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

Not Applicable

Terminated

• Conditions: Infertility
• Interventions: Drug: LH Suppression

• Registration Number: NCT04052607
• Lead Sponsor: Ibn Sina Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-08
• Study First Submitted QC: 2019-08-08
• Study First Posted: 2019-08-12
• Study Start: 2019-09-10
• Primary Completion: 2020-04-30
• Study Completion: 2020-04-30
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-12
• Last Update Posted: 2022-06-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 56

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antagonist Suppression	LH 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.
Dydrogesterone Suppression	LH 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.
Dydrogesterone Suppression with minimal stimulation	LH Suppression	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.

Primary Outcome Measures

Name	Time	Method
Live Birth after first Vitrified-warmed cycle	42 weeks of gestation	Delivery of one or more viable infants \> 20th weeks of gestation

Secondary Outcome Measures

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

Trial Locations

Locations (3)

IbnSina IVF Center, IbnSina Hospital; 🇪🇬 Sohag, Egypt

Banon Fertility Center; 🇪🇬 Assiut, Egypt

AlRahma Hospital; 🇪🇬 Sohag, Egypt