The Application of a New Ovarian Stimulation Protocol in IVF

Study Overview
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Brief Summary
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Pituitary down regulation is widely used during in vitro fertilization (IVF) procedures. It can suppress the spontaneous luteinizing hormone (LH) surge, and can also make follicles growth evenly. At present, standard gonadotropin releasing hormone analogue (GnRH-a) long protocol is used in around 85% patients in the investigator's center. However, patients have to inject short term GnRH-a 0.05mg or 0.1mg daily for around 3 weeks in one IVF cycle. Long term GnRH-a, which is usually used in patients with endometriosis,has been shown to increase IVF outcome by altering endometrial receptivity. Moreover, it is also very convenient because patients do not have to inject GnRH-a daily. In order to make patients feel more comfortable during IVF treatment, the investigators have used a new ovarian stimulation protocol since the beginning of 2015. The investigators give patients long term GnRH-a (3.75mg) once at menstrual cycle D2, and begin the use of Gn to stimulate follicle growth around 30 days later based on the hormone levels and follicle size. In the pilot observational study of several patients, no LH surge occurred during ovarian stimulation. The aim of this randomized controlled study is to compare the efficiency of this new protocol and standard GnRH-a long protocol in the investigator's center.

Detailed Description
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The primary outcome is ongoing pregnancy rate. Other parameters include number of oocytes retrieved, 2 pronucleus (2PN) fertilization rate, high quality embryo formation rate, implantation rate, spontaneous abortion rate, and ectopic pregnancy rate.

Official Title
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The Application of a New Ovarian Stimulation Protocol in IVF: a Randomized Controlled Study

Conditions
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Clinical Pregnancy Rate, Ovulation Induction

Intervention / Treatment
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* Drug: GnRH-a
* Drug: GnRH-a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First IVF cycle; With normal ovarian reserve(FSH < 10 mIU/mL; antral follicle count>5); With normal uterine. Exclusion Criteria: Pre-implantation genetic diagnosis cycles; Oocyte donation or sperm donation cycles.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 38 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: New protocol group<br>Use long term GnRH-a 3.75mg at day 2 of menstrual cycle. Around 30 days later, controlled ovarian hyperstimulation using gonadotropins is initiated. | Drug: GnRH-a<br>* In experimental group, patients use long term GnRH-a; Patients' serum or follicle fluid will be collected if needed.<br>|
| Active Comparator: Standard GnRH-a long protocol<br>Use short GnRH-a 0.1mg at luteal phase of last menstrual cycle for 10 days and 0.05mg for another 4 days. Once pituitary down regulation is achieved,controlled ovarian hyperstimulation using gonadotropins is initiated. During ovarian stimulation, short GnRH-a is used daily at the dose of 0.05mg until human chorionic gonadotrophin (HCG) trigger. | Drug: GnRH-a<br>* In control group, patients use short term GnRH-a. Patients' serum or follicle fluid will be collected if needed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate | 12 weeks after embryo transfer, gestational sac with fetal heart present inside uterus | 12 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes retrieved |  | 1 day at oocyte retrieved day | 
| 2 pronucleus (2PN) fertilization rate | Number of 2PN/Matured oocytes | 48 hours after oocyte retrieved day |