Plain English Summary
Background and study aims
Frozen Embryo Transfer (FET) is an assisted reproductive technology procedure in which a previously frozen embryo is thawed and transferred into an appropriately prepared uterus (womb) in order to have a baby. In preparation for FET, the lining of the uterus (endometrium) must reach an appropriate thickness. Among various methods for endometrial preparation, the use of estradiol, either through oral (tablet) or transdermal (direct contact on skin), has been shown to be an effective method. However, women usually complain of side effects of using oral estradiol, in some cases leading to them to stop using the medication. The researchers believe that transdermal estradiol can help to reduce these side effects and be a useful way to increase the chance of having a baby. The aim of this study is to compare transdermal estradiol to oral estradiol in terms of effectiveness and acceptability.
Who can participate?
Women aged 18-45 undergoing IVF with FET
What does the study involve?
If the women join the research, they will randomly use either transdermal estradiol or oral estradiol. Beginning at day 3 of the menstrual cycle, they will take one transdermal dosage twice a day or one tablet twice a day for 7 days. The researchers will perform an ultrasound scan at day 10 of the menstrual cycle to evaluate the thickness of the endometrium then gradually increase the dosage. When the thickness of endometrium reaches 8-14 mm, both groups will be prescribed progesterone before transfer and undergo IVF cycles. The researcher will assess the pregnancy outcomes in both groups.
What are the possible benefits and risks of participating?
Participants will be able to contribute to the advancement of the understanding of the effects of transdermal estradiol on endometrial preparation in frozen-thawed embryo transfer cycles. There is minimal risk since estradiol is generally safe and well-known as a hormonal medication for many conditions.
Where is the study run from?
Hung Vuong Hospital (Viet Nam)
When is the study starting and how long is it expected to run for?
January 2020 to August 2021
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Dr Thi Diem Tuyet Hoang
Dr Tuyet Hoang
128 Hong Bang Street
Ho Chi Minh city
Efficiency assessment of transdermal estradiol on endometrial preparation in frozen-thawed embryo transfer cycles: a randomized clinical trial
Is patient usage of transdermal estradiol more effective than oral estradiol on endometrial preparation in frozen-thawed embryo transfer cycles?
Approved 11/06/2020, Hung Vuong Ethics Committee (128 Hong Bang Street, Ward 12, District 5, Ho Chi Minh City; +84 (0)28 3855 8532; no email provided), no ref provided
Randomized controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Women undergoing IVF
Comparison of the effectiveness between transdermal estradiol and oral estradiol on the endometrium of frozen embryo transfer (FET) at Hung Vuong Hospital between January 2020 to August 2021. Patients who indicated frozen-thawed embryo transfer, have at least one excellent/good frozen embryo before thawing, age 18-45 years will be invited to participate in the trial.
A list of randomized groups will be divided using www.random.org software – Appendix 4. The block randomization method (2, 4, 6, 8) and the permutation block size were used. A randomized staff who is outside the study will print the forms with consecutive signs A and B, which are placed into sealed envelopes and randomly assigned following the result table in Appendix 4. Each individual participating in the study has an equal probability (1:1) to be selected for the sample, using drawing method after screening and signing a consent form. Then, the envelopes will be numbered in ascending order from top to bottom. Participants were grouped in turn according to the open of envelope with the form inside and then received drugs as follow:
A: oral estradiol
B: transdermal estradiol
All members including doctors, midwives, staff were blinded to the randomized table. The pharmacists who provide drugs for patients are not blinded to the drug but they do not play any role in this study.
Study group: Transdermal estradiol regimen
1. Begin at day 3 of the menstrual cycle, daily 5 g dosage during 7 days which is equivalent to 1 transdermal dosage twice a day. 1 ruler dosage equals to 2.5 g
2. Perform an ultrasound scan at day 10 of the menstrual cycle: evaluate the thickness of endometrium then gradually increase the dosage up to a maximum of 20 g/day
Control group: Oral estradiol valerate regimen
1. Begin at day 3 of the menstrual cycle, 4 mg of dosage daily in 7 days which is equivalent to 1 tablet twice a day
2. Perform an ultrasound scan at day 10 of the menstrual cycle: evaluate the thickness of endometrium then gradually increase the dosage up to a maximum of 16 g/day
3. Perform an ultrasound scan to measure the thickness of endometrium 8-14 mm
4. Use 600 microgram progesterone daily during 3 days before day-3 embryo transfer
5. Use 600 microgram progesterone daily during 5 days before day-5 embryo transfer
6. Test the estradiol/blood concentration on progesterone day
Estradiol gel, oral estradiol
Primary outcome measure
1. Thickness and shape of endometrium measured using vaginal ultrasound examination at baseline and on progesterone day
2. Serum estradiol concentration measured using immunoassay on progesterone day
3. Mean duration of treatment, recorded at time of procedure
Secondary outcome measures
1. Cycle cancellation rate of FET measured from medical records at the time of the patient who is indicated to cancel FET cycle such as insufficient endometrial thickness, loss of embryo viability during thawing, other
2. Implantation rate (number of gestational sacs containing a living embryo implanted in the uterus divided by the number of embryos transferred) measured from medical records 6 weeks after embryo transfer
3. Clinical pregnancy rate as measured by rising beta hCG levels starting at 14 days post embryo transfer, presence of gestational sac at 6-7 weeks post embryo transfer, and presence of fetal heartbeat at 6-7 weeks post embryo transfer
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
1. Women aged 18-45
2. No history of uterine intervention: suction or endoscopy
3. Has FET indication
4. Has at least one excellent/good frozen embryo before thawing
5. No pathological background: diabetes, high prolactin level, thyroid disorders, adrenal gland disorders.
6. Agree with FET indication
7. Volunteer to the study and has full contact information
Target number of participants
Participant exclusion criteria
1. BMI > 30
2. Egg or embryo donor/receiver
3. Estradiol contraindication
4. Estradiol usage > 27 days
5. Not qualified for FET
6. Abnormal uterine, fallopian tube related to implantation
7. Endocrine disorders (kidney, liver or cardiac disease)
8. Patient does not agree to participate in the study
9. Patient does not adhere to the study
10. Does not follow drug prescription:
10.1. Patient forgot to consume drug for more than 2 consecutive or non-consecutive days
10.2. Patient stops using drug due to personal reasons
11. Late follow-up examination
12. Cannot read or write Vietnamese
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Hung Vuong Hospital
128 Hong Bang Street Ward 12 Province 5
Ho Chi Minh city
Hung Vuong Hospital
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
The study protocol is not published. The researchers plan to publish their trial data as an article in a journal listed in the ISI Web of Science.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
Participant level data
To be made available at a later date
Basic results (scientific)