Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment

Abstract

Infertility affects one in six of the population and increasingly couples require treatment with assisted reproductive techniques. In vitro fertilization (IVF) treatment is most commonly conducted using exogenous FSH to induce follicular growth and human chorionic gonadotropin (hCG) to induce final oocyte maturation. However, hCG may cause the potentially life-threatening iatrogenic complication “ovarian hyperstimulation syndrome” (OHSS), which can cause considerable morbidity and, rarely, even mortality in otherwise healthy women. The use of GnRH agonists (GnRHas) has been pioneered during the last two decades to provide a safer option to induce final oocyte maturation. More recently, the neuropeptide kisspeptin, a hypothalamic regulator of GnRH release, has been investigated as a novel inductor of oocyte maturation. The hormonal stimulus used to induce oocyte maturation has a major impact on the success (retrieval of oocytes and chance of implantation) and safety (risk of OHSS) of IVF treatment. This review aims to appraise experimental and clinical data of hormonal approaches used to induce final oocyte maturation by hCG, GnRHa, both GnRHa and hCG administered in combination, recombinant LH, or kisspeptin. We also examine evidence for the timing of administration of the inductor of final oocyte maturation in relationship to parameters of follicular growth and the subsequent interval to oocyte retrieval. In summary, we review data on the efficacy and safety of the major hormonal approaches used to induce final oocyte maturation in clinical practice, as well as some novel approaches that may offer fresh alternatives in future.

Clinical Translational Studies of Kisspeptin and Neurokinin B

“…29 OHSS is predominantly caused by hCG stimulating the release of vascular endothelial growth factor (VEGF) from the ovary, which increases vascular permeability and leakage of fluid into the third spaces of the body, resulting in ascites, pleural effusions, renal impairment, and rarely even death. 30 Kisspeptin reduced the odds of severe OHSS by 33.6-fold (95% CI: 12.6-89.5) compared with hCG. 31 More recently, kisspeptin has been hypothesized to play a direct role in the pathogenesis of OHSS, by directly reducing estradiol-induced VEGF production.…”

Endocrine Requirements for Oocyte Maturation Following hCG, GnRH Agonist, and Kisspeptin During IVF Treatment

“…The World Health Organization recognizes subfertility as the fifth most serious global disability, affecting 1 in 6 couples ( 1 ). In vitro fertilization (IVF) is a supraphysiological process that simulates many of the physiological processes apparent during the natural menstrual cycle ( 2 ). The number of IVF cycles carried out annually is increasing ( 3 ), however 11.8% of cycles commenced did not progress to oocyte retrieval ( 3 ).…”

“…The “trigger” of oocyte maturation replicates the function of the mid-cycle ovulatory luteinizing hormone (LH) surge of the natural cycle ( 2 ) and provides LH-like exposure such that oocytes resume meiosis and advance to the metaphase II stage of development to acquire competence for fertilization ( 5 ). This LH-like activity can be provided by human chorionic gonadotropin (hCG), gonadotropin releasing hormone agonist (GnRHa), or kisspeptin.…”

Oocyte Maturation in Starfish

“…Oocyte maturation is a process by which an immature oocyte resumes meiosis to become a fertilizable egg or to attain competence for normal fertilization after ovulation/spawning [7][8][9][10]. Therefore, the study of in vivo maturation of ovarian oocytes as well as in vitro maturation of isolated oocytes is still required.…”