Study Characteristics
The characteristics of each study selected for this review are presented in Table 1. Studies were conducted in Europe (n = 23), Canada (n = 3), The United States (n = 2) and Asia (n = 6). Twenty-nine studies were retrospective cohort studies, [17, 19, 20, 22, 25–27, 29–43, 46–52] while five were prospective cohort studies. [18, 21, 28, 44, 45] Twenty-two of the selected studies were hospital based cohort studies, [18–21, 25–28, 31–34, 36–41, 44, 46, 51, 52] while twelve of the selected studies were population based cohort studies. [17, 22, 29, 30, 35, 42, 43, 45, 47–50] Fourteen studies provided data on exclusively IVF procedures, [17, 19–21, 27–29, 32, 35, 39, 43, 44, 46, 47] and six studies on ICSI procedures. [17, 18, 27, 35, 44, 47] Five studies reported data on fresh embryo transfer and frozen embryo transfer. [22, 25, 35, 40, 50] Additionally, ten studies reported on the type of caesarean section performed, either elective or emergent. [19, 29, 34, 36, 37, 39, 41, 47, 48, 51]
1. IVF/ICSI versus spontaneous conception. Thirty-four studies met the inclusion criteria, [17–22, 25–52] resulting in 164,603 pregnancies following IVF/ICSI compared to 5,702,123 spontaneous conceptions. The pooled OR was 1.93 (95% CI 1.78, 2.09) with high heterogeneity between the studies I2 = 96% (Fig. 2). Eighteen studies were matched cohorts, [17, 19, 22, 25–39] and sixteen unmatched cohorts. [18, 20, 21, 40–52] The quality of studies according to the NOS was moderate to high with NOS scores ranging from 4–9, of which 25 studies had scores of 8 or 9 (Table 1). Publication bias was low as demonstrated by a funnel plot with symmetric distribution (Additional file 2, Fig. 1).
Elective caesarean section. Ten studies met the inclusion criteria and reported data on elective caesarean sections (n = 27,799 pregnancies following IVF/ICSI compared to 2,193,608 spontaneous conceptions). [19, 29, 34, 36, 37, 39, 41, 47, 48, 51] The pooled OR was 2.12 (95% CI 1.63, 2.77) with high heterogeneity between the studies I2 = 96% (Fig. 3). Six studies were matched cohorts, [19, 29, 34, 36, 37, 39] and four unmatched cohorts. [41, 47, 48, 51] The quality of studies was moderate to high with NOS scores ranging from 7–9 (Table 1).
Emergent Caesarean Section. Eight studies also met the inclusion criteria and reported data on emergent caesarean sections (n = 19,862 pregnancies following IVF/ICSI compared to 1,955,866 spontaneous conceptions). [19, 29, 34, 36, 37, 39, 48, 51] The pooled OR was 1.57 (95% CI 1.27, 1.95) with high heterogeneity between the studies I2 = 87% (Fig. 3). Six studies were matched cohorts, [19, 29, 34, 36, 37, 39] and two unmatched cohorts. [48, 51] The quality of studies was high with NOS scores ranging from 8–9 (Table 1).
2. In vitro fertilization (IVF) versus spontaneous conception. Fourteen studies met the inclusion criteria (n = 71,685 IVF pregnancies vs. 3,419,104 spontaneous conceptions). [17, 19–21, 27–29, 32, 35, 39, 43, 44, 46, 47] The pooled OR was 2.07 (95% CI 1.87, 2.30) with high heterogeneity between the studies I2 = 94% (Fig. 4). Eight studies were matched cohorts, [17, 19, 27–29, 32, 35, 39] and six unmatched cohorts. [20, 21, 43, 44, 46, 47] The quality of studies according to the NOS was moderate to high with NOS scores ranging from 6–9 (Table 1).
3. Intracytoplasmic sperm injection (ICSI) versus spontaneous conception. Six studies met the inclusion criteria (n = 15,926 ICSI pregnancies vs. 277,187 spontaneous conceptions). [17, 18, 27, 35, 44, 47] The pooled OR was 1.66 (95% CI 1.29, 2.15) with high heterogeneity between the studies I2 = 97% (Fig. 4). Three studies were matched cohorts, [17, 27, 35] and three unmatched cohorts. [18, 44, 47] The quality of studies according to the NOS was moderate to high with NOS scores ranging from 6–9 (Table 1).
4. Fresh embryo transfer versus spontaneous conception. Five studies met the inclusion criteria (n = 60,767 following fresh embryo transfer compared to 878,654 spontaneous conceptions). [22, 25, 35, 40, 50] The pooled OR was 1.55 (95% CI 1.42, 1.69) with high heterogeneity between the studies I2 = 85% (Fig. 5). Three studies were matched cohorts, [22, 25, 35] and two unmatched cohorts. [40, 50] The quality of studies was moderate to high with NOS scores ranging from 7–9 (Table 1).
5. Frozen embryo transfer versus spontaneous conception. Five studies met the inclusion criteria (n = 9,597 pregnancies following frozen embryo transfer compared to 878,654 spontaneous conceptions). [22, 25, 35, 40, 50] The pooled OR was 1.68 (95% CI 1.41, 2.00) with high heterogeneity between the studies I2 = 86% (Fig. 5). Three studies were matched cohorts, [22, 25, 35] and two unmatched cohorts. [40, 50] The quality of studies was moderate to high with NOS scores ranging from 7–9 (Table 1).