Clinical trial NCT03787901: Comparing the Ongoing Pregnancy Rate for Vitrification of Day-4 Morula With Day-5 Blast
Official title: The Ongoing Pregnancy Rate for Vitrification of Day-4 Morula and Day-5 Blastocyst
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Infertility
Lead sponsor: Egyptian Foundation of Reproductive Endocrinology
Sponsor class: OTHER
Collaborators: name: Al Hayat ICSI Centre of Alexandria, Egypt
name: Agial IVF/ICSI Unit of Alexandria, Egypt
name: Al Madina Fertility centre of Alexandria, Egypt
name: Rahem Fertility Center of Zagazig, Egypt
First posted: 2018-12-26
Enrollment: 53
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: The ongoing pregnancy rate
timeFrame: 12 weeks
Secondary outcomes:
measure: Biochemical pregnancy rate
timeFrame: 14 days
measure: Implantation rate
timeFrame: 12 weeks
measure: Cumulative implantation rate
timeFrame: One year
measure: Clinical pregnancy rate
timeFrame: 7 weeks
measure: Cumulative clinical pregnancy rate
timeFrame: One year
measure: Cumulative ongoing pregnancy rate
timeFrame: One year
measure: Twin pregnancy rate
timeFrame: One year
measure: Embryo survival rate after thawing
timeFrame: Five days of culture
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Agial
city: Alexandria
country: Egypt
facility: Al Hayat ICSI Centre of Alexandria
city: Alexandria
country: Egypt
facility: AlMadina IVF and ICSI Centre
city: Zagazig
country: Egypt
facility: Rahem Fertility Centre of Zagazig
Study officials:
References: