Document Type : Original Research Article
Department of Obstetrics and Gynecology, Tanta University, Tanta, Egypt
Background & Objective: Multifetal reduction not only lowers the number of fetuses but also improves pregnancy outcomes. A great conflict emerges when obstetrician faces triplet or higher order multifetal pregnancies. Decision-making is so difficult whether to continue pregnancy as such with its risks or reduce the number of fetuses to improve outcomes. This study aimed to assess the obstetrical outcomes of Embryo Reduction to Twins (ERTT) procedures in IVF/ICSI centers in Egypt.
Materials & Methods: This retrospective cross-sectional study was conducted from June 2017 to December 2020. Data of the patients in five IVF/ICSI centers were accessed using the computer-stored patients' files. Patients who got pregnant spontaneously or after IVF/ICSI procedures with 3 or more embryos were recruited in the study. The patients were counseled for ERTT and those who accepted the procedure were included. The measured obstetrical outcomes were abortion rate, preterm labor, and preeclampsia, premature rupture of membranes, and neonatal morbidity and mortality.
Results: One hundred and twenty four cases were included in this study from 5 IVF/ICSI centers. Most cases (83.87%) of multifetal pregnancies were due to IVF/ICSI procedures. The mean age was 28.3 ± 2.5 years and the mean gestational age at reduction was 8.4 ± 0.6 weeks. The great majority of cases (72.58%) were operated by aspiration. The abortion rate was 29.84%. The mean gestation age at delivery was 34.51 ± 1.82 weeks. The incubator admission rate was 41.93% and the overall postoperative complication was 9.68%.
Conclusion: Embryo Reduction to Twins in triplets or higher order pregnancies was considered feasible, safe and linked to minimal complications. The ERTT procedure improved obstetrical and neonatal outcomes.
Nowadays, assisted reproductive technologies increased the incidence of triplet and higher order pregnancies. These techniques eventually have led to an increase in the incidence of miscarriages, preterm labor, subsequent prematurity, and its health and economic burdens. A recent study showed that fetal loss occurs commonly before 24 weeks and that early preterm delivery occurs before 32 weeks and these complications are among the commonest comp-lications of triplet pregnancies (1).
Several procedures and drugs were investigated to reduce the risks associated with triplets and higher order pregnancies, including progesterone supplementation, cerclage, combined cerclage and progesterone, and embryo reduction (ER). A recent study showed that ER in higher order pregnancies is a safe and preferred approach in reducing morbidity and mortality (2).
Although multifetal pregnancy reduction is considered a safe and effective technique in reducing perinatal complications, it is difficult for couples to accept such an approach. ER procedure is associated with emotional pain, stress, fear, and sensation of guilt in the 2/3 of cases that underwent this procedure. Therefore, adequate counseling is necessary before undertaking this procedure (3,4).
Literature review revealed contradictory results where some studies advocated ER and some did not. In this study, the obstetrical and neonatal outcomes of ERTT in multifetal pregnancies were investigated.
Study Design and Settings
This retrospective cross-sectional multi-center study was conducted at five IVF/ICSI centers in Egypt. The centers included were the Fertility Unit of Tanta Educational Hospital, Egyptian Consultant Center, Quret Ain Fertility Center, Engab Fertility Center, and Om Elqura Fertility Center. The study was conducted from June 1, 2017, to December 31, 2020.
The files of the patients who were pregnant with 3 or more embryos were reviewed. The patients who accepted ERTT were included in the study either pregnancy was spontaneous or through IVF/ICSI.
All data including the patients' age, gravidity, parity, infertility type and duration, origin of multiple pregnancies, gestational age at reduction, abortion rate, incidence of preterm labor, preeclampsia, premature rupture of membranes (PROM) and other adverse outcomes, the gestational age at delivery, and neonatal morbidity or mortality were recorded.
The data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL., USA). The statistical procedures were descriptive statistical tests, including mean, standard deviation and percentage.
One hundred and eighty six files of triplets and higher order pregnancies were evaluated. From them, 124 patients who underwent ERRT procedures were included in this study.
The demographic data of enrolled patients are presented in Table 1. The mean age was 28.3 ± 2.5 years, mean gravidity was 1.80 ± 0.34, and mean parity was 1.33 ± 0.61. The majority of cases [86 (69.35%)] presented with primary infertility with mean duration of infertility at 4.77 ± 1.20 years. The great majority of cases [104 (83.87%)] resulted from IVF/ICSI procedures, while 15 cases (12.10%) resulted from ovulation induction and 5 cases (4.03%) occurred spontaneously.
