Krocina, Improves in Vitro Fertilization Outcomes in Patients With Diminished Ovarian Reserve: A Randomized Controlled Trial
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 14 No. 4 (2024),
12 October 2024
https://doi.org/10.32598/ijmtfm.v14i4.45683
Abstract
Background: Diminished ovarian reserve (DOR) is a clinical syndrome with reproductive and endocrine disorders. This study aimed to examine the effect of crocin on oxidative stress, gene expression, oocyte maturation, and embryo quality in DOR patients who underwent a controlled ovarian hyperstimulation (COH) cycle.
Methods: As a clinical trial, this study involved 34 DOR patients trying to conceive by assisted reproductive technique who were divided into two groups (17 each): An intervention group receiving crocin (15 mg, once daily, for 12 weeks) and a control group receiving a placebo (tablets with the same form of the drug). Pre- and post-intervention, demographic information was gathered, and hormonal levels (follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2)) were measured. In the subsequent COH cycle, oocyte maturation, embryo quality, level of both superoxide dismutase (SOD) and reactive oxygen species (ROS) in follicular fluid, expression of GDF9, BMP15, and Nrf2 genes in granulosa cells were measured.
Results: The collected data as a comparison between groups showed alteration of criteria in the intervention group as follows: Significant reduction of FSH (P<0.01), increased level of SOD in the follicular fluid (P<0.0001), decreased level of oxidative stress in the granulosa cells (P<0.0001), increased expression of Nrf2 gene (P<0.08), and of GDF9, BMP15 genes (P<0.0001) in the granulosa cells. The rate of oocyte maturation and embryo quality were significantly higher in the intervention group compared to the control group (P<0.05 and P<0.005, respectively).
Conclusion: Our study discussed how the Krocina supplement can slow down the progression of the disease by reducing the level of FSH, and oxidative stress, increasing the maturation rate of oocytes, and increasing the quality of embryos in women with DOR. Further research is needed to investigate the effect of crocin in improving fecundity for women with DOR.
- Crocin
- Diminished ovarian reserve (DOR)
- Oxidative stress
- Oocyte maturation
- Embryo quality
How to Cite
References
Li HX, Shi L, Liang SJ, Fang CC, Xu QQ, Lu G, et al. Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway. Journal of Integrative Medicine. 2022; 20(2):163-72. [DOI:10.1016/j.joim.2022.01.007] [PMID]
Huanga M, Cuib X, Xiaoc X. Advances in clinical research in chinese medicine for decreased ovarian reserve function. International Journal of Frontiers in Medicine. 2022; 4(5):29-35. [Link]
Devine K, Mumford SL, Wu M, DeCherney AH, Hill MJ, Propst A. Diminished ovarian reserve in the United States assisted reproductive technology population: Diagnostic trends among 181,536 cycles from the society for assisted reproductive technology clinic outcomes reporting system. Fertility and Sterility. 2015; 104(3):612-19. [DOI:10.1016/j.fertnstert.2015.05.017] [PMID] [PMCID]
Ağaçayak E, Yaman Görük N, Küsen H, Yaman Tunç S, Başaranoğlu S, İçen MS, et al. Role of inflammation and oxidative stress in the etiology of primary ovarian insufficiency. Turkish Journal of Obstetrics and Gynecology. 2016; 13(3):109-115. [DOI:10.4274/tjod.00334] [PMID] [PMCID]
Wang S, Lin S, Zhu M, Li C, Chen S, Pu L, et al. Acupuncture reduces apoptosis of granulosa cells in rats with premature ovarian failure via restoring the PI3K/Akt signaling pathway. Int J Mol Sci. 2019; 20(24):6311. [DOI:10.3390/ijms20246311] [PMID] [PMCID]
Roshankhah SH, Salahshoor MR, Jalili F, Karimi F, Sohrabi M, Jalili C. Crocin effects on the nicotine-induce ovary injuries in female rat. International Journal of Life Science and Pharma Research. 2017; 7(4):1-8. [Link]
Godugu C, Pasari LP, Khurana A, Anchi P, Saifi MA, Bansod SP, et al. Crocin, an active constituent of Crocus sativus ameliorates cerulein induced pancreatic inflammation and oxidative stress. Phytotherapy Research 2020; 34(4):825-35. [DOI:10.1002/ptr.6564] [PMID]
Elham MN, Yasmin M, Mohammed M, Mohammed MS. Effect of crocin on letrozole-induced polycystic ovarian syndrome. Medical Journal of Cairo University. 2019; 87(December):5237-43. [DOI:10.21608/mjcu.2019.89762]
Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder--A plea for universal definitions. Journal of Assisted Reproduction and Genetics. 2015; 32(12):1709-12. [DOI:10.1007/s10815-015-0595-y] [PMID] [PMCID]
Weissman A, Howles CM, Shoham Z. Textbook of assisted reproductive techniques. Boca Raton: CRC Press; 2018. [DOI:10.1201/9781351228244]
