Volume 7, Issue 1, January 2019, Page: 1-7
Melatonin and Myoinositol: A Foreword Step Toward IVF Success, a Prospective Clinical Trial
Atyaf Hasan, Department of Iraqi Speciality Center for In-Vitro Fertilization, Baghdad, Iraq
Al-Quraan Elena, Department of Family Medicine, Faculty of Medicine, Princess Basma Teaching Hospital, Irbid, Jordan
Al-Quraan Ghassan, Department of Iraqi Speciality Center for In-Vitro Fertilization, Baghdad, Iraq
Tayseer Rimawi, Department of Iraqi Speciality Center for In-Vitro Fertilization, Baghdad, Iraq
Said Nasrallah, Department of Iraqi Speciality Center for In-Vitro Fertilization, Baghdad, Iraq
Received: Dec. 2, 2018;       Accepted: Jan. 25, 2019;       Published: Feb. 19, 2019
DOI: 10.11648/j.jgo.20190701.11      View  37      Downloads  20
Abstract
Many subfertile couples, who failed to conceive naturally, seek help by means of artificial reproduction techniques such as in vitro fertilization (IVF) to achieve pregnancy. It is clear that oocyte and embryo quality depression are widely considered to be the main challenge of IVF in assisted reproduction. The aim of the study was to assess the effect and the role of melatonin combined with myoinositol on oocyte quality and to investigate its correlation with pregnancy outcome. A total of 315 patient, aged between 30-40, in a 12 month study period from Jan. 2017 to Dec. 2017, with history of one or multiple unsuccessful IVF cycles due to poor oocyte quality were included in this study. The study group (group 1, n=166) was treated with melatonin combined with myoinositol (Seidivid plus, SEIDLAB) for 3 months prior to a new IVF cycle and the control group (group 2, n =149) just received a standard IVF cycle without melatonin and myoinositol. IVF outcomes were compared between the two groups. Primary endpoint was the number of morphologically mature oocytes retrieved (MII oocytes). Secondary endpoints were fertilization rate per number of mature oocytes, embryo quality and pregnancy rate. After treatment, the number of mature oocytes, the fertilization rate, the number of top-quality embryos transferred and pregnancy rate were statistically higher compared to the previous IVF cycle, while there was no difference in the number of retrieved oocyte. The mean number of oocytes retrieved differ between the two groups being (11.56) in group 1 and (10.9) in control one (1920 vs. 1629) and the percentage of mature oocytes was significantly higher in melatonin-treated group (77.03% vs. 69.1%). Concurrently, the mean number of immature oocytes (germinal vesicles) was reduced (22.9% vs. 39.9%). Furthermore, the melatonin –myoinositol treated group showed an increase in fertilization rate (80.2% vs. 77.7%) and the mean number of grade one embryos resulted was also higher (60.05% vs. 49.5%). Clinical pregnancy rate was in tendency higher in the group treated with melatonin and myoinositol (48.3% vs. 40.8%), In the current study It was concluded that Melatonin and myoinositol treatment is likely to become a significant option for improving oocyte and embryo quality in women who cannot become pregnant because of poor oocyte quality.
Keywords
Melatonin, Myoinositol, IVF Cycle, Intracytoplasmic Sperm Injection, Oocyte Quality, Pregnancy Outcome
To cite this article
Atyaf Hasan, Al-Quraan Elena, Al-Quraan Ghassan, Tayseer Rimawi, Said Nasrallah, Melatonin and Myoinositol: A Foreword Step Toward IVF Success, a Prospective Clinical Trial, Journal of Gynecology and Obstetrics. Vol. 7, No. 1, 2019, pp. 1-7. doi: 10.11648/j.jgo.20190701.11
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Pacchiarotti A. Antioxidative capacity of melatonin in follicular fluid of aged IVF patients: beneficial effects on oocytes and embryo. J Gynecol Neonatal Biol 2015; 1: 1–5.
[2]
Andersen AN, Witjes H, Gordon K, et al. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod 2011; 26: 3413–23.
[3]
Palini S, Benedetti S, Tagliamonte MC, De Stefani S, Primiterra M, Polli V, Rocchi P, Catalani S, Battistelli S, Canestrari F, Bulletti C: Influence of ovarian stimulation for IVF/ICSI on the antioxidant defence system and relationship to outcome. Reprod Biomed Online 2014, 29: 65.
[4]
Yoshida M, Ishigati K, Nagai T, Chikyu M, Pursel V: Glutathione concentration during maturation and after fertilisation in pig oocytes: relevance to the ability of oocytes to form male pronucleus. Biol Reprod 1993, 49: 89–94.
[5]
Fatehi A, Roelen B, Colenbrander B, Schoevers E, Gadella B, Beverst M, van den Hurk R: Presence of cumulus cells during in-vitro fertilisation protects the bovine oocyte against oxidative stress and improves first cleavage but does not affect further development. Zygote 2005, 13: 177–185.
