Back to resultsEstrogen (Gel)Transdermal vs Oral Estrogen for Endometrial Preparation
Primary Purpose
Frozen Embryo Transfer, Infertility, Female
Status
Not yet recruiting
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
17-beta Estradiol gel 0.06% w/w(ESTOGEL.Intas pharma)
Estradiol Hemihydrate(Estrabet Tablet, abbott pharma)
Sponsored by
About this trial
This is an interventional treatment trial for Frozen Embryo Transfer focused on measuring Transdermal Estrogen, FET, Oral Estrogen, IVF/ICSI
Eligibility Criteria
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.
Sites / Locations
- Indira IVF Hospital Private Limited
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Other
Arm Label
Transdermal Gel
Oral Estradiol
Arm Description
In the Estradiol gel group patients will be administered transdermal Estradiol gel (17-beta Estradiol gel 0.06%)
In the Oral Estradiol group, all women will be given oral Estradiol valerate tablets
Outcomes
Primary Outcome Measures
Endometrial thickness (ET)
Average endometrial thickness achieved on day 14 of HRT
Secondary Outcome Measures
Cycle cancelation rate
Number of cycles cancelled before embryo transfer × 100
Average E2 consumption
Total E2 consumed till 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.
Clinical pregnancy rates (CPR)
Detection of a foetal heartbeat on transvaginal ultrasound at the 6th gestational week per embryo transfer cycle
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 .
Patient satisfaction score
It is measured using visual analogue scale(VAS) score
Full Information
NCT ID
NCT05802303
First Posted
February 21, 2023
Last Updated
April 4, 2023
Sponsor
Indira IVF Hospital Pvt Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05802303
Brief Title
Estrogen (Gel)Transdermal vs Oral Estrogen for Endometrial Preparation
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 2023 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indira IVF Hospital Pvt Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Frozen Embryo Transfer, Infertility, Female
Keywords
Transdermal Estrogen, FET, Oral Estrogen, IVF/ICSI
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
All cases undergoing frozen embryo transfer with own or donor gametes.
Allocation
Randomized
Enrollment
510 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Transdermal Gel
Arm Type
Active Comparator
Arm Description
In the Estradiol gel group patients will be administered transdermal Estradiol gel (17-beta Estradiol gel 0.06%)
Arm Title
Oral Estradiol
Arm Type
Other
Arm Description
In the Oral Estradiol group, all women will be given oral Estradiol valerate tablets
Intervention Type
Drug
Intervention Name(s)
17-beta Estradiol gel 0.06% w/w(ESTOGEL.Intas pharma)
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Estradiol Hemihydrate(Estrabet Tablet, abbott pharma)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Endometrial thickness (ET)
Description
Average endometrial thickness achieved on day 14 of HRT
Time Frame
14 to 21 days after start of estrogen
Secondary Outcome Measure Information:
Title
Cycle cancelation rate
Description
Number of cycles cancelled before embryo transfer × 100
Time Frame
21 days after starting HRT
Title
Average E2 consumption
Description
Total E2 consumed till embryo transfer
Time Frame
On 1 day of embryo transfer
Title
Implantation rates (IR)
Description
The number of gestational sacs observed by transvaginal ultrasound at the 6th gestational week per the number of embryos transferred.
Time Frame
4 weeks + 2 weeks after embryo transfer
Title
Clinical pregnancy rates (CPR)
Description
Detection of a foetal heartbeat on transvaginal ultrasound at the 6th gestational week per embryo transfer cycle
Time Frame
4 weeks + 2 weeks after embryo transfer
Title
Miscarriage rates (MR)
Description
Number of spontaneous pregnancy losses in which a gestational sac was previously observed (before gestation week <20 weeks) per 100 clinical pregnancy .
