Estrogen (Gel)Transdermal vs Oral Estrogen for Endometrial Preparation

NCT05802303 | Terminated DMC

• 1 other identifier: IIHPL-UDR/RCT/002_2022
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

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.

Conditions

Frozen Embryo Transfer; Infertility, Female

Keywords

Transdermal Estrogen; FET; Oral Estrogen; IVF/ICSI

Outcome Measures

Primary Outcomes (1)

• Endometrial thickness (ET)

  Average endometrial thickness achieved on day 14 of HRT

  14 to 21 days after start of estrogen

Secondary Outcomes (6)

• Cycle cancelation rate

  21 days after starting HRT

• Average E2 consumption

  On 1 day of embryo transfer

• Implantation rates (IR)

  4 weeks + 2 weeks after embryo transfer

• Clinical pregnancy rates (CPR)

  4 weeks + 2 weeks after embryo transfer

• Miscarriage rates (MR)

  Within 20 weeks of gestation

Other Outcomes (1)

• Undesirable side effects between both the groups

  Till 12 weeks of pregnancy

Study Arms (2)

Transdermal Gel

ACTIVE COMPARATOR

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)

Oral Estradiol

OTHER

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

Drug: Estradiol Hemihydrate(Estrabet Tablet, abbott pharma)

Interventions

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

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).

Transdermal Gel

Estradiol Hemihydrate(Estrabet Tablet, abbott pharma) DRUG

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.

Oral Estradiol

Eligibility Criteria

• Age: 25 Years - 35 Years
• Gender Eligibility Details: All women planned for Frozen embryo transfer
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indira IVF Hospital Pvt Ltd: lead

Study Sites (1)

Indira IVF Hospital Private Limited

Udaipur, Rajasthan, 313001, India

Location

Related Publications (8)

• 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.

  PMID: 29529202 BACKGROUND

• 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.

  PMID: 32991118 BACKGROUND

• 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.

  PMID: 31969591 BACKGROUND

• 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.

  PMID: 10098476 BACKGROUND

• 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.

  PMID: 32666854 BACKGROUND

• 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.

  PMID: 31502111 BACKGROUND

• Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril. 2011 Sep;96(3):530-5. doi: 10.1016/j.fertnstert.2011.07.1097.

  PMID: 21880274 BACKGROUND

• 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.

  PMID: 29675488 BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: All cases undergoing frozen embryo transfer with own or donor gametes.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Clinical Lab Operations

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: April 6, 2023
• Study Start: July 25, 2023
• Primary Completion: March 26, 2024
• Study Completion: March 26, 2024
• Last Updated: March 28, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After 6 months of publication of primary results

Locations

IN (1)