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

Sponsor

Zekai Tahir Burak Women's Health Research and Education Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01367912

Collaborator

(none)

301

Enrollment

Location

Arms

Duration (Months)

33.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: estradiol tablet Drug: estradiol tablet	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

301 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2008

Actual Primary Completion Date :

Nov 1, 2008

Actual Study Completion Date :

Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Progesterone only group 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 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 received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel Other Names: estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark
Active Comparator: Progesterone+Late estradiol group 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 received 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel. Other Names: estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark

Arm

Intervention/Treatment

No Intervention: Progesterone only group

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

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

received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel

Other Names:

estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark

Active Comparator: Progesterone+Late estradiol group

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

received 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel.

Other Names:

estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark

Outcome Measures

Primary Outcome Measures

Clinical pregnancy rate [sixth gestational week.]
Clinical pregnancies were detected with the confirmation of positive fetal cardiac activities by transvaginal sonography in the sixth gestational week.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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