Background
Over the past few decades, there has been a dramatic increase in the incidence of multifoetal pregnancies (MFPs) due to advancing maternal age, the widespread application of assisted reproductive technology (ART) and the use of ovulation induction drugs [
1‐
3]. As a result of restrictions on the number of embryos transferred in women undergoing ART, a decline in MFPs has been observed in recent years [
4,
5]. However, the splitting of one embryo into two embryos may lead to higher-order multiple pregnancies (HOMPs), including triplet pregnancies containing monochorionic (MC) twins [
5‐
8].
Compared with singleton and twin pregnancies, HOMPs are associated with a higher risk of maternal-perinatal and long-term complications [
9‐
12] and increased hospital costs [
13]. Compared with singleton and twin pregnancies, triplet pregnancies are at a higher risk of miscarriage and preterm birth [
5,
14‐
17]. To reduce the risks associated with triplet pregnancies and HOMPs [
18,
19], multifoetal pregnancy reduction (MFPR) has been performed in recent years, and several methods have been described [
20,
21]. There is ample evidence that reducing quadruplet-or-higher pregnancies to twins is associated with more favourable outcomes, including advanced gestational age (GA) at delivery [
15,
16,
22]. A meta-analysis [
23] showed that trichorionic triplet pregnancy reduction to a twin pregnancy is associated with a lower risk of preterm delivery with no significant increase in the miscarriage rate. However, data on the perinatal outcomes of women with dichorionic triamniotic (DCTA) triplet pregnancies who undergo MFPR are lacking, and two meta-analyses on this subject reported that the numbers are insufficient to recommend one technique over another or to draw clear conclusions on the perinatal outcomes of DCTA pregnancies [
3,
23].
The aim of this study was to investigate the pregnancy and obstetric outcomes of women with DCTA pregnancies conceived by IVF-ET that were managed expectantly or were reduced to singleton pregnancies (foetus with a separate placenta) or monochorionic diamniotic (MCDA) twin pregnancies at 11–13+ 6 gestational weeks.
Results
Eighty-four DCTA triplets were reduced to MC singleton pregnancies (group A), 149 DCTA triplet pregnancies were reduced to MCDA twin pregnancies (group B), and 65 DCTA pregnancies were managed expectantly (group C).
Groups A, B and C were statistically similar regarding maternal age (29.6 ± 4.2 vs. 29.4 ± 3.9 vs. 28.4 ± 3.7 years), body mass index (21.5 ± 2.7 vs. 21.7 ± 3.0 vs. 21.9 ± 3.1 kg/m
2), infertility duration (4.4 ± 3.5 vs. 4.3 ± 2.8 vs. 4.1 ± 3.2 years), transfer cycles (1.2 ± 0.5 vs. 1.1 ± 0.5 vs. 1.1 ± 0.5), infertility type, cause of infertility, and insemination methods (
P > 0.05) (Table
1).
Table 1Comparison of the maternal demographic characteristics among groups A, B and C
Maternal age (years) | 29.6 ± 4.2 | 29.4 ± 3.9 | 28.4 ± 3.7 | NS | NS | NS |
BMI (kg/m2) | 21.5 ± 2.7 | 21.7 ± 3.0 | 21.9 ± 3.1 | NS | NS | NS |
Infertility duration (years) | 4.4 ± 3.5 | 4.3 ± 2.8 | 4.1 ± 3.2 | NS | NS | NS |
Infertility type | NS | NS | NS |
Primary, n (%) | 39 (46.4) | 62 (41.6) | 36 (55.4) |
Secondary, n (%) | 45 (53.6) | 87 (58.4) | 29 (44.6) |
Cause of infertility | NS | NS | NS |
