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1.
Dehydroepiandrosterone Shifts Energy Metabolism to Increase Mitochondrial Biogenesis in Female Fertility with Advancing Age.
Li, CJ, Lin, LT, Tsui, KH
Nutrients. 2021;(7)
Abstract
Female reproductive aging is an irreversible process associated with a decrease in oocyte quality, which is a limiting factor for fertility. Previous studies have shown that dehydroepiandrosterone (DHEA) has been shown to improve in vitro fertilization (IVF) outcomes in older women. Herein, we showed that the decline in oocyte quality with age is accompanied by a significant decrease in the level of bioenergetic metabolism genes. We compared the clinical characteristics between groups of infertile women who either received DHEA or did not. Treatment with DHEA may enhance oocyte quality by improving energy production and metabolic reprogramming in cumulus cells (CCs) of aging women. Our results showed that compared with the group without DHEA, the group with DHEA produced a large number of day-three (D3) embryos, top-quality D3 embryos, and had improved ongoing pregnancy rate and clinical pregnancy rate. This may be because DHEA enhances the transport of oxidative phosphorylation and increases mitochondrial oxygen consumption in CCs, converting anaerobic to aerobic metabolism commonly used by aging cells to delay oocyte aging. In conclusion, our results suggest that the benefit of DHEA supplementation on IVF outcomes in aging cells is significant and that this effect may be mediated in part through the reprogramming of metabolic pathways and conversion of anaerobic to aerobic respiration.
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2.
Levonorgestrel IUD: is there a long-lasting effect on return to fertility?
Dinehart, E, Lathi, RB, Aghajanova, L
Journal of assisted reproduction and genetics. 2020;(1):45-52
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Abstract
Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were conducted to evaluate return to fertility after removal of IUDs, majority of them were focused on multiparous women using copper IUDs. Current trends indicate increased use of levonorgestrel (LNG) IUDs in nulliparous women for very long periods of time, with both nulliparity and long duration of LNG-IUD use being potentially associated with trends towards longer time to conception post removal. Understanding the effects that LNG-IUDs may have on endometrial morphology and gene expression has important implications to further understanding their mechanism of action. Studies examining endometrial gene expression show persistent changes in receptivity markers up to 1 year after removal of an inert IUD, and no similar studies have been performed after removal of LNG-IUDs. Given the current gap in the literature and trends in LNG-IUD use in nulliparous young women, studies are needed that specifically look at the interaction of nulliparity, long-term use of LNG-IUD, and return to normal fertility. Herein, we review the available literature on the mechanism of action of IUDs with a specific focus on the effect on endometrial gene expression profile changes associated with IUDs.
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3.
Effect of a short-term vitamin E supplementation on oxidative stress in infertile PCOS women under ovulation induction: a retrospective cohort study.
Chen, J, Guo, Q, Pei, YH, Ren, QL, Chi, L, Hu, RK, Tan, Y
BMC women's health. 2020;(1):69
Abstract
BACKGROUND Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown. METHODS This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively. RESULTS It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05). CONCLUSIONS A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle. TRIAL REGISTRATION ChiCTR-OOC-14005389, 2014.
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4.
Antioxidants for female subfertility.
Showell, MG, Mackenzie-Proctor, R, Jordan, V, Hart, RJ
The Cochrane database of systematic reviews. 2020;(8):CD007807
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Abstract
BACKGROUND A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. OBJECTIVES To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. SEARCH METHODS We searched the following databases (from their inception to September 2019), with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. MAIN RESULTS We included 63 trials involving 7760 women. Investigators compared oral antioxidants, including: combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I2 = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I2 = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I2 = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I2 = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I2 = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I2 = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. AUTHORS' CONCLUSIONS In this review, there was low- to very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.
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Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis.
Zhang, Y, Zhang, C, Shu, J, Guo, J, Chang, HM, Leung, PCK, Sheng, JZ, Huang, H
Human reproduction update. 2020;(2):247-263
Abstract
BACKGROUND Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. OBJECTIVE AND RATIONALE The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. SEARCH METHODS Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). OUTCOMES Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). WIDER IMPLICATIONS For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.
