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

Study Overview
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Brief Summary
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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.

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

Conditions
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Infertility

Intervention / Treatment
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* Drug: LH Suppression


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women age of ≥ 18 to ≤ 40; BMI of ≤ 31; All indication for freeze-all PCOS; Women who have ≥ 1 year of primary or secondary infertility; Tubal factor (unilateral, bilateral obstruction or salpingectomy); Fresh ejaculate sperm of any count provided they have ≥ 1% normal forms and a motile fraction; Women undergoing their first ICSI cycle or following a previous successful attempt; Women undergoing only frozen-thawed embryo transfer; Women with > 8 mm endometrial thickness at the day of progesterone supplementation in the transfer cycle; Women with no detected uterine abnormality on transvaginal ultrasound (e.g. submucosal myomas, polyps or septa). Exclusion Criteria: Unilateral oophorectomy; Uterine pathology or abnormality; Abnormal karyotyping for them or their male partners; History of repeated abortions or implantation failure; Uncontrolled diabetes; Liver or renal disease; History of malignancy or borderline pathology; Endometriosis; Plan for PGD-A; Severe male factor includes surgical sperm retrieval or cryopreserved sperm.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dydrogesterone Suppression<br>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<br>* Stimulation protocols<br>|
| Experimental: Dydrogesterone Suppression with minimal stimulation<br>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<br>* Stimulation protocols<br>|
| Active Comparator: Antagonist Suppression<br>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<br>* Stimulation protocols<br>|

What is the study measuring?
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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 |