Timing of Estrogen Support During the Luteal Phase of in Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) Cycle

Study Overview
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Brief Summary
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To test the hypothesis that adding estradiol (E2) to progesterone supplementation later in the luteal phase of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, rather than earlier in the luteal phase, improves clinical pregnancy rates (PRs).

Detailed Description
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Several studies reported that elevated E2 may have a detrimental effect on endometrial receptivity and embryo. This conflict was the starting point of our study. The investigators thought that this luteal decrease in E2 level could be prevented by adding estradiol just before the receptivity window is open, instead of adding earlier in the luteal phase which could result in defective embryo implantation.

Official Title
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Timing of Estrogen Support During the Luteal Phase of IVF / Intracytoplasmic Sperm Injection Cycle: a Randomized Controlled Trial

Conditions
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Infertility

Intervention / Treatment
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* Drug: estradiol tablet
* Drug: estradiol tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients on long GnRH agonist protocol with controlled ovarian hyperstimulation who were seen in our IVF clinic between February and November 2008, and who have E2 levels on the day of hCG administration >2500 pg/dl Exclusion Criteria: Presence of azoospermia requiring testicular sperm extraction procedure endometriosis greater than stage II unilateral oophorectomy, polycystic ovarian syndrome (PCOS) secondary infertility age greater than 40 yrs and a basal follicle stimulating hormone (FSH) level higher than 12 mIU/ml were exclusion criteria

Ages Eligible for Study
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Maximum Age: 40 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Progesterone only group<br>received a single daily application of vaginal progesterone gel beginning from the day of OPU and continued at least until pregnancy was ruled out by a negative serum ß-hCG measurement performed on the 14th day after embryo transfer with no E2 added | |
| Active Comparator: Progesterone+Early Estradiol group<br>received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel | Drug: estradiol tablet<br>* received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel<br>* Other names: estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark;|
| Active Comparator: Progesterone+Late estradiol group<br>received 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel | Drug: estradiol tablet<br>* received 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel.<br>* Other names: estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Clinical pregnancies were detected with the confirmation of positive fetal cardiac activities by transvaginal sonography in the sixth gestational week. | sixth gestational week. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Luteal phase support, estradiol supplementation, IVF/ICSI, clinical pregnancy rate