Male factor , n (%) | 58 (69.0) | 94 (63.1) | 47 (72.3) |
Female factor , n (%) | 3 (3.6) | 3 (2.0) | 1 (1.5) |
Female + male factors, n (%) | 23 (27.4) | 49 (32.9) | 14 (21.5) |
Unexplained, n (%) | 0 (0) | 3 (2.0) | 3 (4.6) |
Transfer cycle | 1.2 ± 0.5 | 1.1 ± 0.5 | 1.1 ± 0.5 | NS | NS | NS |
1, n (%) | 72 (85.7) | 135 (90.6) | 58 (89.2) | NS | NS | NS |
≥2, n (%) | 12 (14.3) | 14 (9.4) | 7 (10.8) |
Insemination methods | NS | NS | NS |
IVF, n (%) | 49 (58.3) | 96 (64.4) | 45 (69.2) |
ICSI, n (%) | 9 (10.7) | 20 (13.4) | 9 (13.8) |
IVF/ICSI, n (%) | 26 (31.0) | 33 (22.1) | 11 (16.1) |
Group A had significantly lower rates of preterm birth (8.3 vs. 84.6%; odds ratio (OR) 0.017, 95% confidence interval (CI) 0.006–0.046), VPB (2.6 vs. 22.4%; OR 0.092, 95% CI 0.020–0.428), LBW (9.2 vs. 93.2%; OR 0.007, 95% CI 0.003–0.020) and perinatal death (1.3 vs. 9.8%; OR 0.122, 95% CI 0.016–0.930) than group C (
P < 0.05). GA at delivery (38.5 ± 2.1 vs. 33.4 ± 3.0 weeks) and live birth weight (3168 ± 557 vs. 1827 ± 441 g) were significantly higher in group A than in group C (
P < 0.001). There was no significant difference in the miscarriage rate (8.3 vs. 10.8%) and the live birth rate (90.5 vs. 83.1%) between groups A and C (
P > 0.05) (Table
2).
Table 2Pregnancy and obstetric outcomes in group A and group C
Pregnancy | 84 | 65 | | |
Miscarriage rate, % (n) | 8.3 (7/84) | 10.8 (7/65) | 0.613 | 0.753 (0.250–2.267) |
Preterm birth rate, % (n) | 8.3 (7/84) | 84.6 (55/65) | < 0.001 | 0.017 (0.006–0.046) |
Term birth rate, % (n) | 83.3 (70/84) | 4.6 (3/65) | < 0.001 | 103.333 (28.361–376.496) |
Caesarean section rate, % (n) | 68.8 (53/77) | 87.9 (51/58) | 0.009 | 0.303 (0.120–0.765) |
Babies born | 77 | 174 | | |
Live births | 76 | 162 | | |
Live birth rate, % (n) | 90.5 (76/84) | 83.1 (162/195) | 0.109 | 1.935 (0.853–4.390) |
Perinatal death, % (n) | 1.3 (1/77) | 9.8 (17/174) | 0.016 | 0.122 (0.016–0.930) |
IUD rate, % (n) | 1.3 (1/77) | 6.9 (12/174) | 0.071 | 0.178 (0.023–1.391) |
NND rate, % (n) | 0 (0/77) | 2.9 (5/174) | 0.327 | – |
Gestational age at delivery (weeks) | 38.5 ± 2.1 | 33.4 ± 3.0 | < 0.001 | |
≥ 37 weeks, % (n) | 90.9 (70/77) | 5.2 (3/58) | < 0.001 | 183.333 (45.307–741.858) |
< 37 weeks, % (n) | 9.1 (7/77) | 94.8 (55/58) | < 0.001 | 0.005 (0.001–0.022) |
VPB 24-31+6 weeks, % (n) | 2.6 (2/77) | 22.4 (13/58) | < 0.001 | 0.092 (0.020–0.428) |
Live birth weight (g) | 3168 ± 557 | 1827 ± 441 | < 0.001 | |
≥ 2500 g, % (n) | 90.8 (69/76) | 6.8 (11/162) | < 0.001 | 135.312 (50.304–363.975) |
LBW < 2500 g, % (n) | 9.2 (7/76) | 93.2 (151/162) | < 0.001 | 0.007 (0.003–0.020) |
VLBW < 1500 g, % (n) | 0 (0/76) | 17.9 (29/162) | < 0.001 | – |
Group B had significantly lower rates of preterm birth (47.0 vs. 84.6%; OR 0.161, 95% CI 0.076–0.340), VPB (7.2 vs. 22.4%; OR 0.270, 95% CI 0.111–0.660) and LBW (58.7 vs. 93.2%; OR 0.103, 95% CI 0.053–0.200) than group C (
P < 0.05). In addition, GA at delivery (35.7 ± 3.1 vs. 33.4 ± 3.0 weeks) and live birth weight (2348 ± 488 vs. 1827 ± 441 g) were significantly higher in group B than in group C (
P < 0.001). There was no significant difference in the miscarriage rate (7.4 vs. 10.8%) and the live birth rate (85.2 vs. 83.1%) between groups B and C (
P > 0.05) (Table
3).
