Objective To investigate the effect of coenzyme Q10 pretreatment on polycystic ovary syndrome (PCOS) ) outcomes of patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods A total of 100 patients with PCOS who received IVF-ET treatment in Shiyan Taihe Hospital Reproductive Medicine Center from August 2019 to August 2020 were selected and divided into control group and observation group according to random number table method. Adjustment, the observation group received coenzyme Q10 oral treatment for 3 months on the basis of lifestyle adjustment, and then started IVF-ET treatment. The general condition, metabolic level, superovulation process, embryo laboratory outcome and pregnancy outcome of the two groups of patients were compared and analyzed. . Results The level of fasting insulin (FINS) and insulin resistance index (HOMA-IR) in the observation group were significantly lower than those in the control group (P<0.05). The number of embryos, normal fertilization rate, and excellent embryo rate were significantly higher than those in the control group, and the difference was statistically significant (P<0.05). There was no significant difference in the number of oocytes, blastocyst formation rate, embryo transfer rate, implantation rate and clinical pregnancy rate (P>0.05). Conclusion Coenzyme Q10 pretreatment can improve the fertilization rate and increase the number of high-quality embryos in PCOS patients undergoing IVF-ET. Although there is no statistical difference in the clinical pregnancy rate, there is an increasing trend.
[Key words] coenzyme Q10; polycystic ovary syndrome; in vitro fertilization-embryo transfer Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder, and it is a common endocrine and metabolic disorder. The incidence in women is 5% to 10%, accounting for 75% of anovulatory infertility patients . The main clinical manifestations of PCOS are oligomenorrhea or amenorrhea, ovarian polycystic changes, hyperandrogenism and/or biochemical manifestations. At present, the main clinical treatment for PCOS infertility patients is letrozole or clomiphene citrate to induce ovulation. However, after ovulation induction therapy, there are still some patients who fail to conceive successfully and require assisted reproductive technology. Endocrine and metabolic abnormalities in PCOS patients not only affect follicular development and lead to ovulation disorders, but also affect egg quality and increase the risk of spontaneous abortion .
The etiology of PCOS is still unclear, and it is mostly believed to be the result of the combined action of genetic and environmental factors. Recent studies have shown that oxidative stress is closely related to the pathogenesis of PCOS. The author’s previous research also proved that the PCOS animal model in vivo There is an imbalance between oxidation and antioxidants , and studies have shown that oxidative stress affects the outcomes of invitrofertilizing (IVF) fertility in PCOS patients [4-5]. Coenzyme Q10 (ubiquinone) is a natural antioxidant and cell metabolism promoter produced by the cell itself. It exists on the inner mitochondrial membrane. Synthesis; on the other hand, coenzyme Q10 can prevent and control the peroxidation of proteins and lipids, scavenge free radicals, and avoid oxidative stress damage without any toxic side effects [6-7]. Coenzyme Q10 is widely used in the prevention and treatment of cardiovascular diseases and tumors, and has a certain curative effect, and in the field of assisted reproduction, it has been widely accepted for elderly patients with decreased ovarian reserve. Few reports have used it as an adjuvant drug for PCOS patients undergoing in vitro fertilization-embryotransfer (IVF-ET). Therefore, this study investigated the effect of coenzyme Q10 on the outcomes of IVF-ET assisted pregnancy in PCOS patients through a prospective randomized controlled trial.
1 Materials and Methods
Subjects 100 PCOS patients who received IVF-ET treatment at the Reproductive Medicine Center of Shiyan Taihe Hospital Affiliated to Hubei Medical College from August 2019 to August 2020. According to the random number table method, they were divided into an observation group (receiving coenzyme Q10 treatment) and a control group (not receiving coenzyme Q10 treatment), with 50 cases in each. Age, years of infertility, body mass index (BMI), antral follicle count (AFC), basal sex hormone levels, fasting plasma glucose (FPG), and fasting insulin (fasting insulin,
< p>FINS) and insulin resistance index (homeostasismodelassess-mentofinsulinresistance, HOMA-IR) were not significantly different (both P>0.05), see Table 1.
