Therapeutics · Emerging Therapies
Abstract
Ovarian aging, a major contributor to declining fertility in women of advanced reproductive age (ARA), is strongly associated with impaired mitochondrial function within oocytes. Although current mitochondrial-targeted strategies can improve ovarian function, their clinical application remains limited by cost and side effects. In this study, 630 nm light-emitting diode (LED) phototherapy is shown to ameliorate ovarian aging phenotypes in ARA mice by enhancing mitochondrial complex II activity via upregulation of succinate dehydrogenase subunit B (SDHB). This intervention restores oocyte adenosine triphosphate (ATP) production, improves meiotic progression, and significantly increases blastocyst formation. To assess translational feasibility, a wearable 630 nm LED phototherapy device is developed and evaluated in a pilot clinical study in women with diminished ovarian reserve (DOR). After treatment, the antral follicle count (AFC) significantly increases from a median of 2 (IQR 1-5) to 6 (IQR 2-7; p = 0.011), and the number of oocytes retrieved showed a non-significant tendency to increase from 2 (IQR 1-5) to 5 (IQR 2-7; p = 0.083), indicating a potential improvement in ovarian reserve. These findings demonstrate that 630 nm LED phototherapy enhances mitochondrial function and oocyte competence, providing a promising non-invasive strategy to improve fertility in women affected by ovarian aging.
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Prenatal ambient air pollution associations with DNA methylation in asthma- and allergy-relevant genes: findings from ECHO
Palmore M et al., 2025 · Environ Epigenet · Free full text on PubMed Central
Prenatal exposure to air pollution is an important risk factor for child health outcomes, including asthma. Identification of DNA methylation changes associated with air pollutant exposure can provide new intervention targets to improve children's health. The aim of this study is to test the association between prenatal air pollutant exposure and DNA methylation in developmental and asthma-/allergy-relevant biospecimens (placenta, buccal, cord blood, nasal mucosa, and lavage). A subset of 2294 biospecimens collected from 1906 child participants enrolled in the Environmental Influences on Child Health Outcomes program with prenatal air pollutant and high-quality Illumina Asthma&Allergy DNA methylation array measures (n = 37 197 probes) were included. Prenatal ozone, nitrogen dioxide, and fine particulate matter were derived using residential history during pregnancy and spatiotemporal models. For each pollutant, biospecimen type, and prenatal exposure window, we estimated the effects of air pollution on gene DNA methylation levels. We compared results across pollutants, biospecimen types, and trimesters and tested for critical months of exposure using distributed lag models. DNA methylation levels at 154 out of 4746 tested genes were associated with air pollution; over 95% were exposure window, pollutant, and biospecimen-type specific. The fewest gene associations were detected in trimester 2, relative to other exposure windows. A variety of trends in methylation patterns were observed in response to lagged monthly pollution levels. Child DNA methylation changes at specific respiratoryand immune-relevant genes are associated with prenatal air pollutant exposures. Future studies should examine the relationship between these pollution-sensitive genes and child health.
Efficacy of acupuncture on pelvic pain in patients with endometriosis: study protocol for a randomized, single-blind, multi-center, placebo-controlled trial
Liang R et al., 2018 · Trials · Free full text on PubMed Central
Endometriosis is a chronic gynecological disease that is characterized by the presence of endometrial tissue outside the uterine cavity. The main symptoms include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. These symptoms impair the lives of most of the women suffering from the disease. Surgical resection of endometriotic lesions is an effective means of treating dysmenorrhea, but the risk of recurrence is high. Western medicine has limited use for treating it due to side effects and ineffectiveness. The purpose of this study is to verify the effectiveness and safety of acupuncture. This trial will be carried out in four parts. A total of 106 eligible patients with pelvic pain related to endometriosis will be randomly assigned into two groups, in a 1:1 ratio, as the treatment group or the control group. The participants assigned to the treatment group will be treated with acupuncture treatment at Guanyuan (CV4), Sanyinjiao (SP6), Taichong (LR3), Zhaohai (KI6) and Qichong (ST30) while the control group will receive acupuncture at non-acupoints. The trial will include three menstrual cycles of treatment and three menstrual cycles of follow-up. The primary outcome is pelvic pain that will be assessed by means of a 10-cm visual analog scale (VAS). At each stage, we will evaluate the safety of the acupuncture treatment. The study will compare the effectiveness and safety of acupuncture with comfort needles on pelvic pain related to endometriosis in the hope of providing significant evidence for using acupuncture on pelvic pain related to endometriosis. ClinicalTrials.gov, ID: NCT03125304 . Registered on 30 April 2017.
