Coenzyme Q10 supplementation of human oocyte in vitro maturation reduces postmeiotic aneuploidies.
Ma Long,Cai Lingbo,Hu Mengting,Wang Jing,Xie Jiazi,Xing Yan,Shen Jiandong,Cui Yugui,Liu X Johné,Liu Jiayin
Fertility and sterility
OBJECTIVE:To evaluate the effect of coenzyme Q10 (CoQ10) supplementation on oocyte maturation rates and postmeiotic aneuploidy rates during in vitro maturation (IVM) of human oocytes. DESIGN:Clinical laboratory observation. SETTING:Hospital and university laboratories. PATIENT(S):Forty-five patients aged ≥38 years and 18 patients aged ≤30 years undergoing in vitro fertilization. INTERVENTION(S):The germinal vesicle-stage oocytes and associated cumulus cells were cultured in IVM media for 24-48 hours with or without 50 μmol/L CoQ10. Oocyte maturation rates were determined based on the presence or absence of the first polar body. Postmeiotic aneuploidies were determined using next-generation sequencing analyses of biopsied polar bodies. MAIN OUTCOME MEASURE(S):Oocyte maturation rates, postmeiotic oocyte aneuploidy rates, and chromosome aneuploidy frequencies. RESULT(S):In women aged 38-46 years, 50 μmol/L CoQ10 significantly increased oocyte maturation rates (82.6% vs. 63.0%; P=.035), reduced oocyte aneuploidy rates (36.8% vs. 65.5%; P=.020), and reduced chromosome aneuploidy frequencies (4.1% vs. 7.0%; P=.012. In women aged ≤30 years, we failed to demonstrate an effect of CoQ10 on oocyte maturation rates or postmeiotic aneuploidies. CONCLUSION(S):CoQ10 supplementation during IVM increased oocyte maturation rates and reduced postmeiotic aneuploidies for older women.
10.1016/j.fertnstert.2020.04.002
The Efficacy and Safety of GF101 and Its Antioxidant Effect on In Vitro Fertilization Outcomes: A Double-Blind, Non-Inferiority, Randomized, Controlled Trial with Coenzyme Q10.
Antioxidants (Basel, Switzerland)
(1) Background: Oxidative stress adversely affects fertility by impairing oocyte fertilization potential, primarily due to meiotic segregation errors and cohesion loss. Superoxide dismutase (SOD) and Coenzyme Q10 (CoQ10) are prominent antioxidants known to mitigate oxidative damage. (2) Methods: This study recruited 86 patients undergoing in vitro fertilization (IVF) at a single center for a 12-week, randomized, double-blind, active-comparator-controlled trial. Participants were allocated into two groups: one receiving CoQ10 as an antioxidant (the CoQ10 group) and the other receiving GF antioxidative enzyme SOD (the GF101 group). The primary endpoints were changes in serum oxidative markers (SOD and catalase) and IVF outcomes, including clinical pregnancy, miscarriage, and live birth rates. Follicular fluid (FF) SOD and catalase concentrations on the day of retrieval, the metaphase II (MII) oocyte rate, the fertilization rate, and lipid profiles were measured. (3) Results: Initially, 86 patients were enrolled, with 65 completing the protocol (30 in the GF101 group and 34 in the CoQ10 group). There were no significant differences between the GF101 and CoQ10 groups in serum SOD ( = 0.626) and catalase levels ( = 0.061) over 12 weeks. However, within the GF101 group, a significant increase in serum catalase from baseline to 12 weeks was observed ( = 0.004). The non-inferiority analysis for IVF outcomes indicated risk differences in the clinical pregnancy rate, live birth rate, and miscarriage rate of -6.27% (95% CI: -30.77% to 18.22%), -1.18% (95% CI: -25.28% to 22.93%), and -13.49% (95% CI: -41.14% to 14.15%), respectively, demonstrating non-inferiority for the GF101 group. Furthermore, the GF101 group experienced significant reductions in total cholesterol ( = 0.006) and low-density lipoprotein (LDL) levels ( = 0.009) in intra-group comparisons, with both groups exhibiting comparable safe profiles. (4) Conclusions: GF101 may be non-inferior to CoQ10 in treating infertility in women and potentially offers additional benefits for women with dyslipidemia.
