Study question

What is the impact of blastocyst stage and inner cell mass (ICM) grade on the formation of blighted ovum in in vitro fertilization?

Summary answer

Analysis indicates blastocyst stage influences gestational sac formation, while ICM grade significantly predicts blighted ovum occurrence, highlighting potential predictive markers

What is known already

It is well known that the blastocyst grading, encompassing stage, ICM and trophectoderm (TE) is correlated with the pregnancy outcome. Although Gardner criteria is widely used for blastocyst grading, the significance and clinical implications of each component remain challenging to assess. A blight ovum, a presence of GSAC without advancement to FHT, commonly results from fetal aneuploidy. The quality of ICM, evolving into the fetus, is thought to reflect fetal euploidy, whereas TE develops into the placenta. However, the specific influence of these blastocyst grading components on blighted ovum incidence remains underexplored.

Study design, size, duration

This study analyzed 897 patient clinical data from 2011 to 2022, collected from three IVF clinics. It included maternal age, embryo transfer method (fresh or frozen), and outcomes (GSAC, FHT). Day 5 embryos were graded for blastocyst stage, ICM, and TE using Gardner criteria.

Participants/materials, setting, methods

Of 897 IVF cycles, 416 led to GSAC formation and 379 to FHT. Thirty-seven cycles resulted in blighted ovum. Logistic regression analyzed blastocyst stage, ICM, and TE grades’ effects on GSAC and FHT, accounting for confounding factors. Due to the small sample size, propensity score matching (PSM) was performed at 1:3 and 1:4 ratios matched blighted ovum cases with controls based on age and embryo status.

Main results and the role of chance

As anticipated, ANOVA and logistic regression analyses identified blastocyst stage, ICM, and TE as significant predictors of GSAC and FHT development, underscoring the relevance of Gardner criteria. However, the limited number of blighted ovum cases necessitated further analysis. Propensity score matching (PSM) was thus applied to 37 blighted ovum cases, compared against non-blighted ovum cases at ratios of 1:3 and 1:4, selected randomly from the dataset. The standardized mean differences pre- and post-PSM were 0.14 and 0, indicating well-balanced group characteristics. GSAC formation probability increased with advanced blastocyst stages (5,6) compared to earlier stages (3,4), with ICM and TE grades showing no significant impact. Conversely, FHT advancement from GSAC was unaffected by blastocyst stage, but the likelihood of FHT occurrence was 3.618 and 3.476 times higher for ICM grades A or B compared to C, at 1:3 and 1:4 ratios respectively.

Limitations, reasons for caution

The study accounted for age and cycle type (fresh or thawed) as confounding factors affecting pregnancy outcomes. To further minimize potential biases, controlling additional factors is crucial. Moreover, with data derived from three clinics, external validation is vital to substantiate the findings.

Wider implications of the findings

Blighted ovum, an early form of miscarriage, is deeply distressing for patients. This study highlights the potential role of ICM grades in predicting blighted ovum occurrences. Such insights could be invaluable for embryo selection and patient counseling.