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Effect of melatonin on the clinical outcome of patients with repeated cycles after failed cycles of in vitro fertilization and intracytoplasmic sperm injection

Published online by Cambridge University Press:  28 February 2022

Qi Zhu
Affiliation:
Department of Biomedical Engineering, Anhui Medical University, Hefei, China
Kaijuan Wang
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
Chao Zhang
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
Beili Chen
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
Huijuan Zou
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
Weiwei Zou
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
Rufeng Xue
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
Dongmei Ji
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, China Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, China
Zhaojuan Yu
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
Bihua Rao
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
Ran Huo
Affiliation:
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
Yunxia Cao
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
Ding Ding*
Affiliation:
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
Zhiguo Zhang*
Affiliation:
Department of Biomedical Engineering, Anhui Medical University, Hefei, China Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China NHC Key Laboratory of study on abnormal gametes and reproductive tract (Anhui Medical University), Hefei, China Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, Hefei, China
*
Authors for correspondence: Ding Ding and Zhiguo Zhang. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China. Email: (DD) [email protected]; (ZZ) [email protected]
Authors for correspondence: Ding Ding and Zhiguo Zhang. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, China. Email: (DD) [email protected]; (ZZ) [email protected]

Summary

To explore whether embryo culture with melatonin (MT) can improve the embryonic development and clinical outcome of patients with repeated cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure, immature oocytes from controlled ovarian superovulation cycles were collected for in vitro maturation (IVM) and ICSI. The obtained embryos were cultured in 0, 10–11, 10–9, 10–7 and 10–5 M MT medium respectively, and 10–9 M was screened out as the optimal concentration. Subsequently, 140 patients who underwent failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with a medium containing 10–9 M MT, these 140 MT culture cycles were designated as the experimental group (10–9 M group), and the control group was the previous failed cycles of patients (0 M group). The results showed that the fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10–9 M group were significantly higher than those of the 0 M group (P < 0.01; P < 0.01; P < 0.0001; P < 0.0001; P < 0.0001). To date, in total, 50 vitrified-warmed cycle transfers have been performed in the 10–9 M group and the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher than those in the 0 M group (all P < 0.0001). Two healthy infants were delivered successfully and the other 18 women who achieved clinical pregnancy also had good examination indexes. Therefore the application of 10–9 M MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and had good clinical outcomes.

Trial registration: ChiCTR2100045552.

Type
Research Article
Copyright
© The Author(s), 2022. Published by Cambridge University Press

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Footnotes

The first two authors are joint first authors.