①Female age is 20~40 years old
②Clinical diagnosis of PCOS according to Rotterdam criteria , that is, meeting 2 of the following 3 items, and excluding other diseases that may cause hyperandrogenism: oligomenorrhea or amenorrhea; clinical or Biochemical manifestations; Ultrasound examination showed ovarian polycystic changes;
③The first IVF-ET assisted pregnancy;
④IVF fertilization was adopted.
①Endometri-osis (EMS) and (or) endometrial lesions and (or) Uterine malformation;
③systemic diseases such as systemic lupus erythematosus and other immune diseases;④endocrine diseases such as diabetes, abnormal thyroid function, hyperprolactinemia Symptoms, etc.;
⑤History of smoking, drinking, exposure to toxic substances;
⑥Received oral contraceptives or ovulation induction therapy 1 month before enrollment;
< p>⑦ The man has mild, moderate and severe oligospermia and/or asthenozoospermia. Each patient carefully read and signed the informed consent form before participating in the study. This study has been approved by the medical ethics committee of the hospital (approval number: 2021KS050).
1.2.1 Superovulation stimulation
All patients were confirmed to use the long-term follicular phase protocol to stimulate ovulation when they were enrolled. treat. The control group underwent lifestyle adjustment, controlled diet, and insisted on aerobic exercise for more than 30 minutes each time, no less than 3 times a week. In addition to the above lifestyle adjustments, the observation group took supplemental supplements.Enzyme Q10 was taken for a total of 2 months. After 2 months, both groups were given subcutaneous injection of goserelin on the 2nd to 4th day of menstruation for pituitary downregulation, and 28 to 35 days later, they were given recombinant follicle-stimulating hormone (r-FSH) and human menopausal gonadotropin. (humanmeno-pausalgonadotropin, HMG), the initial dose is 100-150U/d, and the dose is adjusted according to the development of follicles and changes in blood hormone levels. The observation group was given coenzyme Q10 until the day of human chorionic gonadotropin (HCG) injection. HCG 5000~10000U was given on the day of HCG injection, and 34~36h after intramuscular injection, the eggs were retrieved under the guidance of ultrasound.
1.2.2 Transfer and Pregnancy
Fresh cleavage stage embryos were transferred on the 3rd day after fertilization according to the condition of the embryos. Or transfer fresh blastocysts on the 5th day; for patients who cancel the fresh embryo transfer, prepare the endometrium for thawed embryo transfer after 3 months of artificial cycle. Luteal support was routinely given after transplantation. The blood β-HCG level was detected at 12-14 days after transplantation, and it was considered to be biochemical pregnancy if it was greater than 5 U/L; vaginal ultrasonography was performed at about 30 days after transplantation.
1.2.3 Comparison of observation indicators
Ovulation induction, laboratory conditions and clinical outcomes between the two groups. HOMA-IR=FPG×FINS/22.5; normal fertilization rate=pronucleus (2PN) and polar body (2PB) eggs/total number of fertilized eggs×100%; excellent embryo rate=high-quality embryos/normal fertilization Number of eggs × 100%; blastocyst formation rate = number of blastocysts at stage 2 and above/total number of cleavage-stage embryos cultured with blastocysts × 100%; clinical pregnancy rate = number of clinical pregnancy cycles/number of transfer cycles × 100%; The miscarriage rate = the number of miscarriage cycles/the number of clinical pregnancy cycles × 100%. High-quality embryos refer to embryos derived from normal fertilized eggs, with 7-9 embryonic cells on the 3rd day after fertilization, the cell size is consistent with the developmental stage, the degree of fragmentation is less than 10%, and there is no multinucleate embryo.
1.3 Statistical methods
All data were analyzed by SPSS25.0 software. Measurement data were compared by t test or nonparametric test according to whether they conformed to normal distribution; count data were compared by χ2 test. P<0.05 indicated that the difference was statistically significant.
2.1 Comparison of general data between the two groups after treatment
After treatment, there were still no significant differences in BMI, AFC, basal hormone levels, and FPG between the two groups (all P>0.05), but the levels of HOMA-IR and FINS in the observation group were significantly lower than those in the control group, and the differences were statistically significant Academic significance (all P<0.05). See Table 2.
