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

• Sponsor: El Shatby University Hospital for Obstetrics and Gynecology (Other)
• Overall Status: Completed
• CT.gov ID: NCT04537078
• Collaborator: (none)
• Enrollment: 90
• Location: 1
• Arms: 2
• Actual Duration (Months): 12
• Patients Per Site Per Month: 7.5

Study Details

Study Description

Brief Summary

The worldwide prevalence of primary and secondary infertility is estimated at ~2% and 10.5%, respectively, among women aged 20-44 years and attempting to conceive. Poor ovarian responders (PORs) involve 9-24% of patients undergoing in-vitro fertilization (IVF). proper tailoring of the ovarian stimulation protocol in order to maximize the number of oocytes collected represents a crucial step for them to eventually conceive.

Recent evidence indicates that in the same menstrual cycle, there are multiple follicular recruitment waves. This coincides with the theory that folliculogenesis occurs in a wave-like fashion. Thus, within a single menstrual cycle, there can theoretically be multiple opportunities for a clinician to collect oocytes, as opposed to the conventional single cohort of antral follicles during the follicular phase.

Utilizing this concept, clinicians have been attempting to retrieve oocytes from poor responders using both the follicular-phase stimulation (FPS) and the luteal-phase stimulation (LPS) protocols to increase the number of oocytes collected shorter within shorter period of time. By increasing the number of the retrieved oocytes collected, a better clinical can be assured since there is a clear relationship between the number of oocytes collected and live birth rates across all female age groups.

which protocol is the most effective remains controversial and the efficacy of PPOS in POR compared with that of conventional protocols is unclear.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Female	Drug: Duphaston; Drug: Gonadotropin; Drug: Cetrotide Injectable Product; Drug: Decapeptyl; Drug: Chorionic Gonadotropin; Drug: Combined Oral Contraceptive; Drug: Cyclo-Progynova; Drug: progesterone	Phase 3

Detailed Description

The study will be conducted on 90 infertile women indicated for ICSI with criteria of poor ovarian response defined by Bologna criteria All participants will be informed about the nature of the study and informed consent will be taken from all of them.

Group 1:45 patients will be given the progestin primed double stimulation protocol.

Group 2: 45 patients will be given the flexible GnRh antagonist follicular controlled ovarian stimulations will be done in 2 cycles.

Written informed consents will be obtained from all participants who accept to participate in the research protocol.

Work up:

1. Complete history taking and full assessment of different infertility factors.

2. Hormonal investigations

• FSH, LH, E2, Prolactin

• AMH, TSH

1. Basal transvaginal ultrasound

Clinical and embryological procedures:

Group 1:

1. The follicular phase of the double stimulation protocol

1. luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week (0.03 mg ethinyl estradiol, gestodene 0.075 mg, Gynera tab, Bayer Pharma AG., Berlin, Germany).

2. 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.

3. Dydrogesterone (Duphaston, Abbott company, Illinois, United states) at 20 mg/day will be started from the first day of the ovulation induction.

4. Patient response will be monitored by:

5. Transvaginal follicular scanning and the dose of the gonadotropins will be modified according to the response.

6. Serum estradiol.

7. Serum progesterone and LH on the day of triggering.

8. GnRh agonist triggering (Decapeptyl, Ferring, SAINT-PREX Switzerland) in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter.

9. Oocyte pickup will be done 36 hours after GnRh administration with precaution of leaving the follicles measuring 11 mm or less.

10. After the pick-up, oocytes will be denuded. The denuded oocytes are then assessed for nuclear status. Mature oocytes will be used for ICSI.

1. The luteal phase of the double stimulation protocol

Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started the next day after the previous oocyte pickup simultaneously with Dydrogesterone (Duphaston, Abbott company, Illinois, United states) at 20 mg/day.

The rest will be as the follicular phase.

III. Fertilization and embryo quality:

The fertilization check, which will be performed 16 to 20 hours after ICSI. The resultant embryos will be scored, and they will be vitrified for subsequent transfer.

1. Embryo transfer

• Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets); Bayer, Germany) daily. From Day 10 onwards, endometrium growth will be monitored by transvaginal ultrasound. When endometrial thickness ≥ 7 mm. Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be initiated and 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.

