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Effects of Electrical Stimulation on Diminished Ovarian Reserve: A Meta-Analysis
Background: The effects of electrical stimulation therapy on ovarian function in patients with reduced ovarian reserve were systematically evaluated and meta-analyzed to assess its potential for improving ovarian function and provide clinical evidence for treatment. Methods: A comprehensive search was conducted in PubMed, Embase, The Cochrane Library, CNKI, Wanfang, and other Chinese and English databases for randomized controlled trials (RCTs) related to electrostimulation and ovarian hypofunction. The search covered studies published from inception through November 2024. Two independent researchers screened the literature, extracted relevant data, and assessed the risk of bias in the included studies. Meta-analysis was performed using RevMan 5.3. Results: Our analysis included nine randomized controlled trials with 728 patients. Electrical stimulation therapy, alone or combined with drug therapy, significantly improved estrogen (E2) levels compared to drug therapy or placebo (SMD = 0.91, 95% CI [0.03, 1.78], p = 0.04). However, no significant effects were observed on FSH (p = 0.13), LH (p = 0.10), antral follicle count (p = 0.74), ovarian volume (p = 0.37), or ovarian blood flow (p = 0.42). Subgroup analysis showed that combined therapy was more effective than electrical stimulation alone (SMD = 1.01 vs. 0.82) and led to a greater reduction in FSH and LH levels (p < 0.05). Younger patients (< 35 years) demonstrated better responses, with greater improvements in E2 levels (SMD = 1.05) and better regulation of FSH and LH compared to those aged ≥ 35 years (p < 0.05). Conclusion: Electrical stimulation therapy, particularly when combined with drug therapy, may benefit patients with diminished ovarian reserve by improving estradiol levels and regulating gonadotropin levels, with younger patients achieving the best outcomes.
[1] Moolhuijsen L, Visser J, 2020, Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function. J Clin Endocrinol Metab, 105(11): 3361–3373.
[2] Steiner A, Pritchard D, Stanczyk F, et al., 2017, Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age. JAMA, 318(14): 1367–1376.
[3] May-Panloup P, Boucret L, Chao J, et al., 2016, Ovarian Ageing: The Role of Mitochondria in Oocytes and Follicles. Hum Reprod Update, 22(6): 725–743.
[4] Zhu Q, Li Y, Ma J, et al., 2023, Potential Factors Resulting in Diminished Ovarian Reserve: A Comprehensive Review. J Ovarian Res, 16(1): 208.
[5] Zhang C, Song S, Yang M, et al., 2023, Diminished Ovarian Reserve Causes Adverse ART Outcomes Attributed to Effects on Oxygen Metabolism Function in Cumulus Cells. BMC Genomics, 24(1): 655.
[6] Park S, Walsh L, Berkowitz K, 2021, Mechanisms of Ovarian Aging. Reproduction, 162(2): R19–R33.
[7] Expert Group of Consensus on Clinical Diagnosis and Management of Diminished Ovarian Reserve, et al., 2022, Consensus on Clinical Diagnosis and Management of Diminished Ovarian Reserve. Journal of Reproductive Medicine, 31(4): 425–434.
[8] Zhou J, Pan X, Lin J, et al., 2022, Effects of Bushen Yiqi Huoxue Decoction in Treatment of Patients with Diminished Ovarian Reserve: A Randomized Controlled Trial. Chin J Integr Med, 28(3): 195–201.
[9] Stener-Victorin E, Kobayashi R, Watanabe O, et al., 2004, Effect of Electroacupuncture Stimulation of Different Frequencies and Intensities on Ovarian Blood Flow in Anaesthetized Rats with Steroid-Induced Polycystic Ovaries. Reprod Biol Endocrinol, 2: 16.
[10] Stener-Victorin E, Waldenström U, Tägnfors U, et al., 2000, Effects of Electroacupuncture on Anovulation in Women with Polycystic Ovary Syndrome. Acta Obstet Gynecol Scand, 79(3): 180–188.
[11] Stener-Victorin E, Lundeberg T, Waldenström U, et al., 2000, Effects of Electroacupuncture on Nerve Growth Factor and Ovarian Morphology in Rats with Experimentally Induced Polycystic Ovaries. Biol Reprod, 63(5): 1497–1503.
[12] Janson P, Albrecht I, 1975, Methodological Aspects of Blood Flow Measurement in Ovaries Containing Corpora Lutea. J Appl Physiol, 38(2): 288–293.
[13] Stener-Victorin E, Lindholm C, 2004, Immunity and Beta-Endorphin Concentrations in Hypothalamus and Plasma in Rats with Steroid-Induced Polycystic Ovaries: Effect of Low-Frequency Electroacupuncture. Biol Reprod, 70(2): 329–333.
[14] Liberati A, Altman D, Tetzlaff J, et al., 2009, The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration. PLoS Med, 6(7): e1000100.
[15] Anonymous, 2016, Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015: Elaboration and Explanation. BMJ, 354: i4086.
