The effect of mild stimulation with letrozole for endometrial preparation in blastocyst frozen-thawed embryo transfer cycles in patients with polycystic ovary syndrome:a randomized clinical trial
The aim of study is the comparison of pregnancy outcomes after endometrial preparation and blastocyst embryo transfer between intervention and control groups..
Design
A randomized clinical trial with the control group (parallel groups) masked outcome assessment. Centralized and computerized randomization is performed by a statistician using the blocking method .
Settings and conduct
The randomized clinical trial at Royan institute
Participants/Inclusion and exclusion criteria
Eligible patients with polycystic ovary syndrome who have been referred for frozen embryo transfer are screened. The objectives of the plan are explained to the patients and they will enter the study if they have written and informed consent.
Intervention groups
In the intervention group, endometrial preparation is performed using gentle stimulation of the ovary by letrozole and gonadotropin to stimulate the growth of recombinant follicles (rFSH). If the follicle is over 18 mm and the endometrium is above 7 mm and the progesterone level is above 5 ng/ml, a 5000 HCG ampoule is injected and 7 days after HCG injection, the blastocyst embryo transfer is regulated. In the control group, endometrial preparation is performed by routine artificial hormonal methods (estrogen and progesterone) with ovarian suppression by GnRH agonist. In both groups, if the optimal endometrial thickness is not achieved after 20 days, embryo transfer will be canceled. To support the luteal phase for patients in both groups, a progesterone suppository of 400 mg (two daily) will be used. Depending on the patient's age, up to two embryos are transferred in the blastocyst stage.
Main outcome variables
The main outcome of the study is to evaluate the rate of clinical pregnancy. Secondary outcome include abortion rates, live birth rates, and pregnancy complications.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20080831001141N38
Registration date:2021-09-20, 1400/06/29
Registration timing:registered_while_recruiting
Last update:2021-09-20, 1400/06/29
Update count:1
Registration date
2021-09-20, 1400/06/29
Registrant information
Name
Kiandokht Kiani
Name of organization / entity
Royan Institute
Country
Iran (Islamic Republic of)
Phone
+98 21 2230 7960
Email address
kiandokht.kiani@royaninstitute.org
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-08-23, 1400/06/01
Expected recruitment end date
2023-02-09, 1401/11/20
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The effect of mild stimulation with letrozole for endometrial preparation in blastocyst frozen-thawed embryo transfer cycles in patients with polycystic ovary syndrome:a randomized clinical trial
Public title
Letrozole for endometrial preparation in frozen embryo transfer
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Diagnosis of polycystic ovary syndrome (PCOS) based on Rotterdam criteria
Women's age between 20-39 years
Having at least 3 good quality frozen embryos in the cleavage stage to nominate for blastocyst embryo transfer
Patient consent to participate in the study
Exclusion criteria:
Patients with severe male infertility (sperm extraction with TESE, PESA method)
The treatment cycles with preimplantation genetic diagnosis (PGD) indication, use of donated oocyte or embryo, and use of surrogate uterus
Patients with moderate to severe endometriosis and unilateral or bilateral endometrioma
History of uterine surgery as well as the presence of submucosal and intramural fibroids larger than 5 cm or the presence of uterine polyps
Patients with a history of recurrent miscarriage (≥ 2 abortions )
Age
From 20 years old to 39 years old
Gender
Female
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
250
Randomization (investigator's opinion)
Randomized
Randomization description
The block randomization method is designed by an epidemiologist using STATA software version 13 and the number of blocks considered is 4. The random allocation list for patients is solely available to the epidemiologist. In order to hide the random allocation process, a total of 250 envelopes are prepared, and only the methodologist has been aware of the table of random numbers. When the doctor declared the patient's eligibility, the methodologist provided the doctor with the envelope. The group will be selected and based on the type of group mentioned in the envelope.
The presence of a gestational sac with fetal heartbeat on the vaginal ultrasound
Secondary outcomes
1
Description
Miscarriage rate
Timepoint
20 weeks after embryos transfer
Method of measurement
Loss of clinical pregnancy before 20 weeks of gestation confirmed by uterine ultrasound
2
Description
Live birth rate
Timepoint
24 to 42 weeks after embryo transfer
Method of measurement
A live birth is the complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of pregnancy, which, after such separation, breathes or shows any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or any definite movement of voluntary muscles, whether or not the umbilical cord has been cut or the placenta is attached.
3
Description
The incidence rates of pregnancy complications gestational diabetes, preeclampsia and preterm delivery
Timepoint
20 to 42 weeks of pregnancy
Method of measurement
Diagnosed cases of gestational diabetes, preeclampsia and preterm labor will be followed up and recorded by a gynecologist during pregnancy in all patients.
Intervention groups
1
Description
Intervention group: Endometrial preparation is performed using mild ovarian stimulation by taking letrozole tablets (Femara, Novartis; 2.5 mg, twice daily) orally for 5 days from the 3rd day of menstruation or bleeding due to progesterone discontinuation. Becomes. On the seventh and ninth day of the cycle, gonadotropin-stimulated gonadotropin-stimulated growth of recombinant follicle growth (rFSH) (75 units) is injected. From the tenth day, the ultrasound monitoring cycle is performed every other day, if necessary, this medication process is repeated. Hormonal testing of LH, progesterone, and estrogen is done serially. If the follicle is above 18 mm and the endometrium is above 7 mm and the progesterone level is above 5 ng / ml, a 5000 unit HCG ampule is injected and 7 days after the HCG injection is adjusted for blastocyst embryo transfer.
Category
Treatment - Other
2
Description
Control group: In this group, endometrial preparation is performed by routine hormonal replacement protocol. GnRH-agonist (Superfect; Iran) administration started from day 17-17 of the previous luteal phase with a subcutaneous dose of 500 micrograms (0.5cc) is administration. On day 2-3 of the next cycle to confirm pituitary down-regulation, a baseline ultrasound scan is performed to determine the endometrial thickness and ovarian suppression. after approval of down-regulation, the dose of GnRH-agonist is halved (0.2 cc) and oral 4 mg of estradiol valerate (Aboureihan Co.) daily is started. After 10 days of estradiol administration, ultrasound monitoring is performed and endometrial thickness is measured until a suitable endometrium (thickness greater than 7 mm and a three-line view) is observed, and then 2 to 400 mg progesterone suppositories (Cyclogest, Actoverco) are administered for 5 days. Embryonic blastocyst transfer is planned. If, after 7 days of estradiol administration, the thickness of the endometrium was less than optimal, the dose is gradually increased to 8 mg daily until the thickness of the endometrium reached the desired level of fetal transfer.
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Not applicable
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
A clinical study report by published article
When the data will become available and for how long
After the publication of the article
To whom data/document is available
The study data will be available only to researchers working in academic and scientific institutions.
Under which criteria data/document could be used
Request for access to data must be formal and through correspondence from the relevant university.
From where data/document is obtainable
The published article will be made available to the public.
What processes are involved for a request to access data/document
Request for access to data must be formal and through correspondence from the relevant university. After the approval of the Vice President of Research , the data will be provided to the researchers.