1. Luteal support - Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be continued until pregnancy testing 18 days after embryo transfer. The pregnant cases will continue the luteal support till the 12 weeks of gestation.

Group 2:

1. The flexible GnRH antagonist protocol controlled ovarian stimulation This controlled ovarian stimulation will be done twice in two different cycles

In each cycle:

1. luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week (0.03 mg ethinyl estradiol, gestodene 0.075 mg , Gynera tab, Bayer Pharma AG., Berlin, Germany).

2. 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.

3. GnRH antagonist ( Cetrotide , Merck Serono, Darmstadt, Germany) will be given daily as the biggest oocyte reaches size 14 mm.

4. Patient response will be monitored by:

5. Transvaginal follicular scanning and the dose of the gonadotropins will be modified according to the response.

6. Serum estradiol.

7. Serum progesterone on the day of triggering.

8. GnRh agonist triggering (Decapeptyl, Ferring, Saint-Prex Switzerland) in a dose of 2 ampules 0.2 mg will be administered when leading follicle >18 mm in diameter. While in the second cycle HCG triggering (Choriomon, IBSA, Lugano, Switzerland) in a dose of 10,000 IU will be administered when the leading follicle >18 mm in diameter.

9. Oocyte pickup will be done 36 hours after GnRh administration.

10. After the pick-up, oocytes will be denuded. The denuded oocytes are then assessed for nuclear status. Mature oocytes will be used for ICSI.

VII. Fertilization and embryo quality:

The fertilization check, which will be performed 16 to 20 hours after ICSI. The resultant embryos will be scored.

Embryos of the first cycle will be vitrified while embryos of the second cycle will be freshly transferred unless there is excess for vitrification for subsequent trials of transfer.

1. Embryo transfer

• Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be initiated on the day of the oocyte pick up of the second cycle. 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.

1. Luteal support Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be continued until pregnancy testing 18 days after embryo transfer. The pregnant cases will continue the luteal support till the 12 weeks of gestation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Progestin Primed Double Stimulation Protocol Versus Flexible GnRH Antagonist Protocol in Poor Responders
• Actual Study Start Date: Sep 1, 2020
• Actual Primary Completion Date: Mar 1, 2021
• Actual Study Completion Date: Sep 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.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.	Drug: Duphaston; will be used for pituitary suppression in the first arm:20 mg/day will be started from the first day of the ovulation induction in the follicular phase and in the luteal phase will be started the next day after oocyte pickup at 20 mg/day.; Drug: Gonadotropin; will be used for controlled ovarian hyperstimulation in both arms; Other Names: Fostimon Menopure Menogon Gonapure ; Drug: Decapeptyl; will be used for ovulation triggering.in the first arm:in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter. in the second arm:in a dose of 2 ampules 0.2 mg will be administered when leading follicle >18 mm in diameter in the first cycle only.; Drug: Combined Oral Contraceptive; luteal phase priming from day 21 of the cycle before controlled ovarian stimulation for one week .; Other Names: Gynera ; Drug: Cyclo-Progynova; Starting from cycle Day 3 of the intented cycle for thawed embryo transfer, patients will receive the white tablets of Cyclo-Progynova daily. From Day 10 onwards, endometrium growth will be monitored by transvaginal ultrasound.; Drug: progesterone; in the intended cycle of embryo transfer when endometrial thickness ≥ 7 mm. Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be continued until pregnancy testing 18 days after embryo transfer and in pregnant cases will continued till the 12 weeks of gestation.; Other Names: prontogest
Active Comparator: 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. 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.	Drug: Gonadotropin; will be used for controlled ovarian hyperstimulation in both arms; Other Names: Fostimon Menopure Menogon Gonapure ; Drug: Cetrotide Injectable Product; will used in the second arm for pituitary suppression in the second group daily when the biggest oocyte reaches size 14 mm till ovulation triggering; Drug: Decapeptyl; will be used for ovulation triggering.in the first arm:in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter. in the second arm:in a dose of 2 ampules 0.2 mg will be administered when leading follicle >18 mm in diameter in the first cycle only.; Drug: Chorionic Gonadotropin; will be used in the second cycle of the second arm for ovulation triggering in a dose of 10,000 IU when the leading follicle >18 mm in diameter.; Other Names: choriomon ; Drug: Combined Oral Contraceptive; luteal phase priming from day 21 of the cycle before controlled ovarian stimulation for one week .; Other Names: Gynera ; Drug: Cyclo-Progynova; Starting from cycle Day 3 of the intented cycle for thawed embryo transfer, patients will receive the white tablets of Cyclo-Progynova daily. From Day 10 onwards, endometrium growth will be monitored by transvaginal ultrasound.; Drug: progesterone; in the intended cycle of embryo transfer when endometrial thickness ≥ 7 mm. Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be continued until pregnancy testing 18 days after embryo transfer and in pregnant cases will continued till the 12 weeks of gestation.; Other Names: prontogest

