Estrogen (Gel)Transdermal vs Oral Estrogen for Endometrial Preparation

Infertility, Female Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05802303
• Other study ID #: IIHPL-UDR/RCT/002_2022
• Status: Terminated
• Phase: N/A
• Start date: July 25, 2023
• Est. completion date: March 26, 2024

Study information

• Verified date: March 2024
• Source: Indira IVF Hospital Pvt Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 172
• Est. completion date: March 26, 2024
• Est. primary completion date: March 26, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Frozen Embryo Transfer
• Infertility
• Infertility, Female

Intervention

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).
• 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.

Locations

Country	Name	City	State
India	Indira IVF Hospital Private Limited	Udaipur	Rajasthan

Sponsors (1)

Lead Sponsor	Collaborator
Indira IVF Hospital Pvt Ltd

Country where clinical trial is conducted

India, 

References & 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. — View 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. — View 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. — View 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Undesirable side effects between both the groups	Symptoms like rash, itching ,burning, thromboembolic event	Till 12 weeks of pregnancy
Primary	Endometrial thickness (ET)	Average endometrial thickness achieved on day 14 of HRT	14 to 21 days after start of estrogen
Secondary	Cycle cancelation rate	Number of cycles cancelled before embryo transfer × 100	21 days after starting HRT
Secondary	Average E2 consumption	Total E2 consumed till embryo transfer	On 1 day of embryo transfer
Secondary	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
Secondary	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
Secondary	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
Secondary	Patient satisfaction score	It is measured using visual analogue scale(VAS) score	on 1 day of embryo transfer