Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS?

Abstract

Human pre-ovulatory follicular fluid (FF) contains a higher concentration of melatonin than serum. The aim of this study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcomes of an in-vitro maturation (IVM) IVF-embryo transfer programme for patients with polycystic ovarian syndrome (PCOS). Melatonin concentrations in the culture media of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes after using IVM media with or without melatonin were analysed. In the culture media of GC or COC, melatonin concentrations gradually increased. When human chorionic gonadotrophin priming protocols were used, implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control group (P<0.05). Pregnancy rates were also higher, although not significantly. The findings suggest that the addition of melatonin to IVM media may improve the cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes. It is speculated that follicular melatonin may be released from luteinizing GC during late folliculogenesis and that melatonin supplementation may be used to improve the clinical outcomes of IVM IVF-embryo transfer. Melatonin is primarily produced by the pineal gland and regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. Interestingly, human pre-ovulatory follicular fluid contains a higher concentration of melatonin than serum. However, in contrast to animal studies, the direct role of melatonin on oocyte maturation in the human system has not yet been investigated. So, the aim of the study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcome of an in-vitro maturation (IVM) IVF-embryo transfer programme for PCOS patients. The melatonin concentrations in culture medium of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes of IVM IVF-embryo transfer using IVM medium alone or supplemented with melatonin were analysed. In the culture media of GC or COC, the melatonin concentration gradually increased. With human chorionic gonadotrophin priming, the pregnancy and implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control (P<0.05). Our findings suggest that follicular melatonin is released from luteinizing GC during late folliculogenesis and plays a positive role in oocyte maturation. Therefore, addition of melatonin into IVM medium may improve cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes.

Clinical relevance of melatonin in ovarian and placental physiology: a review

“…Conversely, of 59 women not given supplemental melatonin fertility was not changed (relative to the previous cycle). In a more recent study, Kim and co-workers [59] reported that the incubation of ova from infertile women with polycystic ovarian syndrome in a melatonincontaining solution also improved the implantation and pregnancy rates during IFV-ET. For several reasons, the outcome of these studies has important implications and should encourage further tests on the usefulness of melatonin to overcome infertility and improve IVF-ET outcome.…”

Melatonin Scavenger Properties against Oxidative and Nitrosative Stress: Impact on <em>In Vitro</em> Embryo Production in Mammals

“…[104] Deer Animal Subcutaneous implantation of 40 mg Elevates the serum FSH and LH levels, increases number of corpora luteal and the number of embryos [105] Human Oocytes 10 µmol/L during in vitro maturation Increases the preimplantation and pregnancy rate [106] Sheep Animal Subcutaneous implantation of 40 or 80 mg Increases corpus luteal, the number of recovered embryos, the pregnancy and birth rates, and the lambs born per embryo [107] Porcine Donor cell and embryos 10 -10 M in the medium for donor cell and 10 -9 M during in vitro culture of embryos produced by SCNT Increases the proliferation of fetal fibroblasts, blastocysts rate, reduces the apoptotic nuclei. Also, it upregulates BCL2L1 and downregulates BAX and p53.…”

In vitromaturation of human oocytes: Its role in infertility treatment and new possibilities

“…In the Fertility Center of the CHA Gangnam Medical Center, hCG priming has been significantly more successful than no priming for implantation (26.4% vs. 22.6%) and for the pregnancy rate (61.9% vs. 45.7%) [23]. Determining the optimal timing for oocyte collection is the most significant dilemma for IVM.…”