Melatonin exchange in infertile women with repeated implantation failures
DOI:
https://doi.org/10.18370/2309-4117.2024.71.94-102Keywords:
infertility, repeated implantation failure, endometrium, melatonin, 6-sulfatoxymelatoninAbstract
Background. Repeated implantation failure occurs in approximately 10–15% of women undergoing in vitro fertilization and embryo transfer (IVF-ET) cycles. One of the important factors is the changed morpho-functional state of the endometrium and chronodestruction in the woman’s body.
Objective of the study: to determine the characteristics of melatonin (MT) metabolism in infertile women with repeated implantation failures in IVF-ET cycles.
Material and methods. 103 women of reproductive age with infertility and repeated implantation failures who were treated in IVF-ET cycles were observed. Depending on the onset of pregnancy in the current IVF-ET cycle, women were divided into 2 groups: group A – 35 women with the onset of pregnancy, group B – 68 patients without the onset of pregnancy. The control group (group C) included 32 healthy fertile women. The MT level in blood serum and 6-sulfatoxymelatonin (aMT6s) in urine was determined.
Results. The initial levels of MT in patients of group A (11.38 ± 0.38 pg/ml) and in group B (9.55 ± 0.27 pg/ml) were lower than in group C (13.67 ± 0.65 pg/ml) in 1.20 (p < 0.01) and 1.43 (p < 0.01) times, respectively. At the same time, the level of MT in women of group A was 1.19 times higher than in the group B (p < 0.03). Excretion of aMT6s in urine in group A (5.09 ± 0.19 ng/ml Cr) and in group B (3.03 ± 0.09 ng/ml Cr) were lower than in group C (6.12 ± 0.21 ng/ml Cr) respectively in 1.20 (p < 0.01) and 2.02 (p < 0.01) times. The aMT6s concentration in urine in patients of group A was 1.68 times higher than in group B (p < 0.01). A direct relationship was established between the levels of serum MT and urinary aMT6s, which was most adequately approximated by a polynomial dependence: y = 0.0139x2 – 0.1127x + 3.2978, R² = 0.2994, r = 0.51, p < 0.01.
Conclusions. Women with repeated implantation failures are characterized by a decrease in the level of MT in blood serum and its main metabolite aMT6s in urine, which may be one of the key factors of implantation failure.
References
- Ma J, Gao W, Li D. Recurrent implantation failure: A comprehensive summary from etiology to treatment. Front Endocrinol (Lausanne). 2023 Jan 5:13:1061766. doi: 10.3389/fendo.2022.1061766
- Kim S. M, Kim JS. A Review of Mechanisms of Implantation. Dev Reprod. 2017 Dec;21(4):351–9. doi: 10.12717/DR.2017.21.4.351
- Sun Y, Zhang Y, Ma X, et al. Determining Diagnostic Criteria of Unexplained Recurrent Implantation Failure: A Retrospective Study of Two vs Three or More Implantation Failure. Front Endocrinol (Lausanne). 2021 Jul 22:12:619437. doi: 10.3389/ fendo.2021.619437
- Cimadomo D, Craciunas L, Vermeulen N, et al. Definition, diagnostic and therapeutic options in recurrent implantation failure: an international survey of clinicians and embryologists. Hum Reprod. 2021 Jan 25;36(2):305–17. doi: 10.1093/humrep/deaa317
- Thornhill AR, deDie-Smulders CE, Geraedts JP, et al.; ESHRE PGD Consortium. ESHRE PGD Consortium ‘Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Hum Reprod. 2005 Jan;20(1):35–48. doi: 10.1093/humrep/deh579
- ESHRE Working Group on Recurrent Implantation Failure; Cimadomo D, de Los Santos MJ, Griesinger G, et al. ESHRE good practice recommendations on recurrent implantation failure. Hum Reprod Open. Jun 15;2023(3):hoad023. doi: 10.1093/hropen/hoad023
- Pantos K, Grigoriadis S, Maziotis E, et al. The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature. Int J Mol Sci. 2022 Feb 16;23(4):2198. doi: 10.3390/ijms23042198
- Chuffa LGA, Lupi LA, Cucielo MS, et al. Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms. Int J Mol Sci. 2019 Dec 31;21(1):300. doi: 10.3390/ijms21010300
- Hsing A. W, Meyer TE, Niwa S, et al. Measuring serum melatonin in epidemiologic studies. Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):932– 7. doi: 10.1158/1055-9965.EPI-10-0004
