Perinatal Outcomes in Assisted Reproduction: Maternal vs Treatment Effects

Peter Kovacs, MD, PhD


April 26, 2018

The Outcomes of Assisted Reproduction

Perinatal outcomes are poorer in pregnancies conceived through assisted reproductive technology (ART) when compared with spontaneously conceived pregnancies.[1] For a long time, the increased risk was attributed to the higher prevalence of multiple pregnancies. However, available evidence suggests that even singleton pregnancies conceived through ART are affected by a higher rate of adverse perinatal outcomes: preterm delivery, low birth weight, and maternal complications.[2]

To attempt to separate maternal from treatment effects, a recent retrospective cohort study[3] compared perinatal outcomes from gestational surrogates with their own spontaneous pregnancies. The study included 124 gestational surrogates, who were identified from a 15-year period. A total of 494 pregnancies were analyzed, 312 spontaneous/natural and 182 gestational surrogate pregnancies. The outcomes of gestational surrogate pregnancies significantly differed from those of spontaneous pregnancies. Miscarriages and extrauterine pregnancies occurred with similar frequency, but there were more twin gestational surrogate pregnancies (32% vs 1%).

Of the 494 pregnancies, 352 were singletons. Gestational age at delivery was lower (38.8 ± 2.1 weeks vs 39.7 ± 1.4 weeks), mean birthweight was on average 105 g lower, and the rate of preterm delivery was higher (10.7% vs 3.1%) in gestational surrogate pregnancies compared with spontaneous pregnancies. Maternal complications (gestational diabetes, hypertension, placenta previa, and cesarean section) were more common in gestational surrogate pregnancies.


Differences in neonatal and maternal outcomes following ART pregnancies may result from differences in the gametes, variations in laboratory procedures, or from differences between the fertile and infertile populations (age, semen parameters, comorbid conditions, uterine factors, immunologic parameters, etc.). To determine what is responsible for suboptimal outcomes, Woo and colleagues[3] sought to control for certain aspects of ART pregnancies.

One would expect uterine environmental factors to be similar in gestational surrogate and spontaneous pregnancies, but this study has shown that the outcome is different when the same mother conceives spontaneously or when she acts as a gestational surrogate. There are some potential explanations for these findings, however. In a gestational surrogate cycle, the uterus still must be prepared for implantation, and although synthetic estradiol and progesterone mimic the natural cycle, the two are not the same. Age is another factor known to influence perinatal outcomes, and women are typically older in gestational surrogate pregnancies compared with their spontaneous pregnancies. With age, the risk for undiagnosed medical problems is also likely to be higher. And male factors cannot be controlled for in gestational surrogate cycles.

We also have to consider that laboratory manipulations induced epigenetic changes that affected the perinatal outcome. Stimulation used during ART may have an adverse impact on uterine receptivity, because frozen thawed embryos do better than those that implant in a fresh cycle. The perinatal outcome of pregnancy in a freeze-thaw cycle is worse than in a spontaneously conceived cycle.[4]

In conclusion, although subfertility itself is a risk factor for adverse perinatal outcomes, the laboratory handling of gametes/embryos also contributes to the increased risk. Through judicious use of stimulation, laboratory manipulations, and embryo culture, and by reducing the number of embryos transferred, we can improve the outcomes of ART pregnancies.


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