Elective embryo transfers on Day 6 reduce implantation compared with transfers on Day 5

TY - JOUR

T1 - Elective embryo transfers on Day 6 reduce implantation compared with transfers on Day 5

AU - Poulsen, V.

AU - Ingerslev, H. J.

AU - Kirkegaard, K.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - STUDY QUESTION: Is there a difference in pregnancy rates between embryos transferred electively on Day 5 and Day 6, respectively? SUMMARY ANSWER: The chance of pregnancy is significantly reduced (odds ratio (OR): 0.34; 95% CI 0.22-0.52) if transfer is performed on Day 6 compared with Day 5. WHAT IS KNOWN ALREADY: Several studies report that Day 5 transfers have higher implantation rates (IRs) when compared with Day 6 transfers. These studies were based on non-elective Day 6 transfers, where transfers on Day 6 were performed with developmentally delayed embryos. Traditionally, difference in IRs has therefore been explained by an impaired embryo quality. An alternative explanation is that endometrial receptivity is higher on Day 5 compared with Day 6. STUDY DESIGN, SIZE, DURATION: The study was conducted as a retrospective cohort follow-up study on single blastocyst transfers from February 2011 until August 2015 in patients aged <38 years, with ≤eight oocytes retrieved and no diagnosis of endometriosis. Nonelective Day 6 transfers were excluded. Post hoc power-calculations (two-sided level of significance 0.05, power of 0.80) indicate that 91 embryos were needed in each group to detect a reduction in IR (primary outcome) from 40 to 20%. PARTICIPANTS/MATERIALS, SETTING, METHODS: Day 5 or Day 6 transfers were implemented accordingly: from 2011 till 2013, transfers were performed on Day 6. If Day 6 was a Sunday, patients received Day 5 transfers. From 2013 onward, blastocysts were transferred on Day 5. If Day 5 was a Sunday, the transfer was delayed to Day 6. Univariable logistic regression analysis was performed to identify potential confounders. Factors with a P-value <0.1 were included in the multivariable logistic regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: We included 334 single elective Day 5 and 268 elective Day 6 transfers. The unadjusted odds for implantation between Day 5 and Day 6 groups were 0.35 (95% CI 0.25-0.49). A univariable logistic regression analysis identified maternal age, BMI, cumulative FSH dose, number of cryopreserved embryos, score of inner cell mass and trophectoderm and day of transfer as predictors of clinical pregnancy. When adjusting for these variables in a multivariable logistic regression analysis, the implantation odds for Day 5 transfer remained significantly higher than Day 6 (OR 0.34; 95% CI 0.22-0.52). LIMITATIONS, REASONS FOR CAUTION: The study was conducted on good prognosis patients. The majority of Day 6 transfers were performed in the beginning of the study period. Day 5 transfers were generally performed in the end of the study period. This difference in time of recruitment may cause a minor variation in the data but a subanalysis indicates that this potential variation is negligible. Day 5 scores were higher in the Day 5 transfer group. WIDER IMPLICATIONS OF THE FINDINGS: Based on the findings in this study, transfers should be performed on Day 5. If Day 5 transfers are logistically impossible to perform, it is be preferable to cryopreserve the blastocyst and transfer in another cycle on Day 5, as Day 6 transfers should be avoided.

AB - STUDY QUESTION: Is there a difference in pregnancy rates between embryos transferred electively on Day 5 and Day 6, respectively? SUMMARY ANSWER: The chance of pregnancy is significantly reduced (odds ratio (OR): 0.34; 95% CI 0.22-0.52) if transfer is performed on Day 6 compared with Day 5. WHAT IS KNOWN ALREADY: Several studies report that Day 5 transfers have higher implantation rates (IRs) when compared with Day 6 transfers. These studies were based on non-elective Day 6 transfers, where transfers on Day 6 were performed with developmentally delayed embryos. Traditionally, difference in IRs has therefore been explained by an impaired embryo quality. An alternative explanation is that endometrial receptivity is higher on Day 5 compared with Day 6. STUDY DESIGN, SIZE, DURATION: The study was conducted as a retrospective cohort follow-up study on single blastocyst transfers from February 2011 until August 2015 in patients aged <38 years, with ≤eight oocytes retrieved and no diagnosis of endometriosis. Nonelective Day 6 transfers were excluded. Post hoc power-calculations (two-sided level of significance 0.05, power of 0.80) indicate that 91 embryos were needed in each group to detect a reduction in IR (primary outcome) from 40 to 20%. PARTICIPANTS/MATERIALS, SETTING, METHODS: Day 5 or Day 6 transfers were implemented accordingly: from 2011 till 2013, transfers were performed on Day 6. If Day 6 was a Sunday, patients received Day 5 transfers. From 2013 onward, blastocysts were transferred on Day 5. If Day 5 was a Sunday, the transfer was delayed to Day 6. Univariable logistic regression analysis was performed to identify potential confounders. Factors with a P-value <0.1 were included in the multivariable logistic regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: We included 334 single elective Day 5 and 268 elective Day 6 transfers. The unadjusted odds for implantation between Day 5 and Day 6 groups were 0.35 (95% CI 0.25-0.49). A univariable logistic regression analysis identified maternal age, BMI, cumulative FSH dose, number of cryopreserved embryos, score of inner cell mass and trophectoderm and day of transfer as predictors of clinical pregnancy. When adjusting for these variables in a multivariable logistic regression analysis, the implantation odds for Day 5 transfer remained significantly higher than Day 6 (OR 0.34; 95% CI 0.22-0.52). LIMITATIONS, REASONS FOR CAUTION: The study was conducted on good prognosis patients. The majority of Day 6 transfers were performed in the beginning of the study period. Day 5 transfers were generally performed in the end of the study period. This difference in time of recruitment may cause a minor variation in the data but a subanalysis indicates that this potential variation is negligible. Day 5 scores were higher in the Day 5 transfer group. WIDER IMPLICATIONS OF THE FINDINGS: Based on the findings in this study, transfers should be performed on Day 5. If Day 5 transfers are logistically impossible to perform, it is be preferable to cryopreserve the blastocyst and transfer in another cycle on Day 5, as Day 6 transfers should be avoided.

KW - BIRTH

KW - CULTURE-MEDIUM

KW - GOOD PROGNOSIS PATIENTS

KW - IVF

KW - PROSPECTIVE COHORT

KW - SINGLE BLASTOCYST TRANSFER

KW - blastocyst

KW - elective single embryo transfer

KW - extended culture

KW - implantation rate

UR - http://www.scopus.com/inward/record.url?scp=85026909853&partnerID=8YFLogxK

U2 - 10.1093/humrep/dex059

DO - 10.1093/humrep/dex059

M3 - Journal article

C2 - 28398477

SN - 0268-1161

VL - 32

SP - 1238

EP - 1243

JO - Human Reproduction

JF - Human Reproduction

IS - 6

ER -