References

Acuña-Castroviejo, D, Escames, G, Venegas, C, Díaz-Casado, ME, Lima-Cabello, E, López, LC, Rosales-Corral, S, Tan, DX and Reiter, RJ (2014). Extrapineal melatonin: Sources, regulation, and potential functions. Cell Mol Life Sci 71, 29973025.CrossRefGoogle ScholarPubMed
An, Q, Peng, W, Cheng, Y, Lu, Z, Zhou, C, Zhang, Y and Su, J (2019). Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos. J Cell Physiol 234, 17370–81.CrossRefGoogle ScholarPubMed
Barros, VRP, Monte, APO, Santos, JMS, Lins, TLBG, Cavalcante, AYP, Gouveia, BB, Müller, MC, Oliveira, JL, Donfack, NJ, Araújo, VR and Matos, MHT (2020b). Melatonin improves development, mitochondrial function and promotes the meiotic resumption of sheep oocytes from in vitro grown secondary follicles. Theriogenology 144, 6773.CrossRefGoogle ScholarPubMed
Barros, VRP, Monte, APO, Santos, JMS, Lins, TLBG, Cavalcante, AYP, Gouveia, BB, Müller, MC, Oliveira Junior, JL, Barberino, RS, Donfack, NJ, Araújo, VR and Matos, MHT (2020a). Effects of melatonin on the in vitro growth of early antral follicles and maturation of ovine oocytes. Domest Anim Endocrinol 71, 106386.CrossRefGoogle ScholarPubMed
Brom-De-Luna, JG, Salgado, RM, Canesin, HS, Diaw, M and Hinrichs, K (2019). Equine blastocyst production under different incubation temperatures and different CO2 concentrations during early cleavage. Reprod Fertil Dev 31, 1823–9.CrossRefGoogle ScholarPubMed
Camargos, MGRS, Rodrigues, JK, Lobach, VN, El Cury-Silva, T, Nunes, MEG, Camargos, AF and Reis, FM (2019). Human oocyte morphometry before and after cryopreservation: A prospective cohort study. Cryobiology 88, 81–6.CrossRefGoogle ScholarPubMed
Ding, D, Wang, QS, Li, XY, Chen, BL, Zou, WW, Ji, D, Hao, Y, Xue, RF, Zou, HJ, Wei, ZL, Zhou, P, Cao, YX and Zhang, ZG (2020). Effects of different polyvinylpyrrolidone concentrations on intracytoplasmic sperm injection. Zygote 28, 148–53.CrossRefGoogle Scholar
Esteves, SC, Humaidan, P, Roque, M and Agarwal, A (2019). Female infertility and assisted reproductive technology. Panminerva Med 61, 12.CrossRefGoogle ScholarPubMed
Gardner, DK and Schoolcraft, WB (1999). Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 11, 307–11.CrossRefGoogle ScholarPubMed
Hiroshi, T, Mai, J, Manabu, T, Yuichiro, S, Yumiko, M, Masahiro, S, Isao, T, Ryo, M, Shun, S, Toshiaki, T, Akihisa, T, Russel, JR and Norihiro, S (2020). Importance of melatonin in assisted reproductive technology and ovarian aging. Int J Mol Sci 21, 1135.Google Scholar
Imesch, P, Scheiner, D, Xie, M, Fink, D, Macas, E, Dubey, R and Imthurn, B (2013). Developmental potential of human oocytes matured in vitro followed by vitrification and activation. J Ovarian Res 6, 30.CrossRefGoogle ScholarPubMed
Izyumov, DS, Domnina, LV, Nepryakhina, OK, Avetisyan, AV, Golyshev, SA, Ivanova, OY, Korotetskaya, MV, Lyamzaev, KG, Pletjushkina, OY, Popova, EN and Chernyak, BV (2010). Mitochondria as source of reactive oxygen species under oxidative stress. Study with novel mitochondria-targeted antioxidants—The “Skulachev-ion” derivatives. Biochemistry (Mosc) 75, 123–9.CrossRefGoogle ScholarPubMed
Kang, JT, Koo, OJ, Kwon, DK, Park, HJ, Jang, G, Kang, SK and Lee, BC (2009). Effects of melatonin on in vitro maturation of porcine oocyte and expression of melatonin receptor RNA in cumulus and granulosa cells. J Pineal Res 46, 22–8.CrossRefGoogle ScholarPubMed
Keefe, D, Kumar, M and Kalmbach, K (2015). Oocyte competency is the key to embryo potential. Fertil Steril 103, 317–22.CrossRefGoogle ScholarPubMed
Li, CY, Hao, HS, Zhao, YH, Zhang, PP, Wang, HY, Pang, YW, Du, WH, Zhao, SJ, Liu, Y, Huang, JM, Wang, JJ, Ruan, WM, Hao, T, Reiter, RJ, Zhu, HB and Zhao, XM (2019). Melatonin improves the fertilization capacity of sex-sorted bull sperm by inhibiting apoptosis and increasing fertilization capacitation via MT1. Int J Mol Sci 20, 3921.CrossRefGoogle ScholarPubMed
Li, X, Mu, Y, Elshewy, N, Ding, D, Zou, H, Chen, B, Chen, C, Wei, Z, Cao, Y, Zhou, P and Zhang, Z (2021). Comparison of IVF and IVM outcomes in the same patient treated with a modified IVM protocol along with an oocytes-maturing system containing melatonin: A pilot study. Life Sci 264, 118706.CrossRefGoogle ScholarPubMed
Lin, T, Lee, JE, Kang, JW, Oqani, RK, Cho, ES, Kim, SB and Il Jin, D (2018). Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor-quality porcine oocytes via anti-oxidative and anti-apoptotic effects. Mol Reprod Dev 85, 665–81.CrossRefGoogle ScholarPubMed
Liu, J, Zhang, X, Yang, Y, Zhao, J, Hao, D, Zhang, J, Liu, Y, Wu, W and Wang, X (2016). Long-time vs. short-time insemination of sibling eggs. Exp Ther Med 12, 3756–60.CrossRefGoogle ScholarPubMed
