Infertility
Conditions
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.
Interventions
OTHERMorula Vitrification
Evaluating the ongoing pregnancy rate following Morula vitrification compared with Blastocyst Vitrification.
Sponsors
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
Egyptian Foundation of Reproductive Endocrinology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The ongoing pregnancy rate | 12 weeks | Continued pregnancy at \> gestational week 12 or more per initiated cycle |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Clinical pregnancy rate | 7 weeks | Sacs with a positive heartbeat on ultrasound at ≥ 7 weeks of gestation per initiated cycle |
| Biochemical pregnancy rate | 14 days | positive b-hCG at ≥ 14 days following embryo transfer per initiated cycle |
| Cumulative ongoing pregnancy rate | One year | continued pregnancy after gestational week 12 per initiated cycle within one year from randomization |
| Twin pregnancy rate | One year | ≥ two foetuses with a heartbeat per initiated cycle |
| 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 |
| 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 |
Countries
Egypt
Outcome results
None listed