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Effect of amlodipine on blood flow of preovulatory follicle in women with clomiphene resistant polycystic ovaries: a randomized controlled trial.
Torky, HA, Shata, A, Ahmad, AM, Ragab, M, Abo-Louz, A, Hussein, A, Aly, R
Archives of gynecology and obstetrics. 2020;(3):845-850
Abstract
OBJECTIVE To detect whether amlodipine could increase pre-ovulatory follicular blood flow, thus enhancing ovulation and creating a better chance of conception in women with PCOS. METHODS 165 women were screened of which 124 were qualified and women were equally randomized to 62 receiving clomiphene citrate and amlodipine and 62 receiving clomiphene citrate and placebo. The primary outcome was to detect if amlodipine can improve pre-ovulatory follicle blood flow studied by colour and power Doppler Pulsatility index of ovarian arteries, with drug administration. The secondary outcomes were endometrial thickness and clinical pregnancy. RESULTS The mean value of the ovarian arteries Pulsatility Index was significantly lower in the amlodipine group when compared to those of the placebo group (1.36 and 1.82, respectively, with P value 0.002). Mean endometrial thickness, for all women in both groups, on the day of detecting a mature follicle was significantly higher in the amlodipine group compared to the placebo group (8.99 and 7.0, respectively, with P value 0.003), and clinical pregnancy increased from 11% to 37% in the amlodipine group compared to the placebo group. CONCLUSION Amlodipine improves ovarian blood flow and increases the chances of conception. TRIAL REGISTRATION Pan African Clinical Trial Registry (http://www.pactr.org). Trial No: PAC TR201708002485292.
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Mediterranean diet improves embryo yield in IVF: a prospective cohort study.
Sun, H, Lin, Y, Lin, D, Zou, C, Zou, X, Fu, L, Meng, F, Qian, W
Reproductive biology and endocrinology : RB&E. 2019;(1):73
Abstract
BACKGROUND Mediterranean diet (MediDiet) had been reported to be beneficial to human health. However the relationship between diet pattern and outcomes of in vitro fertilization (IVF) treatment was scarcely researched. This study was aimed to explore the correlation between MediDiet pattern of infertile women and their clinical outcomes of IVF cycles. METHODS An observational prospective cohort study was conducted in the reproductive center from September 2016 to December 2017. Seven hundred infertile women about to undergo IVF treatment were asked to conduct a questionnaire survey. Patients were assigned to higher MediDiet adherence group or lower MediDiet adherence group according to their Mediterranean diet scores. Laboratory parameters and clinical outcomes were compared and those were different between groups were further analyzed for their relationship with MediDiet adherence. RESULTS A total of 590 women were finally included in the study. According to MediDiet scores, 228 participants were categorized as higher MediDiet adherence group and 362 others as lower MediDiet adherence group. No significant differences were found in baseline characteristics between groups. Higher MediDiet adherence group showed larger number of embryos available (8.40 ± 5.26 vs 7.40 ± 4.71, P = 0.028). Clinical pregnancy rate and implantation rate were similar between the two groups. In further correlation tests and multivariate linear regression analysis, number of fertilized oocytes and embryo yield were positively correlated to MediDiet adherence of participants. CONCLUSION Infertile women with greater adherence to Mediterranean diet pattern were likely to obtain more embryos available in IVF cycle.
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Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial.
Mendoza, N, Diaz-Ropero, MP, Aragon, M, Maldonado, V, Llaneza, P, Lorente, J, Mendoza-Tesarik, R, Maldonado-Lobon, J, Olivares, M, Fonolla, J
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(8):695-700
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Abstract
The purpose of this study was to evaluate the effect of two doses of D-chiro-inositol (DCI) in combination with Myo-inositol (MYO) in women with PCOS undergoing ICSI. This was a multicenter controlled, randomized, double-blind parallel group study with two MYO-DCI formulations for 12 weeks. The study group (SG) was administered 550 mg of MYO + 150 mg of DCI twice daily; the control group (CG) was administered 550 mg of MYO + 13.8 mg of DCI twice daily. The participants comprised 60 women with PCOS undergoing ICSI. At baseline, no differences were found between the two groups regarding age, BMI, HOMA-IR or testosterone levels. The pregnancy and live birth rates were significantly higher in the SG than in the CG (65.5 vs. 25.9 and 55.2 vs. 14.8, respectively) [risk ratio (RR) = 0.4; 95%CI (0.2, 0.79); p = .003 and RR = 0.27; 95%CI (0.10, 0.70); p = .002 respectively]. The risk of ovarian hyperstimulation syndrome (OHSS) was lower in the SG (3.44 vs. 18.5%, p = .07). The combination of MYO-DCI at high doses of DCI improves the pregnancy rates and reduces the risk of OHSS in women with PCOS undergoing ICSI.
