GnRH Agonist and hCG (Dual Trigger) Versus hCG Trigger for Final Oocyte Maturation in Expected Normal Responders With a High Immature Oocyte Rate: Study Protocol for a Randomized, Superiority, Parallel Group, Controlled Trial

Abstract

IntroductionThe choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate.Methods and AnalysisWe propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: recombinant hCG (6500 IU) will be injected only 36 hours before OPU for final oocyte maturation (hCG-only trigger); co-administration of GnRH-a and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (Dual trigger). The primary outcome is metaphase-II (MII) oocytes rate. Secondary outcomes are number of oocytes retrieved, fertilization rate, top-quality embryos rate, blastula formation rate, embryo implantation rate, clinical pregnancy rate, miscarriage rate, live birth rate, cumulative pregnancy/live birth rates, and ovarian hyperstimulation syndrome (OHSS) rate.Ethics and DisseminationThe reproductive ethics committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine certified this study (Identifier: SDUTCM/2021.7.26) as ethical. All individuals will sign written informed consent. All data and biological samples will be protected according to law. The results of this study will be disseminated in a peer-reviewed scientific journal.Clinical Trial Registration[chictr.gov.cn], identifier [ChiCTR2100049292].

Oocyte retrieval in social fertility preservation: challenging traditional beliefs on gonadotropin dosing and follicular size

“…For this demographic, triggering at a point where large or medium follicles are dominant has been associated with superior oocyte quality. Conversely, for patients ages 35 and older, optimal outcomes have been observed when the proportion of medium follicles is no less than that of small follicles [19]. In the present study, results regarding younger patients differed from those of Yang et al, with trends indicating that a higher proportion of large follicles correlated with less favorable outcomes.…”

“…A strategy commonly employed in IVF treatments involves initiating the trigger when several follicles achieve diameters of 17 to 18 mm [9,14], a protocol our findings seem to align with. In contrast, Yang et al [19] highlighted the significance of follicle size and quantity, particularly for patients younger than 35 years of age. For this demographic, triggering at a point where large or medium follicles are dominant has been associated with superior oocyte quality.…”

Dual trigger for final oocyte maturation in expected normal responders with a high immature oocyte rate: a randomized controlled trial

“…This study was a registered randomized controlled trial (RCT, http://www.chictr.org.cn/ , identifier: ChiCTR2100049292) carried out in the reproductive center, affiliated hospital of Shandong University of Traditional Chinese Medicine, between July 2021 to November 2022 ( 14 ).…”

Dual trigger for final oocyte maturation in expected normal responders with a high immature oocyte rate: A randomized controlled trial

“…This study was a registered randomized controlled trial (RCT, http://www.chictr.org.cn/, identi er: ChiCTR2100049292) carried out in the reproductive center, a liated hospital of Shandong University of Traditional Chinese Medicine, between July 2021 to January 2023 (12).…”