Present study demonstrated that the VTS had no detrimental effect on the growth and development of children(0–3 years) with FET after the propensity matching. However, the number of embryos transferred in the VTS group was significantly higher than that in the non-VTS group(p<0.0001).The height measurements and head circumferences of children in the VTS group were significantly lower than those in the non-VTS group at three months.
The study indicated that the VTS did not have a detrimental effect on the growth and development of offspring aged 0–3 years.Although there were lower height measurements and head circumferences at 3 months in the VTS group, these differences were within the normal range and did not persist as the children continued to develop, suggesting that they may not be clinically significant.Currently, it is yet unknown whether VTS has an impact on an offspring's development.Theoretically the remaining embryos may have adverse effects on the surviving fetus.The first and foremost aspect is the potential direct impacts including reabsorption of nonviable fetoplacental tissues[18]. Necrotic fetoplacental tissue reabsorption changes the fetoplacental blood flow in addition to causing an increase in proinflammatory cytokine and prostaglandin release, which starts an inflammatory process [12, 14]. Consequently, these changes temporarily decrease the nutrition supplement to the surviving fetus, resulting in relative placental insufficiency[19–21].However, our findings confirm that VTS does not affect the growth and development of children aged 0–3 years, which may be due to the fact that the earlier occurrences the VTS and may not affect the surviving fetus as much in our study. It is also possible that we only followed up to three years old and only followed up a limited number of indicators, and a longer and more comprehensive follow-up verification is needed.
Present study discovered that there was no difference in GW, PTB, LBW and fetal malformation between the VTS group and non-VTS group. These results speculated that the occurrence of VTS did not affect the obstetric outcomes. The cause might be that the occurrences of VTS relatively early, around 5–8 weeks in our study.Relevant evidence also demonstrates that, irrespective of growth stage, surviving singletons following VTS that occurred before 14 weeks have similar obstetric outcomes, including GW, PTB, and LBW as original singletons[22–24]. On the other hand, VTS that happened after 14 weeks was associated with significantly lower GA, lower BW, and higher risks of PTB and LBW in comparison to the original singletons[25]. There would be no difference in GW, PTB, and LBW between a singleton and a singleton with VTS when the sac reduced in VTS was an empty gestational sac; However, the loss of a fetus with heart activity is linked to significantly worse obstetric outcomes.[26–31].In our study, the occurrence of VTS was before 5 to 8 weeks and most of the fetal heart beats were not observed.
In our study, we found that the number of embryos transferred in the VTS group was significantly higher than that in the non-VTS group. Consistent with the previous studies,present results confirmed that the number of transplanted embryos not only increased the occurrence of multiple pregnancies rate, but also increased the occurrence of VTS. It was known that the rate of multiple pregnancies rate in ART is about 20%-30% and previous studies have found that the rate of VTS will increase as the rate of multiple births increases. We know that an increase in the rate of multiple pregnancies can cause many complications in obstetrics such as premature birth, LBW etc., which seriously affect the healthy development of the offspring, in order to reduce the rate of multiple births in ART ,the researcher in ART has also taken some effective measures, extending the time of in vitro culture and optimizing the transfer of embryos with high implantation potential.The current study did not find that VTS affected the growth and development of 0–3 years old, and the long-term health effects are still inconclusive. Therefore, under the premise of ensuring the embryo implantation rate, clinicians can appropriately reduce the number of transplanted embryos, which can not only reduce the rate of multiple births to prevent obstetric complications, but also reduce the occurrence of VTS.
Several strengths of this study are worth mentioned. First, the primary advantage of the present study is that it is a matched cohort study, the first to assess dynamic development in children aged 0–3 years. Second, in this study, the growth and development indexes of the offspring were detected dynamically (not at a certain age point), which provided a theoretical basis for the subsequent research. Furthermore, in the use of statistical methods, we used propensity matching to eliminate the confounding factors of the patient basic characteristics in the two groups. Furthermore, to ensure the reliability and authenticity of the retrospective results, the physical examination center provides detailed data, which is measured by professional doctors using a unified standard scale. This data is also the most important reference for the growth and development of children in school and medical treatment.
However, there are several limitations to this study that should be mentioned. First, the sample size of the study was constrained, which was mainly determined by the proportion of patients with the VTS and single birth rate.However, when compared to the data on ART single births at our center, it was clear that it was accurately represented. Admittedly, setting a higher match ratio would result in higher power, but further verification with a large multi-center sample is required. Second, although this study is well designed to take the effects of confounding factors into account as thoroughly as possible, residual confounding factors may remain, such the children lifestyle and sleep quality. Third, due to the time limitation of follow-up, we refer to the follow-up up to the age of three. We also have limited follow-up indicators, which lack intelligence, language, social and other indicators. More reasonable, comprehensive and long-term follow-up results are needed for further verification.
In conclusion, the occurrence of VTS did not detrimental affect the growth and development of offspring(0-3years) from FET. More reasonable, comprehensive and long-term follow-up results are needed for further verification. More than one embryo transfer not only increases the rate of multiple births, but also increases the occurrence of VTS in assisted reproductive technology.