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Table 1 Summary of human studies assessing the use of melatonin in IVF

From: Melatonin: shedding light on infertility? - a review of the recent literature

Study Design NICE Level of evidence Sample size Intervention Control Outcomes
Melatonin alone
Tamura et al. 2012 [36] Uncontrolled before - after study 2 9 3 mg melatonin po from day 5 of menstrual cycle to oocyte collection (n = 9) Previous cycle without melatonin (n = 9) Higher rate of good embryos in melatonin cycle (65% vs 27%)*
Tamura et al. 2008 [125] Prospective cohort 2+ 115 3 mg melatonin po from day 5 to oocyte collection (n = 56) No melatonin (n = 59) No difference in fertilisation or clinical pregnancy rate
Tamura et al. 2008 [125] Uncontrolled before - after study 2 112 3 mg melatonin po from day 5 to oocyte collection (n = 56) Previous cycle without melatonin (n = 56) Higher fertilisation rate in melatonin cycle (50% vs 20.2%)*
No difference in pregnancy rate
Eryilmaz et al. 2011 [137] Unblinded randomised controlled trial 1 60 3 mg melatonin po from day 3–5 until HCG injection (n = 30) No melatonin (n = 30) Higher number of oocytes in melatonin group (11.5 vs 6.9)*
Higher MII oocyte counts (9 vs 4.4)*
Higher G1 embryo transfer rate (69.3 vs 44.8)*
No differences in fertilisation, implantation or clinical pregnancy rates
Batioglu et al. 2012 [138] Single-blinded randomised controlled trial (only embryologists were blinded) 1 85 3 mg melatonin po (n = 40) No melatonin (n = 45) Higher percentage of MII oocytes in melatonin group (81.9% vs 75.8%)*
Higher number of G1 embryos (3.2 vs 2.5)*
No difference in number of oocytes, fertilisation rate or clinical pregnancy rate
Nishihara et al. 2014 [134] Uncontrolled before - after study 2 97 3 mg melatonin po for at least 2 weeks leading up to HCG trigger in second cycle (n = 97) No melatonin in first cycle (n = 97) Higher ICSI fertilisation rate in melatonin group (77.5% vs 69.3%)*
Higher rate of good quality embryos (Day 3) (65.6% vs 48.0%)*
No difference in maturation rate, blastocyst rate or good quality blastocysts (Day 5)
Combinations with melatonin
Rizzo et al. 2010 [139] Unblinded randomised controlled trial 1 65 3 mg melatonin daily +2 g myo-inositol po bd +200mcg folic acid po bd from day of GnRH administration (n = 32) 2 g myo-inositol po bd +200mcg folic acid po bd from day of GnRH administration (n = 33) Higher number of MII oocytes in melatonin group (6.56 vs 5.76)*
Lower number of immature oocytes (1.31 in vs 1.90)*
No difference in fertilisation rate, embryos transferred, implantation rate or clinical pregnancy rate
Unfer et al. 2011 [165] Uncontrolled before - after study 2 46 2 g myo-inositol po +200mcg folic acid po in the morning and 3 mg melatonin po +2 g myo-inositol po +200mcg folic acid po in the evening for 3 months leading to second cycle of IVF No trial medication in first cycle Higher number of MI and MII oocytes in treatment cycle (3.11 vs 2.35)*
Higher number of G1 or G2 embryos transferred (0.35 vs 0.13)*
Clinical pregnancy rate 19.6% in treatment cycle
No differences in number of oocytes or fertilisation rate
Pacchiarotti et al. 2013 [164] Double-blinded randomised controlled trial 1+ 388 3 mg melatonin po +4 g myo-inositol po +400mcg folic acid po (n = 178) 4 g myo-inositol +400mcg folic acid po (n = 180) Higher percentage of mature oocytes in melatonin group (48.2% vs 35.0%)*
Higher percentage of G1 embryos (45.7% vs 30.4%)*
  1. IVF: In-vitro fertilisation; NICE: National Institute for Health and Care Excellence; *statistically significant; G1: Grade 1; G2: Grade 2; MI: Meiosis I; MII: Meiosis II; ICSI: Intracytoplasmic sperm injection; HCG: Human chorionic gonadotrophin; po: per oral; bd: Twice per day.