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 could 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 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 per cent of the ART pregnancies were exposed, compared to only 0.6 per cent of naturally conceived pregnancies.
In later trimesters, the trend persisted, with 3.4 per cent of ART pregnancies exposed to Category D medications versus 0.6 per cent 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 per cent of pregnancies.
Study leader UniSA researcher Dr Anna Kemp-Casey these differences in exposure were 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.
“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 said.
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, said 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,” Professor Hart said.
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.
Professor Hart said more research was 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 was published in the Australian and New Zealand Journal of Obstetrics and Gynaecology.