Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study.

This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact StatementWhat is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient.What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran.What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.

Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1 promoter in primordial follicles.

Premature ovarian failure during chemotherapy is a serious problem for young women with cancer. To preserve the fertility of these patients, approaches to prevent chemotherapy-induced ovarian failure are needed. In a previous study, we reported that melatonin treatment prevents the depletion of the dormant follicle pool via repression of the simultaneous activation of dormant primordial follicles by cisplatin. However, melatonin's protective effect was only partial and thus insufficient. In this study, we found that the hormone ghrelin enhances the protective effect of melatonin against cisplatin-induced ovarian failure in mouse model. Co-administration of melatonin and ghrelin more effectively prevented cisplatin-induced follicle disruption. Simultaneous treatment with melatonin and ghrelin almost restored the number of primordial follicles and the corpus luteum in cisplatin-treated ovaries, compared with single administration. We found melatonin and ghrelin receptors on the cell membrane of premature oocytes of primordial follicles. In addition, melatonin and ghrelin co-administration inhibited the cisplatin-induced phosphorylation of PTEN and FOXO3a that induces cytoplasmic translocation of FOXO3a. Inhibition of FOXO3a phosphorylation by melatonin and ghrelin increased the binding affinity of FOXO3a for the p27Kip1 promoter in primordial follicles. Co-administration of melatonin and ghrelin in cisplatin-treated ovaries restored the expression of p27Kip1 , which is critical for retention of the dormant status of primordial follicles. In conclusion, these findings suggest that melatonin and ghrelin co-administration is suitable for use as a fertoprotective adjuvant therapy during cisplatin chemotherapy in young female cancer patients.