10.3390/antiox13030321
Antioxidants and Fertility in Women with Ovarian Aging: A Systematic Review and Meta-Analysis.
Advances in nutrition (Bethesda, Md.)
Ovarian aging is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios, but their effects on fertility in women with ovarian aging are still unclear. To address this, a meta-analysis was performed to evaluate the effectiveness and safety of antioxidants on fertility in women with ovarian aging. A total of 20 randomized clinical trials with 2617 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryo rates but also reduced the dose of gonadotropin, contributing to higher clinical pregnancy rates. According to the subgroup analysis of different dose settings, better effects were more pronounced with lower doses; in terms of antioxidant types, coenzyme Q10 (CoQ10) tended to be more effective than melatonin, myo-inositol, and vitamins. When compared with placebo or no treatment, CoQ10 showed more advantages, whereas small improvements were observed with other drugs. In addition, based on subgroup analysis of CoQ10, the optimal treatment regimen of CoQ10 for improving pregnancy rate was 30 mg/d for 3 mo before the controlled ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from CoQ10 treatment, especially those aged <35 y. Our study suggests that antioxidant consumption is an effective and safe complementary therapy for women with ovarian aging. Appropriate antioxidant treatment should be offered at a low dose according to the patient's age and ovarian reserve. This study was registered at PROSPERO as CRD42022359529.
10.1016/j.advnut.2024.100273
Mitochondria as therapeutic targets in assisted reproduction.
Human reproduction (Oxford, England)
Mitochondria are essential organelles with specialized functions, which play crucial roles in energy production, calcium homeostasis, and programmed cell death. In oocytes, mitochondrial populations are inherited maternally and are vital for developmental competence. Dysfunction in mitochondrial quality control mechanisms can lead to reproductive failure. Due to their central role in oocyte and embryo development, mitochondria have been investigated as potential diagnostic and therapeutic targets in assisted reproduction. Pharmacological agents that target mitochondrial function and show promise in improving assisted reproduction outcomes include antioxidant coenzyme Q10 and mitoquinone, mammalian target of rapamycin signaling pathway inhibitor rapamycin, and nicotinamide mononucleotide. Mitochondrial replacement therapies (MRTs) offer solutions for infertility and mitochondrial disorders. Autologous germline mitochondrial energy transfer initially showed promise but failed to demonstrate significant benefits in clinical trials. Maternal spindle transfer (MST) and pronuclear transfer hold potential for preventing mitochondrial disease transmission and improving oocyte quality. Clinical trials of MST have shown promising outcomes, but larger studies are needed to confirm safety and efficacy. However, ethical and legislative challenges complicate the widespread implementation of MRTs.
10.1093/humrep/deae170
Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.
Xu Yangying,Nisenblat Victoria,Lu Cuiling,Li Rong,Qiao Jie,Zhen Xiumei,Wang Shuyu
Reproductive biology and endocrinology : RB&E
BACKGROUND:Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. METHODS:This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age < 35, poor ovarian reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. RESULTS:A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p < 0.05. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical pregnancy and live birth rates per embryo transfer and per one complete stimulation cycle tended to be higher in CoQ10 group but did not achieve statistical significance. CONCLUSION:Pretreatment with CoQ10 improves ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.
10.1186/s12958-018-0343-0
Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging.
Ben-Meir Assaf,Burstein Eliezer,Borrego-Alvarez Aluet,Chong Jasmine,Wong Ellen,Yavorska Tetyana,Naranian Taline,Chi Maggie,Wang Ying,Bentov Yaakov,Alexis Jennifer,Meriano James,Sung Hoon-Ki,Gasser David L,Moley Kelle H,Hekimi Siegfried,Casper Robert F,Jurisicova Andrea
Aging cell
Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age-related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri-phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age-related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte-specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte-specific Pdss2-deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age-associated oocyte deficits causing infertility.
10.1111/acel.12368