Congenital Malformations Among 911 Newborns Conceived After Infertility Treatment With Letrozole or Clomiphene Citrate
Bibliographic record
Abstract
Clomiphene citrate (CC) reliably produces ovulation, but reported pregnancy rates remain low at 10% to 40%. Gonadotropin treatment yields higher pregnancy rates than CC but are expensive and may lead to ovarian hyperstimulation syndrome and/or multiple gestations. For these reasons, aromatase inhibitors—particularly letrozole—have been proposed as ovulation-inducing agents. They are easy to use, cost relatively little, and have only minor side effects. Studies have suggested higher pregnancy rates than with CC. When used along with gonadotropins, letrozole can lower the required dose of gonadotropin while yielding as many pregnancies as gonadotropin alone. The investigators sought to establish the risk of congenital malformations in 911 newborn infants conceived after CC or letrozole treatment at one of 5 Canadian fertility centers. They underwent ovulation induction or augmentation for timed intercourse or intrauterine insemination with the aid of either CC or letrozole, each administered orally for 5 days from cycle days 3 to 7. Data were complete for 514 infants whose mothers received letrozole and 397 whose mothers were given CC. Approximately half the women given letrozole also took follicle-stimulating hormone (FSH). Similarly, 104 women in the CC group also received FSH. Women in the different treatment groups were similar in age, birth weights of their infants, and the incidence of multiple births. Chromosomal abnormalities or congenital malformations were identified in 2.4% of the letrozole group and 4.8% of those in the CC group. The respective rates of major malformations were 1.2% and 3.0%—not a significant difference. Four infants in the CC group and one in the letrozole group had a ventricular septal defect. The rate of all congenital cardiac anomalies was significantly higher in the CC group (1.8% vs 0.2%). Minor malformations were found in 1.6% of infants in the letrozole group and 1.8% of those exposed to CC. In both groups, a small number of women took metformin or supplemental progesterone, smoked, or had gestational diabetes. None of the women in either group had used recreational drugs or marijuana while pregnant. These findings fail to justify concern that letrozole, when used to induce ovulation, may be teratogenic. Congenital cardiac anomalies were less frequent in infants exposed to letrozole than in newborn infants whose mothers received CC.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".