The procedure of embryo reduction to twins (ERTT) has been explained in Table 2. The mean gestational age at reduction was 8.4 ± 0.6 weeks. The most commonly used method was embryo aspiration which was used in 90 cases (72.58%) and the remaining 34 (27.42%) were managed by fetal cardiac tapping. The mean duration of the procedure was 26.11 ± 5.26 minutes. Most cases who underwent ERTT [108 (87.10%)] were triplets, while 16 cases (12.90%) were quadruplets. The procedure was linked to some complications like sub-chorionic hematoma in 6 cases (4.84%) and vaginal bleeding in 4 cases (3.23%). Two cases (1.61%) were complicated by bladder puncture by a needle. The total post-surgery complication rate was 9.68%.
Obstetrical outcomes are shown in Table 3. The total abortion rate was 37/124 (29.84%) and most cases aborted between 20-28 weeks. Regarding the timing of delivery, most cases (60.48%) delivered prematurely while only 9.68% delivered at full term with mean gestational age of 34.51 ± 1.82 weeks at delivery. The other obstetrical outcomes such as preeclampsia (16.93%), PROM (28.23%) and antepartum hemorrhage (21.77%) also occurred. The majority of cases were delivered by cesarean section (61.29%). Neonatal outcomes are also presented in Table 3, where the mean birth weight, incubation admission rate, and mortality rate were 1645.87 ± 130.21 gr, 41.93% and 10.48%, respectively.
Table 1. Demographic data of enrolled patients (n=124)
|Type of infertility (n, %)|
|Duration of infertility (years)||Range||Mean±SD|
|Origin of multiple pregnancy (n, %)|
Table 2. Procedures of ERTT (n=124)
|Gestational age at reduction (weeks)||7-12||8.4±0.6|
|Embryo reduction method (n,%)|
|Embryo cardiac tapping||34||27.42%|
|Duration of procedure (minutes)||18-30||26.11±5.26|
|Embryos number (n, %)|
|Immediate complications (n, %)|
|Bladder injury by needle||2||1.61%|
|Total postoperative complications||12||9.68%|
|Abortion (n, %)|
|Within 2 weeks of procedure||7||5.64%|
|Before 20 weeks||12||9.68%|
|Total abortion rate||37||29.84%|
|Delivery timing (n,%)|
|Antepartum hemorrhage (n, %)|
|Total antepartum hemorrhage||27||21.77%|
|Mode of delivery (n, %)|
|Gestational age at delivery||Range||Mean±SD|
|Neonatal weight (g)||Range||Mean±SD|
|Incubation admission (n, %)||52||41.93%|
|Neonatal mortality (n, %)||13||10.48%|
The current study was designed to develop some information that could be helpful in counseling women with triplet or higher order pregnancies regarding fetal reduction to twins and expectant management. The current study aimed at the evaluation of fetal reduction of triplet or higher order pregnancies to twin pregnancy and weather this would be helpful to prolong pregnancy and avoid prematurity and its perinatal complications.
In the current study, 18 pregnancies ended with abortion, which constitutes 29.84% of the cases of which 5.64% were within 2 weeks of the fetal reduction procedure, 9.68% before 20 weeks and 14.52% between 20-28 weeks. Therefore, most cases aborted between 20-28 weeks. We reported postoperative complications in 9.68% of the cases.
Our results were in agreement with the reports by Papageorghiou et al., (1) and Chaveeva et al., (5) that mentioned fetal loss before 24 weeks of gestation increased after fetal reduction procedures. Mandiola et al., reported fetal losses after ER procedure in 14.8% and post-surgery complications in 3.7% of the cases (6). On the other hand, our results contradicted the results of Drugan et al. (7) and Shiva et al. (8) which showed that fetal loss rate before 24 weeks did not differ between reduced and nonreduced pregnancies (12.3% vs 12.1%).
Miscarriages that occurred 2 weeks after fetal reduction were due to faulty fetal reduction technique rather than resorption of the dead fetoplacental tissue. This was in agreement with the findings of Papageorghiou et al. (1). This is important for adequate counseling of patients in order to choose the best option of treatment. Sunol reported the loss of all embryos after the reduction procedure in 4.5% of study populations (9). This finding was not uncommon; it is comparable with triplets' spontaneous loss rate, which varies from 2.6% to 8.3% (10-12).
The mean gestational age at delivery was 34.5 weeks and the risk of delivery before 34 weeks was 52.4%. This was in concordance with Antsaklis et al., who compared 185 trichorionic triplet pregnancies that were reduced to twins with 70 triplet pregnancies that were managed expectantly where the incidence of preterm delivery was 40.5% in the reduced group (13). Similarly, Papageorghiou et al., found a reduction in the rate of preterm delivery (from 23.9% to 9.7 %) with fetal reduction (1).
