GnRH Agonist (GnRHa) Withdrawal at Late Stage of Long Protocol and the Incidence of Ovarian Hyper-stimulation

Study of Effect of GnRHa Withdrawal at Late Stage of Long Protocol on the Risk of Ovarian Hyper-stimulation in Patients With Polycystic Ovary (PCO) Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

To test whether GnRHa withheld 2-3 days before ovulation trigger reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in infertile high-risk patients with polycystic ovaries (PCOs) who have been treated with gonadotropins for in vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI).

Study Overview

• Status: Unknown
• Conditions: Infertile High-risk Patients With Polycystic Ovaries
• Intervention / Treatment: Drug: a drug withdrawal during the long protocol

Detailed Description

All the patients received a midluteal long GnRH agonist (GnRH-a) and a gonadotropins (recombinant FSH) stimulation protocol. Pituitary down-regulation with GnRH agonist (triptorelin, 0.1mg/d, ×10d, then 0.05mg/d until E2 ≤40 pg/ml in serum), was initiated during the luteal phase on the cycle-day 21. Two weeks later, if E2 in serum was ≤40 pg/ml and absence of follicular activity was detected, the stimulation of ovaries was started by recombinant follicle-stimulating hormone (recFSH, Gonal-F, Serono, Switzerland) with doses ranging 150-250 IU/d. Doses were adjusted accordingly with ovarian monitoring and follicles growth. GnRHa (0.05mg/d) was injected stimulously with FSH before dominant follicles were ≥ 14 mm. When the diameter of one or more follicles was ≥ 14 mm, GnRHa (0.05mg/d) was withheld in the study group. In the control group, GnRHa was used to the day of ovulation trigger. Ovulation was induced with HCG (5000-10000 IU) when at least three follicles greater than 16mm in diameter were detected on ultrasound examination and the leading follicles reached ≥ 18 mm in diameter. Oocytes retrieval for IVF or ICSI was performed 34-36 hours later under transvaginal ultrasound guidance.

Main Outcome Measure(s): Serum E2 levels, VEGF levels in Serum and follicular fluids, retrieved oocytes, fertilization, implantation rate and pregnancy rate (PR), the rate of OHSS.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing city, Jiangsu, China, 210008
      • Recruiting
      • Research Room of Reproductive Medicine, The Outpatient Building of Drum Tower Hospital
      • Contact: Bin Wang, Master; Phone Number: 86-25-8310-7170; Email: wangbin_429@sina.com
      • Principal Investigator: Lin-jun Ding, ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

ninety-six infertile patients with PCOs (12 or more follicles 2-9 mm in diameter were detected in ovaries by ultrasound detection) undergoing IVF treatment were enrolled.

Exclusion Criteria:

the subjects included the followings: a basal FSH level of > 10IU/L; age >35 years; a body mass index (BMI) > 30 kg/m2; ovarian surgery radiotherapy or chemotherapy; ovarian dysfunction; endometriosis; hyperprolactinemia; thyroid dysfunction; the presence of organic pelvic diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GnRH agonist withdrawal; All the patients received a midluteal long GnRH agonist (GnRH-a) and a gonadotropins (recombinant FSH) stimulation protocol. When the diameter of one or more follicles was ≥ 14 mm, GnRHa (0.05mg/d) was withheld in the study group.	Drug: a drug withdrawal during the long protocol; GnRHa (triptorelin,0.05mg/d) was injected stimulously with FSH before dominant follicles were ≥ 14 mm. When the diameter of one or more follicles was ≥ 14 mm, GnRHa (triptorelin,0.05mg/d) was withheld in the study group.; Other Names: GnRH agonist wihtholding or GnRH agonist coasting
No Intervention: control group; All the patients received a midluteal long GnRH agonist (GnRH-a) and a gonadotropins (recombinant FSH) stimulation protocol. In the control group, GnRHa (triptorelin, 0.05mg/d,)was used to the day of ovulation trigger.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of ovarian hyperstimulation	Ovarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe. Symptoms are set into 3 categories: mild, moderate, and severe.	two weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
pregnancy rate in the patients with IVF or ICSI	one month

Collaborators and Investigators

• Sponsor: Nanjing University
• Investigators: Study Director: Hai-xiang Sun, ph.D, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Publications and helpful links

General Publications

• Ho Yuen B, Nguyen TA, Cheung AP, Leung PC. Clinical and endocrine response to the withdrawal of gonadotropin-releasing hormone agonists during prolonged coasting. Fertil Steril. 2009 Aug;92(2):499-507. doi: 10.1016/j.fertnstert.2008.06.039. Epub 2008 Aug 15.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Anticipated): June 1, 2013

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 6, 2012

Study Record Updates

• Last Update Posted (Estimate): July 10, 2012
• Last Update Submitted That Met QC Criteria: July 7, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: VEGF; OHSS; E2; GnRH agonist withdrawal
• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome
• Other Study ID Numbers: NJGLHRMCSUN1