Fertility Treatments Not Linked to Psychiatric Disorders in Offspring

Some reassuring findings for people pursuing assisted reproduction: babies born through the fertility procedures do not appear to be at increased risk of developing major psychiatric illnesses as they move through adolescence and into adulthood.

The results, reported Wednesday in JAMA Psychiatry, come from an analysis of more than 31,000 people conceived via assisted reproduction techniques (ART) in Sweden between 1994 and 2006. The researchers, from Sweden and the United States, found that in this group, rates of depression and suicidal behaviors were not elevated compared with the general population.

“We welcome null findings in our study,” said Chen Wang, MPH, a doctoral student at the Karolinska Institutet (KI) in Stockholm, and the lead author on the study. “Overall we found no greater concern for poorer psychiatric health in adolescents conceived with ART compared with the general population, except for an elevated risk of OCD [obsessive-compulsive disorder] that may be explained by differences in parental characteristics.”

“Couples and individuals undergoing or considering ART can indeed be reassured in the sense that our study found no indication that the treatment per se could make children vulnerable to poor mental health later in life,” added Anna Sara Öberg, MD, PhD, the senior author of the paper, who holds appointments in epidemiology at the KI and the Harvard T.H. Chan School of Public Health, in Boston.

ART has been linked to several potentially unwanted outcomes, including birth defects, preterm delivery, low birth weight, imprinting disorder, and possibly neurodevelopmental disorders. Previous research from Wang’s team showed that children conceived with ART do not appear to be more likely to have attention-deficit/hyperactivity disorder or poor school performance than children conceived spontaneously. The new study expands on that earlier work, which was published this year in the journal Pediatrics.

Large Database Analyzed

From a Swedish database of more than 1.2 million people born between 1994 and 2006, Wang’s group identified 31,565 individuals born via ART ― defined as in vitro fertilization with or without intracytoplasmic sperm injection and transfer of fresh or frozen-thawed embryos ― during that period. At the time of final follow-up, in December 2018, participants in the study were between the ages of 12 and 25 years.

To assess the risk of mental illness, the researchers looked for diagnoses in medical records from hospitals and outpatient clinics. They also included death certificates, to determine if suicide was the cause, and prescriptions of antidepressants to see if patients were being treated for depression.

Adolescents conceived via ART were not at elevated risk of developing depression or suicidal behaviors compared to other teens, the researchers found. Nor was the type of ART procedure associated with worse mental health outcomes. In fact, the data pointed to a small advantage of fresh, but not frozen, embryo transfer and the risk for mood disorders when compared with children born to parents with infertility who did not seek ART procedures (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.83 – 0.97).

“Whether the findings could be due to a beneficial causal effect or perhaps more plausibly unmeasured confounding, we note that they raise no concerns for the procedures’ potential influence on psychiatric health,” the authors write.

In an unadjusted analysis, the rate of OCD was higher among study participants conceived through ART (aHR, 1.35; 95% CI, 1.20 – 1.51). However, after adjusting for parental factors linked to the condition, including demographics, maternal health, and psychiatric history, the effect did not persist. The researchers did observe a small increase in the risk of anxiety, but they attributed that almost entirely to the link to OCD.

The researchers note that their study was limited by the fact that anxiety and depression often arise after adolescence, so the group might not be old enough to reflect an increased risk of developing these conditions, and that their analysis may have been unable to fully control for confounding variables. They also point out that single-embryo transfer is the norm in Sweden, which in 2003 made the practice routine ― which might affect the generalizability of the results to other countries.

Dale W. Stovall, MD, FACOG, a professor of obstetrics and gynecology at the Texas Christian University School of Medicine in Dallas, agreed that the new data should be “reassuring to potential parents of children conceived from ART. This is an important paper because it assesses an important outcome, mental health, in children born after conception from an ART procedure.”

Stovall, who is spokesperson for the American College of Obstetricians and Gynecologists and was not involved in the study, added, “We need more long-term studies of children born from ART procedures to assess both adolescent and adult health issues in these individuals.”

Öberg said her group is currently looking at other long-term outcomes among children born via ART, including asthma and cancer; however, the results of those inquiries are unpublished.

The study was funded by Forte and the US National Institutes of Health. The researchers reported no relevant financial relationships.

JAMA Psych. Published online December 15, 2021. Full text

Adam Marcus is editorial director for primary care at Medscape.

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