Comparing the Ongoing Pregnancy Rate for Vitrification of Day-4 Morula With Day-5 Blast

Study Overview
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Brief Summary
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Comparing the vitrification at Day-4 (morula stage) with the blastocyst stage vitrification outcomes with the transfer of all day 5 after warming seems need evaluation. To the best of our knowledge, there has been no random-controlled trial conducted such comparison. Altogether, this trial is to evaluate the morula stage vitrification to blastocyst vitrification on the ongoing pregnancy rate after ICSI.

Detailed Description
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Vitrification of human embryos has been a paradigm-shifting procedure for higher survival rate compared with the slow freezing protocol. The evidence is scarce to support superior results for vitrifying certain stages of preimplantation embryos. Anecdotal evidence suggests that blastocyst vitrification is more forgiving than cleavage stages. However, data obtained from the procedure of assisted shrinkage of blastocysts before vitrification show a higher survival rate, suggesting that fluid accumulation insides the blastocyst can be a barrier for cryoprotectant to reach the cells. Although reassuring, whether facilitating the cryoprotectants transfer to cells by the laser-assisted shrinkage or other modalities is completely safe remains elusive. Moreover, other claims compare between day-3 embryos vitrification and blastocyst stage, suggesting no difference exists. One of the most critical stages in embryo development is the maternal to zygotic genome activation (MZA), which occurs at the 4 to 8 cell stages. Therefore, it seems the morula stage is still cleavage but passed the MZA. Morula in the most grading system has compaction for all or the majority of cells so if vitrified, the morula stage can bypass the earlier stage of vitrification as well as the need for the artificial shrinkage for blastocyst stage. Therefore, comparing the vitrification at Day-4 (morula stage) with the blastocyst stage vitrification outcomes with the transfer of all day 5 after warming seems need evaluation. To the best of our knowledge, there has been no random-controlled trial conducted such comparison. Altogether, this trial is to evaluate the morula stage vitrification to blastocyst vitrification on the ongoing pregnancy rate after ICSI.

Official Title
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The Ongoing Pregnancy Rate for Vitrification of Day-4 Morula and Day-5 Blastocyst

Conditions
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Infertility

Intervention / Treatment
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* Other: Morula Vitrification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women age of ≥ 18 to ≤ 40 BMI of ≤ 31 Normal responder (≥ 12 antral follicle count (AFC) during basal ultrasound examination) or hyper responder The freeze-all groups including PCOS, OHSS, or high Progesterone at trigger day Women who have ≥ 1 year of primary or secondary infertility Tubal factor (unilateral, bilateral obstruction or salpingectomy) Fresh semen ejaculates but not frozen or surgically retrieved sperm Male factor: oligoasthenozoospermia but not globozoospermia or pinhead sperm Women who are undergoing their first or second ICSI attempts with a previously successful attempt Women who undergo only freeze-all embryo Freeze-all for poor endometrium at the fresh cycle Freeze-all due to abnormal endometrial findings such as polyp or myoma with a decision for freeze all for surgical correction. Women who have normal endometrial thickness (≥ 8) and echo-pattern at the time of progesterone start in the proposed vitrified warmed cycle Exclusion Criteria: Women who have uncorrectable uterine pathology or abnormality including submucous myoma Women or their husbands who have abnormal karyotyping Women with a history of recurrent abortions or repeated implantation failures Women who have uncontrolled diabetes Women with diagnosed or undiagnosed liver or renal disease Women who had a history of malignancy or borderline pathology Women who will not meet the inclusion criteria Women who will refuse to participate in the study Women with endometriosis Patient undergoing PGS or PGD Surgically retrieved, frozen-thawed and pinpoint sperm or globozoospermia Adenomyosis Severe medical condition

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Morula Vitrification Arm<br> | Other: Morula Vitrification<br>* Evaluating the ongoing pregnancy rate following Morula vitrification compared with Blastocyst Vitrification.<br>|
| Active Comparator: Blastocyst Vitrification Arm<br> | Other: Morula Vitrification<br>* Evaluating the ongoing pregnancy rate following Morula vitrification compared with Blastocyst Vitrification.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ongoing pregnancy rate | Continued pregnancy at > gestational week 12 or more per initiated cycle | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical pregnancy rate | positive b-hCG at ≥ 14 days following embryo transfer per initiated cycle | 14 days | 
| Implantation rate | Sacs with a heartbeat on ultrasound per embryo transferred | 12 weeks | 
| Cumulative implantation rate | Sacs with a heartbeat on ultrasound per embryo transferred within one year from randomization | One year | 
| Clinical pregnancy rate | Sacs with a positive heartbeat on ultrasound at ≥ 7 weeks of gestation per initiated cycle | 7 weeks | 
| Cumulative clinical pregnancy rate | Sacs with a positive heartbeat on ultrasound at ≥ 7 weeks of gestation per initiated cycle within one year from randomization | One year | 
| Cumulative ongoing pregnancy rate | continued pregnancy after gestational week 12 per initiated cycle within one year from randomization | One year | 
| Twin pregnancy rate | ≥ two foetuses with a heartbeat per initiated cycle | One year | 
| Embryo survival rate after thawing | Blastocyst re-expansion for day 5 vitrified embryo after two hours and blastocyst formation on day 5 for embryo vitrified on day 4 | Five days of culture |