Time Frame
Within 20 weeks of gestation
Title
Patient satisfaction score
Description
It is measured using visual analogue scale(VAS) score
Time Frame
on 1 day of embryo transfer
Other Pre-specified Outcome Measures:
Title
Undesirable side effects between both the groups
Description
Symptoms like rash, itching ,burning, thromboembolic event
Time Frame
Till 12 weeks of pregnancy
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
All women planned for Frozen embryo transfer
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nihar R Bhoi
Phone
+91 7205783512
Email
drnihar.bhoi@indiraivf.in
First Name & Middle Initial & Last Name or Official Title & Degree
Vipin Chandra
Phone
+91-9567971239
Email
ifa@indiraivf.in
Facility Information:
Facility Name
Indira IVF Hospital Private Limited
City
Udaipur
State/Province
Rajasthan
ZIP/Postal Code
313001
Country
India
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vipin Chandra, DGO
Phone
+91 9567971239
Email
ifa@indiraivf.in
First Name & Middle Initial & Last Name & Degree
Nihar R Bhoi, MD
Phone
+91 7205783512
Email
drnihar.bhoi@indira.ivf.in
First Name & Middle Initial & Last Name & Degree
Vipin Chandra, DGO
First Name & Middle Initial & Last Name & Degree
Jaydeep Kale, DNB
First Name & Middle Initial & Last Name & Degree
Madhu Patil, DNB,DGO
First Name & Middle Initial & Last Name & Degree
Pratibha Binwal, DGO
First Name & Middle Initial & Last Name & Degree
Anjali Gahlan, MS,DNB
First Name & Middle Initial & Last Name & Degree
Amol Wankhede, MS
First Name & Middle Initial & Last Name & Degree
Puja Rani, MS
First Name & Middle Initial & Last Name & Degree
A Jhansi Rani, DGO
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be shared with other researchers after publication of primary results
IPD Sharing Time Frame
After 6 months of publication of primary results
Citations:
PubMed Identifier
29529202
Citation
Bourdon M, Santulli P, Kefelian F, Vienet-Legue L, Maignien C, Pocate-Cheriet K, de Mouzon J, Marcellin L, Chapron C. Prolonged estrogen (E2) treatment prior to frozen-blastocyst transfer decreases the live birth rate. Hum Reprod. 2018 May 1;33(5):905-913. doi: 10.1093/humrep/dey041.
Results Reference
background
PubMed Identifier
32991118
Citation
Scheffer JB, Scheffer BB, Aguiar APS, Franca JB, Lozano DM, Fanchin R. A comparison of the effects of three different estrogen used for endometrium preparation on the outcome of day 5 frozen embryo transfer cycle. JBRA Assist Reprod. 2021 Feb 2;25(1):104-108. doi: 10.5935/1518-0557.20200059.
Results Reference
background
PubMed Identifier
31969591
Citation
Corroenne R, El Hachem H, Verhaeghe C, Legendre G, Dreux C, Jeanneteau P, Descamps P, May-Panloup P, Bouet PE. Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen. Sci Rep. 2020 Jan 22;10(1):985. doi: 10.1038/s41598-020-57730-3.
Results Reference
background
PubMed Identifier
10098476
Citation
Devroey P, Pados G. Preparation of endometrium for egg donation. Hum Reprod Update. 1998 Nov-Dec;4(6):856-61. doi: 10.1093/humupd/4.6.856.
Results Reference
background
PubMed Identifier
32666854
Citation
Garimella S, Karunakaran S, Gedela DR. A prospective study of oral estrogen versus transdermal estrogen (gel) for hormone replacement frozen embryo transfer cycles. Gynecol Endocrinol. 2021 Jun;37(6):515-518. doi: 10.1080/09513590.2020.1793941. Epub 2020 Jul 15.
Results Reference
background
PubMed Identifier
31502111
Citation
Ranisavljevic N, Raad J, Anahory T, Grynberg M, Sonigo C. Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review. J Assist Reprod Genet. 2019 Nov;36(11):2217-2231. doi: 10.1007/s10815-019-01576-w. Epub 2019 Sep 9.
Results Reference
background
PubMed Identifier
21880274
Citation
Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril. 2011 Sep;96(3):530-5. doi: 10.1016/j.fertnstert.2011.07.1097.
Results Reference
background
PubMed Identifier
29675488
Citation
Shahrokh Tehraninejad E, Kabodmehri R, Hosein Rashidi B, Jafarabadi M, Keikha F, Masomi M, Hagholahi F. Trans dermal estrogen (oestrogel) for endometrial preparation in freeze embryo transfer cycle: An RCT. Int J Reprod Biomed. 2018 Jan;16(1):51-56.
Results Reference
background
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Estrogen (Gel)Transdermal vs Oral Estrogen for Endometrial Preparation
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