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A recent study conducted in Australia has shed light on why pregnancies achieved through assisted reproductive technology (ART) may be more prone to birth defects when compared with naturally conceived pregnancies.
Researchers discovered that pregnancies resulting from in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) exhibited a significantly higher exposure to teratogenic medications during the critical first trimester, which could negatively affect fetal development.
These medications are classified under Category D and X by the Therapeutic Goods Administration (TGA) in Australia.
While the potential risks associated with Category D medications may be justifiable in specific clinical scenarios, such as treating mental health disorders or epilepsy, Category X medications are strictly prohibited during pregnancy due to their high potential for causing fetal harm.
The research team, comprising experts from the University of South Australia (UniSA), The University of Western Australia (UWA), and The Kids Research Institute Australia, reviewed over 57,000 pregnancies across four groups over a two-year timeframe. The groups included women undergoing ART (2041), those using medication to induce ovulation (590), untreated sub-fertile women (2063), and naturally fertile pregnancies (52,987).
The analysis indicated that pregnancies achieved via ART had the greatest exposure to Category D medications in the first trimester, with 4.9% of ART pregnancies affected, compared to a mere 0.6% among naturally conceived pregnancies.
As the study progressed into the later trimesters, the pattern continued, with 3.4% of ART pregnancies exposed to these potentially harmful medications, while the rate remained at 0.6% for naturally conceived pregnancies.
Exposure to Category X medications, which carry the highest risk during pregnancy, remained low across all groups and trimesters, with less than 0.5% of pregnancies being affected.
According to Dr. Anna Kemp-Casey of UniSA, who led the study, “The disparities in exposure levels are largely tied to medications used to manage treatment following ART, aimed at preventing recurrent miscarriages or implantation failures rather than addressing chronic health issues.”
Dr. Kemp highlighted that ART pregnancies typically had more exposure to progestogens such as medroxyprogesterone acetate, which could be used to manage threatened or repeated miscarriages.
The most commonly used Category D/X medications, regardless of fertility status, included paroxetine, lamotrigine, valproic acid, carbamazepine, and treatments for nicotine dependence.
Co-researcher Professor Roger Hart from UWA, who also practices as an IVF clinician, noted that the heightened exposure to these medications during the first trimester of ART pregnancies might play a role in the increased rates of birth defects seen in babies conceived through these methods.
Professor Hart commented, “Even though ART pregnancies are planned meticulously, the medications administered during fertility treatments could unintentionally escalate the risk for birth defects, particularly during crucial stages of fetal growth.”
The researchers stress that while most IVF infants are healthy and ART pregnancies are generally safe, the findings underscore the necessity for individualized medical care for women undergoing ART and the importance of vigilant monitoring during early pregnancy.
More investigation is warranted to understand the effects of exposure to Category D and X medications during pregnancy, as well as the impact of pre-existing maternal health conditions on birth defect risks in ART babies, according to Professor Hart.
This study has been published in the Australian and New Zealand Journal of Obstetrics and Gynaecology.
Furthermore, a study from 2021 conducted in the United States involving 1.2 million births found that infants conceived through IVF faced an 18% increased risk of birth defects, with the risk escalating to 36% for ICSI births, particularly when ICSI was applied to address male factor subfertility, which soared to a 42% increased risk and 30% for non-male factor subfertility.
In the IVF process, sperm is introduced to a dish with eggs allowing for natural fertilization, whereas in ICSI, a lone sperm is directly injected into each egg—this technique is frequently employed to tackle male infertility but is also utilized for unexplained fertility cases.
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