[16] Feng X, Jia Z, Li N, et al., 2020, Effect of Electroacupuncture Combined with Yuyin Pill on Sex Hormone and Th2 Cytokines in Patients with Decreased Ovarian Reserve Function with Liver-Kidney Yin Deficiency. Chinese Acupuncture and Moxibustion, 40(9): 959–963.
[17] Li C, Lyu N, Meng S, 2024, Effect of Bioelectric Stimulation Combined with Artificial Cycle on Uterine Receptivity and Serum GDF-9, STB and BMP-10 Levels in Patients with Diminished Ovarian Reserve. Chinese Journal of Human Sexuality, 33(6): 83–87.
[18] Li Y, 2019, Short-Term Therapeutic Effect of Bionic Bioelectrical Stimulation on Patients with Decreased Ovarian Reserve Function. Chinese and Foreign Medical Research, 17(35): 42–44.
[19] Liang L, 2013, Preliminary Research on Bionic Electrical Stimulation Treatment in Decreased Ovarian Reserve, thesis, South Medical University.
[20] He S, Liang L, Huang H, et al., 2013, Effect of Bioelectric Stimulation on Patients with Decreased Ovarian Reserve Function. Guangdong Medical Journal, 34(12): 1851–1855.
[21] Zheng Y, 2016, Effects of Transcutaneous Electrical Acupoint Stimulation on Ovarian Reserve in Patients with Diminished Ovarian Reserve Under IVF-ET, thesis, Shandong University.
[22] Ma L, Zheng X, Yang L, et al., 2023, Clinical Observation on Transcutaneous Electrical Acupoint Stimulation Combined with Kidney-Tonifying and Blood-Activating Chinese Medicine in Patients with Low Ovarian Reserve Undergoing ART. Modern Diagnosis and Treatment, 34(1): 1–4 + 7.
[23] Yang L, 2022, TEAS Improves Ovarian Function by Regulating BDNF Content, thesis, Shandong University of Traditional Chinese Medicine.
[24] Li J, 2023, Clinical Effect of Low-Frequency Electric Stimulation Combined with Yijing Decoction in Reduced Ovarian Reserve Function, thesis, Guangzhou University of Chinese Medicine.
[25] Practice Committee of the American Society for Reproductive Medicine, et al., 2021, Obesity and Reproduction: A Committee Opinion. Fertil Steril, 116(5): 1266–1285.
[26] Vollenhoven B, Hunt S, 2018, Ovarian Ageing and the Impact on Female Fertility. F1000Res, 7: 1835.
[27] Shi W, Liu X, 2024, Expert Consensus on Acupuncture and Moxibustion Diagnosis and Treatment for Diminished Ovarian Reserve. Journal of Hunan University of Chinese Medicine, 44(4): 612–616.
[28] Shen J, Gao Y, Lu G, et al., 2022, Effect of Electroacupuncture on Endometrial Receptivity and IVF-ET Outcomes in Patients with Diminished Ovarian Reserve. Chinese Acupuncture and Moxibustion, 42(8): 879–883.
[29] Lian F, Chen C, Xiang S, 2015, Improvement of Oocyte Quality with Electroacupuncture in Infertility Patients with Kidney Deficiency Pattern. Zhongguo Zhen Jiu, 35(2): 109–113.
[30] Huang L, Fang G, Zhang H, et al., 2017, Effect of PHENIX-8PLUS Bioelectric Stimulation on Ovarian Blood Flow in Perimenopausal Patients. Hebei Medical Journal, 39(23): 3629–3631.
[31] Shuai Z, Zhang W, 2024, Mechanism of Transcutaneous Electric Acupoint Stimulation on Ovarian Granulosa Cell Apoptosis in Premature Ovarian Insufficiency Rats. China Medical Herald, 21(7): 27–30.
[32] Liu Z, Li F, Xue J, et al., 2020, Esculentoside A Rescues Granulosa Cell Apoptosis and Folliculogenesis in Mice with Premature Ovarian Failure. Aging (Albany NY), 12(17): 16951–16962.
[33] Huang L, Chen Y, Luo M, et al., 2019, Acupuncture for Patients with Premature Ovarian Insufficiency: A Systematic Review Protocol. Medicine (Baltimore), 98(18): e15444.
[34] Zheng Y, Feng X, Mi H, et al., 2015, Effects of Transcutaneous Electrical Acupoint Stimulation on Ovarian Reserve in IVF-ET Cycles. J Obstet Gynaecol Res, 41(12): 1905–1911.
[35] Estienne A, et al., 2021, Energy Sensors and the Hypothalamo–Pituitary–Ovarian Axis in Female Mammals: Role of mTOR, AMPK and SIRT1. Mol Cell Endocrinol, 521: 111113.
[36] Miller N, et al., 2022, High Physical Activity and Ovarian Reserve: A Prospective Study of Normo-Ovulatory Professional Athletes. J Ovarian Res, 15(1): 107.
[37] Flont M, et al., 2020, Synergistic Effect of Combination Therapy on Ovarian Cancer Cells Under Microfluidic Conditions. Anal Chim Acta, 1100: 138–148.