From the initial pool 39,477 cycles, 39,154 cycles have complete ABO and Rh blood type information with the female age > 25 years and < 35 years. We excluded potential confounders may cause spontaneous abortion or affect ART outcomes: chromosome abnormality(n = 976), congenital disease (n = 258), cervical incompetence (n = 345), uterine malformation (n = 1031), hypomenorrhea (n = 25), endometriosis or ovarian surgery history (n = 581), POI / oocyte maturation disorder (36), uterine fibroids (n = 216), endometrial lesions (n = 2), trophoblastic disease (n = 15), cervical cancer (n = 2), Male: azoospermia (n = 1981), necrozoospermia (n = 16), severe oligoasthenospermia (n = 2953). A total of 30,717 cycles met the inclusion criteria.
The distribution of these patients based on blood type was as follows: 8846 (28.80%) females with blood type A; 3257 (10.60%) females with blood type AB; 9712 (31.62%) females with blood type B; and 8902(28.98%) females with blood type O. For Rh blood type, 98 (0.032%) females with blood type Rh-; 30,619 (99.68%) females with blood type Rh+; This distribution of blood types is similar to the males’: 8624 (28.08%) males with blood type A; 3257 (10.76%) males with blood type AB; 9771 (31.81%) males with blood type B; and 9016(29.35%) males with blood type O. For Rh blood type, 120 (0.039%) females with blood type Rh-; 330597 (99.61%) females with blood type Rh+. As shown in Fig. 1 and Supplemental Table 1, there was no difference in the distribution of blood type between infertile females and males.
Demographic and clinical characteristics of study population are shown in Table 1 and Supplemental Table 1. The women's average age was 30.0 ± 2.83 years. There was no difference in the age, BMI, duration of subfertility, primary subfertility by blood type in both female and male groups.
Given the small sample size of patients having Rh negative in population, especially when it was split into the four ABO blood groups, we do not include rhesus factor for downstream association test.
Table 1
Overall demographics and patients characteristics of female group stratified by blood type (n = 30,717)
Characteristics | All | A(n = 8846) | B(n = 9712) | AB(n = 3257) | O(n = 8902) | P value |
Age | 30.06 ± 2.83 | 30.09 ± 2.84 | 30.06 ± 2.85 | 29.98 ± 2.82 | 30.05 ± 2.81 | 0.236 |
BMI | 22.83 ± 3.22 | 22.82 ± 3.20 | 22.83 ± 3.19 | 22.91 ± 3.36 | 22.82 ± 3.20 | 0.554 |
Duration of subfertility (m) | 48.22 ± 33.58 | 48.47 ± 33.31 | 48.36 ± 34.09 | 47.68 ± 32.06 | 48.03 ± 33.83 | 0.613 |
Primary subfertility | 44.93% (13801/30717) | 45.16% (3995/8846) | 45.53% (4422/9712) | 45.26% (1474 /3257) | 43.92% (3910/8902) | 0.145 |
Note: Data presented as mean ± SD or n (%). |
History of Spontaneous Miscarriage Association Analysis
We investigated the potential interaction between ABO blood group of husband/wife mating and the history of spontaneous miscarriage by three models as described before. There was a statistically significantly higher percentage of combination of female blood type AB and male blood type O in couples with at least one spontaneous miscarriage history (odds ratio [OR] 1.03; 95% confidence interval [CI], 1-1.05; P = 0.0234) than for the rest. However, no statistically significant difference was observed in Dosage and Continuous models (OR 1.01; 95% CI, 1-1.01; P 0.243 and OR 1.03; 95% CI, 1-1.06; P 0.08 respectively), as shown in Table 2.
Table 2
Multivariate logistic regression analyzes between history of spontaneous miscarriage and parental blood types combinations.
