Meta-analysis of the effects of smooth endoplasmic reticulum aggregation on birth outcome

Abstract

Background: Smooth endoplasmic reticulum aggregation (SERa, SER+) has been reported to increase the risk of birth malformations and other abnormal outcomes, miscarriage, and perinatal complications. Other studies, however, suggest that SER+ embryos may develop into healthy infants. One report indicates that 25% of in vitro fertilization (IVF) centers discard SER+ oocytes. Thus, we investigated the effect of SER+ on birth outcomes in IVF and intracytoplasmic sperm injection.

Methods: We performed a literature search using PubMed, ScienceDirect, Cochrane, Embase, Ovid, and Scopus. We found a total of 1500 relevant studies between 1978 and 2020 and conducted a meta-analysis to study the effects of SER+ on live births, birth weight, and the number of metaphase II (MII) oocytes retrieved per cycle.

Results: Eleven eligible studies were included. If the SER+ zygote was evaluated again at the embryo transfer (ET) stage, SER+ did not affect birth or infant body weight. Stimulated ovaries producing too many oocytes per cycle were positively correlated with SER+ (OR = 1.28, 95% CI = 0.41-2.15; p = 0.004). SER+ was positively correlated with oocyte maturation rate, and observed heterogeneity in a previous meta-analysis was likely due to maternal age. Our data also showed that SER+ cycles produced more oocytes but achieved the same number of births from ET.

Conclusions: The use of SER+ MII oocytes is rare, with the collection of many oocytes in 1 cycle potentially inducing SER+. SER+ may be more common than we originally thought, as some SER+ is found in all oocytes. Although SER+ positively affected oocyte maturation rate, it did not affect births. We hypothesized that this is because the best embryos are chosen at every step of the process, and the oocytes with the poorest characteristics are removed. We therefore suggest a standard method for measuring SER+. Although embryos produced from SER+ cycles can be used, they should only be transferred when no other suitable embryos are available over several cycles.

Keywords: Aggregation; Births; Oocyte; Smooth endoplasmic reticulum (SER).

Fig. 1

Summary of study selection. A total of 1500 studies were searched, 997 duplicate articles were removed, and 117 reports that were not related were excluded according to the title and abstract. After reading 386 studies, two additional articles were uncovered from the references. Finally, 11 studies were selected

Fig. 2

Forest plot of SER and births. a. Effect of SER+ cycles on births. Analysis of SER+ cycle and SER− cycle groups. There was no effect on birth. b. SER MII oocyte effect on births. Analysis of SER+ MII oocytes and SER− MII oocyte groups. There was no effect on birth. Total means of ET numbers, with the calculation based upon ET embryo number. CI = 95% confidence interval

Fig. 3

Forest plot of SER effect on birth weight. a. SER cycle effect on birth weight. Analysis of SER+ cycle and SER− cycle groups. There was no effect on birth weight. b. SER MII oocyte effect on birth weight. Analysis of SER+ MII oocyte and SER− MII oocyte groups. There was no effect on birth weight. Total indicates the birth number. CI = 95% confidence interval

Fig. 4

Forest plot of effect of MII oocytes per cycle on SER. a. Analysis of SER+ cycle and SER− cycle groups. SER+ cycles produced more MII oocytes. Stimulated ovaries producing too many oocytes per cycle were positively correlated with SER+. b. Analysis of SER+ MII oocyte-maturation rate. SER+ was positively correlated with oocyte maturation rate. CI = 95% confidence interval

Fig. 5

Forest plot of MII-oocyte use. Total indicates the number of MII oocytes. Analysis of SER+ cycle and SER− cycle groups. No statistical differences were observed between groups, with the calculation based upon MII-oocyte number. CI = 95% confidence interval