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The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial.
Akbari Sene, A, Tabatabaie, A, Nikniaz, H, Alizadeh, A, Sheibani, K, Mortezapour Alisaraie, M, Tabatabaie, M, Ashrafi, M, Amjadi, F
Archives of gynecology and obstetrics. 2019;(6):1701-1707
Abstract
PURPOSE The aim of the present study was to evaluate the effect of myo-Inositol administration on oocyte quality, fertilization rate and embryo quality in patients with PCOS during assisted reproductive technology (ART) cycles. METHODS Fifty infertile PCOS patients were randomly designated in two groups. In the study group, patients received daily doses of 4 g myo-Inositol combined with 400 mg folic acid and in the control group patients received only 400 mg folic acid from 1 month before starting the antagonist cycle until the day of ovum pick up. Oocyte and embryo qualities were assessed according to European Society of Human Reproduction and Embryology (ESHRE) guidelines. The gene expression of PGK1, RGS2 and CDC42 as a factor of oocyte quality in granulosa cells was analyzed using real-time RT-PCR. Levels of total antioxidant capacity (TAC) and reactive oxygen species (ROS) were evaluated by chemiluminescence assay in follicular fluid. RESULTS The percentage of metaphase II oocyte, fertilization rate and embryo quality significantly improved in the study group (p < 0.05), but the number of retrieved oocytes and follicle count were not statistically different between groups. Furthermore, the gene expression of PGK1, RGS2 and CDC42 was significantly higher in the study group (p < 0.05) but no differences were found between two groups in terms of TAC and ROS levels. CONCLUSIONS The present study findings suggest that myo-Inositol alters the gene expression in granulosa cells and improves oocyte and embryo quality among PCOS patients undergoing ART.
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Conventional polymerase chain reaction and amplification refractory mutation system-multi-gene/ multi-primer PCR in the diagnosis of female genital tuberculosis.
Bhanothu, V, Venkatesan, V
Archives of microbiology. 2019;(3):267-281
Abstract
This review mainly summarizes disease, immune-pathology and the clinical usefulness, advances, potential applications and limitations of new, cutting-edge technology (MG/MP-PCR and/or ARMS-MG/MP-PCR) in the detection of female genital tuberculosis (FGTB) disease and gene polymorphism among infertile patients. The investigation was set in the Department of Zoology, Osmania University and National Institute of Nutrition, Hyderabad, India. Desired articles were critically reviewed and analysed. Keywords and NET searches were conducted in all electronic databases starting from September, 2006. Full-text English-language reviews and research articles describing FGTB, infertility, gene polymorphism, conventional polymerase chain reaction (PCR) and multigene (MG)/multiprimer (MP)-PCR were included. The current review provides a comprehensive overview on the PCR and types (multiplex, nested, RT etc.) including the reagents, cycling conditions and pitfalls in the detection of FGTB disease and gene polymorphism among infertile patients. It provides limited information on MG/MP-PCR. At present, conventional PCR, MG/MP-PCR and/or amplification refractory mutation system (ARMS)-MG/MP-PCR have emerged as scientific innovations and perform significant function in medical research, mutational analysis and clinical investigations. This review admits that MG/MP-PCR and/or ARMS-MG/MP-PCR has the capacity to diagnose disease rapidly and to genotype a large number of samples. MG/MP-PCR and/or ARMS-MG/MP-PCR are considered as simple, reliable, non-isotopic, low-cost, fast, accurate and relatively easy-to-perform procedure. This review suggests that this method needs to be critically evaluated using huge number of clinical samples occurring across the world and then can be accredited for clinical utilization.