Female Blood Type | Male Blood Type | Dosage model | Dominant model | Continuous model |
OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value |
AB | B | 1.00 (0.99–1.01) | 0.874 | 0.99(0.97–1.01) | 0.433 | 0.99(0.96–1.02) | 0.384 |
AB | A | 1.00 (0.99–1.01) | 0.753 | 0.99(0.97–1.01) | 0.348 | 1.00(0.97–1.03) | 0.843 |
AB | O | 1.01(1.00-1.01) | 0.243 | 1.03(1.00-1.05) | 0.023 | 1.03(1.00-1.06) | 0.080 |
AB | AB | 0.99(0.98–1.01) | 0.304 | 0.99(0.96–1.02) | 0.426 | 0.98(0.94–1.02) | 0.323 |
B | B | 1.00 (0.99-1.00) | 0.521 | 1.00 (0.99–1.01) | 0.871 | 0.99(0.97–1.01) | 0.438 |
B | A | 1.00(0.99–1.01) | 0.966 | 1.01(0.99–1.02) | 0.262 | 1.01(0.99–1.03) | 0.213 |
B | O | 1.00 (1.00-1.01) | 0.443 | 0.99(0.98–1.01) | 0.214 | 0.99(0.98–1.01) | 0.566 |
B | AB | 1.00 (0.99–1.01) | 0.963 | 1.00 (0.98–1.03) | 0.646 | 1.00 (0.98–1.03) | 0.802 |
A | B | 1.00 (1.00-1.01) | 0.465 | 1.01(0.99–1.02) | 0.433 | 1.02(1.00-1.04) | 0.113 |
A | A | 1.00 (0.99-1.00) | 0.467 | 0.99(0.98–1.01) | 0.355 | 0.99(0.97–1.01) | 0.166 |
A | O | 1.00 (0.99-1.00) | 0.525 | 1.00 (0.98–1.01) | 0.561 | 0.99(0.97–1.01) | 0.388 |
A | AB | 1.00 (1.00-1.01) | 0.373 | 1.01(0.99–1.03) | 0.308 | 1.01(0.98–1.04) | 0.370 |
O | B | 1.00 (0.99–1.01) | 0.993 | 1.00 (0.99–1.01) | 0.910 | 1.00 (0.98–1.02) | 0.816 |
O | A | 1.00 (1.00-1.01) | 0.321 | 1.00 (0.99–1.02) | 0.676 | 1.00 (0.98–1.02) | 0.806 |
O | O | 1.00 (0.99-1.00) | 0.356 | 1.00 (0.99–1.02) | 0.731 | 1.00 (0.98–1.02) | 0.767 |
O | AB | 1.00 (0.99–1.01) | 0.885 | 0.99(0.97–1.01) | 0.348 | 0.99(0.96–1.02) | 0.635 |
Embryo Quality parameters Association Analysis
We also assessed the association between husband/wife blood types combinations and embryo quality parameters, including fertilization rate, cleavage rate and high-quality embryo rate, by adjusting the number of transfer embryos. The combination of female blood type B and male blood type A has a negative association with fertilization rate (OR 0.98; 95% CI, 0.97-1; P 0.01), while the combination of female blood type O and male blood type A has a slightly negative association with cleavage rate (OR 1; 95% CI, 0.99-1; P 0.027). As evident in Table 3, no statistically significant difference was observed between ABO blood group of husband/wife mating blood types and High-Quality Embryo Rate.
