The Impact of Estrogen Administration Duration in Hormonally Prepared Frozen Embryo Transfer Cycles

Sponsor

Akdeniz University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05825885

Collaborator

(none)

500

Enrollment

Location

Anticipated Duration (Months)

12.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This prospective controlled study aimed to investigate the effect of the duration of estrogen (E2) administration prior to progesterone (P) initiation on live birth rates (LBR) in frozen embryo transfer (FET) cycles.

The study was conducted at a single tertiary-care in vitro fertilization (IVF) center and included 486 patients undergoing high-quality frozen blastocyst transfer in a hormone replacement therapy (HRT) cycle. Patients scheduled for E2 therapy were administered either 5-7, 8-10, or 11-13 days of treatment, depending on their presentation day. After the E2-only phase, if the endometrial thickness was above 7mm, P was initiated (daily 300mg of vaginal micronized P tablets), and FET was performed on the 6th day of P treatment. The primary outcome measure was LBR.

Condition or Disease	Intervention/Treatment	Phase
Duration of Estrogen Administration	Drug: E2

Detailed Description

The timing of P initiation in HRT cycles depends on the thickness and morphology of the endometrium, which are influenced by the duration of E2 treatment. Although numerous studies have examined the effect of E2 treatment duration on endometrial thickness and morphology, the results have been inconsistent, and the impact on live birth rates (LBR) remains unclear. Previous research has explored the impact of standard 12-day E2 therapy and prolonged periods of E2 administration on pregnancy outcomes. However, the present study aims to compare the effects of standard 12-day E2 therapy with shorter-term E2 application and evaluate their impact on treatment outcomes.

To test our hypothesis, we conducted a prospective analysis of about 500 hormonally prepared frozen embryo transfer (FET) cycles performed between January 2020 and December 2021 at our center. The objective of this study was to determine the optimal duration of estrogen (E2) therapy prior to progesterone (P) initiation for FET cycles in terms of live birth rate (LBR).

In our center, patients with frozen embryos routinely applied to the center on weekdays (Monday, Wednesday, and Friday) as part of a predetermined treatment plan. Patients who presented to the clinic during their menstrual periods were scheduled to receive E2 therapy for a duration of either 5-7, 8-10, or 11-13 days, depending on the day they presented. After the application of micronized E2 at a daily dose of 4-6mg, transvaginal ultrasonography was performed to assess endometrial thickness. If the endometrial thickness was found to be above 7mm, daily 300mg of vaginal micronized P tablets were initiated, and FET was performed on the 6th day of P treatment. Patients whose endometrial thickness was less than 7 millimeters on transvaginal ultrasonography after the application of E2 treatment for the specified day and who had to continue estrogen therapy were not included in the study.

The duration of E2 administration prior to P initiation was categorized into three groups:

5-7 days, 8-10 days, and 11-13 days. The primary outcome of this study was LBR, which was defined as the delivery of a live-born infant after 24 weeks of gestation. Secondary outcomes included implantation rate, clinical pregnancy rate, and miscarriage rate.

Study Design

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Impact of Estrogen Administration Duration on Live Birth Rates in Hormonally Prepared Frozen Embryo Transfer Cycles: A Prospective Controlled Study

Actual Study Start Date :

Jan 1, 2020

Actual Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
5-7 days E2 therapy Patient group treated with e2 for 5-7 days	Drug: E2 micronized E2 at a daily dose of 4-6mg,
8-10 days E2 therapy Patient group treated with e2 for 5-7 days	Drug: E2 micronized E2 at a daily dose of 4-6mg,
11-13 days E2 therapy Patient group treated with e2 for 5-7 days	Drug: E2 micronized E2 at a daily dose of 4-6mg,

Arm

Intervention/Treatment

5-7 days E2 therapy

Patient group treated with e2 for 5-7 days

Drug: E2

micronized E2 at a daily dose of 4-6mg,

8-10 days E2 therapy

Patient group treated with e2 for 5-7 days

Drug: E2

micronized E2 at a daily dose of 4-6mg,

11-13 days E2 therapy

Patient group treated with e2 for 5-7 days

Drug: E2

micronized E2 at a daily dose of 4-6mg,

Outcome Measures

Primary Outcome Measures

live birth rate [2 years]
the birth ratio of a baby who showed any sign of life

Secondary Outcome Measures

implantation rate [2 years]
the percentage of embryos which successfully undergo implantation compared to the number of embryos transferred in a given period.
clinical pregnancy rate [2 years]
the number of clinical pregnancy divided by the number of embryo transfer cycle for each group
miscarriage rate [2 years]
rate of the spontaneous loss of a pregnancy before the 20th week

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Inclusion Criteria:

Exogenous hormone preparation of the endometrial lining
High embryo quality ((≥2BB) according to Alpha criteria
Embryo transfer at the blastocyst stage

Exclusion Criteria:

- Patients whose treatments were canceled for any reason before the embryo transfer procedure
Patients who underwent embryo transfer in the cleavage stage
Presence of low-quality (<2BB) blastocysts
15% loss of viability of the embryo during embryo thawing,