Trial Outcomes & Findings for Progestin Primed Double Stimulation Protocol Versus Flexible GnRH Antagonist Protocol in Poor Responders (NCT NCT04537078)

Results Overview

it is the number of M2 oocytes retrieved that were being assessed after denudation

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

90 participants

Primary outcome timeframe

1-2 hours after oocyte retrieval

Results posted on

2022-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	the Progestin Primed Double Stimulation Group luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle. .
Overall Study STARTED	45	45
Overall Study COMPLETED	41	42
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	the Progestin Primed Double Stimulation Group luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle. .
Overall Study Protocol Violation	3	2
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Progestin Primed Double Stimulation Protocol Versus Flexible GnRH Antagonist Protocol in Poor Responders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	the Progestin Primed Double Stimulation Group n=41 Participants luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist n=42 Participants This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter. While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.	Total n=83 Participants Total of all reporting groups
Age, Continuous	34.05 years STANDARD_DEVIATION 5 • n=5 Participants	35.48 years STANDARD_DEVIATION 6.99 • n=7 Participants	34.77 years STANDARD_DEVIATION 6.09 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	42 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	41 Participants n=5 Participants	42 Participants n=7 Participants	83 Participants n=5 Participants
Region of Enrollment Egypt	41 participants n=5 Participants	42 participants n=7 Participants	83 participants n=5 Participants
duration of infertility	5 years n=5 Participants	5 years n=7 Participants	5 years n=5 Participants
previous ICSI trials had no previous ICSI trials	22 participants n=5 Participants	26 participants n=7 Participants	48 participants n=5 Participants
previous ICSI trials had 1 failed ICSI trial	17 participants n=5 Participants	14 participants n=7 Participants	31 participants n=5 Participants
previous ICSI trials had 2 failed ICSI trials	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants

PRIMARY outcome

Timeframe: 1-2 hours after oocyte retrieval

it is the number of M2 oocytes retrieved that were being assessed after denudation

Outcome measures

Outcome measures
Measure	the Progestin Primed Double Stimulation Group n=41 Participants luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist Group n=42 Participants This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.
the Number of M2 Oocytes Retrieved	6 oocytes Interval 3.0 to 7.0	4.5 oocytes Interval 3.0 to 8.0

PRIMARY outcome

Timeframe: 16 to 20 hours after microinjection of the oocytes with the sperms

percentage transformation of micro injected oocytes into two pronuclei. it is done 16 to 20 hours after microinjection of the oocytes by the sperms

Outcome measures

Outcome measures
Measure	the Progestin Primed Double Stimulation Group n=41 Participants luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist Group n=42 Participants This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.
the Fertilization Rate	71.43 percentage of transformation Interval 66.67 to 100.0	80.91 percentage of transformation Interval 66.67 to 100.0

PRIMARY outcome

Timeframe: the embryos number counted day 3 or 4or 5 after fertilization

it is the resultant embryos number counted day 3 or 4 or 5 after fertilization

Outcome measures

Outcome measures
Measure	the Progestin Primed Double Stimulation Group n=41 Participants luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist Group n=42 Participants This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.
the Resultant Embryos Number	4 number of embryos Interval 3.0 to 5.0	3 number of embryos Interval 2.0 to 6.0

PRIMARY outcome

Timeframe: at the 6 th week of pregnancy

it is calculated as the number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos at the 6 th week of pregnancy and then multiplied by 100

Outcome measures

Outcome measures
Measure	the Progestin Primed Double Stimulation Group n=7 Participants luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist Group n=8 Participants This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.
the Implantation Rate	50 percentage Interval 50.0 to 100.0	50 percentage Interval 33.33 to 50.0

PRIMARY outcome

Timeframe: at the 6 th weeks of pregnancy

percentage of cases in which observation of a gestational sac with fetal heart beat by transvaginal ultrasound at 6 weeks of pregnancy

Outcome measures

Outcome measures
Measure	the Progestin Primed Double Stimulation Group n=41 Participants luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist Group n=42 Participants This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.
the Clinical Pregnancy Rate.	7 percentage of participants	8 percentage of participants

SECONDARY outcome

Timeframe: At the 20 th week of gestation

Assessing the difference in the ongoing pregnancy rate when the pregnancy had completed ≥20 weeks of gestation

Outcome measures

Outcome measures
Measure	the Progestin Primed Double Stimulation Group n=41 Participants luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle \>18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	the Flexible GnRh Antagonist Group n=42 Participants This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle \>18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle \>18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.
the Difference in the Ongoing Pregnancy Rate in Both Protocols.	6 percentage of participants	5 percentage of participants

SECONDARY outcome

Timeframe: From the first day of ovarian stimulation till the last day of ovarian stimulation in each phase ,the follicular and the luteal, of stimulation