Table 3
Female Blood Type | Male Blood Type | Dosage model | Dominant model | Continuous model |
OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value |
AB | B | 1.00 (0.99–1.01) | 0.874 | 0.99(0.97–1.01) | 0.433 | 0.99(0.96–1.02) | 0.384 |
AB | A | 1.00 (0.99–1.01) | 0.753 | 0.99(0.97–1.01) | 0.348 | 1.00(0.97–1.03) | 0.843 |
AB | O | 1.01(1.00-1.01) | 0.243 | 1.03(1.00-1.05) | 0.023 | 1.03(1.00-1.06) | 0.080 |
AB | AB | 0.99(0.98–1.01) | 0.304 | 0.99(0.96–1.02) | 0.426 | 0.98(0.94–1.02) | 0.323 |
B | B | 1.00 (0.99-1.00) | 0.521 | 1.00 (0.99–1.01) | 0.871 | 0.99(0.97–1.01) | 0.438 |
B | A | 1.00(0.99–1.01) | 0.966 | 1.01(0.99–1.02) | 0.262 | 1.01(0.99–1.03) | 0.213 |
B | O | 1.00 (1.00-1.01) | 0.443 | 0.99(0.98–1.01) | 0.214 | 0.99(0.98–1.01) | 0.566 |
B | AB | 1.00 (0.99–1.01) | 0.963 | 1.00 (0.98–1.03) | 0.646 | 1.00 (0.98–1.03) | 0.802 |
A | B | 1.00 (1.00-1.01) | 0.465 | 1.01(0.99–1.02) | 0.433 | 1.02(1.00-1.04) | 0.113 |
A | A | 1.00 (0.99-1.00) | 0.467 | 0.99(0.98–1.01) | 0.355 | 0.99(0.97–1.01) | 0.166 |
A | O | 1.00 (0.99-1.00) | 0.525 | 1.00 (0.98–1.01) | 0.561 | 0.99(0.97–1.01) | 0.388 |
A | AB | 1.00 (1.00-1.01) | 0.373 | 1.01(0.99–1.03) | 0.308 | 1.01(0.98–1.04) | 0.370 |
O | B | 1.00 (0.99–1.01) | 0.993 | 1.00 (0.99–1.01) | 0.910 | 1.00 (0.98–1.02) | 0.816 |
O | A | 1.00 (1.00-1.01) | 0.321 | 1.00 (0.99–1.02) | 0.676 | 1.00 (0.98–1.02) | 0.806 |
O | O | 1.00 (0.99-1.00) | 0.356 | 1.00 (0.99–1.02) | 0.731 | 1.00 (0.98–1.02) | 0.767 |
O | AB | 1.00 (0.99–1.01) | 0.885 | 0.99(0.97–1.01) | 0.348 | 0.99(0.96–1.02) | 0.635 |
Multivariate logistic regression analyzes between embryo quality parameters and couple blood types combinations by adjusting for controlled ovarian hyperstimulation protocols. |
Table 3
Multivariate logistic regression analyzes between embryo quality parameters and parental blood types combinations by adjusting for controlled ovarian hyperstimulation protocols.
Female Blood Type | Male Blood Type | Fertilization Rate | Cleavage Rate | High Quality Embryo Rate |
OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value |
B | A | 0.98(0.97-1.00) | 0.010 | 1.00(1.00-1.01) | 0.251 | 0.99(0.97–1.01) | 0.354 |
B | O | 1.01(0.99–1.02) | 0.245 | 1.00 (1.00–1.00) | 0.942 | 1.02(1.00-1.04) | 0.110 |
B | B | 1.01(0.99–1.02) | 0.315 | 1.00 (1.00–1.00) | 0.783 | 0.99(0.97–1.01) | 0.442 |
B | AB | 1.01(0.98–1.03) | 0.563 | 1.00 (0.99-1.00) | 0.254 | 1.00 (0.97–1.03) | 0.843 |
AB | A | 1.00 (0.98–1.02) | 0.813 | 1.00 (1.00-1.01) | 0.343 | 0.99(0.96–1.02) | 0.564 |
AB | O | 1.00 (0.98–1.03) | 0.854 | 1.00 (0.99-1.00) | 0.386 | 1.01(0.98–1.04) | 0.520 |
AB | B | 1.00 (0.98–1.02) | 0.847 | 1.00 (0.99–1.01) | 0.818 | 1.01(0.98–1.04) | 0.529 |
AB | AB | 1.01(0.97–1.04) | 0.701 | 1.00 (0.99–1.01) | 0.832 | 0.98(0.94–1.02) | 0.313 |
A | A | 1.01(0.99–1.02) | 0.278 | 1.00 (1.00-1.01) | 0.654 | 1.01(0.99–1.03) | 0.510 |
A | O | 1.00 (0.99–1.02) | 0.839 | 1.00 (0.99-1.00) | 0.464 | 0.98(0.96-1.00) | 0.061 |
A | B | 0.99(0.98–1.01) | 0.282 | 1.00 (1.00–1.00) | 0.992 | 1.01(0.99–1.03) | 0.308 |
