Effect of Age and Morphology on Live Birth Rate After Cleavage Stage Embryo Transfer

Abstract

Accurate knowledge of the live birth rate for cleavage stage embryos is essential to determine an appropriate number of embryos to transfer at once. Results from previous studies lack details needed for practical use. This is a mathematical analysis and model building study of day 3 cleavage stage embryo transfers. A total of 996 embryos were transferred in 274 fresh and 83 frozen embryo transfers. Embryo morphology was divided into 4 groups based on number of cells and fragmentation percentage. Each embryo transfer was modeled as an equation equating the sum of the live birth rates of the transferred embryos to the number of live births that resulted. The least squares solution to the system of embryo transfer equations was determined using linear algebra. This analysis was repeated for ages 35 to 42 years old at oocyte retrieval. The best fit live birth rates per embryo in the age group centered on 35 years old were 29%, 13%, 10%, and 9% for embryos in the 8-cell with ≤ 5% fragmentation, 8-cell with > 5% fragmentation, 9–12 cell, and 6–7 cell groups, respectively. Cleavage stage embryos with fewer than 6 cells on day 3 had very low best fit live birth rates close to 0% at age 39 years and were excluded from the primary analysis to prevent overfitting. These live birth rates can be used with a simple embryo transfer model to predict rates of single and multiple gestation prior to a planned cleavage stage embryo transfer.

Effect of age and morphology on sustained implantation rate after euploid blastocyst transfer

“…There is strong biological plausibility that with increasing age the sustained implantation and live birth rates will either remain the same or decrease gradually. Our previous analysis on LBR of cleavage stage embryos and unbiopsied blastocysts is consistent with this (Awadalla et al, 2020b(Awadalla et al, , 2020a). An overfitted model is easy to spot because the outcome rate will increase and decrease with increasing age in a manner that is not biologically plausible.…”

“…Our IVF protocols have been described previously (Awadalla et al, 2020a(Awadalla et al, , 2020bMcDaniel et al, 2020). In brief, we use a combination of GnRH antagonist, GnRH agonist suppression, and GnRH flare ovarian stimulation protocols.…”

“…We have described our use of linear algebra and moving age groups previously (Awadalla et al, 2020b(Awadalla et al, , 2020a. Although linear algebra is more commonly used in engineering applications than medicine, it is very similar to multiple linear regression.…”

A validated model for predicting live birth after embryo transfer

“…Including embryo morphology in a predictive model increases the complexity of validating the universal factors model and is more suited for a separate focused study. We have recently analyzed the association of cleavage stage and blastocyst morphology with live birth and described how morphology can be incorporated into the predictive model 19 , 21 . Using a live birth rate assuming average embryo morphologic quality seems reasonable and is clinically useful for patient counseling both before retrieval and prior to transfer.…”

“…UNI, universal factors fraction; LBR e1 , live birth rate for embryo 1; LBR e2 , live birth rate for embryo 2. This figure is being reproduced from a previous publication 19 . …”