Table 3Pregnancy and obstetric outcomes in group B and group C
Pregnancy | 149 | 65 | | |
Miscarriage rate, % (n) | 7.4 (11/149) | 10.8 (7/65) | 0.412 | 0.660 (0.244–1.788) |
Preterm birth rate, % (n) | 47.0 (70/149) | 84.6 (55/65) | < 0.001 | 0.161 (0.076–0.340) |
Term birth rate, % (n) | 45.6 (68/149) | 4.6 (3/65) | < 0.001 | 17.350 (5.212–57.756) |
Caesarean section rate, % (n) | 86.2 (119/138) | 87.9 (51/58) | 0.749 | 0.860 (0.340–2.171) |
Babies born | 276 | 174 | | |
Live births | 254 | 162 | | |
Live birth rate, % (n) | 85.2 (254/298) | 83.1 (162/195) | 0.519 | 1.176 (0.719–1.924) |
Perinatal death, % (n) | 9.1 (25/276) | 9.8 (17/174) | 0.8 | 0.920 (0.481–1.758) |
IUD rate, % (n) | 8.0 (22/276) | 6.9 (12/174) | 0.674 | 1.169 (0.563–2.427) |
NND rate, % (n) | 1.1 (3/276) | 2.9 (5/174) | 0.270 | 0.371 (0.088–1.574) |
Gestational age at delivery (weeks) | 35.7 ± 3.1 | 33.4 ± 3.0 | < 0.001 | |
≥ 37 weeks, % (n) | 49.3 (68/138) | 5.2 (3/58) | < 0.001 | 17.810 (5.316–59.665) |
< 37 weeks, % (n) | 50.7 (70/138) | 94.8 (55/58) | < 0.001 | 0.056 (0.017–0.188) |
VPB 24-31+6 weeks, % (n) | 7.2 (10/138) | 22.4 (13/58) | 0.003 | 0.270 (0.111–0.660) |
Live birth weight (g) | 2348 ± 488 | 1827 ± 441 | < 0.001 | |
≥ 2500 g, % (n) | 41.3 (105/254) | 6.8 (11/162) | < 0.001 | 9.674 (4.994–18.737) |
LBW < 2500 g, % (n) | 58.7 (149/254) | 93.2 (151/162) | < 0.001 | 0.103 (0.053–0.200) |
VLBW < 1500 g, % (n) | 4.3 (11/254) | 17.9 (29/162) | < 0.001 | 0.208 (0.100–0.429) |
Group A had significantly lower rates of preterm birth (8.3 vs. 47.0%; OR 0.103, 95% CI 0.044–0.237), LBW (9.2 vs. 58.7%; OR 0.071, 95% CI 0.032–0.162) and perinatal death (1.3 vs. 9.1%; OR 0.132, 95% CI 0.018–0.991) than group B (
P < 0.05). Additionally, GA at delivery (38.5 ± 2.1 vs. 35.7 ± 3.1 weeks) and live birth weight (3168 ± 557 vs. 2348 ± 488 g) were significantly higher in group A than in group B (
P < 0.001). However, there was no significant difference in the miscarriage rate (8.3 vs. 7.4%) and the live birth rate (90.5 vs. 85.2%) between groups A and B (
P > 0.05) (Table
4).