Lord, T, Nixon, B, Jones, KT and Aitken, RJ (2013). Melatonin prevents postovulatory oocyte aging in the mouse and extends the window for optimal fertilization in vitro . Biol Reprod 88, 67.CrossRefGoogle ScholarPubMed
Lu, X, Liu, Y, Cao, X, Liu, SY and Dong, X (2019). Laser-assisted hatching and clinical outcomes in frozen–thawed cleavage-embryo transfers of patients with previous repeated failure. Lasers Med Sci 34, 1137–45.CrossRefGoogle ScholarPubMed
Manchester, LC, Coto-Montes, A, Boga, JA, Andersen, LPH, Zhou, Z, Galano, A, Vriend, J, Tan, DX and Reiter, RJ (2015). Melatonin: An ancient molecule that makes oxygen metabolically tolerable. J Pineal Res 59, 403–19.CrossRefGoogle ScholarPubMed
Martín, M, Macías, M, Escames, G, León, J and Acuña-Castroviejo, D (2000). Melatonin but not vitamins C and E maintains glutathione homeostasis in t-butyl hydroperoxide-induced mitochondrial oxidative stress. FASEB J 14, 1677–9.CrossRefGoogle ScholarPubMed
Miyara, F, Aubriot, FX, Glissant, A, Nathan, C, Douard, S, Stanovici, A, Herve, F, Dumont-Hassan, M, LeMeur, A, Cohen-Bacrie, P and Debey, P (2003). Multiparameter analysis of human oocytes at metaphase II stage after IVF failure in non-male infertility. Hum Reprod 18, 1494–503.CrossRefGoogle ScholarPubMed
Nakano, M, Kato, Y and Tsunoda, Y (2012). Effect of melatonin treatment on the developmental potential of parthenogenetic and somatic cell nuclear-transferred porcine oocytes in vitro. Zygote 20, 199207.CrossRefGoogle ScholarPubMed
Niu, YJ, Zhou, W, Nie, ZW, Shin, KT and Cui, XS (2020). Melatonin enhances mitochondrial biogenesis and protects against rotenone-induced mitochondrial deficiency in early porcine embryos. J Pineal Res 68, e12627.CrossRefGoogle ScholarPubMed
Olcese, JM (2020). Melatonin and female reproduction: an expanding universe. Front Endocrinol 11, 85.CrossRefGoogle Scholar
Rafael, G, Ediane, M, Allain, A and Heitor, OS (2019). The usefulness of melatonin in the field of obstetrics and gynecology. Pharmacol Res 147, 104337.Google Scholar
Reiter, RJ (1995). Functional pleiotropy of the neurohormone melatonin: Antioxidant protection and neuroendocrine regulation. Front Neuroendocrinol 16, 383415.CrossRefGoogle ScholarPubMed
Reiter, RJ, Tan, DX and Galano, A (2014). Melatonin: Exceeding expectations. Physiology (Bethesda) 29, 325–33.Google ScholarPubMed
Ribas-Maynou, J and Benet, J (2019). Single and double strand sperm DNA damage: Different reproductive effects on male fertility. Genes (Basel) 10, 105.CrossRefGoogle ScholarPubMed
Rodríguez-Varela, C and Labarta, E (2020). Clinical application of antioxidants to improve human oocyte mitochondrial function: A review. Antioxidants 9, 1197.CrossRefGoogle ScholarPubMed
Sacha, CR, Kaser, DJ, Farland, LV, Srouji, S, Missmer, SA and Racowsky, C (2018). The effect of short-term exposure of cumulus-–oocyte complexes to in vitro maturation medium on yield of mature oocytes and usable embryos in stimulated cycles. J Assist Reprod Genet 35, 841–9.CrossRefGoogle ScholarPubMed
Tarahomi, M, Vaz, FM, van Straalen, JP, Schrauwen, FAP, van Wely, M, Hamer, G, Repping, S and Mastenbroek, S (2019). The composition of human preimplantation embryo culture media and their stability during storage and culture. Hum Reprod 34, 1450–61.CrossRefGoogle ScholarPubMed
Tomás, C, Orava, M, Tuomivaara, L and Martikainen, H (1998). Low pregnancy rate is achieved in patients treated with intracytoplasmic sperm injection due to previous low or failed fertilization in in-vitro fertilization. Hum Reprod 13, 6570.CrossRefGoogle ScholarPubMed
Wang, F, Tian, X, Zhang, L, Gao, C, He, C, Fu, Y, Ji, P, Li, Y, Li, N and Liu, G (2014). Beneficial effects of melatonin on in vitro bovine embryonic development are mediated by melatonin receptor 1. J Pineal Res 56, 333–42.CrossRefGoogle ScholarPubMed
Yang, M, Tao, J, Chai, M, Wu, H, Wang, J, Li, G, He, C, Xie, L, Ji, P, Dai, Y, Yang, L and Liu, G (2017). Melatonin improves the quality of inferior bovine oocytes and promoted their subsequent IVF embryo development: Mechanisms and results. Molecules 22, 2059.CrossRefGoogle ScholarPubMed
Zhao, XM, Hao, HS, Du, WH, Zhao, SJ, Wang, HY, Wang, N, Wang, D, Liu, Y, Qin, T and Zhu, HB (2016). Melatonin inhibits apoptosis and improves the developmental potential of vitrified bovine oocytes. J Pineal Res 60, 132–41.CrossRefGoogle ScholarPubMed
Zou, HJ, Chen, BL, Ding, D, Gao, M, Chen, DW, Liu, Y, Hao, Y, Zou, WW, Ji, DM, Zhou, P, Wei, ZL, Cao, YX and Zhang, ZG (2020). Melatonin promotes the development of immature oocytes from the COH cycle into healthy offspring by protecting mitochondrial function. J Pineal Res 68, e12621.CrossRefGoogle ScholarPubMed