The Effects of Estrogen on Artificial Endometrium

The Effects of Transdermal Estradiol and Oral Estradiol Valerate on Clinical Outcomes of Frozen-thawed Embryo Transfer Cycles: A Randomized Clinical Trial

In this prospective randomized trial, the parameters of the frozen-thawed embryo transfer (FET) cycles were analyzed. This study was undertaken in the Department of Assisted Reproductive Technologies and Reproductive Genetics Center at Istanbul Memorial Hospital with approval of the local ethics committee. The aim of this prospective randomized clinical trial was to compare two methods of endometrial preparation for FET, oral estradiol and estradiol transdermal patch.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: oral estrogen replacement therapy; Drug: Estradiol transdermal patch

Detailed Description

In this prospective randomized trial, the parameters of the frozen-thawed embryo transfer (FET) cycles were analyzed. This study was undertaken in the Department of Assisted Reproductive Technologies and Reproductive Genetics Center at Istanbul Memorial Hospital with approval of the local ethics committee. The aim of this prospective randomized clinical trial was to compare two methods of endometrial preparation for FET, oral estradiol and estradiol transdermal patch.

A total number of 317 patients who underwent frozen -thawed embryo transfer cycles were enrolled in this study and randomized to two groups including 160 patients with the usage of 6 milligrams/day oral estradiol and 154 patients with the usage of 3.9 milligrams estradiol transdermal patch. Randomization was done with http://www.randomization.com. The patients were given sufficient information to provide written informed consent. All the women underwent intracytoplasmic sperm injection (ICSI).

Treatment protocols: All the patients selected for the research were primed for a frozen transfer using two different ways of exogenous steroid therapy.

In the study group with transdermal route (n=154), 3.9 milligrams of estradiol transdermal patch was applied every other day from the second day of menstruation cycle, and each patch was removed after day. In the control group with oral route (n=160), at the time of cycle, 6 milligrams of oral estradiol valerate was started daily. In both groups, clinical monitoring was done by transvaginal ultrasound from the 11th day of the cycle to measure endometrial thickness. If endometrial thickness was more than 7 millimeter, 90 milligrams vaginal natural progesterone was added. Embryo transfer was done after 5 days.

The primary outcome measure was endometrial thickness on the day of progesterone administration. The secondary outcome measures were chemical and clinical pregnancy, implantation rates, abortion rates, live birth rates, and cycle cancellation rate.

• Study Type: Interventional
• Enrollment (Actual): 317
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey
    • Memorial Sisli Hospital ART and Genetics Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All the women with at least one day 5 or 6 blastocyst
• Appropriate endometrial thickness is more than 7 millimeters on the 14th day of artificial endometrial preparation cycle
• Age under 38 years
• Follicle stimulating hormone less than 12 IU/Liter
• No more than 2 previous treatment cycles
• No history of recurrent spontaneous abortions

Exclusion Criteria:

• Polycystic ovarian syndrome (> 30 cumulus oocyte complexes retrieved at the pick-up)
• Endocrine or metabolic disorder
• Endometriosis
• Embryos derived from donated gametes
• Any underlying diseases (kidney, liver or heart diseases)
• Bad-quality embryos
• Uterine malformation
• Endometrial polyp
• Severe male factor (Azoospermia)
• Body mass index more than 30
• Thrombophilia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: oral estradiol group; patients with the usage of 6 milligrams/day oral estradiol	Drug: oral estrogen replacement therapy; oral estradiol group for endometrial preparation
ACTIVE_COMPARATOR: estradiol transdermal patch group; patients with the usage of 3.9 milligrams estradiol transdermal patch	Drug: Estradiol transdermal patch; transdermal estradiol group for endometrial preparation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial thickness on the day of progesterone administration	In frozen thawed embryo transfer cycles, endometrial preparation with estrogen was performed. Estrogen was applied from the second day of menstruation cycle to 11th day of cycle. Endometrial thickness was measured by transvaginal ultrasound. If endometrial thickness was more than 7 millimeters, endometrial thickness was ready for embryo transfer on the day of progesterone administration.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	The effects of transdermal estradiol and oral estradiol valerate on implantation rates were evaluated. Implantation rates are described as gestational sacs seen by transvaginal ultrasound per embryo transfer.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Pregnancy rate	The effects of transdermal estradiol and oral estradiol valerate on clinical pregnancy rate were evaluated. Clinical pregnancy rate is measured with a pregnancy where an ultrasound scan has shown at least one fetal heartbeat per embryo transfer.	12 months
Live birth rate	The effects of transdermal estradiol and oral estradiol valerate on live birth rate were evaluated. Live birth rate is described as live birth per embryo transfer.	12 months

Collaborators and Investigators

• Sponsor: Memorial Sisli Hospital, Istanbul

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2017
• Primary Completion (ACTUAL): October 1, 2017
• Study Completion (ACTUAL): September 1, 2018

Study Registration Dates

• First Submitted: May 10, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (ACTUAL): May 16, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 2, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estradiol; Estrogens
• Other Study ID Numbers: EndometrialpreparingSK002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No