The Effect of Melatonin Supplementation on Cumulus Cells and IVF Outcomes

Official title

The Effect of Melatonin Supplementation on Cumulus Cells and Reproductive Outcomes in Older Women Undergoing IVF Cycles

Overview

This study investigates the effects of melatonin supplementation on cumulus cell gene expression and in vitro fertilization (IVF) outcomes in women over 35 years old. In the study group, patients will receive melatonin supplementation for at least two months prior to their IVF cycles. Cumulus cells will be collected after oocyte retrieval, and IVF outcomes will be assessed.

Detailed description

Aging in female reproductive cells, particularly cumulus granulosa cells, is associated with various dysfunctions that compromise fertility. Melatonin, a hormone primarily produced by the pineal gland, is renowned for its multifaceted roles in regulating physiological processes, including sleep-wake cycles, immune function, and antioxidative defense. Melatonin's antioxidant action is mediated through direct scavenging of free radicals, upregulation of antioxidant enzymes, and improvement of mitochondrial efficiency. These properties make melatonin a promising candidate for mitigating the adverse effects of aging on cellular function. This study aims to explore the effects of melatonin supplementation on cumulus cell gene expression and in vitro fertilization (IVF) outcomes in women over 35 years old. In the study group, patients will receive melatonin supplementation for at least two months prior to their IVF cycles. In the control group, patients will proceed directly to IVF cycles without melatonin supplementation. Cumulus cells will be collected after oocyte retrieval, and gene expression will be measured. Additionally, clinical pregnancy rate, live birth rate, and miscarriage rate between the two groups will be evaluated.

Interventions

• Dietary supplement Melatonin
  In the study group, patients will receive melatonin supplementation for at least two months prior to IVF cycles

Primary outcome measures

• Live birth rate (%) [Time frame: through study completion, an average of 4 year]
• oxygen consumption rate of mitochodria (%) [Time frame: through study completion, an average of 4 year]
• mRNA levels of cumulus cell genes [Time frame: through study completion, an average of 4 year]

Secondary outcome measures (3)

• Clinical pregnancy rate (%) [Time frame: through study completion, an average of 4 year]
• Ongoing pregnancy rate (%) [Time frame: through study completion, an average of 4 year]
• Amount of ATP production (moles/min) of mitochodria [Time frame: through study completion, an average of 4 year]

Eligibility criteria

Inclusion criteria

• Age 35-45 years
• BMI 18-30 kg/m2
• planning to undergo IVF cycles

Exclusion criteria

• Primary ovarian insufficiency
• history of oophorectomy
• receiving oocyte donation
• Chromosome anomaly
• Congenital uterine anomaly
• Severe intrauterine adhesion
• Malignancy
• Using hormone therapy or supplements in recent 3 months

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, T — Kaohsiung City

Publications

• Kandil OM, Rahman SMAE, Ali RS, Ismail EA, Ibrahim NM. Effect of melatonin on developmental competence, mitochondrial distribution, and intensity of fresh and vitrified/thawed in vitro matured buffalo oocytes. Reprod Biol Endocrinol. 2024 Apr 5;22(1):39. doi: 10.1186/s12958-024-01209-7. PMID 38580962
• Navid S, Saadatian Z, Talebi A. Assessment of developmental rate of mouse embryos yielded from in vitro fertilization of the oocyte with treatment of melatonin and vitamin C simultaneously. BMC Womens Health. 2023 Oct 4;23(1):525. doi: 10.1186/s12905-023-02673-w. PMID 37794412
• He C, Wang J, Zhang Z, Yang M, Li Y, Tian X, Ma T, Tao J, Zhu K, Song Y, Ji P, Liu G. Mitochondria Synthesize Melatonin to Ameliorate Its Function and Improve Mice Oocyte's Quality under in Vitro Conditions. Int J Mol Sci. 2016 Jun 14;17(6):939. doi: 10.3390/ijms17060939. PMID 27314334
• Yang M, Tao J, Chai M, Wu H, Wang J, Li G, He C, Xie L, Ji P, Dai Y, Yang L, Liu G. Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their Subsequent IVF Embryo Development: Mechanisms and Results. Molecules. 2017 Nov 27;22(12):2059. doi: 10.3390/molecules22122059. PMID 29186876
• Zhao XM, Wang N, Hao HS, Li CY, Zhao YH, Yan CL, Wang HY, Du WH, Wang D, Liu Y, Pang YW, Zhu HB. Melatonin improves the fertilization capacity and developmental ability of bovine oocytes by regulating cytoplasmic maturation events. J Pineal Res. 2018 Jan;64(1). doi: 10.1111/jpi.12445. Epub 2017 Oct 11. PMID 28833478
• Dai X, Lu Y, Zhang M, Miao Y, Zhou C, Cui Z, Xiong B. Melatonin improves the fertilization ability of post-ovulatory aged mouse oocytes by stabilizing ovastacin and Juno to promote sperm binding and fusion. Hum Reprod. 2017 Mar 1;32(3):598-606. doi: 10.1093/humrep/dew362. PMID 28137755
• Miao Y, Zhou C, Bai Q, Cui Z, ShiYang X, Lu Y, Zhang M, Dai X, Xiong B. The protective role of melatonin in porcine oocyte meiotic failure caused by the exposure to benzo(a)pyrene. Hum Reprod. 2018 Jan 1;33(1):116-127. doi: 10.1093/humrep/dex331. PMID 29112712
• Zhang M, Dai X, Lu Y, Miao Y, Zhou C, Cui Z, Liu H, Xiong B. Melatonin protects oocyte quality from Bisphenol A-induced deterioration in the mouse. J Pineal Res. 2017 Apr;62(3). doi: 10.1111/jpi.12396. Epub 2017 Mar 1. PMID 28178360

Identifiers

NCT: NCT06546774 · KSVGH21-CT1-43

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