Around 48 million couples and 186 million people worldwide have infertility; of these, approximately 85% have an identifiable cause, the most common being ovulatory dysfunctions, male infertility, polycystic ovary syndrome, and tubule disease. The remaining 15% have infertility for unknown reasons, including lifestyle and environmental factors. The regulation of the hypothalamic- pituitary-adrenal axis (HPA) is crucial for the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which are essential for female reproductive functions. GnRH is the primary reproductive axis regulator. The pattern of GnRH, FSH, and LH release is determined by its pulsatile secretion, which in turn controls endocrine function and gamete maturation in the gonads. Peptides called Kisspeptin (KP), Neurokinin-B (NKB), and Orexin influence both positive and negative feedback modulation of GnRH, FSH, and LH secretion in reproduction. This review article mainly focuses on the historical perspective, isoform, and signaling pathways of KP, NKB, and Orexin novel peptide-based targets including clinical and preclinical studies and having a promising effect in the management of infertility.
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