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

Not Applicable

Terminated

• Conditions: Infertility
• Interventions: Other: Morula Vitrification

• Registration Number: NCT03787901
• Lead Sponsor: Egyptian Foundation of Reproductive Endocrinology

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-12-20
• Study First Submitted QC: 2018-12-22
• Study First Posted: 2018-12-26
• Study Start: 2019-01-15
• Primary Completion: 2020-05-31
• Study Completion: 2020-06-01
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-10
• Last Update Posted: 2022-06-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 53

Inclusion Criteria

1. Women age of ≥ 18 to ≤ 40
2. BMI of ≤ 31
3. Normal responder (≥ 12 antral follicle count (AFC) during basal ultrasound examination) or hyper responder
4. The freeze-all groups including PCOS, OHSS, or high Progesterone at trigger day
5. Women who have ≥ 1 year of primary or secondary infertility
6. Tubal factor (unilateral, bilateral obstruction or salpingectomy)
7. Fresh semen ejaculates but not frozen or surgically retrieved sperm
8. Male factor: oligoasthenozoospermia but not globozoospermia or pinhead sperm
9. Women who are undergoing their first or second ICSI attempts with a previously successful attempt
10. Women who undergo only freeze-all embryo
11. Freeze-all for poor endometrium at the fresh cycle
12. Freeze-all due to abnormal endometrial findings such as polyp or myoma with a decision for freeze all for surgical correction.
13. Women who have normal endometrial thickness (≥ 8) and echo-pattern at the time of progesterone start in the proposed vitrified warmed cycle

Exclusion Criteria

1. Women who have uncorrectable uterine pathology or abnormality including submucous myoma
2. Women or their husbands who have abnormal karyotyping
3. Women with a history of recurrent abortions or repeated implantation failures
4. Women who have uncontrolled diabetes
5. Women with diagnosed or undiagnosed liver or renal disease
6. Women who had a history of malignancy or borderline pathology
7. Women who will not meet the inclusion criteria
8. Women who will refuse to participate in the study
9. Women with endometriosis
10. Patient undergoing PGS or PGD
11. Surgically retrieved, frozen-thawed and pinpoint sperm or globozoospermia
12. Adenomyosis
13. Severe medical condition

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Morula Vitrification Arm	Morula Vitrification	-
Blastocyst Vitrification Arm	Morula Vitrification	-

Primary Outcome Measures

Name	Time	Method
The ongoing pregnancy rate	12 weeks	Continued pregnancy at \> gestational week 12 or more per initiated cycle

Secondary Outcome Measures

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

Trial Locations

Locations (4)

AlMadina IVF and ICSI Centre; 🇪🇬 Alexandria, Egypt

Al Hayat ICSI Centre of Alexandria; 🇪🇬 Alexandria, Egypt

Agial; 🇪🇬 Alexandria, Egypt

Rahem Fertility Centre of Zagazig; 🇪🇬 Zagazig, Egypt