FET cycles. INTERVENTIONS: A combination of transdermal and intravaginal ozone therapy along with Pulsed Electro-Magnetic Field (PEMF) therapy. OUTCOMES: Ozone with PEMF, both of which are known to have vasodilatatory, anti-inflammatory, and anti-oxidant actions, were successful in improving the thickness of the endometrial lining in all 3 patients. Two out of 3 patients became pregnant following single embryo transfer. LESSONS: Ozone with PEMF constitute a novel experimental approach for women with persistently thin endometrial lining undergoing FET. This novel approach needs validation by large well-designed studies.

Ozone therapy: a potential therapeutic adjunct for improving female reproductive health.

Ozone is emerging as a new adjunct therapeutic agent for female infertility. We here present a review of the literature, to date, pertaining to the effect of ozone therapy on tubal, ovarian, endometrial, and vaginal factors that could potentially affect female fertility. It also presents data pertaining to the relationship of ozone therapy on pelvic adhesion formation. Most data were performed on animals and very few human studies existed in the literature. Results suggested that ozone therapy could have beneficial effect on tubal occlusion, could protect from endometritis and vaginitis, might protect ovaries from ischemia and oocyte loss and finally might lead to less formation of pelvic adhesions. There is a critical need for human studies pertaining to ozone therapy, especially using safe methods of administration, such as transdermally or intravaginally, on female fertility.

Crosstalk between advanced glycation end products and vitamin D: A compelling paradigm for the treatment of ovarian dysfunction in PCOS.

Women with PCOS have elevated levels of the harmful advanced glycation end products (AGEs) and low serum levels of vitamin D. AGEs and their receptors may contribute to the pathogenesis of PCOS and its metabolic and reproductive consequences. On the other hand, vitamin D might improve PCOS phenotype and could alleviate the detrimental effects of AGEs. A literature review using PubMed was performed. Critical analysis was carried out for articles pertaining to: 1) the role of AGEs and their receptors in the pathophysiology of PCOS, in particular ovarian dysfunction, and 2) the action of vitamin D in attenuating the adverse effects of AGEs in women with PCOS at both the serum and the cellular levels. Data from in vitro experiments, animal models, and human studies provide compelling evidence that AGEs and their receptors may contribute to the pathogenesis of ovarian dysfunction in PCOS. The actions of AGEs in PCOS might be attenuated and/or reversed by the presence or supplementation of vitamin D. Once a mechanistic understanding of the relationship between AGEs and vitamin D is established, this knowledge might contribute to the subsequent development of new-targeted pharmacological therapies for improving ovarian health in women with PCOS.

Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review.

OBJECTIVE: To report an update on the role of vitamin D (VD) in ovarian physiology with a focus on genes involved in steroidogenesis, follicular development, and ovarian reserve, as well as ovulatory dysfunction associated with polycystic ovary syndrome (PCOS), and ovarian response to assisted reproductive technology (ART). DESIGN: Systematic review. SETTING: Not applicable. PATIENT(S): Human, animal, and cell culture models. INTERVENTION(S): Pubmed literature search. MAIN OUTCOME MEASURE(S): Granulosa cell function, serum antimüllerian hormone (AMH), AMH and its receptor gene expression, soluble receptor for advanced glycation end-products (sRAGE), PCOS parameters, and ART outcome. RESULT(S): In human granulosa cells, VD alters AMH signaling, FSH sensitivity, and progesterone production and release, indicating a possible physiologic role for VD in ovarian follicular development and luteinization. In the serum, 25-hydroxyvitamin D (25OH-D) is positively correlated with AMH, and appropriate VD supplementation in VD-depleted women can suppress the seasonal changes that occur in serum AMH. In VD-deficient women with PCOS, VD supplementation lowers the abnormally elevated serum AMH levels, possibly indicating a mechanism by which VD improves folliculogenesis. The antiinflammatory sRAGE serum levels significantly increase in women with PCOS after VD replacement. Although follicular fluid 25OH-D correlates with IVF outcomes, there is a lack of data pertaining to the impact of VD supplementation on pregnancy rates following IVF. CONCLUSION(S): This review underscores the need for understanding the mechanistic actions of VD in ovarian physiology and the critical need for randomized trials to elucidate the impact of VD supplementation on controlled ovarian hyperstimulation/IVF outcome and ovulatory dysfunction associated with PCOS.

Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS.

CONTEXT: Elevation of serum proinflammatory advanced glycation end products (AGEs) is involved in the pathogenesis of polycystic ovary syndrome (PCOS). The soluble receptor for AGEs (sRAGE) acts as a decoy by binding circulating AGEs. Vitamin D supplementation attenuates the deposition of AGEs in the vascular system of diabetic animals and improves some metabolic aspects of vitamin D-deficient women with PCOS. Additionally, serum anti-Mullerian hormone (AMH) is elevated in women with PCOS, reflecting abnormal ovarian folliculogenesis. OBJECTIVE: The objective of the study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (vit D3) supplementation on serum sRAGE and AMH in vitamin D-deficient women with PCOS. DESIGN, SETTINGS, PARTICIPANTS, AND INTERVENTION: Sixty-seven women with (n = 22) or without (control; n = 45) PCOS who were diagnosed with vitamin D deficiency were enrolled. Fifty-one women were replaced with oral vit D3 for 8 weeks (16 with PCOS and 35 controls) and 16 women were not treated (six with PCOS and 10 controls). Serum 25-hydroxyvitamin D (25 OH-D), sRAGE, and AMH concentrations were measured at baseline and after vit D3 supplementation in the treated group and 8 weeks apart in the nontreated group. MAIN OUTCOME MEASURE(S): Changes in serum sRAGE and AMH concentrations after vit D3 replacement were measured. RESULTS: In all participants, there was a negative correlation between body mass index and serum sRAGE levels (r = -0.3, P = .01). In women with PCOS, but not in controls, vit D3 increased serum sRAGE (P = .03) and decreased serum AMH levels (P < .001). The increase in serum sRAGE positively correlated with the increase in serum 25 OH-D after supplementation in women with PCOS (r = 0.6, P = .01). CONCLUSION: In women with PCOS, vit D3 might exert a protective effect against the inflammatory action of AGEs by increasing circulating sRAGE. The normalization in serum AMH induced by vit D3 replacement suggests an improvement in folliculogenesis.

Gulf Coast oil disaster: impact on human reproduction.

The catastrophic British Petroleum oil spill in the Gulf of Mexico has reached the shores of the United States, along with unpredictable effects on the health of local communities. The potential impact of the disaster on female and male reproduction will be discussed in this report, to provide greater clinician awareness about the potential consequences of this calamity and to call for more research on this subject.