Outcome Measures

Primary Outcome Measures

1. the Number of M2 Oocytes Retrieved [1-2 hours after oocyte retrieval]

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

2. the Fertilization Rate [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

3. the Resultant Embryos Number [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

4. the Implantation Rate [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

5. the Clinical Pregnancy Rate. [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

Secondary Outcome Measures

1. the Difference in the Ongoing Pregnancy Rate in Both Protocols. [At the 20 th week of gestation]

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

2. the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Total Days of Controlled Ovarian Hyperstimulation [From the first day of ovarian stimulation till the last day of ovarian stimulation in each phase ,the follicular and the luteal, of stimulation]

   the total number of days of the controlled ovarian hyperstimulation in both follicular and luteal phase of the progestin primed double stimulation protocol are studied so as to asses the difference between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

3. the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Total Dosage of Gonadotropins Used in the Controlled Ovarian Hyperstimulation [From the first day of ovarian stimulation till the last day of ovarian stimulation in each phase ,the follicular and the luteal, of stimulation]

   Assessing the difference between the follicular phase and the luteal phase of the progestin primed double stimulation protocol regarding the total dosage of gonadotropins used in the controlled ovarian hyperstimulation so as to the difference between the two phases

4. the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Number of M2 Oocytes Retrieved [1-2 hours after oocyte retrieval]

   it is the number of M2 oocytes retrieved that were being assessed after denudation so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

5. the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Fertilization Rate. [16 to 20 hours after microinjection of the oocytes with the sperms]

   percentage of transformation of micro injected oocytes into two pronuclei at 16 -20 hours after microinjection of the oocytes by the sperms so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

6. the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Resultant Embryos Number [the embryos number counted day 3 or 4or 5 after fertilization]

   the resultant embryos number are counted day 3 or 4 or 5 after fertilization so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

7. Assessing the Difference Between the Follicular Phase of the Progestin Primed Double Stimulation Protocol and the First Round of the Conventional GnRH Antagonist Protocol Regarding the Number of M2 Oocytes Retrieved . [1-2 hours after oocyte retrieval]

   it is the number of M2 oocytes retrieved that were being assessed after denudation.so as to study the effect of the progestin used on the ovarian response in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group

8. Assessing the Difference Between the Follicular Phase of the Progestin Primed Double Stimulation Protocol and the First Round of the Conventional GnRH Antagonist Protocol Regarding the Fertilization Rate. [16 to 20 hours after microinjection of the oocytes by the sperms]

   it is percentage transformation of micro injected oocytes into two pronuclei.so as to study the effect of the progestin used on the ovarian response and its results in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group

9. Assessing the Difference Between the Follicular Phase of the Progestin Primed Double Stimulation Protocol and the First Round of the Conventional GnRH Antagonist Protocol Regarding the Resultant Embryos Number. [at day 3 or 4or 5 after fertilization]

   it is the number of the resultant embryos counted at day 3 or 4 or 5 after fertilization.so as to study the effect of the progestin used on the ovarian response and the resultant embryos number in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

poor ovarian responders patients defined by Bologna criteria

Exclusion Criteria:

1. Male factor infertility due to azoospermia.

2. Patients with uncorrected uterine pathology.

3. Patients with the diagnosis of severe endometriosis.

4. Patients with BMI over 35.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Elshatby University Maternity Hospital	Alexandria		Egypt

Sponsors and Collaborators

• El Shatby University Hospital for Obstetrics and Gynecology

Investigators

• Principal Investigator: Aly A Hussein, Ass.lecturer, Elshatby University hospital
• Principal Investigator: Sherif S Gaafar, Professor, Elshatby University hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 26, 2022

