Ovarian Stimulators, Intrauterine Insemination, and Assisted Reproductive Technologies Use and the Risk of Major Congenital Malformations-The AtRISK Study.
OBJECTIVE
To quantify the risk of major congenital malformations (MCMs) associated with the use of ovarian stimulators alone, intrauterine insemination (IUI), and assisted reproductive technologies (ARTs).


METHODS
We conducted a case-control analysis using a birth cohort, built with the linkage of data obtained by a self-administered questionnaire, medical, pharmaceutic, and birth databases. Cases were pregnancies with at least one live birth with an MCM. Controls were pregnancies that did not result in major or minor congenital malformations. Multiple logistic regression models were used to calculate the odds ratios (ORs) and confidence intervals (CIs).


RESULTS
Among the 5021 pregnancies identified, 825 were cases of MCM and 4196 were controls. Compared with spontaneous conception, the use of ART increased the risk of major urogenital malformations (adjusted OR, 3.11; 95% CI, 1.33-7.27). The use of IUI was associated with an increased risk of major musculoskeletal malformations (adjusted OR, 2.02; 95% CI, 1.10-3.71). Among the 471 women who used fertility treatments for conception, the use of ART was associated with an increased risk of any MCM (adjusted OR, 1.66; 95% CI, 1.00-2.79) and urogenital malformations (adjusted OR, 7.18; 95% CI, 1.59-32.53) when compared with ovarian stimulators used alone.


CONCLUSIONS
The use of ART and IUI was associated with an increased risk of major musculoskeletal and urogenital malformations. ART was associated with a higher risk of MCM compared to ovarian stimulators used alone. Even the adjustment, a contribution of the underlying subfertility problems cannot completely ruled out given the differences in the severity of subfertility.
Research Center, CHU Ste-Justine, Montreal, Quebec, Canada.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Sonia
S
Chaabane
Research Center, CHU Ste-Justine, Montreal, Quebec, Canada.
Odile
O
Sheehy
Department of Obstetrics and Gynecology, Royal Victoria Hospital, University Reproductive Center, Montreal, Quebec, Canada.|Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Patricia
P
Monnier
OVO Fertility Clinic, Montreal, Quebec, Canada.
François
F
Bissonnette
Faculty of Medicine, McGill University, Montreal, Quebec, Canada.|Departments of Pediatrics, Human Genetics and Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada.|Research Institute at the Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Jacquetta M
JM
Trasler
Department of Obstetrics and Gynecology, University of Sherbrooke, Sherbrooke, Quebec, Canada.|Faculty of Medicine, University of Montreal, Quebec, Canada.
William
W
Fraser
Research Center, CHU Ste-Justine, Montreal, Quebec, Canada.|Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Anick
A
Bérard
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D000013:Congenital Abnormalities / Q000209:etiology*; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D007314:Insemination; D008019:Life Style; D016015:Logistic Models; D010062:Ovulation Induction; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D012307:Risk Factors; D012959:Socioeconomic Factors; D016896:Treatment Outcome; D055815:Young Adult
assisted reproduction; congenital malformation; in vitro fertilization; intrauterine insemination; observational study and epidemiology; ovarian stimulation; risk