Effect of Estradiol Pretreatment on Antagonist ICSI Cycles

Study Overview
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Brief Summary
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Depended on the hypothesis that growth asynchrony of antral follicles is a consequence of the gradual follicle stimulating hormone (FSH) elevation that occurs during the late luteal phase, the aim of this work is to study the effect of estradiol pretreatment on follicular synchronization and intracytoplasmic sperm injection (ICSI) outcome in antagonist cycles

Detailed Description
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Gonadotropin-releasing hormone antagonist (GnRH-ant) cycles are characterized by higher patient acceptability with more attention being directed to the potential effect of steroid pretreatment to program antagonist protocol cycles, as marked size discrepancies of growing follicles reflect incoordinated maturation of follicular-oocyte complexes and complicates clinical criteria for human chorionic gonadotropin (hCG) administration. This phenomenon is associated with fewer mature oocytes and resulting embryos, which limits sufficient embryo selection for embryo transfer. Indeed, the large number of available embryos represented an important prognostic factor of invitro-fertilization (IVF) outcome, particularly in poor prognosis patients, possibly by increasing the probability that at least one good-quality embryo will be selected for embryo transfer. During COH, a better understanding of follicular development has resulted in the improvement of strategies for ovarian stimulation. This approach represents a potential and more physiological alternative to GnRH agonist or oral contraceptive pills pre-treatment in a trial to synchronize multi-follicular development and improve controlled ovarian hyperstimulation (COH) results. The present study is a randomized controlled trial that investigated whether E2 pre-treatment during the luteal phase affects developmental characteristics of growing follicles during COH. It depended on the hypothesis that growth asynchrony of antral follicles is a consequence of the gradual FSH elevation that occurs during the late luteal phase, thus testing for detection of the effect of luteal estradiol on follicular synchronization and its effect on ICSI outcome.

Official Title
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Studying The Effect of Estradiol Pretreatment on Follicular Synchronization and Intracytoplasmic Sperm Injection (ICSI) Outcome in Antagonist Cycles

Conditions
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Female Infertility

Intervention / Treatment
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* Drug: Estradiol Valerate 4mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women age 20-37 years. Anti-mullerian (AMH) level greater than 1.2 ng/ml. Body mass index between 18 and 29 kg/m2. Undergoing a first or second ICSI cycles. Exclusion Criteria: Endometriosis. Uterine disorders such as fibroids and uterine anomalies. Antral follicular counts (AFC) less than 10. Azoospermic males.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 37 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Cases who received estradiol pretreatment then underwent ICSI. | Drug: Estradiol Valerate 4mg<br>* Estradiol valerate 2 mg (two tablet once daily) started 5 days before expected menses (or 7 days after ovulation of previous cycle). After start of menses, estradiol pretreatment was stopped and controlled ovarian stimulation started.<br>* Other names: Progynova;|
| No Intervention: group 2<br>Cases who underwent ICSI directly without receiving any pretreatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of stimulation. | number of days from the start of controlled ovarian stimulation on day 2 of menses until the day of hCG administration until day of hCG administration | 7-16 days after start of controlled ovarian stimulation. | 
| Total number of gonadotropin ampoules used. | number of gonadotropin ampules used from the start of controlled ovarian stimulation on day 2 of menses until the day of hCG administration | 7-16 days after start of controlled ovarian stimulation. | 
| Total number of follicles by U/S on day of hCG. | number of follicles by ultrasound scan on day of hCG administration | 7-16 days after start of controlled ovarian stimulation. | 
| Serum estradiol and progesterone level on day of hCG . | serum level of estradiol pg/dl and progesterone ng/dl on day of hCG administration | 7-16 days after start of controlled ovarian stimulation. | 
| Endometrial thickness on day of hCG. | thickness of endometrium in mm on day of hCG | 7-16 days after start of controlled ovarian stimulation. | 
| Number of mature oocytes | number of metaphase II oocytes after denudation | 36 hours after oocyte retrieval. | 
| Number of good quality embryos. | number of grade 1 and grade 2 day 3 embryos | 3 days after oocyte retrieval. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy rate | the number of positive pregnancies (defined as serum B-hCG more than 5 miu/ml measured 14 days after embryo transfer) divided by the number of embryo transfer procedures. | 14 days after embryo transfer | 
| Clinical pregnancy rate | The number of clinical pregnancies (defined as the presence of a gestational sac with positive heart beat detected by transvaginal ultrasound scan 2 weeks after positive pregnancy test) divided by the number of embryo transfer procedures | 2 weeks after positive pregnancy test |