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

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

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 Overview

• Status: Terminated
• Conditions: Infertility
• Intervention / Treatment: Other: Morula Vitrification

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 Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 12345
    • Agial
  • Alexandria, Egypt, 12345
    • Al Hayat ICSI Centre of Alexandria
  • Alexandria, Egypt, 12345
    • AlMadina IVF and ICSI Centre
  • Zagazig, Egypt, 12345
    • Rahem Fertility Centre of Zagazig

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 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. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Morula Vitrification Arm	Other: Morula Vitrification; Evaluating the ongoing pregnancy rate following Morula vitrification compared with Blastocyst Vitrification.
Active Comparator: Blastocyst Vitrification Arm	Other: Morula Vitrification; Evaluating the ongoing pregnancy rate following Morula vitrification compared with Blastocyst Vitrification.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Egyptian Foundation of Reproductive Endocrinology
• Collaborators: Al Hayat ICSI Centre of Alexandria, Egypt; Agial IVF/ICSI Unit of Alexandria, Egypt; Al Madina Fertility centre of Alexandria, Egypt; Rahem Fertility Center of Zagazig, Egypt

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Actual): May 31, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 22, 2018
• First Posted (Actual): December 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: EFRE Vitrification Trial

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