Estrogen (Gel)Transdermal vs Oral Estrogen for Endometrial Preparation

Sponsor

Indira IVF Hospital Pvt Ltd (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05802303

Collaborator

(none)

510

Enrollment

Location

Arms

17.1

Anticipated Duration (Months)

29.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this randomized study trial is to comparing transdermal estradiol gel and oral estradiol for endometrial preparation in the Frozen Embryo Transfer Cycle. The main question[s] it aims to answer is: • Can Transdermal estrogen (gel) can be equally efficacious as compared to oral estrogen in hormone replacement FET (HRT- FET) cycles ? The Transdermal gel would have the added benefit of a higher patient comfort with fewer side effects and a better safety profile. Participants planned for Frozen embryo transfer will undergo H-P-O axis suppression on previous cycle D21 of menses with gonadotropin-releasing hormone(GnRH) agonist depot preparation (Inj. Decapeptyl 3.75 mg) IM . The study will compare Transdermal E2 gel with Oral E2 tabs. The patients will be randomized into an oral and gel group, and all patients will participate only once in the study.

Condition or Disease	Intervention/Treatment	Phase
Frozen Embryo Transfer Infertility, Female	Drug: 17-beta Estradiol gel 0.06% w/w(ESTOGEL.Intas pharma) Drug: Estradiol Hemihydrate(Estrabet Tablet, abbott pharma)	N/A

Detailed Description

Estrogen priming is essential for the induction of progesterone receptors and to build endometrial thickness, both of which play an important role in regulating endometrial receptivity . Different routes of Estrogen administration are oral (tablets), transdermal (patch/gel), and vaginal (tablets).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

510 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Masking Description:

All cases undergoing frozen embryo transfer with own or donor gametes.

Primary Purpose:

Treatment

Official Title:

Safety and Efficacy of Transdermal Estrogen (Gel) Versus Oral Estrogen for Endometrial Preparation in Down-regulated Frozen Embryo Transfer (FET) Cycles-An Open-label Multi Centric Randomized Controlled Trial

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Transdermal Gel In the Estradiol gel group patients will be administered transdermal Estradiol gel (17-beta Estradiol gel 0.06%)	Drug: 17-beta Estradiol gel 0.06% w/w(ESTOGEL.Intas pharma) In the Estradiol gel group patients will be administered transdermal Estradiol gel (17-beta Estradiol gel 0.06% w/w) 2 puffs thrice a day (each application contains 1.25 mg with 0.75 mg of the drug).
Other: Oral Estradiol In the Oral Estradiol group, all women will be given oral Estradiol valerate tablets	Drug: Estradiol Hemihydrate(Estrabet Tablet, abbott pharma) In the oral Estradiol group, all women will be given 2 mg of Estradiol valerate tablets, one tablets thrice a day within 30 days of injection triptorelin depot. Endometrial assessment will be performed on D10 of HRT. Please see the flow diagram (in the annexure) for details.

Arm

Intervention/Treatment

Active Comparator: Transdermal Gel

In the Estradiol gel group patients will be administered transdermal Estradiol gel (17-beta Estradiol gel 0.06%)

Drug: 17-beta Estradiol gel 0.06% w/w(ESTOGEL.Intas pharma)

In the Estradiol gel group patients will be administered transdermal Estradiol gel (17-beta Estradiol gel 0.06% w/w) 2 puffs thrice a day (each application contains 1.25 mg with 0.75 mg of the drug).

Other: Oral Estradiol

In the Oral Estradiol group, all women will be given oral Estradiol valerate tablets

Drug: Estradiol Hemihydrate(Estrabet Tablet, abbott pharma)

In the oral Estradiol group, all women will be given 2 mg of Estradiol valerate tablets, one tablets thrice a day within 30 days of injection triptorelin depot. Endometrial assessment will be performed on D10 of HRT. Please see the flow diagram (in the annexure) for details.

Outcome Measures

Primary Outcome Measures

Endometrial thickness (ET) [14 to 21 days after start of estrogen]
Average endometrial thickness achieved on day 14 of HRT

Secondary Outcome Measures

Cycle cancelation rate [21 days after starting HRT]
Number of cycles cancelled before embryo transfer × 100
Average E2 consumption [On 1 day of embryo transfer]
Total E2 consumed till embryo transfer
Implantation rates (IR) [4 weeks + 2 weeks after embryo transfer]
The number of gestational sacs observed by transvaginal ultrasound at the 6th gestational week per the number of embryos transferred.
Clinical pregnancy rates (CPR) [4 weeks + 2 weeks after embryo transfer]
Detection of a foetal heartbeat on transvaginal ultrasound at the 6th gestational week per embryo transfer cycle
Miscarriage rates (MR) [Within 20 weeks of gestation]
Number of spontaneous pregnancy losses in which a gestational sac was previously observed (before gestation week <20 weeks) per 100 clinical pregnancy .
Patient satisfaction score [on 1 day of embryo transfer]
It is measured using visual analogue scale(VAS) score

Other Outcome Measures

Undesirable side effects between both the groups [Till 12 weeks of pregnancy]
Symptoms like rash, itching ,burning, thromboembolic event

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Infertile patients aged 23-35 years.
BMI 18.5 to 29.9 kg/m2.
A normal uterine cavity assessed by 3D ultrasound (USG)/hysteroscopy.
Patients who underwent IVF/ICSI and who have cryopreserved their embryos.
Those receiving donor oocytes or donor embryos.
Patients undergoing hormonal replacement frozen embryo transfer (HRT-FET) cycles with GnRH agonist suppression.
Embryo Transfers of good quality embryos -2/3/4/5 AA, AB, BA(As per Gardner Grading System).

Exclusion Criteria:

Preimplantation Genetic Testing for Aneuploidies (PGT-A) cycles.
Patients who had a FET performed in natural or stimulated cycles.
Patients who had more than 2 failed transfers due to thin endometrium.
Patients having uterine anomalies.
Known cases of adenomyosis and endometriosis.
Underlying cardiac/renal/hepatic/thromboembolic disorders, h/o anxiety or depression.
E2 >50 pg./ml, P4 > 1 ng/ml and on D2 of menses.
On D2 scan presence of a cyst or a dominant follicle.
Patients with a history of recurrent 1st-trimester abortions.