Progestin Priming Ovarian Stimulation (PPOS) Compared With Antagonist Protocol for Freeze-all Cycles (ANTA-PPOS)

Progestin Priming Ovarian Stimulation (PPOS) Compared With Antagonist Protocol on Live Birth Rate for Freeze-all Cycles: Recruitment is Slow Due to COVID19

Stimulation protocols for IVF underwent several cycles of upgrading aiming to achieve reasonable outcomes with low-cost cycles. Antagonist protocols have been introduced as effective and comparable to long agonist regarding the outcomes. However, these protocols are still costly. Alternative protocols using progestin suppressions appear options for consideration.

Study Overview

• Status: Terminated
• Conditions: Infertility
• Intervention / Treatment: Drug: LH Suppression

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Banon Fertility Center
  • Sohag, Egypt, 12345
    • IbnSina IVF Center, IbnSina Hospital
  • Sohag, Egypt
    • AlRahma Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women age of ≥ 18 to ≤ 40;
2. BMI of ≤ 31;
3. All indication for freeze-all
4. PCOS;
5. Women who have ≥ 1 year of primary or secondary infertility;
6. Tubal factor (unilateral, bilateral obstruction or salpingectomy);
7. Fresh ejaculate sperm of any count provided they have ≥ 1% normal forms and a motile fraction;
8. Women undergoing their first ICSI cycle or following a previous successful attempt;
9. Women undergoing only frozen-thawed embryo transfer;
10. Women with > 8 mm endometrial thickness at the day of progesterone supplementation in the transfer cycle;
11. Women with no detected uterine abnormality on transvaginal ultrasound (e.g. submucosal myomas, polyps or septa).

Exclusion Criteria:

1. Unilateral oophorectomy;
2. Uterine pathology or abnormality;
3. Abnormal karyotyping for them or their male partners;
4. History of repeated abortions or implantation failure;
5. Uncontrolled diabetes;
6. Liver or renal disease;
7. History of malignancy or borderline pathology;
8. Endometriosis;
9. Plan for PGD-A;
10. Severe male factor includes surgical sperm retrieval or cryopreserved sperm.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dydrogesterone Suppression; Dydrogesterone 30 mg on stimulation day 5 till the trigger day to prevent luteinizing hormone (LH) surge. The stimulation is with 150-300 IU FSH/HMG starting on cycle day 2 and adjusted according to the AFC and AMH.	Drug: LH Suppression; Stimulation protocols
Experimental: Dydrogesterone Suppression with minimal stimulation; Dydrogesterone 30 mg on stimulation day 5 till the trigger day to prevent LH surge. The stimulation is with clomifene citrate 50 mg three times daily with150 IU FSH starting on cycle day 2 and continued every other day and adjusted according to the AFC and AMH.	Drug: LH Suppression; Stimulation protocols
Active Comparator: Antagonist Suppression; cetrorelix acetate 0.25 started on stimulation day 6 till the trigger day to prevent LH surge. The stimulation is with150-300 IU FSH starting on cycle day 2 and continued daily and adjusted according to the AFC and AMH.	Drug: LH Suppression; Stimulation protocols

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live Birth after first Vitrified-warmed cycle	Delivery of one or more viable infants > 20th weeks of gestation	42 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical pregnancy	positive human chorionic Gonadotrophin (βhCG) ≥ 10 IU/L	14 days after egg retrieval
Clinical pregnancy	registered sacs with a heartbeat on ultrasound at 7th weeks of gestation	within 12 weeks of gestation
Ongoing pregnancy	continued viable pregnancy > 20th weeks of gestation	within 24 weeks of pregnancy
Miscarriage	loss of pregnancy ≤ 20th weeks of gestation	Within 20 weeks of pregnancy
Term live-birth for vitrified-warmed transfer	Delivery of one or more viable infants ≥37 weeks of gestation	Within 42 weeks of gestation
Preterm Birth	delivery of one or more viable infants < 37th weeks of gestation	Within 42 weeks of gestation
Very preterm birth	delivery of one or more viable infants < 32nd weeks of gestation	Within 42 weeks of gestation
Low birth weight babies	Babies with < 2500 gm	Within 24 hours of delivery
Congenital malformation	delivery of congenitally malformed babies	Within one month of delivery
Still birth	delivery of nonviable babies > 20 weeks of gestation	Within 42 weeks of gestation
Cumulative live birth	Registered viable neonates after two vitrified-warmed transfers within one year of randomization	One year from randomization
Fertilization	presence of 2 pronuclei 17±1 hr after oocyte injection	Within 6 days of culture
Embryo cleavage	Cleaved embryos per fertilized oocyte	Within 6 days of culture
Top-quality embryo on day 3	(7-8 cells with appropriate-sizes blastomeres and less than 10% fragmentation by volume	Within 6 days of culture
Blastocyst formation on day 5 or 6	formed blastocysts per fertilized oocyte	Within 6 days of culture
Top-quality blastocyst on day 5	Rounded and dense inner cell mass with many trophectodermal cells creating a connected zone and a blastocoel more than 100% by volume; ≥ 311 grade per fertilized oocyte	Within 6 days of culture
Cryopreservation	Cryopreserved embryos per fertilized oocyte	Within 6 days of culture
Live-birth-implantation rate	Number of viable neonates per number of embryos transferred	Within 42 weeks of gestation
Utilized embryos	Number of cryopreserved plus transferred embryos per fertilized oocyte	Within 6 days of culture
Top-quality utilized embryos	Number of high-quality embryos transferred plus cryopreserved per fertilized oocyte	Within 6 days of culture
Metaphase II oocyte	Mature oocyte per oocyte collected	Within 24 hours of oocyte retrieval

Collaborators and Investigators

• Sponsor: Ibn Sina Hospital
• Investigators: Principal Investigator: Mohamed Fawzy, Ibnsina Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2019
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2022
• Last Update Submitted That Met QC Criteria: June 12, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: IbnSina-PPOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No