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%)* | ||||||