Table 4Pregnancy and obstetric outcomes in group A and group B
Pregnancy | 84 | 149 | | |
Miscarriage rate, % (n) | 8.3 (7/84) | 7.4 (11/149) | 0.794 | 1.140 (0.425-3.063) |
Preterm birth rate, % (n) | 8.3 (7/84) | 47.0 (70/149) | <0.001 | 0.103 (0.044-0.237) |
Term birth rate, % (n) | 83.3 (70/84) | 45.6 (68/149) | <0.001 | 5.956 (3.084-11.502) |
Caesarean section rate, % (n) | 68.8 (53/77) | 86.2 (119/138) | 0.002 | 0.353 (0.178-0.698) |
Babies born | 77 | 276 | | |
Live births | 76 | 254 | | |
Live birth rate, % (n) | 90.5 (76/84) | 85.2 (254/298) | 0.216 | 1.646 (0.743-3.647) |
Perinatal death, % (n) | 1.3 (1/77) | 9.1 (25/276) | 0.021 | 0.132 (0.018-0.991) |
IUD rate, % (n) | 1.3 (1/77) | 8.0 (22/276) | 0.036 | 0.152 (0.020-1.146) |
NND rate, % (n) | 0 (0/77) | 1.1 (3/276) | 1.000 | - |
Gestational age at delivery (weeks) | 38.5 ± 2.1 | 35.7 ± 3.1 | <0.001 | |
≥ 37 weeks, % (n) | 90.9 (70/77) | 49.3 (68/138) | <0.001 | 10.294 (4.419-23.979) |
< 37 weeks, % (n) | 9.1 (7/77) | 50.7 (70/138) | <0.001 | 0.097 (0.042-0.226) |
VPB 24-31+6 weeks, % (n) | 2.6 (2/77) | 7.2 (10/138) | 0.219 | 0.341 (0.073-1.600) |
Live birth weight (g) | 3168 ± 557 | 2348 ± 488 | <0.001 | |
≥ 2500 g, % (n) | 90.8 (69/76) | 41.3 (105/254) | <0.001 | 13.988 (6.182-31.651) |
LBW < 2500 g, % (n) | 9.2 (7/76) | 58.7 (149/254) | <0.001 | 0.071 (0.032-0.162) |
VLBW < 1500 g, % (n) | 0 (0/76) | 4.3 (11/254) | 0.075 | - |
Discussion
In the present study, we analysed the pregnancy and obstetric outcomes of women with DCTA pregnancies conceived by IVF-ET who underwent MFPR at 11–13+ 6 gestational weeks or expectant management. We found that the MFPR of DCTA pregnancies to either MC singleton or MCDA twin pregnancies improved the pregnancy and obstetric outcomes by significantly decreasing the risks of preterm birth, VPB and LBW and significantly increasing the GA at delivery and live birth weight, with no significant reduction in the miscarriage risk. Specifically, among the management options, the reduction of DCTA pregnancies to MC singleton pregnancies resulted in the lowest risks for VPB, perinatal death and LBW and in maximal GA at delivery and live birth weight.
Women with DCTA pregnancies carry both the risks associated with triplets, such as VPB, selective growth restriction and foetal malformation, and those associated with MC twins due to vascular anastomoses in the single placental bed, such as twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (SIUGR) [
5,
29]. Patients should be informed in detail about all possible complications. Data from previous studies [
30,
31] demonstrated that MFPR is feasible and effective at decreasing the risk of some adverse outcomes for pregnancies with MC twins.
The most frequently applied method for MFPR is the ultrasound-guided transabdominal injection of KCl into the foetal heart or thoracic cavity, which has been shown to be relatively safe [
32]. In the present study, MFPR was performed for 233 DCTA pregnancies using the injection technique. Ultrasound examination within 24 h of the procedure demonstrated that all retained MC singletons or MCDA twins were alive, and only 1.3% (3/233) of cases (2 cases of DCTA pregnancy reduced to a singleton pregnancy and 1 case of DCTA pregnancy reduced to a MCDA twin pregnancy) resulted in miscarriage in the subsequent 2 weeks. The procedure was technically successful in all cases.
