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IRCT20080831001141N38 IRCT 2021-09-20 Royan Institute Letrozole for endometrial preparation in frozen embryo transfer 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 2021-08-23 anticipated 250 Complete https://irct.ir/trial/57810 interventional Randomization: Randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: The randomized list for clinical trials will be created by the design epidemiologist colleague from he Sealed Envelope website Randomization and online databases for clinical trials (https://www.sealedenvelope.com/), which is based on the blocked randomization method with 2 and 4 sizes. The random allocation of patients will be managed solely by the project's main collaborator. When an eligible patient is referred to them, the clinical doctor of the study will be informed based on the randomized list of the treatment group. 3 Condition 1: Polycystic ovarian syndrome. Condition 2: Implantation of embryo. Intervention 1: Intervention group: The preparation of the endometrium will be done by using mild stimulation, in this way letrozole tablet (Femati®, Atipharmed company, Iran) will be prescribed from the 2rd or 3rd day of menstruation or bleeding due to progesterone withdrawal, for 5 days orally with a daily dose of 5 mg. On the eighth and ninth day of the cycle (75 units), gonadotropin ampoule (rFSH: Cinnal-F®, CinnaGen company, Iran) is administered to stimulate follicle growth. Ultrasound monitoring was conducted from the 10th or 11th day of the cycle for 1 to 3 days, depending on the growth of the follicle. Hormonal examination of LH, progesterone, and estrogen was performed with every ultrasound monitoring. If a follicle was observed above 18 to 20 mm and the endometrium was above 7 mm, the final oocyte trigger will be performed using two ampoules of 5000 units of human chorionic gonadotropin (HCG) (Choriomon®, IBSA company). The transfer of the blastocyst embryo will be scheduled for 7 days after the injection of hCG. If there was no dominant follicle after 20 days of ovarian stimulation and the thickness of the endometrium was less than 7 mm, the embryo transfer cycle will be canceled. To support the luteal phase, a progesterone suppository (400 mg) (Cyclogest, Actoverco, Iran) is used from the day of embryo transfer. In case of a positive pregnancy, progesterone usage would be ongoing until the fetal heart was visible, after which it would be discontinued. Intervention 2: Control group: In this group, endometrial preparation is performed by routine hormonal replacement protocol. The GnRH-agonist (SinnaFact, Iran) will be initiated between days 17-19 of the luteal phase of the preceding cycle at a dosage of 500 micrograms (0.5 cc) subcutaneously and will be continued for a duration of 14 days. On days 2-3 of the subsequent cycle, a basic ultrasound scan will be conducted to verify the pituitary down regulation by assessing the endometrial thickness and ovarian status. If the endometrial thickness is below 5 mm, serum estradiol is less than 50 pg/ml, and no visible follicles of 9 mm is observed, the GnRH agonist dose will be decreased to 200 micrograms (0.20 cc) and endometrial preparation will be initiated with daily oral estradiol valerate (Aburaihan Pharmaceutical Co., Iran) doses of 4-6 mg. Following 10 to 12 days of estradiol administration, ultrasound monitoring is performed to measure endometrial thickness until an appropriate level (> 7 mm with a three-line view) will be achieved. Subsequently, luteal phase support is provided using a 50 mg ampoule of progesterone (Aburaihan Pharmaceutical Co., Tehran, Iran) for 5 days, will be followed by embryo blastocyst transfer. If the endometrial thickness remained suboptimal after 12 days of estradiol administration, the dose is increased to 8 mg daily for 5 to 7 days until reaching the desired thickness for embryo transfer. Failure to achieve the appropriate endometrial thickness (>7 mm) resulted in the cancellation of the embryo transfer cycle. In case of a positive pregnancy, the administration of estradiol valerate and progesterone will be continued until the fetal heartbeat is detected. Subsequently, the estradiol pill is gradually discontinued within 2 weeks, while progesterone ampoule (50 mg) will be changed to two progesterone suppositories (400mg) daily and is continued for 10 to 12 weeks of pregnancy. Yes - There is a plan to make this available What will be shared: A clinical study report by published article When: After the publication of the article To whom: The study data will be available only to researchers working in academic and scientific institutions. Conditions: Request for access to data must be formal and through correspondence from the relevant university. Where to obtain: The published article will be made available to the public. How to obtain: 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. Comments:
public Dr.Maryam Hafezi
No. 12, East Hafez Avenue, Banihashem Street, Shahid Soleimani Highway, Tehran, Iran
Tehran Iran (Islamic Republic of) 1665659911 +98 21 2356 2640 maryamhafezi90@yahoo.com Royan Institute scientific Dr. Maryam Hafezi
No. 12, East Hafez Avenue, Banihashem Street, Shahid Soleimani Highway, Tehran, Iran
