Estrogen (Gel)Transdermal vs Oral Estrogen for Endometrial Preparation

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Frozen Embryo Transfer, Infertility, Female

Intervention / Treatment
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* Drug: 17-beta Estradiol gel 0.06% w/w(ESTOGEL.Intas pharma)
* Drug: Estradiol Hemihydrate(Estrabet Tablet, abbott pharma)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 35 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 |
| --- | --- |
| Active Comparator: Transdermal Gel<br>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)<br>* 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).<br>|
| Other: Oral Estradiol<br>In the Oral Estradiol group, all women will be given oral Estradiol valerate tablets | Drug: Estradiol Hemihydrate(Estrabet Tablet, abbott pharma)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial thickness (ET) | Average endometrial thickness achieved on day 14 of HRT | 14 to 21 days after start of estrogen | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transdermal Estrogen, FET, Oral Estrogen, IVF/ICSI