GnRH Agonist Versus hCG Trigger in Ovulation Induction With Intrauterine Insemination.

GnRH Agonist Versus hCG Trigger in Ovulation Induction With Intrauterine Insemination: a Randomized Controlled Trial

This study aims to compare clinical pregnancy rates (CPR) in patients who are administered either Gonadotropin-releasing hormone agonists (GnRHa) or human chorionic gonadotropin (hCG) for ovulation trigger in intrauterine insemination (IUI) cycles. A prospective randomized comparative study was conducted at Hue University Hospital in Vietnam. Total of 197 infertile women were randomly assigned to receive either GnRHa trigger (n=98 cycles) or hCG trigger (n= 99 cycles) for ovulation trigger. Patients returned for ultrasound monitoring 24 hours after IUI to confirm ovulation. A clinical pregnancy was defined as the presence of gestational sac with fetal cardiac activity.

Study Overview

• Status: Completed
• Conditions: Ovulation Induction
• Intervention / Treatment: Drug: GnRHa (Fertipeptil 0.1mg); Drug: hCG (Pregnyl 5000IU)

Detailed Description

Study design A prospective randomized comparative study was conducted at Hue University Hospital in Vietnam from April 2016 to June 2017 in 197 infertile women undergoing IUI. The study was approved by the Ethics Committee at Hue University of Medicine and Pharmacy.

Study population A total of 217 women were recruited into the sample at the first stage. Inclusion criteria were women with bilateral tubal patency, at least one follicle ≥ 18mm in diameter on the day of trigger, and men with more than five millions total motile sperm after preparation. Only the first cycles of IUI were studied and there were 197 infertile women who obtained at least 1 mature follicle at the first cycle were included in analysis. Patients were randomly assigned to receive either GnRHa trigger (n=98 cycles) or hCG trigger (n= 99 cycles) for ovulation trigger.

Intervention All patients included in the study were subjected to complete history and physical. Patients with a history of abnormal menstrual cycles (amenorrhea, oligomenorrhea) underwent ovarian stimulation. Stimulation was started on cycle day eight with 75 IU Menogon (Ferring Pharm Co, Switzerland) daily. Ultrasound monitoring was required after every 2-3 days of stimulation and adjustments to dose and duration were tailed according the patient's response. Ovulation was triggered when at least one and no more than 3 follicles reached ≥18mm in diameter. Patients were then randomly assigned to receive either two doses of GnRH-a (Fertipeptil 0.1mg x 2 vial; Ferring Pharm Co, Switzerland) or hCG (Pregnyl 5000IU; Organon Pharm Co, Nertheland) for ovulation trigger.

IUI was then performed with sperm preparation by radiant centrifugation 36 hours after the trigger. Luteal phase support with progesterone 200mg daily (Utrogestan; Besins Health Care Com, Belgium) was started in the day of IUI.

Assessment of outcomes Patients returned for ultrasound monitoring 24 hours after IUI to confirm ovulation which is determined by the accumulation of free fluid in peritoneum at Douglas sac and disappearance of the previous mature follicles.

Serum β-human chorionic gonadotropin (βhCG) was collected 14 days after insemination. A biochemical pregnancy was defined by βhCG concentration > 25 mIU/ml (Shapphire 350; Cork Com, Ireland). Two weeks after a positive βhCG test, the patient returned for an ultrasound appointment. A clinical pregnancy was defined as the presence of gestational sac with fetal cardiac activity.

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Infertile women who were indicated for IUI cycles
• bilateral tubal patency
• at least one follicle ≥ 18mm in diameter on the day of trigger, and
• men with more than five millions total motile sperm after preparation.
• Only the first cycles of IUI were studied

Exclusion Criteria:

• No mature follicle
• Disagree to be enrolled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GnRHa trigger; Infertile patients underwent ovarian stimulation, started on cycle day eight with 75 IU Menogon (Ferring Pharm Co, Switzerland) daily. Ultrasound monitoring was required after every 2-3 days of stimulation and adjustments to dose and duration were tailed according the patient's response. Ovulation was triggered when at least one and no more than 3 follicles reached ≥18mm in diameter. Patients were then randomly assigned to receive two doses of GnRH-a (Fertipeptil 0.1mg x 2 vial; Ferring Pharm Co, Switzerland) for ovulation trigger.	Drug: GnRHa (Fertipeptil 0.1mg); Two doses of GnRH-a (Fertipeptil 0.1mg x 2 vial) for ovulation trigger after ovarian stimulation for IUI.
Experimental: hCG trigger; Infertile patients underwent ovarian stimulation, started on cycle day eight with 75 IU Menogon (Ferring Pharm Co, Switzerland) daily. Ultrasound monitoring was required after every 2-3 days of stimulation and adjustments to dose and duration were tailed according the patient's response. Ovulation was triggered when at least one and no more than 3 follicles reached ≥18mm in diameter. Patients were then randomly assigned to receive hCG (Pregnyl 5000IU; Organon Pharm Co, Nertheland) for ovulation trigger.	Drug: hCG (Pregnyl 5000IU); hCG (Pregnyl 5000IU) for ovulation trigger after ovarian stimulation for IUI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effectiveness of GnRHa versus hCG in ovulation induction	To compare the ovulation rate of patients who were triggered with GnRHa versus hCG in patients undergoing either natural cycle or controlled ovarian stimulation with gonadotropins and IUI.	14 months
The effectiveness of GnRHa versus hCG in pregnancy rate	To compare the pregnancy rate of patients who were triggered with GnRHa versus hCG in patients undergoing either natural cycle or controlled ovarian stimulation with gonadotropins and IUI.	14 months

Collaborators and Investigators

• Sponsor: Hue University of Medicine and Pharmacy
• Investigators: Study Director: Minh Tam Le, Prof.MD.PhD, Hue University of Medicine and Pharmacy, Hue University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: January 11, 2019
• First Submitted That Met QC Criteria: January 30, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: ovulation induction; GnRH agonist trigger; hCG trigger
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Chorionic Gonadotropin
• Other Study ID Numbers: H2016/205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No