Table 2.
Clinical trials of melatonin for endometriosis and other female reproduction.
| Studies | Disorder | Sample Size (Melatonin/ Control) |
Age (Means ± SD/ SEM or Range) |
Daily Dose | Duration or Period | Main Outcomes | Adverse Events | Trial Registration Number |
|---|---|---|---|---|---|---|---|---|
| Schwertner 2013 [18] | Endometriosis | 20/20 | 18–45 | 10 mg | 8 weeks | Reduced pain scores and BDNF levels Increased sleep quality |
/ | / |
| Takasaki 2003 [195] |
Infertility | 27/NA | 34 ± 4.4 | 1 or 3 mg |
From 2nd to 5th day of the menstrual cycle to hCG day | Decreased number of degenerate oocytes (only in 3 mg group) | / | / |
| Tamura 2008 [47] |
Infertility | 56/59 | 34.8 ± 4.8 | 3 mg | From 2nd to 5th day of the menstrual cycle to OPU day | Increased oocytes quality and fertility rate | / | / |
| Rizzo 2010 [203] |
Infertility | 32/33 | 35–42 | 3 mg | From GnRH administration day to pregnancy test result was confirmed | Increased tendency on number of mature oocytes, embryo quality, clinical pregnancy rate, and implantation rate | / | / |
| Batioglu 2012 [193] |
Infertility | 40/45 | 20–40 | 3 mg | During the IVF-ET procedure | Increased number and percentage of mature oocytes Increased number of embryos of top quality Increased tendency on clinical pregnancy rate |
/ | / |
| Nishihara 2014 [204] | Infertility | 97/NA | ≤42 | 3 mg | At least 2 weeks | Increased fertilization and embryo quality | / | / |
| Fernando 2018 [205] | Infertility | 32/29 29/29 26/29 |
18–45 | 2, 4, or 8 mg | From 2nd to 5th day of the menstrual cycle to OPU day | No significant differences in daytime Karolinska sleepiness score between groups No differences in objective measures of sleep quantity or quality Improved the subjective sleep quality scores except 8 mg group |
/ | ACTRN12613001317785 |
| Fernando 2018 [194] | Infertility | 41/41 39/41 40/41 |
18–45 | 2, 4, or 8 mg | From 2nd to 5th day of the menstrual cycle to OPU day | There were no differences between all the groups in total oocyte number, number of MII oocytes, number of fertilized oocytes, the number or quality of embryos, clinical pregnancy rate, or live birth rate | Headache, fatigue (no significant difference) | ACTRN12613001317785 |
| Espino 2019 [196] |
Infertility | 20/20 | 3 or 6 mg | From 2nd to 5th day of the menstrual cycle to OPU day | Ameliorated intrafollicular oxidative balance and oocyte quality Increased the rate of pregnancies/live births No significant difference between 3 mg group and 6 mg group |
/ | / | |
| Wdowiak 2020 [206] | Infertility | 50/50 | 20–35 | 1 mg | 6 months | Increased blastocyst and oocyte quality Increased rate of clinical pregnancy |
/ | / |
| Jahromi 2017 [207] |
Diminished ovarian reserve | 40/40 | 22–42 | 3 mg | From 2nd to 5th day of the menstrual cycle to OPU day | Increased serum estradiol level on the triggering day Increased number of MII oocytes, top quality embryos with G1 and G2 |
/ | IRCT2014041417264N1 |
| Tagliaferri 2017 [198] | PCOS | 40/NA | 23.25 ± 4.07 | 2 mg | 6 months |
Improved the menstrual irregularities Decreased biochemical hyperandrogenism |
/ | / |
| Mokhtari 2019 [199] |
PCOS | 98/100 | 28.9 ± 5.5 | 3 mg | From 2nd to 5th day of the menstrual cycle to hCG day | Increased chemical pregnancies and endometrial thickness | / | / |
| Parandavar 2018 [208] | Menopausal women | 98/142 | 53.22 ± 4.21 | 3 mg | 3 months | Increased amount of triglyceride | / | / |
| Chojnacki 2018 [209] | Postmenopausal women | 30/30 | 51–64 | 8 mg | 12 months | Decreased Kupperman Index and body mass index | No adverse influence on patients’ psychosomatic activity | / |
| Miller 2014 [200] |
Fetal growth restriction | 6/6 | / | 8 mg | For the duration of pregnancy | Decreased placental oxidative stress | No adverse maternal or fetal effects | NCT01695070 |
| Parandavar 2014 [202] |
Climacteric symptoms | 99/101 | 40–60 | 3 mg | 3 months | Decreased climacteric symptoms score | Sleepiness, nausea, vomiting, and headache (no significant difference) | / |
| Hobson 2018 [201] |
Preeclampsia | 20/48 | Control: 30.6 ± 0.8 Melatonin: 32.7 ± 1.1 |
30 mg | From recruitment until delivery |
No adverse events and adverse drug reactions Prolonged gestation Reduced the pharmacological need for antihypertensives |
No adverse events | / |
ACTRN, Australian clinical trials registration number; BDNF, Brain-derived neurotrophic factor; hCG, Human chorionic gonadotropin; GnRH, Gonadotropin-releasing hormone; IRCT, Iranian Registry of Clinical Trials; IVF-ET, In vitro fertilization and embryo transfer; MII, Metaphase II; NA, Not applicable; NCT, National clinical trial; OPU, Oocyte pick up; PCOS, Polycystic ovary syndrome; SD, Standard deviation; SEM, Standard error of mean; SOD, Superoxide dismutase.