A | AB | 1.00 (0.97–1.02) | 0.782 | 1.00 (1.00-1.01) | 0.658 | 1.00 (0.97–1.03) | 0.816 |
O | A | 1.01(1.00-1.03) | 0.089 | 1.00 (0.99-1.00) | 0.027 | 1.01(0.99–1.03) | 0.497 |
O | O | 0.99(0.97-1.00) | 0.127 | 1.00 (1.00-1.01) | 0.171 | 1.00 (0.98–1.02) | 0.860 |
O | B | 1.00 (0.99–1.02) | 0.840 | 1.00 (1.00–1.00) | 0.680 | 0.99(0.98–1.01) | 0.508 |
O | AB | 0.99(0.97–1.02) | 0.565 | 1.00 (1.00-1.01) | 0.559 | 1.00 (0.98–1.03) | 0.808 |
ART Outcomes Association Analysis
We have further compared the outcomes of treatment to blood groups, including Biochemical and clinical Pregnancy, early abortion rate, live birth rate. As shown in Table 4, there was a statistically significantly positive association between the combination of female blood type AB and male blood type AB with biochemical pregnancy, clinical pregnancy, and live birth rate (OR 1.36; 95% CI, 1.05–1.78; P 0.02 and OR 1.31; 95% CI, 1.03–1.68; P 0.031 and OR 1.28; 95% CI, 1.01–1.63; P 0.041 respectively). No statistically significant difference was observed between couple combinations for ABO blood groups and early abortion rate.
Table 4
Female Blood Type | Male Blood Type | Fertilization Rate | Cleavage Rate | High Quality Embryo Rate |
OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value |
B | A | 0.98(0.97-1.00) | 0.010 | 1.00(1.00-1.01) | 0.251 | 0.99(0.97–1.01) | 0.354 |
B | O | 1.01(0.99–1.02) | 0.245 | 1.00 (1.00–1.00) | 0.942 | 1.02(1.00-1.04) | 0.110 |
B | B | 1.01(0.99–1.02) | 0.315 | 1.00 (1.00–1.00) | 0.783 | 0.99(0.97–1.01) | 0.442 |
B | AB | 1.01(0.98–1.03) | 0.563 | 1.00 (0.99-1.00) | 0.254 | 1.00 (0.97–1.03) | 0.843 |
AB | A | 1.00 (0.98–1.02) | 0.813 | 1.00 (1.00-1.01) | 0.343 | 0.99(0.96–1.02) | 0.564 |
AB | O | 1.00 (0.98–1.03) | 0.854 | 1.00 (0.99-1.00) | 0.386 | 1.01(0.98–1.04) | 0.520 |
AB | B | 1.00 (0.98–1.02) | 0.847 | 1.00 (0.99–1.01) | 0.818 | 1.01(0.98–1.04) | 0.529 |
AB | AB | 1.01(0.97–1.04) | 0.701 | 1.00 (0.99–1.01) | 0.832 | 0.98(0.94–1.02) | 0.313 |
A | A | 1.01(0.99–1.02) | 0.278 | 1.00 (1.00-1.01) | 0.654 | 1.01(0.99–1.03) | 0.510 |
A | O | 1.00 (0.99–1.02) | 0.839 | 1.00 (0.99-1.00) | 0.464 | 0.98(0.96-1.00) | 0.061 |
A | B | 0.99(0.98–1.01) | 0.282 | 1.00 (1.00–1.00) | 0.992 | 1.01(0.99–1.03) | 0.308 |
A | AB | 1.00 (0.97–1.02) | 0.782 | 1.00 (1.00-1.01) | 0.658 | 1.00 (0.97–1.03) | 0.816 |
O | A | 1.01(1.00-1.03) | 0.089 | 1.00 (0.99-1.00) | 0.027 | 1.01(0.99–1.03) | 0.497 |
O | O | 0.99(0.97-1.00) | 0.127 | 1.00 (1.00-1.01) | 0.171 | 1.00 (0.98–1.02) | 0.860 |
O | B | 1.00 (0.99–1.02) | 0.840 | 1.00 (1.00–1.00) | 0.680 | 0.99(0.98–1.01) | 0.508 |
O | AB | 0.99(0.97–1.02) | 0.565 | 1.00 (1.00-1.01) | 0.559 | 1.00 (0.98–1.03) | 0.808 |
Multivariate logistic regression analyses between ART outcomes and couple blood types combinations with adjusting for number of transfer embryo(s). |
Table 4
Multivariate logistic regression analyses between ART outcomes and parental blood types combinations with adjusting for number of transfer embryo(s).
