A recent study conducted in Australia has identified a potential factor explaining why pregnancies achieved through assisted reproductive technology (ART) may have a higher rate of birth defects compared to those conceived naturally.
Researchers discovered that pregnancies resulting from in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) were most exposed to teratogenic medications that could potentially harm the fetus during the early stages of pregnancy.
These medications fall under Category D and X as defined by Australia’s Therapeutic Goods Administration (TGA).
While the risks associated with Category D medications may be managed in specific cases, like those involving mental health conditions or epilepsy, Category X medications are strongly advised against during pregnancy due to their significant potential for fetal harm.
In a comprehensive study, researchers from the University of South Australia (UniSA), The University of Western Australia (UWA), and The Kids Research Institute Australia examined over 57,000 pregnancies across four conception groups over two years. These groups included women undergoing ART (2041); those receiving medication to induce ovulation (590); untreated sub-fertile women (2063); and women with naturally occurring pregnancies (52,987).
Among the pregnancies arising from ART, the exposure to Category D medications in the first trimester was the highest.
The findings revealed that 4.9% of ART pregnancies were exposed to these medications, while only 0.6% of naturally conceived pregnancies showed similar exposure.
In the later stages of pregnancy, the trend continued, with 3.4% of ART pregnancies having exposure to Category D medications compared to 0.6% of those conceived naturally.
Instances of exposure to Category X medications, known for causing substantial harm during pregnancy, were minimal in all groups and trimesters, accounting for less than 0.5% of pregnancies.
According to UniSA researcher Dr. Anna Kemp-Casey, who directed the study, “These variations in exposure mainly relate to medications administered as supplementary treatment after ART to avoid repeated miscarriages or failed implants, rather than medications for chronic conditions.”
“For instance, during the study, ART pregnancies were more likely to receive progestogens like medroxyprogesterone acetate, often used to address threatened or recurrent miscarriages,” Dr. Kemp explains.
The five most commonly used Category D/X medications among all pregnancies, regardless of fertility status, included paroxetine, lamotrigine, valproic acid, carbamazepine, and treatments for nicotine dependence.
UWA co-researcher Professor Roger Hart, who is also an IVF clinician and national medical director at City Fertility, states that the increased exposure to Category D and X medications during the first trimester of ART pregnancies may play a role in the elevated birth defect rates seen in ART infants.
“Even though ART pregnancies are meticulously planned, the medications utilized during fertility treatments might unintentionally heighten the risks of birth defects, especially during critical developmental stages of the fetus,” Professor Hart adds.
The researchers emphasize that the majority of IVF babies are healthy and that this study does not imply ART pregnancies are unsafe; however, it does highlight the need for personalized medical care for women undergoing ART and diligent monitoring during early pregnancy.
Professor Hart calls for further research to explore the exposure to Category D and X medications during pregnancy, as well as how underlying maternal health conditions could influence the risk of birth defects in babies conceived via ART.
The study has been published in the Australian and New Zealand Journal of Obstetrics and Gynaecology.
A 2021 analysis by US researchers of 1.2 million births indicated an 18% higher likelihood of birth defects among IVF infants, with an overall 36% increased risk for ICSI babies (42% increase when ICSI was used for male factor subfertility and 30% for non-male factor subfertility).
In IVF, sperm is combined with egg cells in a dish to facilitate natural fertilization, while in ICSI, a single sperm is injected directly into an egg. ICSI is primarily used to treat male subfertility but is also available for cases of unexplained infertility.