- Zou H, Chen B, Ding D, et al. Melatonin promotes the development of immature oocytes from the COH cycle into healthy offspring by protecting mitochondrial function. J Pineal Res. 2020 Jan;68(1):e12621. doi: 10.1111/jpi.12621
- Ma X, Wang J, Wang L, et al. The Uterine Melatonergic Systems of AANAT and Melatonin Membrane Receptor 2 (MT2) Are Essential for Endometrial Receptivity and Early Implantation in Mice. Int J Mol Sci. 2023 Apr 12;24(8):7127. doi: 10.3390/ijms24087127
- Reiter RJ, Sharma R, Rosales-Corral S, et al. Melatonin and Pathological Cell Interactions: Mitochondrial Glucose Processing in Cancer Cells. Int J Mol Sci. 2021 Nov 19;22(22):12494. doi: 10.3390/ ijms222212494
- Olcese JM. Melatonin and Female Reproduction: An Expanding Universe. Front Endocrinol (Lausanne). 2020 Mar 6:11:85. doi: 10.3389/fendo.2020.00085
- Zhao D, Yu Y, Shen Y, et al. Melatonin Synthesis and Function: Evolutionary History in Animals and Plants. Front Endocrinol (Lausanne). 2019 Apr 17:10:249. doi: 10.3389/fendo.2019.00249
- Zhao D, Yao Z, Zhang J, et al. Melatonin synthesis genes N-acetylserotonin methyltransferases evolved into caffeic acid O-methyltransferases and both assisted in plant terrestrialization. J Pineal Res. 2021 Oct;71(3):e12737. doi: 10.1111/jpi.12737
- Cipolla-Neto J, Amaral FGD. Melatonin as a Hormone: New Physiological and Clinical Insights. Endocr Rev. 2018 Dec 1;39(6):990–1028. doi: 10.1210/er.2018-00084
- Jiang Y, Shi H, Liu Y, et al. Applications of Melatonin in Female Reproduction in the Context of Oxidative Stress. Oxid Med Cell Longev. 2021 Jul 29:2021:6668365. doi: 10.1155/2021/6668365
- Tamura H, Jozaki M, Tanabe M, et al. Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging. Int J Mol Sci. 2020 Feb 8;21(3):1135. doi: 10.3390/ijms21031135
- Pilehvari S, Yavangui M, Paknahad E, et al. The Boosting Effects of Melatonin on the In Vitro Fertilization (IVF) of Women with Polycystic Ovary Syndrome. Chonnam Med J. 2023 Sep;59(3):188–93. doi: 10.4068/cmj.2023.59.3.188
- Carlomagno G, Minini M, Tilotta M, Unfer V. From Implantation to Birth: Insight into Molecular Melatonin Functions. Int J Mol Sci. 2018 Sep 17;19(9):2802. doi: 10.3390/ijms19092802
- Russo M, Forte G, Oliva MM, et al. Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth. Int J Mol Sci. 2021 Aug 5;22(16):8433. doi: 10.3390/ijms22168433
- Man GCW, Zhang T, Chen X, et al. The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy-An immunological perspective. Am J Reprod Immunol. 2017 Aug;78(2). doi: 10.1111/aji.12715
- Jockers R, Delagrange P, Dubocovich ML, et al. Update on melatonin receptors: IUPHAR Review 20. Br J Pharmacol. 2016 Sep;173(18):2702–25. doi: 10.1111/bph.13536
- Amara, FGD, Cipolla-Neto J. A brief review about melatonin, a pineal hormone. Arch Endocrinol Metab. 2018 Aug;62(4):472–9. doi: 10.20945/2359-3997000000066
- Mosher AA, Tsoulis MW, Lim J, et al. Melatonin activity and receptor expression in endometrial tissue and endometriosis. Hum Reprod. 2019 Jul 8;34(7):1215–24. doi: 10.1093/humrep/dez082
- Sharkey J. T, Puttaramu R, Word RA, Olcese J. Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells. J Clin Endocrinol Metab. 2009 Feb;94(2):421–7. doi: 10.1210/jc.2008-1723
- Olcese J, Beesley S. Clinical significance of melatonin receptors in the human myometrium. Fertil Steril. 2014 Aug;102(2):329–35. doi: 10.1016/j.fertnstert.2014.06.020
- Bejarano I, Monllor F, Marchena A. M, et al. Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa. J Pineal Res. 2014 Oct;57(3):333–9. doi: 10.1111/ jpi.12172
- Zhang L, Zhang Z, Wang F, et al. Effects of melatonin administration on embryo implantation and offspring growth in mice under different schedules of photoperiodic exposure. Reprod Biol Endocrinol. 2017 Oct 2;15(1):78. doi: 10.1186/ s12958-017-0297-7
- He C, Wang J, Li Y, et al. Melatonin-related genes expressed in the mouse uterus during early gestation promote embryo implantation. J Pineal Res. 2015 Apr;58(3):300–9. doi: 10.1111/jpi.12216
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 О.М. Носенко, Р.Я. Демидчик
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.