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Photobiomodulation ameliorates ovarian aging by alleviating oxidative stress and inflammation damage and improving mitochondrial function
He Y et al., 2024 · Journal of photochemistry and photobiology. B, Biology
Ovarian aging is a serious clinical concern. Few safe and effective methods are currently available to improve ovarian functions. Photobiomodulation (PBM) is a safe and noninvasive physical therapy that can modulate a series of biological processes. Recently, several studies have noted its potential to improve the function of ovary and reproductive cells. However, the effects of PBM treatment on natural ovarian aging remain unclear. In this study, we used a naturally reproductive aging mouse model to observe the effect of PBM on ovarian function. Young and aged female ICR mice were treated with or without PBM for 2 months. PBM was performed using a semiconductor InGaAlP laser emitting at 650 nm (80 mW, 6.7 mW/cm2 for 5 or 10 min, resulting in a dose of 2 or 4 J/cm2, respectively). After treatment, the effects of PBM and its role in oxidative stress, inflammation, and mitochondrial function were investigated. We found that PBM (4 J/cm2) effectively recovered the levels of sex hormones, increased the number of primordial and growing follicles, improved angiogenesis, and decreased cell apoptosis in naturally aged mice. Moreover, PBM reduced oxidative stress, inhibited chronic ovarian inflammation, and improved mitochondrial function in aged ovaries. Similar protective effects of PBM were observed in a hydrogen peroxide-induced oxidative stress model of human granulosa cell line (KGN) in vitro. Increased cell viability, cell proliferation, hormone secretion, mitochondrial membrane potential, and adenosine triphosphate levels and decreased apoptosis and oxidative stress were detected in KGN cells after PBM treatment. Collectively, this study suggest that PBM treatment is beneficial for restoring ovarian function in naturally reproductive aging mice and has a significant protective effect against oxidative stress damage in KGN cells. The mechanisms underlying the benefits of PBM in ovarian aging include antioxidant stress, reduction of inflammation, and preservation of mitochondrial function. Therefore, this study emphasizes the potential of PBM as a therapeutic intervention to ameliorate ovarian aging.
The Efficacy of Multiwavelength Red and Near-Infrared Transdermal Photobiomodulation Light Therapy in Enhancing Female Fertility Outcomes and Improving Reproductive Health: A Prospective Case Series with 9-Month Follow-Up
Phypers R et al., 2024 · Journal of clinical medicine
Background/Objectives: Female infertility due to unexpected causes exhibits a great challenge for both clinicians and women who are trying to conceive. The present clinical case series study aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in women and improving reproductive health in unexplained infertility issues. The objectives were to assess the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; (3) and healthy live birth. The inclusion criteria were to related to females who failed to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from in vitro fertilisation (IVF) cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. Case series of three female subjects with unexplained age-related infertility issues, which included a failure to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from IVF cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. In each case, previous conditions were recorded and then compared with outcomes after the patient received a course of PBM treatments. In every case, fertility outcomes improved. Three cases resulted in a full-term pregnancy and the birth of a healthy baby. PBM treatments were given at weekly and/or at two-week intervals using IR and NIR wavelengths between 600 nm and 1000 nm in the lead up to natural conception, IVF oocyte retrieval, blastocyst/embryo implantation, and/or the production of viable embryos. In every case, fertility outcomes improved. Improvements in reproductive health outcomes in each case give reason to suggest that PBM may help to improve unexplained age-related infertility. Our study demonstrated that multiwavelength of red and NIR PBM with either an LED or laser, or a combination, improved female fertility and reproductive health and contributed to healthy live births in females diagnosed with unexplained age-related infertility. Extensive studies with robust data are warranted to validate our PBM dosimetry and treatment protocols. Moreover, understanding the genetic and phenotype biomarkers is important to standardise a range of PBM light dosimetry.
Photobiomodulation in Complex Female Infertility Profile: A Case Report with 12-Month Follow-Up and Review of Current Mechanism in Reproductive Photomedicine
Phypers R et al., 2025 · Photonics
Female infertility from polycystic ovarian syndrome (PCOS) and endometriosis poses a challenge for both clinicians and women who are trying to conceive. The present clinical single case report aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in a woman with PCOS, endometriosis and low ovarian reserve. The observations helped to inform and establish the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; and (3) a healthy live birth. The case report concerns a female who failed to conceive naturally beyond five years and had experienced one unsuccessful IVF cycle. Case report of one female subject with infertility issues, which included failure to conceive naturally beyond five years. Previous conditions were recorded and then compared with outcomes from after the patient received a course of PBM treatments. PBM treatments were given at weekly and/or at two-week intervals over a 5-month period during the follicular stage of the menstrual cycle, using IR and NIR wavelengths between 600 and 1000 nm. After five months a spontaneous conception was achieved. The case resulted in a full-term pregnancy and the birth of a healthy baby. Improvements in reproductive health outcomes in this case give reason to suggest that PBM helped to alleviate PCOS and endometriosis which could have been associated with a low ovarian reserve. The case report indicates that a multiwavelength of red and NIR-PBM laser therapy could have positively contributed to a healthy live birth in a female diagnosed with PCOS, endometriosis and a low ovarian reserve. Extensive studies with large data are warranted to validate our PBM dosimetry and treatment protocols to assess the potential impact of PBM for treating endometriosis and PCOS. Subsequently, to understand the genetic and phenotype biomarkers would be an important step further to standardise a range of PBM light dosimetry.
Photobiomodulation: lasers vs. light emitting diodes?
Heiskanen V et al., 2018 · Photochem Photobiol Sci · Free full text on PubMed Central
Photobiomodulation (PBM) is a treatment method based on research findings showing that irradiation with certain wavelengths of red or near-infrared light has been shown to produce a range of physiological effects in cells, tissues, animals and humans. Scientific research into PBM was initially started in the late 1960s by utilizing the newly invented (1960) lasers, and the therapy rapidly became known as "low-level laser therapy". It was mainly used for wound healing and reduction of pain and inflammation. Despite other light sources being available during the first 40 years of PBM research, lasers remained by far the most commonly employed device, and in fact, some authors insisted that lasers were essential to the therapeutic benefit. Collimated, coherent, highly monochromatic beams with the possibility of high power densities were considered preferable. However in recent years, non-coherent light sources such as light-emitting diodes (LEDs) and broad-band lamps have become common. Advantages of LEDs include no laser safety considerations, ease of home use, ability to irradiate a large area of tissue at once, possibility of wearable devices, and much lower cost per mW. LED photobiomodulation is here to stay.