Kumar M, Pathak D, Venkatesh S, Kriplani A, Ammini AC, Dada R. Chromosomal abnormalities & oxidative stress in women with premature ovarian failure (POF). The Indian Journal of Medical Research. 2012; 135(1):92-7. [DOI:10.4103/0971-5916.93430] [PMID] [PMCID]
Li XH, Wang HP, Tan J, Wu YD, Yang M, Mao CZ, et al. Loss of pigment epithelium-derived factor leads to ovarian oxidative damage accompanied by diminished ovarian reserve in mice. Life Sciences. 2019; 216:129-39. [DOI:10.1016/j.lfs.2018.11.015] [PMID]
Alaee S, Mirani M, Derakhshan Z, Koohpeyma F, Bakhtari A. Thymoquinone improves folliculogenesis, sexual hormones, gene expression of apoptotic markers and antioxidant enzymes in polycystic ovary syndrome rat model. Veterinary Medicine and Science. 2023; 9(1):290-300. [DOI:10.1002/vms3.958] [PMID] [PMCID]
Yang L, Chen Y, Liu Y, Xing Y, Miao C, Zhao Y, et al. The role of oxidative stress and natural antioxidants in ovarian aging. Frontiers in Pharmacology. 2021; 11:617843. [DOI:10.3389/fphar.2020.617843] [PMID] [PMCID]
Ashrafizadeh M, Fekri HS, Ahmadi Z, Farkhondeh T, Samarghandian S. Therapeutic and biological activities of berberine: The involvement of Nrf2 signaling pathway. Journal of Cellular Biochemistry. 2020; 121(2):1575-85. [DOI:10.1002/jcb.29392] [PMID]
Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine. 2018; 54(4):287-93. [DOI:10.1016/j.ajme.2017.09.001]
Gong Y, Zhang K, Xiong D, Wei J, Tan H, Qin S. Growth hormone alleviates oxidative stress and improves the IVF outcomes of poor ovarian responders: A randomized controlled trial. Reproductive Biology and Endocrinology. 2020; 18(1):91. [DOI:10.1186/s12958-020-00648-2] [PMID] [PMCID]
Leone S, Recinella L, Chiavaroli A, Orlando G, Ferrante C, Leporini L, et al. Phytotherapic use of the Crocus sativus L. (Saffron) and its potential applications: A brief overview. Phytotherapy Research. 2018; 32(12):2364-75. [DOI:10.1002/ptr.6181] [PMID]
Mokhber Maleki E, Eimani H, Bigdeli MR, Golkar Narenji A, Abedi R. Effects of crocin supplementation during in vitro maturation of mouse oocytes on glutathione synthesis and cytoplasmic maturation. International Journal of Fertility & Sterility. 2016; 10(1):54-61. [Link]
Mokhber Maleki E, Eimani H, Bigdeli MR, Ebrahimi B, Shahverdi AH, Golkar Narenji A, Abedi R. A comparative study of saffron aqueous extract and its active ingredient, crocin on the in vitro maturation, in vitro fertilization, and in vitro culture of mouse oocytes. Taiwanese Journal of Obstetrics & Gynecology. 2014; 53(1):21-5. [DOI:10.1016/j.tjog.2012.11.004] [PMID]
Khoshandam A, Razavi BM, Hosseinzadeh H. Interaction of saffron and its constituents with Nrf2 signaling pathway: A review. Iranian Journal of Basic Medical Sciences. 2022; 25(7):789-98. [DOI:10.22038/IJBMS.2022.61986.13719] [PMID]
Chen X, Xuan B, Xu D, Wang Q, Cheng M, Jin Y. Crocin supplementation during oocyte maturation enhances antioxidant defence and subsequent cleavage rate. Reproduction in Domestic Animals. 2019; 54(2):300-8. [DOI:10.1111/rda.13361] [PMID]
Zhang HH, Xu PY, Wu J, Zou WW, Xu XM, Cao XY, et al. Dehydroepiandrosterone improves follicular fluid bone morphogenetic protein-15 and accumulated embryo score of infertility patients with diminished ovarian reserve undergoing in vitro fertilization: A randomized controlled trial. Journal of Ovarian Research. 2014; 7:93. [DOI:10.1186/s13048-014-0093-3] [PMID] [PMCID]
Li Y, Li RQ, Ou SB, Zhang NF, Ren L, Wei LN, et al. Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization, and embryo quality in humans. Reproductive Biology and Endocrinology. 2014; 12:81. [DOI:10.1186/1477-7827-12-81] [PMID] [PMCID]
Gong Y, Li-Ling J, Xiong D, Wei J, Zhong T, Tan H. Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders. Journal of Ovarian Research. 2021; 14(1):1. [DOI:10.1186/s13048-020-00757-x] [PMID] [PMCID]
Christoforou ER, Pitman JL. Intrafollicular growth differentiation factor 9: Bone morphogenetic 15 ratio determines litter size in mammals†. Biology of Reproduction. 2019; 100(5):1333-43. [DOI:10.1093/biolre/ioz011] [PMID]
Sajjadi M, Bathaie Z. Comparative study on the preventive effect of saffron carotenoids, crocin and crocetin, in NMU-induced breast cancer in rats. Cell J. 2017; 19(1):94-101. [DOI:10.22074/cellj.2016.3901] [PMID]
Krsmanovic LZ, Hu L, Leung PK, Feng H, Catt KJ. The hypothalamic GnRH pulse generator: Multiple regulatory mechanisms. Trends in Endocrinology and Metabolism. 2009; 20(8):402-8. [DOI:10.1016/j.tem.2009.05.002] [PMID] [PMCID]
- Abstract Viewed: 178 times
- pdf Downloaded: 111 times