More Information

Publications

• Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91. doi: 10.1093/humupd/dmr039. Epub 2011 Nov 8. Review.
• Briggs R, Kovacs G, MacLachlan V, Motteram C, Baker HW. Can you ever collect too many oocytes? Hum Reprod. 2015 Jan;30(1):81-7. doi: 10.1093/humrep/deu272. Epub 2014 Oct 31.
• Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, Polyzos NP. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016 Feb;31(2):370-6. doi: 10.1093/humrep/dev316. Epub 2016 Jan 2.
• Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
• Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.
• Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6.
• Liu C, Jiang H, Zhang W, Yin H. Double ovarian stimulation during the follicular and luteal phase in women ≥38 years: a retrospective case-control study. Reprod Biomed Online. 2017 Dec;35(6):678-684. doi: 10.1016/j.rbmo.2017.08.019. Epub 2017 Aug 24.
• Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356. doi: 10.1371/journal.pmed.1001356. Epub 2012 Dec 18.
• McNatty KP, Hillier SG, van den Boogaard AM, Trimbos-Kemper TC, Reichert LE Jr, van Hall EV. Follicular development during the luteal phase of the human menstrual cycle. J Clin Endocrinol Metab. 1983 May;56(5):1022-31.
• Moffat R, Pirtea P, Gayet V, Wolf JP, Chapron C, de Ziegler D. Dual ovarian stimulation is a new viable option for enhancing the oocyte yield when the time for assisted reproductive technnology is limited. Reprod Biomed Online. 2014 Dec;29(6):659-61. doi: 10.1016/j.rbmo.2014.08.010. Epub 2014 Sep 4.
• Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011 Jul;26(7):1768-74. doi: 10.1093/humrep/der106. Epub 2011 May 10.
• Vanden Brink H, Chizen D, Hale G, Baerwald A. Age-related changes in major ovarian follicular wave dynamics during the human menstrual cycle. Menopause. 2013 Dec;20(12):1243-54. doi: 10.1097/GME.0b013e31828cfb62.
• Wang N, Wang Y, Chen Q, Dong J, Tian H, Fu Y, Ai A, Lyu Q, Kuang Y. Luteal-phase ovarian stimulation vs conventional ovarian stimulation in patients with normal ovarian reserve treated for IVF: a large retrospective cohort study. Clin Endocrinol (Oxf). 2016 May;84(5):720-8. doi: 10.1111/cen.12983. Epub 2015 Dec 21.
• Zhang J. Luteal phase ovarian stimulation following oocyte retrieval: is it helpful for poor responders? Reprod Biol Endocrinol. 2015 Jul 25;13:76. doi: 10.1186/s12958-015-0076-2.
• Zhang Q, Guo XM, Li Y. Implantation rates subsequent to the transfer of embryos produced at different phases during double stimulation of poor ovarian responders. Reprod Fertil Dev. 2017 Jun;29(6):1178-1183. doi: 10.1071/RD16020.

• Responsible Party: Aly Hussein, Assistant lecturer, University of Alexandria, El Shatby University Hospital for Obstetrics and Gynecology
• ClinicalTrials.gov Identifier: NCT04537078
• Other Study ID Numbers: 0201350
• First Posted: Sep 3, 2020
• Last Update Posted: Feb 17, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Infertility; Infertility, Female; Triptorelin Pamoate; Contraceptive Agents; Contraceptives, Oral; Chorionic Gonadotropin; Cetrorelix; Contraceptives, Oral, Combined; Progesterone; Dydrogesterone; Estradiol

Study Results

Participant Flow

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist
Arm/Group Description	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.	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. .
Period Title: Overall Study
STARTED	45	45
COMPLETED	41	42
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	41	42	83
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.05 (5)	35.48 (6.99)	34.77 (6.09)
Sex: Female, Male (Count of Participants)
Female	41 100%	42 100%	83 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	41 100%	42 100%	83 100%
Region of Enrollment (participants) [Number]
Egypt	41 100%	42 100%	83 100%
duration of infertility (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	5	5	5
previous ICSI trials (participants) [Number]
had no previous ICSI trials	22 53.7%	26 61.9%	48 57.8%
had 1 failed ICSI trial	17 41.5%	14 33.3%	31 37.3%
had 2 failed ICSI trials	2 4.9%	2 4.8%	4 4.8%

