A new Australian study has revealed a potential reason why some pregnancies achieved through assisted reproductive technology (ART) may result in birth defects in comparison to naturally conceived pregnancies.
Researchers found that in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies had the highest exposure to teratogenic medicines that potentially can harm the fetus during the first trimester of pregnancy.
These are listed as Category D and X medicines by Australia's Therapeutic Goods Administration (TGA).
The risk associated with the use of Category D medicines in pregnancy may be outweighed by the clinical benefit in individual cases such as management of mental health disorders or epilepsy. Category X medicines on the other hand are strongly discouraged during pregnancy due to the high risk of fetal harm.
Researchers from the University of South Australia (UniSA), The University of Western Australia (UWA) and The Kids Research Institute Australia analysed more than 57,000 pregnancies in four conception groups over a two-year period. The groups comprised women using ART (2041); those taking medication to induce ovulation (590); untreated sub-fertile women (2063); and naturally fertile pregnancies (52,987).
ART pregnancies had the highest exposure to Category D medications taken in the first trimester.
The study found that 4.9% of the ART pregnancies were exposed, compared to only 0.6% of naturally conceived pregnancies.
In later trimesters, the trend persisted, with 3.4% of ART pregnancies exposed to Category D medications versus 0.6% of naturally conceived pregnancies.
Exposure to Category X medications (causing the most harm during pregnancy) was low across all groups and trimesters, at less than 0.5% of pregnancies.
"These differences in exposure are primarily linked to medications used as additional treatment following ART to prevent repeat miscarriages or failed implantation, rather than medications to treat underlying chronic conditions," says UniSA researcher Dr Anna Kemp-Casey, who led the study.
"For example, ART pregnancies, during the study period were more often exposed to progestogens like medroxyprogesterone acetate, which may have been used to treat threatened or recurrent miscarriages," Dr Kemp says.
The five most frequently used Category D/X medications across all pregnancies regardless of conception status were paroxetine, lamotrigine, valproic acid, carbamazepine, and nicotine dependence treatments.
UWA co-researcher Professor Roger Hart, also a practising IVF clinician and the national medical director of City Fertility, says the higher exposure to Category D and X medicines in ART pregnancies during the first trimester may contribute to the higher rate of birth defects observed in ART babies.
"Although ART pregnancies are carefully planned, medications taken during fertility treatments may inadvertently increase exposure to birth defect risks, particularly during critical periods of fetal development," Prof Hart says.
Researchers say the findings demonstrate that the vast majority of IVF babies are healthy, and do not suggest that ART pregnancies are unsafe, but they underscore the importance of personalised medical care for women undergoing ART treatment and close monitoring for women in early pregnancy.
Prof Hart says more research is needed to examine Category D and X medicines exposure in pregnancy as well as underlying maternal medical conditions and their contribution to birth defect risk in ART babies.
The study has been published in the Australian and New Zealand Journal of Obstetrics and Gynaecology.
Notes for editors
"Are assisted reproductive technology pregnancies more likely to be exposed to teratogenic medication? A whole-population study" is authored by researchers from the University of South Australia, Telethon Kids Institute, The University of Western Australia and Curtin University. DOI: 10.1111/ajo.13911
According to the latest ANZARD report, in 2022 more than 20,000 children in Australia (17,963) and New Zealand (2095) were born using ART. Since IVF was introduced in 1978, 10 million children have been born using ART.
A 2021 study by US researchers analysing 1.2 million births found an 18% higher risk of birth defects among IVF babies and a 36% overall greater risk for ICSI births (42% increased risk where ICSI was used to treat male factor subfertility and 30% increased risk with ICSI use for non-male factor subfertility).
In IVF pregnancies, sperm is added to a dish containing eggs, and fertilisation occurs naturally, compared to ICSI where a single sperm is injected directly into each egg. The latter procedure is normally used to treat male subfertility but is also an option for unexplained infertility.