2.2 Comparison of superovulation in two groups
There was no significant difference in the total amount of Gn used, the days of Gn use, the estrogen level on the day of HCG injection, the level of progesterone on the day of HCG injection, and the endometrial thickness on the day of HCG injection between the two groups of patients significant (all P>0.05). See Table 3.
2.3 Comparison of embryo laboratory results between the two groups
The number of 2PN, the number of cleavage stage embryos, the number of available embryos, the number of blastocysts, the normal fertilization rate and the excellent embryo rate in the observation group were higher than those in the control group, and the differences were statistically significant (all P<0.05); there were no significant differences in the number of oocytes retrieved, the number of mature oocytes, the blastocyst formation rate, the number of embryos on the 3rd day of transplantation, and the number of embryos on the 5th day of transplantation between the two groups (all P>0.05). ). See Table 4.
2.4 Comparison of clinical outcomes between the two groups strong>
In the control group, fresh embryo transfer was canceled in 2 cases due to uterine effusion, 4 cases due to elevated progesterone, and 3 cases due to the prevention of ovarian hyperstimulation syndrome (OHSS), and 1 case in the observation group Because of uterine effusion, 5 cases due to elevated progesterone, and 2 cases canceled fresh embryo transfer to prevent OHSS, all underwent thawed embryo transfer 3 months later. The implantation rate, clinical pregnancy rate and multiple birth rate of the observation group were higher than those of the control group, and the abortion rate was lower than that of the control group, but the differences were not statistically significant (all P>0.05). See Table 5.
3 discussion >
Coenzyme Q10 was discovered in 1957 by Professor Crane in the United States in the mitochondria of cattle heart. It is an important coenzyme in the body, which promotes oxidative phosphorylation and the production of energy carrier ATP, and has the functions of scavenging free radicals, resisting apoptosis and stabilizing cell membranes. Because of its strong antioxidant properties, non-toxic, non-teratogenic, and no obvious adverse reactionsThe advantages of it have attracted the attention of more and more researchers.
Oxidative stress is associated with various reproductive dysfunction diseases in women, such as PCOS, premature ovarian insufficiency (POI), EMS, etc. . When mitochondria are attacked by reactive oxygen species, their production of ATP levels decreases, which results in affected meiosis during oocyte formation, resulting in an increased rate of aneuploidy, resulting in decreased egg quality. Exogenous application of antioxidants can improve mitochondrial function and can improve egg quality. Bedaiwy et al  showed that elevated levels of oxidative stress in follicular fluid are not conducive to fertilization by intracytoplasmic sperm injection. Oxidative stress is involved in the occurrence and development of PCOS [10, 12-13]. Coenzyme Q10 is a recognized antioxidant. Therefore, in theory, supplementing exogenous coenzyme Q10 can correct the oxidative stress state in PCOS patients and improve egg quality. Treatment of infertility patients with PCOS may have a positive impact.
Current research reports on coenzyme Q10 supplementation in IVF-ET treatment outcomes mainly focus on elderly patients with POI, and few reports on PCOS patients. The content of coenzyme Q10 in the human body decreases with the increase of age , and the oxidative stress response in elderly women is enhanced, mitochondrial function is decreased, and oocyte development is impaired. Zou Yujie et al took coenzyme Q10 orally daily for 3 months before IVF-ET in elderly women with low ovarian function. The results showed that coenzyme Q10 can improve ovarian reserve and ovarian responsiveness in elderly women, although there was no statistical difference in the effect on IVF outcomes. Learning significance, but there is a certain trend of improvement. A randomized controlled trial from Canada showed that daily intake of 600 mg of coenzyme Q10 in infertile women aged 35 to 43 years for 2 months could increase the clinical pregnancy rate and reduce the aneuploidy rate . In this study, patients with PCOS were given coenzyme Q10 pretreatment for 2 months before IVF assisted pregnancy. The results can improve the fertilization rate and increase the number of high-quality embryos, suggesting that coenzyme Q10 is effective in the treatment of PCOS patients.
