Luteinising hormone-based protocol versus traditional flexible gonadotropin-releasing hormone antagonist protocol in women with normal ovarian response: study protocol for a non-inferiority trial

Abstract

Introduction: Many patients demonstrate an insufficient endogenous luteinising hormone (LH) concentration during ovarian stimulation. With traditional fixed or flexible gonadotropin-releasing hormone (GnRH) antagonist protocols, antagonist administration may further reduce LH activity. Previously, we proved that LH can be used as an indicator for the timing and dosage of antagonist. Patients with a persistently low LH concentration during ovarian stimulation may not require antagonists, whereas antagonist administration can affect reproductive outcomes. To further explore this hypothesis, we designed a randomised clinical trial to compare the LH-based flexible GnRH antagonist protocol with traditional flexible GnRH antagonist protocol in women with normal ovarian response.

Methods and analysis: This study was a multicentre, parallel, prospective, randomised, non-inferiority study. The primary efficacy endpoint was cumulative ongoing pregnancy rate per cycle. The study aimed to prove the non-inferiority of cumulative ongoing pregnancy rate per cycle with an LH-based flexible GnRH antagonist protocol versus traditional flexible GnRH antagonist protocol. Secondary endpoints were the high-quality embryo rate, clinical pregnancy rate and cancellation rate. Differences in cost-effectiveness and adverse events were evaluated. The cumulative ongoing pregnancy rate per cycle in women with normal ovarian response was 70%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 14% (one-sided: α, 2.5%; β, 20%) and a total of 338 patients were needed. Anticipating a 10% drop-out rate, the total number of patients required was 372.

Ethics and dissemination: This trial has been approved by the Institutional Ethical Committee of Beijing Chao-Yang hospital. All participants in the trial will provide written informed consent. The study will be conducted according to the principles outlined in the Declaration of Helsinki and its amendments. Results of this study will be disseminated in peer-reviewed scientific journals.

Trial registration number: ChiCTR1800018077.

Keywords: change management; health economics; sex steroids & HRT.

Figure 1

Flow chart followed the checklist of Standard Protocol Items: Recommendations for Interventional Trials showing patient enrolment, allocation, treatment and follow-up of participants. GnRH, gonadotropin-releasing hormone; LH, luteinising hormone.

Figure 2

Schedule of enrolment, interventions and assessments. ET, embryo transfer; FSH, follicle-stimulating hormone; HBV, hepatitis B virus; HCV, hepatitis C virus; LH, luteinising hormone; OPU, ovum pick up; TORCH, toxoplasmosis, others (Syphilis, Hepatitis B), rubella, Cytomegalovirus (CMV), and herpes simplex.