Hatching status before embryo transfer is not correlated with implantation rate in chromosomally screened blastocysts

Do the reproductive outcomes from the transfer of fully hatched (FH) blastocysts differ from those of not fully hatched (NFH) blastocysts?

Biochemical pregnancy rate (BPR), implantation rate (IR), live birth rate (LBR) and early pregnancy loss (EPL) rate are similar in FH and NFH single euploid blastocyst embryo transfers.

The use of extended culture and PGS often leads to transfer of an embryo that is well developed and frequently FH from the zona pellucida. Without the protection of the zona, an FH embryo could be vulnerable to trauma during the transfer procedure. To date, no other study has evaluated the reproductive competence of an FH blastocyst transfer.

The retrospective study included 808 patients who underwent 808 cycles performed between September 2013 and July 2015 at a private academic IVF center. Of these, 436 cycles entailed transfer of a NFH blastocyst (n = 123 fresh transfer, n = 313 frozen/thawed embryo transfer (FET)) and 372 cycles entailed transfer of an FH blastocyst (n = 132 fresh, 240 FET). Fresh and FET cycles and associated clinical outcomes were considered separately. LBR was defined as the delivery of a live infant after 24 weeks of gestation.

Trophectoderm biopsies were performed on Day 5 (d5) or 6 (d6) for embryos meeting morphology eligibility criteria (set at ≥3BC). Morphologic grading was determined using a modified Gardner-Schoolcraft scale prior to transfer. A single euploid embryo was selected for transfer per cycle on either the morning of d6, for fresh transfers or 5 days after progesterone supplementation for patients with transfer in an FET cycle. Embryos were classified as NFH (expansion Grade 3, 4 or 5) or FH (expansion Grade 6) cohorts. The main outcome measure was IR.

In the fresh transfer group, IR was similar between NFH and FH cycles (53.7% versus 55.3%, P = 0.99, odds ratio (OR) 0.9; 95% confidence interval (CI) 0.6-1.5). Secondary outcomes were also statistically similar between groups: BPR (65.9% versus 66.7%, OR 1.0; 95% CI: 0.6-1.6), LBR (43.1% versus 47.7%, P = 0.45, OR 1.2; 95% CI: 0.7-1.9) and EPL rate (22.8% versus 18.2%, OR 1.3; 95% CI: 0.7-2.4). After adjusting for age, BMI, endometrial thickness at the LH surge and oocytes retrieved in a logistic regression (LR) model, the hatching status remained not associated with IR (P > 0.05). In the FET cycles, IR was similar between NFH and FH cycles (62.6% versus 61.7%, OR 1.0; 95% CI: 0.7-1.5). Secondary outcomes were similar between groups: BPR (74.1% versus 72.9%, respectively, OR 1.1; 95% CI: 0.7-1.6), LBR (55.0% versus 50.0%, OR 0.8; 95% CI: 0.6-1.1) and EPL rate (18.9% versus 22.9%, respectively, OR 0.8; 95% CI: 0.5-1.2). After adjusting for age, BMI, endometrial thickness at the LH surge and oocytes retrieved in an LR model, the hatching status was not shown to be associated with implantation (P > 0.05).

Limitations include the retrospective design and data from a single institution. Additionally, the study was limited to patients that developed high-quality blastocysts suitable for biopsy.

The results suggest that FH embryos are not more fragile or less likely to implant when compared to NFH counterparts. We found no evidence of altered IR or other clinical outcomes in the transfer of FH euploid embryos.

JG is funded by MSTP grant T32 GM007280 (NIH). No additional funding was received. There are no conflicts of interest to declare..