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Table 3 Study outcomes involving oral supplementation of various antioxidants in women

From: Utility of antioxidants during assisted reproductive techniques: an evidence based review

Antioxidant Study type Patient population Intervention (daily dose x duration) Control group (daily dose) Study outcome Reference
Vitamin E   Women with unexplained infertility undergoing ovarian stimulation and then IUI 400 IU/day vitamin E   1. Increased endometrial thickness Cicek et al. [122]
2. No significant increase in implantation and pregnancy rates
Vitamin C Prospective Women undergoing IVF-ET (n = 76) 500 mg vitamin C/day (slow release) to women smokers (n = 19) and women non-smokers (n = 19) Placebo Women non-smokers had higher pregnancy rates than women smokers Crha et al. [123]
Vitamin C Prospective, randomized Infertile women with luteal phase defects (not on IVF-ET) 750 mg ascorbic acid (n = 76) started on first day of third menstrual cycle until positive urine pregnancy test (maximum 6 months) No treatment (n = 46) 1. Increase in progesterone levels Henmi et al. [124]
2. Increase in clinical pregnancy rates
Vitamin C Double blind, placebo-controlled, RCT Women (<40y) undergoing first IVF-ET cycles (n = 620) 1 g or 5 g or 10 g ascorbic acid +30 mg Dydrogesteron x 14 days after follicle aspiration for IVF-ET Placebo (Lactose + citric acid +30 mg Dydrogesteron) No difference in clinical pregnancy and implantation rates Griesinger et al. [125]
Myo-inositol + folic acid Placebo-controlled, RCT Infertile PCOS patients undergoing ovulation induction for ICSI (n = 60) 4 g myo-inositol +400 μg folic acid (n = 30) 400 μg folic acid only (n = 30) Reduced germinal vesicles and degenerated oocytes without compromising the number of oocytes retrieved at ovum pick-up Papaleo et al. [126]
Myo-inositol + folic acid Double blind Infertile PCOS patients undergoing ovulation induction for IVF or ICSI (n = 34) 4 g of myo-inositol +400 μg of folic acid, continuously for 3 months 400 μg of folic acid only 1. Greater number of oocytes recovered during pick up Ciotta et al. [127]
2. Greater number of oocytes with score S1
3. Reduced number of immature oocytes (vesicles germ and degenerated oocytes)
Melatonin Follicular fluid sampled during oocyte retrieval during IVF-ET Women with prior failure of IVF-ET cycle and who are attempting IVF-ET again (n = 115) 3 mg melatonin (n = 56) given on the 5th day of the previous menstrual cycle until the day of oocyte retrieval Without melatonin treatment (n = 59) 1. Improved fertilization rate compared to previous IVF-ET cycle Tamura et al. [128]
2. Improved oocyte quality
Melatonin Prospective, randomized Women with primary infertility undergoing IVF-ET cycles (n = 85) 3 mg melatonin (n = 40) administered continuously from day of GnRH No treatment (n = 45) 1. Higher percentage of morphologically mature oocytes retrieved (MII oocytes) Batioglu et al. [129]
2. Higher mean number of top quality (class I) embryos
3. No improvement in fertilization rates
4. Higher tendency of clinical pregnancy rate (not statistically significant)
Melatonin Prospective, randomized IVF patients with disturbed sleep (insomnia) who were undergoing IVF-ET (n = 60) 3 g melatonin (n = 30) given 3rd to the 5th day of the previous menstrual cycle until the hCG injection day of the controlled ovarian hyperstimulation No treatment (n = 30) 1. Higher mean number of the retrieved oocytes, mean MII oocyte counts, and G1 embryo ratio Eryilmaz et al. [130]
2. No change in sleeping status
Melatonin + myo-inositol + folic acid Prospective, randomized Women undergoing IVF cycles (n = 65) 3 g melatonin +4 g myo-inositol +200 mg folic acid (n = 32) administered continuously from day of GnRH 4 g myo-inositol + folic acid (n = 33) 1. Greater mean number of mature oocytes (and lower mean number of immature oocytes) Rizzo et al. [131]
2. Higher mean number of top quality embryos (class 1 and 2)
3. No improvement in fertilization rates
4. Higher tendency of clinical pregnancy rate and implantation rate (not statistically significant)
Melatonin + myo-inositol + folic acid Prospective, longitudinal, cohort Women with failed IVF cycle (due to poor oocyte quality) who were undergoing a new IVF cycle 3 mg melatonin +4 g myo-inositol +400 mcg folic acid x 3 months (n = 46) Prior cycle of the same women but without treatment 1. Higher number of morphologically mature oocytes retrieved (MII oocytes) Unfer et al. [132]
2. Higher total number of embryo transferred and higher number of top quality (score 1 & 2) embryo transferred
3. Increased fertilization rate