Female Blood Type | Male Blood Type | Biochemical Pregnancy | Clinical pregnancy | Early Abortion Rate | Live Birth Rate |
OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value |
AB | B | 1.04(0.88–1.23) | 0.614 | 0.93(0.79–1.09) | 0.374 | 0.87(0.69–1.10) | 0.255 | 0.91(0.78–1.06) | 0.234 |
AB | A | 0.92(0.78–1.10) | 0.361 | 0.98(0.83–1.16) | 0.824 | 1.08(0.87–1.35) | 0.479 | 0.96(0.82–1.13) | 0.646 |
AB | O | 0.90(0.76–1.07) | 0.239 | 0.97(0.83–1.14) | 0.742 | 1.04(0.83–1.30) | 0.708 | 1.02(0.87–1.20) | 0.769 |
AB | AB | 1.36(1.05–1.78) | 0.020 | 1.31(1.03–1.68) | 0.031 | 1.01(0.71–1.42) | 0.975 | 1.28(1.01–1.63) | 0.041 |
B | B | 0.99(0.89–1.10) | 0.841 | 0.98(0.88–1.09) | 0.749 | 1.19(0.94–1.50) | 0.155 | 0.99(0.90–1.10) | 0.920 |
B | A | 0.97(0.86–1.09) | 0.585 | 1.00(0.90–1.11) | 0.972 | 0.83(0.66–1.05) | 0.119 | 0.99(0.89–1.10) | 0.809 |
B | O | 1.06(0.95–1.19) | 0.305 | 1.05(0.94–1.17) | 0.383 | 0.96(0.76–1.21) | 0.738 | 1.07(0.96–1.19) | 0.222 |
B | AB | 0.97(0.82–1.14) | 0.678 | 0.94(0.80–1.10) | 0.458 | 1.17(0.81–1.65) | 0.395 | 0.90(0.77–1.05) | 0.196 |
A | B | 0.99(0.88–1.11) | 0.861 | 1.03(0.93–1.15) | 0.572 | 1.01(0.71–1.42) | 0.959 | 1.01(0.91–1.13) | 0.802 |
A | A | 1.05(0.93–1.18) | 0.435 | 0.99(0.88–1.10) | 0.806 | 1.13(0.81–1.56) | 0.477 | 1.03(0.93–1.15) | 0.556 |
A | O | 0.97(0.86–1.08) | 0.550 | 0.96(0.86–1.08) | 0.515 | 0.82(0.58–1.16) | 0.275 | 0.92(0.83–1.03) | 0.137 |
A | AB | 1.00(0.84–1.19) | 0.981 | 1.04(0.88–1.23) | 0.623 | 1.15(0.68–1.86) | 0.593 | 1.09(0.92–1.28) | 0.315 |
O | B | 1.00(0.90–1.12) | 0.962 | 1.02(0.92–1.14) | 0.690 | 0.97(0.76–1.23) | 0.781 | 1.04(0.93–1.15) | 0.500 |
O | A | 1.03(0.91–1.15) | 0.680 | 1.02(0.92–1.15) | 0.675 | 1.04(0.83–1.31) | 0.714 | 1.00(0.89–1.11) | 0.971 |
O | O | 1.02(0.91–1.14) | 0.739 | 1.00(0.89–1.11) | 0.966 | 1.08(0.86–1.37) | 0.490 | 1.00(0.9–1.120) | 0.980 |
O | AB | 0.90(0.77–1.07) | 0.242 | 0.91(0.77–1.07) | 0.240 | 0.78(0.53–1.13) | 0.201 | 0.92(0.79–1.08) | 0.303 |
Birth Sex, Weights, Defects Rate Association Analysis
Finally, multivariate logistic regression analysis was performed to determine the relationship between blood type and birth sex, birth weights and birth defects rate after adjusting for the number of live births. As shown in Table 5, no blood type was statistically significantly associated with birth sex, birth weights and birth defects rate.
