Clinical trial NCT05802303: 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
Overall status: TERMINATED
Phase: NA
Conditions: Frozen Embryo Transfer
Infertility, Female
Keywords: Transdermal Estrogen
FET
Oral Estrogen
IVF/ICSI
Lead sponsor: Indira IVF Hospital Pvt Ltd
Sponsor class: OTHER
First posted: 2023-04-06
Enrollment: 172
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Endometrial thickness (ET)
timeFrame: 14 to 21 days after start of estrogen
Secondary outcomes:
measure: Cycle cancelation rate
timeFrame: 21 days after starting HRT
measure: Average E2 consumption
timeFrame: On 1 day of embryo transfer
measure: Implantation rates (IR)
timeFrame: 4 weeks + 2 weeks after embryo transfer
measure: Clinical pregnancy rates (CPR)
timeFrame: 4 weeks + 2 weeks after embryo transfer
measure: Miscarriage rates (MR)
timeFrame: Within 20 weeks of gestation
measure: Patient satisfaction score
timeFrame: on 1 day of embryo transfer
Other outcomes:
measure: Undesirable side effects between both the groups
timeFrame: Till 12 weeks of pregnancy
Locations:
city: Udaipur
country: India
facility: Indira IVF Hospital Private Limited
state: Rajasthan
Study officials:
References:
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.
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.
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.
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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.
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.
citation: Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril. 2011 Sep;96(3):530-5. doi: 10.1016/j.fertnstert.2011.07.1097.
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.