Outcome Measures

1. Primary Outcome

Title	the Number of M2 Oocytes Retrieved
Description	it is the number of M2 oocytes retrieved that were being assessed after denudation
Time Frame	1-2 hours after oocyte retrieval

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist Group
Arm/Group Description	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.	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.
Measure Participants	41	42
Median (Inter-Quartile Range) [oocytes]	6	4.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	the Fertilization Rate
Description	percentage transformation of micro injected oocytes into two pronuclei. it is done 16 to 20 hours after microinjection of the oocytes by the sperms
Time Frame	16 to 20 hours after microinjection of the oocytes with the sperms

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist Group
Arm/Group Description	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.	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.
Measure Participants	41	42
Median (Inter-Quartile Range) [percentage of transformation]	71.43	80.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.219
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	9.48
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	the Resultant Embryos Number
Description	it is the resultant embryos number counted day 3 or 4 or 5 after fertilization
Time Frame	the embryos number counted day 3 or 4or 5 after fertilization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist Group
Arm/Group Description	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.	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.
Measure Participants	41	42
Median (Inter-Quartile Range) [number of embryos]	4	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.269
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	the Implantation Rate
Description	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
Time Frame	at the 6 th week of pregnancy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist Group
Arm/Group Description	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.	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.
Measure Participants	7	8
Median (Inter-Quartile Range) [percentage]	50	50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	the Clinical Pregnancy Rate.
Description	percentage of cases in which observation of a gestational sac with fetal heart beat by transvaginal ultrasound at 6 weeks of pregnancy
Time Frame	at the 6 th weeks of pregnancy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist Group
Arm/Group Description	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.	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.
Measure Participants	41	42
Number [percentage of participants]	7 17.1%	8 19%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	the Difference in the Ongoing Pregnancy Rate in Both Protocols.
Description	Assessing the difference in the ongoing pregnancy rate when the pregnancy had completed ≥20 weeks of gestation
Time Frame	At the 20 th week of gestation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	the Progestin Primed Double Stimulation Group	the Flexible GnRh Antagonist Group
Arm/Group Description	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.	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.
Measure Participants	41	42
Number [percentage of participants]	6 14.6%	5 11.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.720
	Comments
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Total Days of Controlled Ovarian Hyperstimulation
Description	the total number of days of the controlled ovarian hyperstimulation in both follicular and luteal phase of the progestin primed double stimulation protocol are studied so as to asses the difference between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol
Time Frame	From the first day of ovarian stimulation till the last day of ovarian stimulation in each phase ,the follicular and the luteal, of stimulation

Outcome Measure Data

Analysis Population Description

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Arm/Group Title	the Follicular Phase of the Progestin Primed Double Stimulation Group	the Luteal Phase of the Progestin Primed Double Stimulation Group
Arm/Group Description	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	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
Measure Participants	41	41
Median (Inter-Quartile Range) [number of days]	10	12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Total Dosage of Gonadotropins Used in the Controlled Ovarian Hyperstimulation
Description	Assessing the difference between the follicular phase and the luteal phase of the progestin primed double stimulation protocol regarding the total dosage of gonadotropins used in the controlled ovarian hyperstimulation so as to the difference between the two phases
Time Frame	From the first day of ovarian stimulation till the last day of ovarian stimulation in each phase ,the follicular and the luteal, of stimulation

Outcome Measure Data

Analysis Population Description

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Arm/Group Title	the Follicular Phase of the Progestin Primed Double Stimulation Group	the Luteal Phase of the Progestin Primed Double Stimulation Group
Arm/Group Description	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	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
Measure Participants	41	41
Median (Inter-Quartile Range) [IU]	3000	3600

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	600
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Number of M2 Oocytes Retrieved
Description	it is the number of M2 oocytes retrieved that were being assessed after denudation so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol
Time Frame	1-2 hours after oocyte retrieval

Outcome Measure Data

Analysis Population Description

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Arm/Group Title	the Follicular Phase of the Progestin Primed Double Stimulation Group	the Luteal Phase of the Progestin Primed Double Stimulation Group
Arm/Group Description	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	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
Measure Participants	41	41
Median (Inter-Quartile Range) [number of oocytes]	2	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Fertilization Rate.
Description	percentage of transformation of micro injected oocytes into two pronuclei at 16 -20 hours after microinjection of the oocytes by the sperms so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol
Time Frame	16 to 20 hours after microinjection of the oocytes with the sperms