Table 5
Female Blood Type | Male Blood Type | Biochemical Pregnancy | Clinical pregnancy | Early Abortion Rate | Live Birth Rate |
OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value | OR (95%CI) | P value |
AB | B | 1.04(0.88–1.23) | 0.614 | 0.93(0.79–1.09) | 0.374 | 0.87(0.69–1.10) | 0.255 | 0.91(0.78–1.06) | 0.234 |
AB | A | 0.92(0.78–1.10) | 0.361 | 0.98(0.83–1.16) | 0.824 | 1.08(0.87–1.35) | 0.479 | 0.96(0.82–1.13) | 0.646 |
AB | O | 0.90(0.76–1.07) | 0.239 | 0.97(0.83–1.14) | 0.742 | 1.04(0.83–1.30) | 0.708 | 1.02(0.87–1.20) | 0.769 |
AB | AB | 1.36(1.05–1.78) | 0.020 | 1.31(1.03–1.68) | 0.031 | 1.01(0.71–1.42) | 0.975 | 1.28(1.01–1.63) | 0.041 |
B | B | 0.99(0.89–1.10) | 0.841 | 0.98(0.88–1.09) | 0.749 | 1.19(0.94–1.50) | 0.155 | 0.99(0.90–1.10) | 0.920 |
B | A | 0.97(0.86–1.09) | 0.585 | 1.00(0.90–1.11) | 0.972 | 0.83(0.66–1.05) | 0.119 | 0.99(0.89–1.10) | 0.809 |
B | O | 1.06(0.95–1.19) | 0.305 | 1.05(0.94–1.17) | 0.383 | 0.96(0.76–1.21) | 0.738 | 1.07(0.96–1.19) | 0.222 |
B | AB | 0.97(0.82–1.14) | 0.678 | 0.94(0.80–1.10) | 0.458 | 1.17(0.81–1.65) | 0.395 | 0.90(0.77–1.05) | 0.196 |
A | B | 0.99(0.88–1.11) | 0.861 | 1.03(0.93–1.15) | 0.572 | 1.01(0.71–1.42) | 0.959 | 1.01(0.91–1.13) | 0.802 |
A | A | 1.05(0.93–1.18) | 0.435 | 0.99(0.88–1.10) | 0.806 | 1.13(0.81–1.56) | 0.477 | 1.03(0.93–1.15) | 0.556 |
A | O | 0.97(0.86–1.08) | 0.550 | 0.96(0.86–1.08) | 0.515 | 0.82(0.58–1.16) | 0.275 | 0.92(0.83–1.03) | 0.137 |
A | AB | 1.00(0.84–1.19) | 0.981 | 1.04(0.88–1.23) | 0.623 | 1.15(0.68–1.86) | 0.593 | 1.09(0.92–1.28) | 0.315 |
O | B | 1.00(0.90–1.12) | 0.962 | 1.02(0.92–1.14) | 0.690 | 0.97(0.76–1.23) | 0.781 | 1.04(0.93–1.15) | 0.500 |
O | A | 1.03(0.91–1.15) | 0.680 | 1.02(0.92–1.15) | 0.675 | 1.04(0.83–1.31) | 0.714 | 1.00(0.89–1.11) | 0.971 |
O | O | 1.02(0.91–1.14) | 0.739 | 1.00(0.89–1.11) | 0.966 | 1.08(0.86–1.37) | 0.490 | 1.00(0.9–1.120) | 0.980 |
O | AB | 0.90(0.77–1.07) | 0.242 | 0.91(0.77–1.07) | 0.240 | 0.78(0.53–1.13) | 0.201 | 0.92(0.79–1.08) | 0.303 |
Multivariate logistic regression analyzes between birth sex, birth weights and birth defects and couple blood types combinations in single live born cycles. |