A new Australian study has uncovered a possible reason why some pregnancies achieved with the help of assisted reproductive technology (ART) can lead to birth defects compared to naturally conceived pregnancies. Researchers found that pregnancies conceived through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have the highest exposure to teratogenic drugs that can harm the fetus in the first trimester of pregnancy. These are classified as category D and X drugs by the Australian Therapeutic Goods Administration (TGA).
In IVF, eggs are placed in a dish with sperm so that fertilization can occur naturally. However, ICSI involves the direct injection of a single sperm into each egg. This technique is usually used to treat male subfertility but is also an option for unexplained infertility.
How Medication Affects the Fetus
The risk associated with taking category D medications during pregnancy may be outweighed by the clinical benefit in individual cases, for example in the treatment of mental disorders or epilepsy. Taking category X medications during pregnancy is strongly discouraged due to the high risk of fetal damage. Researchers from the University of South Australia (UniSA), the University of Western Australia (UWA) and the Kids Research Institute Australia analyzed more than 57,000 pregnancies in four conception groups over a period of two years. The groups included women who used artificial insemination (2041), women who received medication to trigger ovulation (590), untreated subfertile women (2063) and natural pregnancies (52,987).
ART pregnancies had the highest exposure to category D drugs in the first trimester. The study found that 4.9% of ART pregnancies were exposed, compared to only 0.6% of naturally conceived pregnancies. In later trimesters, the trend continued, with 3.4% of ART pregnancies exposed to category D drugs, compared to 0.6% of naturally conceived pregnancies. Exposure to category X drugs (the most harmful during pregnancy) was low in all groups and trimesters, with less than 0.5% of pregnancies.
“These differences in exposure are primarily related to medications used as additional treatment after ART to prevent repeated miscarriages or failed implantation, rather than medications used to treat chronic underlying conditions,” said UniSA researcher Dr. Anna Kemp-Casey, who led the study. “For example, ART pregnancies were more likely to be exposed to progestogens such as medroxyprogesterone acetate during the study period, which may have been used to treat threatened or recurrent miscarriage,” says Dr. Kemp. The five most commonly used medications in the D/X category in all pregnancies, regardless of conception status, were paroxetine, lamotrigine, valproic acid, carbamazepine and nicotine dependence treatments.
Individualized Medical Care for Women Undergoing ART Treatment
UWA co-researcher Professor Roger Hart, who is also an IVF doctor and national medical director of City Fertility, says the higher exposure to category D and X drugs in first-trimester pregnancies resulting from artificial insemination could contribute to the higher rate of birth defects in babies conceived through artificial insemination.
Researchers explain that the results show that the vast majority of IVF babies are healthy and do not suggest that IVF pregnancies are unsafe, but they do highlight the importance of personalized medical care for women undergoing ART treatment and close monitoring for women in early pregnancy. Prof. Hart says further research is needed to investigate exposure to category D and X drugs in pregnancy, as well as the underlying maternal conditions and their contribution to the risk of birth defects in ART babies.
A 2021 study by US researchers analyzing 1.2 million births found an 18% higher risk of birth defects for IVF babies and an overall 36% higher risk for ICSI births (42% higher risk for ICSI used to treat male subfertility and 30% higher risk for ICSI used to treat non-male subfertility).