Outcome Measure Data

Analysis Population Description

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Arm/Group Title	the Follicular Phase of the Progestin Primed Double Stimulation Group	the Luteal Phase of the Progestin Primed Double Stimulation Group
Arm/Group Description	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	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
Measure Participants	41	41
Median (Inter-Quartile Range) [percentage]	66.67	100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	33.33
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Resultant Embryos Number
Description	the resultant embryos number are counted day 3 or 4 or 5 after fertilization so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol
Time Frame	the embryos number counted day 3 or 4or 5 after fertilization

Outcome Measure Data

Analysis Population Description

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Arm/Group Title	the Follicular Phase of the Progestin Primed Double Stimulation Group	the Luteal Phase of the Progestin Primed Double Stimulation Group
Arm/Group Description	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	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
Measure Participants	41	42
Median (Inter-Quartile Range) [number of embryos]	1	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Assessing the Difference Between the Follicular Phase of the Progestin Primed Double Stimulation Protocol and the First Round of the Conventional GnRH Antagonist Protocol Regarding the Number of M2 Oocytes Retrieved .
Description	it is the number of M2 oocytes retrieved that were being assessed after denudation.so as to study the effect of the progestin used on the ovarian response in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group
Time Frame	1-2 hours after oocyte retrieval

Outcome Measure Data

Analysis Population Description

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Arm/Group Title	The Follicular Phase of the Double Stimulation Group	the First Round of the Conventional GnRH Antagonist Group
Arm/Group Description	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	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
Measure Participants	41	42
Median (Inter-Quartile Range) [number of oocytes]	2	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.851
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Assessing the Difference Between the Follicular Phase of the Progestin Primed Double Stimulation Protocol and the First Round of the Conventional GnRH Antagonist Protocol Regarding the Fertilization Rate.
Description	it is percentage transformation of micro injected oocytes into two pronuclei.so as to study the effect of the progestin used on the ovarian response and its results in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group
Time Frame	16 to 20 hours after microinjection of the oocytes by the sperms

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	The Follicular Phase of the Double Stimulation Group	the First Round of the Conventional GnRH Antagonist Group
Arm/Group Description	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	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
Measure Participants	41	42
Median (Inter-Quartile Range) [percentage]	66.67	91.67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.304
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	25
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Assessing the Difference Between the Follicular Phase of the Progestin Primed Double Stimulation Protocol and the First Round of the Conventional GnRH Antagonist Protocol Regarding the Resultant Embryos Number.
Description	it is the number of the resultant embryos counted at day 3 or 4 or 5 after fertilization.so as to study the effect of the progestin used on the ovarian response and the resultant embryos number in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group
Time Frame	at day 3 or 4or 5 after fertilization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	The Follicular Phase of the Double Stimulation Group	the First Round of the Conventional GnRH Antagonist Group
Arm/Group Description	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	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
Measure Participants	41	42
Mean (Standard Deviation) [percentage]	1.66 (1.44)	1.69 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	the Progestin Primed Double Stimulation Group, the Flexible GnRh Antagonist Group
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.486
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	from the 1 st day of ovarian priming prior to ovarian stimulation till the 20th week of pregnancy.
Arm/Group Title	the Progestin Primed Double Stimulation Group		the Flexible GnRh Antagonist
Arm/Group Description	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.		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.
All Cause Mortality
	the Progestin Primed Double Stimulation Group		the Flexible GnRh Antagonist
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/42 (0%)
Serious Adverse Events
	the Progestin Primed Double Stimulation Group		the Flexible GnRh Antagonist
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	the Progestin Primed Double Stimulation Group		the Flexible GnRh Antagonist
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/41 (29.3%)		10/42 (23.8%)
Gastrointestinal disorders
nausea and abdominal distention	5/41 (12.2%)	15	5/42 (11.9%)	12
Nervous system disorders
headache	4/41 (9.8%)	10	2/42 (4.8%)	5
Reproductive system and breast disorders
pelvic pain	3/41 (7.3%)	10	3/42 (7.1%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.