Tehran Iran (Islamic Republic of) 1665659911 +98 21 2356 2640 maryamhafezi90@yahoo.com Royan Institute Iran (Islamic Republic of) Diagnosis of polycystic ovary syndrome (PCOS) based on Rotterdam criteria Women's age between 20-39 years Body mass index (BMI) ranging from 18 to 30 kg/m2 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 20 years 39 years Female 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 and/or untreated hydrosaplpinx Uterine infertility factor (congenital uterine abnormality except for treated uterine septum, intrauterine adhesions, diagnosis of generalized adenomyosis), history of uterine surgery (myomectomy) as well as the presence of submucosal and intramural fibroids or the presence of uterine polyps Patients with a history of recurrent miscarriage (≥ 2 abortions ) Repeated implantation failure Women with diabetes mellitus, uncontrolled thyroid disease and hypertension diagnosis E28.2 N97.0 Polycystic ovarian syndrome Female infertility associated with anovulation Treatment - Other Treatment - Other Intervention group: The preparation of the endometrium will be done by using mild stimulation, in this way letrozole tablet (Femati®, Atipharmed company, Iran) will be prescribed from the 2rd or 3rd day of menstruation or bleeding due to progesterone withdrawal, for 5 days orally with a daily dose of 5 mg. On the eighth and ninth day of the cycle (75 units), gonadotropin ampoule (rFSH: Cinnal-F®, CinnaGen company, Iran) is administered to stimulate follicle growth. Ultrasound monitoring was conducted from the 10th or 11th day of the cycle for 1 to 3 days, depending on the growth of the follicle. Hormonal examination of LH, progesterone, and estrogen was performed with every ultrasound monitoring. If a follicle was observed above 18 to 20 mm and the endometrium was above 7 mm, the final oocyte trigger will be performed using two ampoules of 5000 units of human chorionic gonadotropin (HCG) (Choriomon®, IBSA company). The transfer of the blastocyst embryo will be scheduled for 7 days after the injection of hCG. If there was no dominant follicle after 20 days of ovarian stimulation and the thickness of the endometrium was less than 7 mm, the embryo transfer cycle will be canceled. To support the luteal phase, a progesterone suppository (400 mg) (Cyclogest, Actoverco, Iran) is used from the day of embryo transfer. In case of a positive pregnancy, progesterone usage would be ongoing until the fetal heart was visible, after which it would be discontinued. Control group: In this group, endometrial preparation is performed by routine hormonal replacement protocol. The GnRH-agonist (SinnaFact, Iran) will be initiated between days 17-19 of the luteal phase of the preceding cycle at a dosage of 500 micrograms (0.5 cc) subcutaneously and will be continued for a duration of 14 days. On days 2-3 of the subsequent cycle, a basic ultrasound scan will be conducted to verify the pituitary down regulation by assessing the endometrial thickness and ovarian status. If the endometrial thickness is below 5 mm, serum estradiol is less than 50 pg/ml, and no visible follicles of 9 mm is observed, the GnRH agonist dose will be decreased to 200 micrograms (0.20 cc) and endometrial preparation will be initiated with daily oral estradiol valerate (Aburaihan Pharmaceutical Co., Iran) doses of 4-6 mg. Following 10 to 12 days of estradiol administration, ultrasound monitoring is performed to measure endometrial thickness until an appropriate level (> 7 mm with a three-line view) will be achieved. Subsequently, luteal phase support is provided using a 50 mg ampoule of progesterone (Aburaihan Pharmaceutical Co., Tehran, Iran) for 5 days, will be followed by embryo blastocyst transfer. If the endometrial thickness remained suboptimal after 12 days of estradiol administration, the dose is increased to 8 mg daily for 5 to 7 days until reaching the desired thickness for embryo transfer. Failure to achieve the appropriate endometrial thickness (>7 mm) resulted in the cancellation of the embryo transfer cycle. In case of a positive pregnancy, the administration of estradiol valerate and progesterone will be continued until the fetal heartbeat is detected. Subsequently, the estradiol pill is gradually discontinued within 2 weeks, while progesterone ampoule (50 mg) will be changed to two progesterone suppositories (400mg) daily and is continued for 10 to 12 weeks of pregnancy Clinical pregnancy rate. Timepoint: 6 - 7 weeks after embryos transfer. Method of measurement: The presence of a gestational sac with fetal heartbeat on the vaginal ultrasound. Chemical pregnancy rate. Timepoint: 14-16 days after embryo transfer. Method of measurement: Positive pregnancy (β-hCG) blood test. Implantation rate. Timepoint: 4-6 weeks after embryo transfer. Method of measurement: It is calculated through the ratio of the number of gestational sacs observed in transvaginal ultrasound to the number of transferred embryos. Blighted ovum rate. Timepoint: 6-8 weeks after embryo transfer. Method of measurement: A blighted ovum is defined as an anembryonic (no embryo) pregnancy and is a leading cause of early pregnancy failure or miscarriage and it is diagnosed by transvaginal ultrasonography. Ectopic pregnancy rate. Timepoint: 6-8 weeks after embryo transfer. Method of measurement: Ectopic pregnancy is a pregnancy in which the fetus develops outside the uterus, typically in a fallopian tube, and it is diagnosed through vaginal ultrasound within 6 to 8 weeks after the embryo transfer. Miscarriage rate. Timepoint: From the beginning of clinical pregnancy diagnosis to 20 weeks of pregnancy. Method of measurement: Loss of clinical pregnancy before 20 weeks of gestation confirmed by uterine ultrasound. Live birth rate. Timepoint: 20 to 42 weeks of pregnancy. 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. The rates of obstetrics complications including gestational diabetes, preeclampsia and preterm birth. 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. Neonatal outcomes. Timepoint: At birth and a week later. Method of measurement: The neonatologist will evaluate the gestational age, baby's sex, birth weight, presence of congenital abnormalities, diagnosis of respiratory distress syndrome, and diagnosis of jaundice within the first week of birth. The details regarding the newborn will be documented and monitored through phone follow-ups. Royan Institute Approved 2021-07-17 Ethics Committee of Royan Institute No. 12, East Hafez Avenue, Banihashem Street, Shahid Soleimani Highway, Tehran, Iran Tehran Tehran Iran (Islamic Republic of)