Discussion
This study indicated that double FBT with one GQE plus one PQE increased LBRs mainly in patients aged 35 and over and in patients received at least 3 cycles of ET when compared with single FBT with only one GQE. Notably, MPR was significantly higher in group GP than in group G regardless of age or prior ET cycles. MR remained comparable no matter two groups were stratified by age or cycles of ET or not.
Several studies have evaluated the impact of double blastocyst transfer (DBT) on clinical outcomes compared with single blastocyst transfer (SBT). Dobson and colleagues demonstrated DBT with one PQE plus one GQE does not increase LBR but increases MPR when compared with SBT with a TQE during fresh or frozen blastocyst transfer 18. However, the only confounder they have adjusted for OR was age. There were likely some other factors which would confound for the results as other studies have reported 19, 20. Our study also resulted in no difference in LBR (OR:0.93, 95%CI:0.77-1.11) between two groups when only adjusted for age before PS matching. Wintner and colleagues also concluded no statistically significant difference in LBR between these two groups 21. However, their study was performed in fresh cycles with ET at cleavage stage or blastocyst stage, which might differ from FBT 22. On the other hand, El-Danasouri and colleagues found that transferring an impaired quality embryo along with a good quality embryo significantly lowered both the pregnancy rate and implantation rate, than transferring the good quality embryo alone 23. However, their study did not demonstrate a statistically significant difference. In contrast to their reports, some investigators demonstrated that transferring two blastocysts in FBT cycles lead to a higher PR, a higher LBR and no doubt a higher MPR 5, 8, which is consistent to our results. In spite of different results in LBR, aforementioned studies concluded consistently that double FBT achieved a significantly higher MPR than single FBT.
Two prior studies have compared the outcomes of DBT with SBT in advanced maternal age. One study found that DBT resulted in a higher live birth than SBT for women aged 35 years and over undergoing vitrified-warmed cycles 6. Another study indicated eSBT is associated with similar LBRs compared to the entire DBT cohort, but the subgroup of women who had elective DBT achieved a higher LBR and a higher MP in advanced maternal age 24. In accordance to their results, our study also observed DBT with one GQE plus one PQE achieved a higher LBR than SBT with only one GQE in women aged 35 and over but not in women under 35 years of age. Our data showed that DBT maintained a similar PR, MPR, MR and LBR between the subgroups stratified by 35 years of age, whereas SBT resulted in a significantly lower LBR due to a lower trend in PR and a statistically higher miscarriage rate. The miscarriage rate significantly increased may possibly because the prevalence of aneuploidy rose along with maternal age 25. Poor quality blastocysts owing to age-related decline in oocyte quality were assessed 25.5% euploid compared with 56% of the top-quality blastocysts 26. Despite higher incidence of aneuploidy and a lower implantation than good quality blastocyst, poor quality blastocysts still contributed an overall increase of live births 27.
Few studies have reported the comparison of double FBT versus single FBT in women failed repeatedly. A study performed by McLernon and his colleagues to develop the prediction model to estimate the chances of a live birth implied the association between number of complete cycles with live birth 28. Although it didn’t meet the definition of recurrent implantation failure, patients underwent at least 3 cycles of embryo transfer implied difficulties of conception with various reasons 10. Our study found that DBT of PQE with GQE achieved a significantly higher LBR in women received over 3 cycles of ET due to a higher PR and a similar MR compared with SBT. The possible explanation of a higher PR might be that the promotion of interaction between embryo and endometrium by an additional embryo led to a more favorable endometrial receptivity29. Anyway, it indicated that poor quality blastocyst had implantation potential to provide additional increase of LBR and should be vitrified for future use in patients with poor prognosis.
A main strength of our study is that it included the largest number of patients on this topic to-date. Second, PS matching was conducted to control for potential confounders which might have effects on the outcomes. It has been proofed that PS matching provides an approach to mimic random assignment as RCT and is superior to conventional regression-based methods in a real world observational study15. Third, the comparisons were not only performed in overall groups, but were also explored in advanced maternal age and in women received at least 3 cycles of ET.
Our study was limited by its retrospectively observational design, and patients’ information were previously recorded by hospital with some missing data. Though PS matching was performed to evaluate the effects of DBT with mixed quality embryo independently from other confounders, the sample decreased after PS and the loss of unmatched cases might have unforeseen effects. Accordingly, results by multivariable GEE models to adjust potential confounders before PS matching was presented relatively.