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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Infertile High-risk Patients With Polycystic Ovaries

Intervention / Treatment
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* Drug: a drug withdrawal during the long protocol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 23 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GnRH agonist withdrawal<br>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<br>* 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.<br>* Other names: GnRH agonist wihtholding or GnRH agonist coasting;|
| No Intervention: control group<br>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?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| pregnancy rate in the patients with IVF or ICSI |  | one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GnRH agonist withdrawal, OHSS, E2, VEGF