[6]
Huang B, Li Z, Ai J, Zhu L, Li Y, Jin L, Zhang H: Antioxidant capacity of follicular fluid from patients undergoing in-vitro fertilisation. Int J Clin Exp Pathol 2014, 7: 2273–2282.
[7]
Serhal PF, Ranieri DM, Kinis A, Marchant S, Davies M, Khadum IM. Oocyte morphology predicts outcome of intracytoplasmic sperm injection. Hum Reprod 1997; 12 (6): 1267–1270.
[8]
Hourvitz A, Machtinger R, Maman E, Baum M, Dor J, Levron J. Assisted reproduction in women over 40 years of age: how old is too old? Reprod Biomed Online 2009; 19: 599-603.
[9]
Macklon NS, Fauser BC. Mild stimulation in in vitro fertilization. Ann NY Acad Sci 2003; 997: 105–111.
[10]
Wiener-Megnazi Z, Vardi L, Lissak A, Shnizer S, Reznick AZ, Ishai D, Lahav-Baratz S, Shiloh H, Koifman M, Dirnfeld M. Oxidative stress indices in follicular fluid as measured by the thermochemiluminescence assay correlate with outcome parameters in in vitro fertilization. Fertil Steril 2004; 82 (Suppl 3): 1171–1176.
[11]
Chattopadhayay R, Ganesh A, Samanta J, Jana SK, Chakravarty BN, Chaudhury K. Effect of follicular fluid oxidative stress on meiotic spindle formation in infertile women with polycystic ovarian syndrome. Gynecol Obstet Invest 2009; 69: 197- 202.
[12]
Berker B, Kaya C, Aytac R, Satiroglu H. Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction. Hum Reprod 2009; 24: 2293-2302.
[13]
Van Loendersloot LL, Van Wely M, Limpens J, Bossuyt PM, Repping S, Van der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update 2010; 16: 577-589.
[14]
Unfer V, Raffone E, Rizzo P, Buffo S. Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol Endocrinol 2011 Apr 5. [Epub ahead of print].
[15]
Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 2002; 17: 1591-1596.
[16]
Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N, Reiter RJ. Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 2009; 92: 328-343.
[17]
Chiu TT, Rogers MS, Briton-Jones C, Haines C. Effects of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod 2003; 18: 408-416.
[18]
Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, De Santis L. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 2009; 91: 1750-1754.
[19]
Rizzo P, Raffone E, Benedetto V. Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial. Eur Rev Med Pharmacol Sci 2010; 14: 555-561.
[20]
Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka F, Lee L, et al. The role of melatonin as an antioxidant in the follicle. J Ovarian Res. 2012; 5: 5. [PMCID: PMC3296634] [PubMed: 22277103].
[21]
Chakravarty S, Rizvi SI: Physiological effects of melatonin: implications on human health. Biomedicine 2008, 28: 252–255.
[22]
Reiter R, Rosales-Corral S, Manchester L, Tan D: Peripheral reproductive organ health and melatonin: ready for prime time. Int J Mol Sci 2013, 14: 7231–7272.
[23]
Carlomagno G, Nordio M, Chiu TT, Unfer V. Contribution of myo-inositol and melatonin to human reproduction. Eur J Obstet Gynecol Reprod Biol. 2011; 159: 267-72. [PubMed: 21835536].
[24]
Turi A, Garzetti GG: The pattern of melatonin in amenorrheic women affected by sterility. Acta Eur Fertil 1993, 24: 71–74.
[25]
Tang P, Chan T, Tang G, Pang S: Plasma melatonin profile and hormonal interactions in the menstrual cycles of anovulatory infertile women treated with gonadotropins. Gynecol Obstet Invest 1998, 45: 247–252.
[26]
Webley GE, Hearn JP: Local production of progesterone by the corpus luteum of the marmoset monkey in response to perfusion with chorionic gonadotrophin and melatonin in-vivo. J Endocrinol 1987, 112: 449–457.
[27]
Boczek-Leszczyk E, Juszczak M: The influence of melatonin on human reproduction. Pol Merkur Lekarski 2007, 23: 128–130.
[28]
Salhab M, Dhorne-Pollet S, Auclair S, Guyader-Joly C, Brisard D, Dalbies-Tran R, Dupont J, Ponsart C, Mermillod P, Uzbekova S: In-vitro maturation of oocytes alters gene expression and signaling pathways in bovine cumulus cells. Mol Reprod Dev 2013, 80: 166–182.
[29]
Itoh M, Ishizuka B, Kuribayashi Y, Amemiya A, Sumi Y: Melatonin, its precursors, and synthesizing enzyme activities in the human ovary. Mol Hum Reprod 1999, 5: 402–408.
[30]
Knapen M, Zusterzeel P, Peters W, Steegers E: Glutathione and glutathione-related enzymes in reproduction: a review. Eur J Obstet Gynecol Reprod Biol 1999, 82: 171–184.
[31]
Reiter R J, Tan DX, Maldonado MD. Melatonin as an antioxidant: Physiology versus pharmacology. J Pineal Res. 2005; 39: 215-6. [PubMed: 16098101].
