Protocol summary
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Study aim
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comparison of hormone replacement therapy and mild ovarian stimulation for endometrial preparation in frozen embryo transfer in patients with polycystic ovarian syndrome
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Design
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Randomized clinical trial study with parallel groups and phases 3 on 100 patients. Randomization will be done according to block randomization method using Random allocation software.
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Settings and conduct
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This study will be conducted on 100 patients referred to the infertility clinic of Al-Zahra Hospital with frozen embryos for embryo transfer without blinding.
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Participants/Inclusion and exclusion criteria
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Patients between the ages of 20 and 40 with the diagnosis of cystic ovarian factor infertility will be included in the study if no cysts are seen in the ovary.And in case of having congenital uterine anomalies ,severe endometriosis Previous history of failed transfer more than twice Endometrial
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Intervention groups
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The hormone replacement therapy group will be given estradiol tablets, and 10–12 days later, transvaginal sonography will be done. Progesterone will be added to the regimen if the endometrial thickness reaches ≥7.5 mm. Embryo transfer will done in the cleavage stage on the fourth day of progesterone injection. 400 mg progesterone suppository will be used twice daily to support the luteal phase, and 50 mg injectable progesterone will be administered once every three days. In the second group, letrozole 5mg will be administrated from the second to third day of menstruation for five days daily. Then, 37.5 - 150 mg of FSH at least 2 or more doses depend o ovarian response will be administrated once every two days or daily. When the diameter of at least one follicle reaches more than 17 mm, HCG will be administrated. Embryo transfer will be performed 5-6 days after HCG administration in the cleavage stage.
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Main outcome variables
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Successful pregnancy has been considered as the main outcome of this study.
General information
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Reason for update
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20130603013566N14
Registration date:
2024-10-14, 1403/07/23
Registration timing:
prospective
Last update:
2025-06-11, 1404/03/21
Update count:
1
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Registration date
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2024-10-14, 1403/07/23
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2024-10-22, 1403/08/01
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Expected recruitment end date
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2025-10-23, 1404/08/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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comparison of hormone replacement therapy and mild ovarian stimulation for endometrial preparation in frozen embryo transfer in patients with polycystic ovarian syndrome
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Public title
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comparison of hormone replacement therapy and mild ovarian stimulation for endometrial preparation in frozen embryo transfer in patients with polycystic ovarian syndrome
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Infertile women aged between 20 and 40 years
Infertility factor of polycystic ovary syndrome
Exclusion criteria:
Congenital uterine anomalies
Uterine fibroids
Severe endometriosis
Previous history of failed transfer more than twice
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Age
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From 20 years old to 40 years old
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Gender
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Female
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Phase
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3
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Groups that have been masked
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No information
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Sample size
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Target sample size:
100
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Patients will be divided into intervention and control groups using block randomization based on generated numbers by Random allocation software. Thus, in this software, first the number of groups and the total number of the sample size will be entered, and then in the block section, the Block randomization method will be implemented. Patients will be allocated to intervention or control groups based on generated numbers.
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Blinding (investigator's opinion)
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Not blinded
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Blinding description
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2024-09-23, 1403/07/02
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Ethics committee reference number
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IR.TBZMED.REC.1403.492
Health conditions studied
1
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Description of health condition studied
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Infertility
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ICD-10 code
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N97.0
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ICD-10 code description
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Female infertility associated with anovulation
Primary outcomes
1
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Description
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Chemical pregnancy
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Timepoint
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14 days after embryo transfer
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Method of measurement
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HCG β blood test
2
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Description
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Number of gestational sacs
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Timepoint
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From week 5 of pregnancy
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Method of measurement
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Vaginal ultrasound
Secondary outcomes
1
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Description
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Fetal growth
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Timepoint
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From the beginning of the intervention until the end of the 12th week of pregnancy
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Method of measurement
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Ultrasound
Intervention groups
1
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Description
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Intervention group A: In the patients of the intervention group, where the preparation of the endometrium will be done by the administration of estrogen and progesterone hormones (artificial or HRT), the 2 mg estradiol pill will start from the second day of the menstrual cycle. On the second and third day, one number every 12 hours and then one number every 8 hours.10 to 12 days after taking estradiol, the next visit will be done and the thickness of the endometrium will be measured by transvaginal ultrasound. If the thickness of the endometrium is equal to or higher than 7.5 mm, injectable progesterone with a dose of 50 mg will be started, first one and then two daily.On the fourth day of starting progesterone, the transfer will be done.Luteal phase support will be done with 400 mg rectal progesterone suppositories every 12 hours and 50 mg progesterone ampoules every three days. In the 10th to 12th day visit, if the thickness of the endometrium is less than 7.5 mm, estradiol will be continued with the same dose or, if needed, higher doses, and the patient will be visited 3 to 4 days later and the endometrial examination will be repeated with ultrasound, and this work will be repeated until reaching The endometrium will continue to be 7.5 mm or more thick.If the thickness of the endometrium does not increase after a maximum of 20 days of taking estradiol, the treatment cycle will be stopped and the patient will be excluded from the study.
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Category
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Treatment - Drugs
2
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Description
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Intervention Group B: In the second group, endometrial preparation will be conducted using a mild ovarian stimulation method. Letrozole 5 mg (2 tablets of 2.5 mg) will be prescribed daily from the second or third day of menstruation for a duration of 5 days. Subsequently, FSH will be administered at a dose of 37.5 to a maximum of 150 mg daily or on alternate days (with a minimum of 2 doses and an increase in dosage if necessary). When at least one follicle exceeds 17 mm in size and the thickness of the uterine endometrium is more than 7.5 mm (provided that there are 14 to 16 follicles or fewer), HCG will be injected. One ampule of 5000 units of HCG will be administered. If more than three follicles are enlarged in total, to prevent OHSS, 1-2 cycles will be canceled, and embryo transfer will not be performed. The next day, a 400 mg rectal progesterone suppository will be started with one unit every night, and then 5-6 days after HCG injection, embryo transfer will be conducted at the cleavage stage. The 400 mg rectal progesterone suppository will continue until the pregnancy test is performed and, in the case of pregnancy, will continue until week 12. The number of transferred embryos and their grades will be recorded for each patient. In both groups, only grade 1 and grade 2 embryos will be transferred. Grade one embryos are defined as having blastomeres of equal size without cytoplasmic fragments. Grade two embryos have blastomeres of equal size with minimal cytoplasmic fragments. Grade three embryos have blastomeres that appear to be of the same size with slight cytoplasmic fragments. Grade four embryos have blastomeres of equal or unequal size with a significant number of cytoplasmic fragments. Finally, grade five embryos are characterized by blastomeres of varying sizes and a very high number of cytoplasmic fragments. Fourteen days after embryo transfer, a beta-hCG test will be conducted, and the pregnancy test results (positive or negative) will be recorded and compared in both groups. In patients with a positive pregnancy test, an abdominal ultrasound will be performed two weeks later to visualize the gestational sac, count, and check for fetal heart rate, and results will be compared in the group. Pregnant women will be monitored for fetal growth and the risk of miscarriage until the end of week 12 of pregnancy.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Vice chancellor for Research, Tabriz University Of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available