Utilisation de la reproduction médicalement assistée, les grossesses multiples et les malformations congénitales majeures

Infertility affects 11 to 15% of couples in Canada. The modalities of medically assisted reproduction (MAR) include ovarian stimulation (OS), intrauterine insemination (IUI) and assisted reproduction techniques (ART). Multiple pregnancies are among the most common side effects of using ART. However, there is no consensus on the magnitude of the risk of multiple pregnancies associated with the use of MAR modalities. In addition, it is unclear whether the modalities of MAR are associated with a high risk of major congenital malformations (MCM) affecting one or more specific organ system. A three-part research project was developed to answer these questions. In the first part, a case-control study was conducted to quantify the risk of multiple births associated with the use of the three MAR modalities. Compared to spontaneous conception (SC), the use of OS alone, IUI, and ART was associated with a significant increase of more than four, nine, and 31 times the risk of multiple births, respectively. Women who used IUI with OS or ART had an increased risk of multiple births (adjusted odds ratio (OR), 1.98; 95%CI, 1.12-3.49; adjusted OR, 6.81; 95%CI, 3.72-12.49, respectively) compared to the use of OS alone. In a second part, a case-control analysis was conducted in order to quantify the risk of MCM associated with the use of MAR modalities. Compared to SC, the use of ART was associated with an increased risk of urogenital malformations (adjusted OR, 3.11; 95%CI, 1.33–7.27) and the use of IUI was associated with increased risk of musculoskeletal malformations (adjusted OR, 2.02; 95% CI, 1.10–3.71). The use of ART was associated with an increased risk of urogenital malformations (adjusted OR, 7.18; 95% CI 1.59-32.53) compared to the use of OS alone. In a third part, results of the systematic review and meta-analysis demonstrated that the use of OS alone and IUI ± OS were associated with a significant increase of nine times the risk of multiple pregnancies compared to a SC. Similar increases have been found following the use of clomiphene citrate alone. Compared to SC, the use of OS alone was associated with a significant 48% increased risk of musculoskeletal malformations, 73% increased risk of malformations of the nervous system, 76% increased risk of digestive system malformations, 68% increased risk of malformations of the eye, ear, face and neck, and more than twice the risk of congenital respiratory system malformations. The use of IUI was associated with a significant 52% increased risk of urogenital malformations and 54% increased risk of musculoskeletal malformations compared to SC. Although the risk of multiple pregnancies associated with ART can be controlled using a single embryo transfer in IVF cycles, monitoring the risk of multiple pregnancies associated with the use of treatments that do not involve embryo transfer is essential. The potential teratogenic effect associated with the use of MAR modalities should be considered when making therapeutic decisions. The establishment of a registry for the surveillance of MAR adverse perinatal outcomes becomes necessary.

Keyphrases: Grossesse multiple, Ovarian stimulation, intrauterine insemination, Clomiphene citrate, Medically assisted reproduction, Multiple pregnancy, Major congenital malformations