Chaveeva et al., compared the outcome of fetal reduction versus expectant management (EM) in trichorionic and dichorionic triplet pregnancies and found a significant reduction in the incidence of preterm birth in trichorionic triamniotic pregnancies, which reduced to twins (20.9 % versus 49.5%) than in EM (5).
In the current study, we found that the incidence of hypertensive disorders was 16.93%. This incidence was comparable to the incidence of pregnancy-related hypertensive conditions in triplet pregnancies reported in many studies (14, 15).
Day et al., found in their study that hypertensive disorders in pregnancy were more common in multiple pregnancies when compared to singleton pregnancies. They found that hypertensive conditions had a greater incidence in twin, triplet, and higher order pregnancies with the following incidence rates (12.7%, 20.0%, and 19.6%, respectively), while the incidence of hypertensive disorders with singleton pregnancies was 6.5% (14).
Chibber et al. found 23% incidence of preeclampsia in triplets, while it was diagnosed in 30% of higher order pregnancies (P<0.05). The authors reported that preeclampsia was mild and well-controlled, with no case reported with eclampsia. They concluded that preeclampsia was found in nearly similar incidence to the reported incidence in literature which was 20–39% for triplets (15).
Premature rupture of membranes occurred in 28.23% of cases included in this study. This is much lower than the incidence of PROM in the literature. In one study, ROM before 37 weeks of gestation occurred in 64% of cases (12.2% between 37 and 34 weeks, 23.5% between 34 and 28 weeks and 28.4% < 28 weeks). The incidence of PROM in triplet pregnancies was much lower in the study by Garg P. et al., who studied prolonged PROM incidence in singleton and multiple pregnancies. They reported that PROM occurred in 27.9% of singleton pregnancies, 22.4% of twins and 12.8% of triplets (16, 17).
Everwijn et al., studied the reduction of triplets to twins in a retrospective study. They found no difference in miscarriage < 24 and preterm labor < 32 weeks for ongoing triplets and triplets reduced to twins (3.8% vs 7.9% and 26.8% vs 22.4%, respectively). They stated no improvement in obstetrical and neonatal outcomes for triplet reduced to twins. Moreover, the risk of pregnancy loss before 24 weeks was higher in reduced twins (18).
Mandiola et al., conducted 54 embryonic reductions during 2005-2006. They found that 38.9% of cases delivered prematurely < 37 week and reported high economic burdens with increased morbidity and mortality. However, they concluded that ER procedures improved perinatal outcomes compared to the gestations without reductions in reducing economic costs. They recommended doing reductions and importantly prevent their occurrence by limiting the number of transferred embryos (6).
Lee et al., conducted a multi-center study in two tertiary care hospitals to study the effect of ER in improving obstetrical and neonatal outcomes in triplets. Their study enrolled 495 triplet pregnancies from 2006 to 2016. They allocated patients into either EM group (n=185) or ER group (n=310). They reported that early preterm delivery (<32 weeks) was higher in the EM group compared to the ER group [33 (18.1%) vs. 20 (6.9%); OR=2.97, 95% CI=1.64-5.36, P<0.001]. They concluded that EM improved fetal survival with good obstetric and neonatal care (19).
A recent meta-analysis of 24 eligible studies compared reduction to non-reduction in multifetal pregnancies. They suggested that reduction procedures were associated with good perinatal outcome (20).
Similarly, Talwar et al., and Tse et al., conducted their studies on 51 and 52 multifetal pregnancies resulting from IVF procedures, respectively. They aimed to prevent and manage the associated medical and obstetric risks by doing transvaginal ultrasound embryo reduction. They found ER procedures safe and effective in improving obstetrical and neonatal outcomes (21, 22).
The strengths of this study were adding to the current evidence that ERTT are safe and effective procedures in multifetal pregnancies, helping obstetricians and couples to make the right decision to continue the pregnancy with twins rather than higher order pregnancies, reducing perinatal mortality and morbidity, and economic burdens. The weak points of this study were the study's retrospective nature and the small size of included patients.
Embryo reduction to twins (ERTT) procedures were safe and effective in reducing the obstetrical complications linked to triplets and higher order pregnancies. Neonatal morbidity and mortality were minimal in ongoing pregnancies. Further randomized controlled studies are recommended to compare such procedures to conservative treatments in higher order pregnancies.
Being a retrospective study, this study was exempt from committee approval by Tanta University ethical committee.
Ayman Dawood: Protocol writing, collection of data, writing manuscript, revision and submission. Mohamed Elnamoury: Writing manuscript, statistical analysis, revision of the manuscript. Waleed Atallah: Writing manuscript, revision and collection of data.
The authors declared no conflict of interest.