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Endocrine requirements for oocyte maturation following hCG, GnRH agonist, and Kisspeptin during IVF treatment

Ali Abbara 1, Tia Hunjan 1, Vu N. A. Ho 2, Sophie A. Clarke 1, Alexander N. Comninos 1, Chioma Izzi-Engbeaya 1, Tuong M. Ho 2, Geoffrey H. Trew 3, Artsiom Hramyka 4, Tom Kelsey 4, Rehan Salim 3, Peter Humaidan 5, Lan N. Vuong 2,6  and Waljit S. Dhillo 1

1 Section of Endocrinology and Investigative Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.

2 IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam

3 In vitro Fertilization Unit, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom

4 School of Computer Science, University of St Andrews, St Andrews, United Kingdom

5 The Fertility Clinic, Skive Regional Hospital and Faculty of Health, Aarhus University, Aarhus,

6 University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam


Objective: The maturation of oocytes to acquire competence for fertilization is critical to the success of in vitro fertilization (IVF) treatment. It requires LH-like exposure, provided by either human chorionic gonadotropin (hCG), or gonadotropin releasing hormone agonist (GnRHa). More recently, the hypothalamic stimulator, kisspeptin, was used to mature oocytes. Herein, we examine the relationship between the endocrine changes following these agents and oocyte maturation.
Design: Retrospective cohort study.
Methods: Prospectively collected hormonal data from 499 research IVF cycles triggered with either hCG, GnRHa, or kisspeptin were evaluated.
Results: HCG-levels (121 iU/L) peaked at 24 h following hCG, whereas LH-levels peaked at ~4 h following GnRHa (140 iU/L), or kisspeptin (41 iU/L). HCG-levels were negatively associated with body-weight, whereas LH rises following GnRHa and kisspeptin were positively predicted by pre-trigger LH values. The odds of achieving the median mature oocyte yield for each trigger were increased by hCG/LH level. Progesterone rise during oocyte maturation occurred precipitously following each trigger and strongly predicted the number of mature oocytes retrieved. Progesterone rise was positively associated with the hCG-level following hCG trigger, but negatively with LH rise following all three triggers. The rise in progesterone per mature oocyte at 12 h was greater following GnRHa than following hCG or kisspeptin triggers.
Conclusion: The endocrine response during oocyte maturation significantly differed by each trigger. Counter-intuitively, progesterone rise during oocyte maturation was negatively associated with LH rise, even when accounting for the number of mature oocytes retrieved. These data expand our understanding of the endocrine changes during oocyte maturation and inform the design of future precision-triggering protocols.

Keywords: trigger, oocyte maturation, fertility, progesterone, in vitro fertilization treatment



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