A Mata analysis of 458 PCOS patients who underwent IVF793 cycles showed that PCOS patients who underwent IVF-ET had a higher oocyte retrieval rate, but a lower clinical fertilization rate and a higher cycle cancellation rate[ 17]. There is an abnormal state of oxidative stress in the follicular fluid of PCOS patients, and this high level of oxidative stress may affect oocyte meiotic spindle formation, thereby affecting egg maturation . And studies have shown that abnormal oxidative stress in granulosa cells can lead to a decline in oocyte quality, which in turn affects the clinical outcome of IVF-ET . Animal experiments have confirmed that coenzyme Q10 can protect the ovary from damage caused by oxidative stress . A prospective randomized controlled study showed that oral administration of coenzyme Q10 (180 mg/d, qd) from the second day of the menstrual cycle to the day of HCG injection in PCOS patients treated with clomiphene citrate ovulation induction therapy found that this method can significantly improve the Ovarian reactivity in PCOS patients with clomiphene resistance increases ovulation rate and endometrial thickness, and improves clinical pregnancy rate . However, there is no report on the use of coenzyme Q10 for pretreatment of PCOS patients undergoing IVF. This study adopted a prospective randomized controlled trial. Use the number of embryos and blastocysts. Coenzyme Q10 may achieve the above-mentioned better clinical outcomes by improving the quality of oocytes. Turi et al.  used high performance liquid chromatography to detect the content of coenzyme Q10 in the follicular fluid of women undergoing IVF-ET superovulation, and confirmed the existence of coenzyme Q10 in human follicular fluid for the first time, and this study found that coenzyme Q10 in the follicular fluid of mature oocytes The content of coenzyme Q10 was significantly higher than that of immature oocytes. Further research found that the embryo grade was also related to the content of coenzyme Q10. The level of coenzyme Q10 in the follicular fluid of oocytes that developed into grades I-II embryos was significantly higher than that of grades III-IV embryos. The level of coenzyme Q10 in the follicular fluid of the mother cell is closely related to the maturity of the oocyte and the quality of the embryo.
The mechanism of CoQ10 improving oocyte quality in PCOS patients still needs further research. In this study, coenzyme Q10 can improve the normal fertilization rate of PCOS patients, thereby increasing the number of high-quality embryos, but it has no significant effect on the clinical pregnancy rate, which may be related to the small sample size of the study. At the same time, clinical pregnancy is not only related to embryo quality and endometrial thickness. , is also associated with the immune response between the embryo and the endometrium.
Samimi et al randomly divided 60 patients with PCOS into an observation group and a control group. The patients in the observation group were orally administered coenzyme Q10 100 mg/d for 12 weeks, and the patients in the control group were orally administered placebo daily for 12 weeks. The glucose metabolism and blood lipids of the patients in the two groups were evaluated respectively, and it was found that compared with the control group, the FPG, serum insulin level, total cholesterol level and low-density lipoprotein level of the patients in the observation group were significantly decreased, which proved that supplementation of coenzyme Q10 in PCOS patients can help. To improve blood sugar and lipid metabolism. And a Meta analysis has shown that coenzyme Q10 can effectively improve blood glucose, blood lipid metabolism, inflammatory state and sex hormone levels in PCOS patients . This study found that administration of coenzyme Q10 could reduce the level of FINS and HOMA-IR in PCOS patients, which was consistent with the above-mentioned results, but did not significantly improve the level of sex hormones. shorter correlation.
To sum up, this study found that coenzyme Q10 can improve the normal fertilization rate of PCOS patients undergoing IVF-ET, and increase the number of available embryos and blastocysts at the cleavage stage, which provides a theoretical basis for clinical adjuvant drugs . However, this study is a single-center and small-sample study, so a large-sample, multi-center randomized controlled study is still needed to verify the conclusions, and in-depth mechanism research is needed.
span>Hu Xue, Xiong Ping’an, Zhang Zhijun
Source:Journal of Clinical Drug Therapy
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