[32]
Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, et al. Chemical and physical properties and potential mechanism: Melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem. 2002; 2: 181-97. [PubMed: 11899100].
[33]
Kojo S: Vitamin C: basic metabolism and its function as an index of oxidative stress. Curr Med Chem 2004, 11: 1041–1064.
[34]
Rahman K: Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2007, 2: 219–236.
[35]
Sugino N. Reactive oxygen species in ovarian physiology. Reprod Med Biol 2005; 4: 31-44.
[36]
Sikka SC. Role of oxidative stress and antioxidants in andrology and assisted reproductive technology. J Androl 2004; 25: 5-18.
[37]
Sugino N. Roles of reactive oxygen species in the corpus luteum. Anim Sci J 2007; 77: 556-565.
[38]
Espey L: Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod 1994, 50: 233–238.
[39]
Reiter R, Rosales-Corral S, Manchester L, Tan D: Peripheral reproductive organ health and melatonin: ready for prime time. Int J Mol Sci 2013, 14: 7231–7272.
[40]
Tamura H, Takasaki A, Miwa I, Taniguchi K, Maekawa R, Asada H, Taketani T, Matsuoka A, Yamagata Y, Shimamura K, Morioka H, Ishikawa H, Reiter RJ, Sugino N: Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilisation rate. J Pineal Res 2008, 44 (3): 280–87.
[41]
Tamura 13. Reiter R, Rosales-Corral S, Manchester L, Tan D: Peripheral reproductive organ health and melatonin: ready for prime time. Int J Mol Sci 2013, 14: 7231–7272.
[42]
Guerin P, El Mouatassim S, Menezo Y: Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 2001, 7: 175–189.
[43]
Yang HW, Hwang KJ, Kwon HC, Kim HS, Choi KW, Oh KS. Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos. Hum Reprod 1998; 13: 998-1002.
[44]
Takahashi T, Takahashi E, Igarashi H, Tezuka N, Kurachi H: Impact of oxidative stress in aged mouse oocytes on calcium oscillations at fertilisation. Mol Reprod Dev 2003, 66: 143–152.
[45]
Du Plessis S, Makker K, Desai N, Agarwal A: Impact of oxidative stress on IVF. Expert Rev Obstet Gynecol 2008, 3: 539–554.
[46]
Combelles C, Gupta S, Agarwal A: Could oxidative stress influence the in vitro maturation of oocytes? Reprod Biomed Online 2009, 18: 864–880.
[47]
El-Raey M, Geshi M, Somfai T, Kaneda M, Hirako M, Abdel-Ghaffar A, Sosa G, El-Roos M, Nagai T: Evidence of melatonin synthesis in the cumulus oocyte complexes and its role in enhancing oocyte maturation in-vitro in cattle. Mol Reprod Dev 2011, 78: 250–262.
[48]
Hardeland R: Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 2005, 27: 119–130.
[49]
Lowes D, Webster N, Murphy M, Galley H: Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis. Br J Anaesth 2013, 110: 472–480.
[50]
Chiu TT, Rogers MS, Briton-Jones C, Haines C. Effect of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod 2003; 18: 408-416.
[51]
Bevilacqua A, Carlomagno G, Gerli S, et al. Results from the International Consensus Conference on myo-inositol and D-chiroinositol in obstetrics and gynecology-assisted reproduction technology. Gynecol Endocrinol 2015; 31: 441–6.
[52]
Facchinetti F, Bizzarri M, Benvenga S, et al. Results from the International Consensus Conference on Myo-inositol and d-chiroinositol in obstetrics and gynecology: the link between metabolic syndrome and PCOS. Eur J Obstet Gynecol Reprod Biol 2015; 195: 72–6.
[53]
Chiu TTY, Rogers MS, Law ELK, et al. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 2002; 17: 1591–6.
[54]
Cohen P. The twentieth century struggle to decipher insulin signalling. Nat Rev Mol Cell Biol 2006; 7: 867-873.
[55]
Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature 1989; 341 (6239): 197-205.
[56]
Indyk HE, Woollard DC. Determination of free myo-inositol in milk and infant formula by high performance liquid chromatography. Analyst 1994; 119: 397-402.
[57]
Fujiwara T, Nakada K, Shirakawa H, Miyazaki S. Development of inositol trisphosphate-induced calcium release mechanism during maturation of hamster oocytes. Dev Biol 1993; 156: 69-79.
[58]
Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 2008; 24: 139-144.
[59]
Costantino D, Minozzi G, Minozzi E, GuaraldI C. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double blind trial. Eur Rev Med Pharmacol Sci 2009; 13: 105-110.
[60]
Giordano D, Corrado F, Santamaria A, Quattrone S, Pintaudi B, DI Benedetto A, D'anna R. Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome: a perspective, randomized, placebo-controlled study. menopause 2011; 18: 102-104.
[61]
Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, De Santis L. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 2009; 91: 1750-1754.
Browse journals by subject