Some studies comparing expectant management to the reduction of dichorionic (DC) triplet pregnancies to MC singleton pregnancies, foetal reduction resulted in a significantly decreased risk of preterm birth (< 32 gestational weeks), a more advanced GA at delivery and an increased birth weight, as well as a non-significantly increased risk of miscarriage (< 24 gestational weeks) [
5,
30,
33]. Similarly, the present data showed that in DCTA pregnancies that were reduced to singleton pregnancies, the VPB rate decreased from 22.4 to 2.6%, the GA at delivery increased from 33.4 weeks to 38.5 weeks, and the live birth weight increased from 1827 g to 3168 g; the impact of foetal reduction on the miscarriage rate (8.3 vs. 10.8%) was limited.
A previous systematic review and meta-analysis compared the reduction of a DCTA pregnancy to a MC twin pregnancy (
n = 15) with expectant management (
n = 200) and found neither a significant increase in the risk of miscarriage (< 24 gestational weeks; 13.3 vs. 8.5%, respectively) nor a significant decrease in the risk of preterm birth (< 34 weeks; 46.2 vs. 51.9%, respectively) [
23]. In contrast, the present study showed a significant decrease in the VPB rate from 22.4 to 7.2% and a slight decrease in the miscarriage rate from 10.8 to 7.4% among DCTA pregnancies reduced to MCDA pregnancies compared to expectant management. The differences in outcomes between the meta-analysis and the present study are potentially due to an inadequate number of patients with DCTA pregnancies reduced to MC twin pregnancies in the meta-analysis.
Reduction by the injection technique is not appropriate in women with a MC twin pregnancy because of inter-twin placental vascular anastomoses. In addition, acute haemorrhage of the surviving twin may occur soon after the death of the co-twin through placental vascular anastomoses, with consequent death or neurodevelopmental impairment [
34,
35]. Women with DCTA triplet pregnancies reduced to MCDA pregnancies were exposed to the risks of TTTS and SIUGR. Relatively new vascular occlusive techniques have enabled the possibility of reducing a triplet pregnancy containing MC twins to a DC twin pregnancy [
3,
36,
37]. Some studies have reported the efficiency of this new technique in women with MC twins; however, it potentially increases the risk of technique-associated complications and the rate of intrauterine demise of the retained co-twin [
3,
34,
36]. Chaveeva P et al. [
38] reported 61 DC triplet pregnancies that were reduced to DC twin pregnancies by intrafoetal laser ablation; although reduction resulted in a relatively lower miscarriage rate (3%), 45.9% of the cases of co-twin miscarriage within the subsequent 2 weeks were likely due to incomplete vascular occlusion and retrograde haemorrhage of the survivor through placental vascular anastomoses into the dead co-twin.
Rong Li et al. [
31] reported that the MFPR of DC triplet pregnancies to singleton pregnancies had better pregnancy outcomes than those reduced to DC twin pregnancies by early transvaginal embryo reduction. The safety of a singleton pregnancy was also demonstrated in the present study. Our data showed that the reduction of DCTA pregnancies to singleton pregnancies decreased the risks of LBW and perinatal death and further increased the live birth weight compared with the reduction to MCDA pregnancies. However, two meta-analyses on the perinatal outcomes of management options for DCTA triplet pregnancies (including expectant management, reduction of the MC twins, reduction of one MC twin and reduction of the foetus with a separate placenta) reported that the number of cases was insufficient to recommend one technique or management method over another or to draw definitive conclusions on perinatal outcomes [
3,
23]. For foetal reduction in DCTA triplet pregnancies, the current choice is mostly based on technical considerations and available instrumentation.
To our knowledge, this is the largest study to examine the outcomes of patients with DCTA pregnancies conceived via IVF-ET who underwent MFPR or expectant management. However, there are some limitations of this study. One limitation is the lack of data regarding morbidity among live infants, which is obviously more important than the live birth rate alone, and successful ART is defined as the delivery of a healthy and living baby by an infertile patient. In addition, our centre is only a reproductive centre, and all pregnancy outcomes were determined by telephone call or fax; therefore, we do not have reliable information about other pregnancy complications, such as gestational hypertension, gestational diabetes and premature rupture of membranes, or data on the frequency of TTTS in DCTA pregnancies reduced to MCDA pregnancies or managed expectantly. This was a retrospective analysis, and we probably missed some information regarding women who conceived DCTA triplets.
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