Comparison of the pregnancy outcomes of carriers with noncarriers in couples with RPL
Eleven studies (n = 6301) reported on the difference in the pregnancy outcomes of carriers versus noncarriers with a history of recurrent pregnancy loss. Eight studies and our own data (PS Zheng 2021) involved both structural and numerical chromosome abnormalities [9, 10, 12-16] and only 3 studies involved single structural chromosome abnormalities[8, 11, 17]. All the studies comprised couples in which one partner had a chromosome abnormality. All the studies evaluated the pregnancy outcome of conceiving naturally in both carriers and noncarriers. Karyotype analysis was the main method used in all the included studies.
When pooling the studies, we found a significant difference in the first pregnancy live birth rate (FPLBR) for couples with RPL between carriers and noncarriers (nine studies; odds ratio (OR): 0.55; 95% CI: 0.46-0.65; I2 =27%; p<0.00001) (Figure 1a). When summing the individual proportions in the 9 studies, we found a mean prevalence of 55.6% (range: 25.0%-75.0%; 95% CI: 0.44–0.67) in non-carriers and 67.8% (range: 35.7%-82.6%; 95% CI 0.57–0.79) in carriers of FPLBR. The detailed prevalence in each study is shown in the Table 2.
When summarizing chromosomally abnormal subtype proportions in the studies using meta-analysis, we found a significantly lower of the FPLBR in translocation carriers (Balanced and Robertsonian, Figure 1b) but no difference was observed in inversion carriers (Figure 1c) compared with noncarriers (six studies; translocation odds ratio (OR): 0.44; 95% CI: 0.31–0.61; I2 =33%; p<0.00001; inversion odds ratio (OR): 0.74; 95% CI: 0.52–1.06; I2 =0%; p=0.1). These results indicate that the decline in the FPLBR of carriers was primarily associated with translocation but not inversion couples. No publication bias was found in the 9 studies as shown in the funnel plot (Figure S2).
Only 4 studies described the accumulated LBR (ALBR) and miscarriage rate (MR). The ALBR was similar between carriers and noncarriers (Figure 2a; four studies; odds ratio (OR): 0.96; 95% CI: 0.90–1.03; I2 =0%; p=0.26), but the miscarriage rate was still significantly higher in the carriers (Figure 2b; four studies; odds ratio (OR): 2.21; 95% CI: 1.69–2.89; I2 =0%; p<0.00001) in the natural conception way. The detailed prevalence in each study is shown in Table 3 and 4. No publication bias was found in the 4 studies, as shown in the funnel plot (Figure S2).