The Controversies and Challenges in the Management of Twin Pregnancy: From the Perspective of International Federation of Gynecology and Obstetrics Guidelines : Maternal-Fetal Medicine

Secondary Logo

Journal Logo


The Controversies and Challenges in the Management of Twin Pregnancy: From the Perspective of International Federation of Gynecology and Obstetrics Guidelines

Liu, Jingyu; Liu, Quanrui; Zhao, Jingya; Li, Danlun; Zhou, Yi

Author Information
doi: 10.1097/FM9.0000000000000170
  • Open



Twin pregnancies account for 2% to 4% of all total births1 and are associated with higher maternal and fetal risks such as preterm birth, fetal growth restriction (FGR), or congenital anomalies. Owing to the rise in use of assisted reproduction techniques, the incidence of monochorionic (MC) twin pregnancy has also increased. Approximately 20% of twin pregnancies result in MC.2 Because it is commonly acknowledged that the fetal outcomes of MC twins are inferior to those of dichorionic (DC) twins, it is important to determine chorionicity in early pregnancy and plan for subsequent perinatal monitoring and interventions.

Many international expert teams such as the International Federation of Gynecology and Obstetrics (FIGO), the Royal College of Obstetricians and Gynecologists (RCOG), the National Institute for Health and Care Excellence (NICE), the American College of Obstetricians and Gynecologists, and the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) have made efforts to standardize the management of twin pregnancy. However, differences in the guidelines hinder consistent results in clinical trials. The aims of this review are to highlight the international consensus of the antenatal care of twin pregnancies, for example, determination of chorionicity, ultrasound surveillance protocol, prenatal diagnosis procedure, and management of twin complications, and analyze the controversies and discrepancies based on the published FIGO guidelines and research.

Determination of chorionicity of twin pregnancy

Chorionicity is one of the most significant parameters for prognosis in twin pregnancy. The risk of intrauterine fetal demise is 11.6% in MC twins compared with DC twins.3 Neurological morbidity is 4 to 5 times higher than in DC twins and consequently 25 to 30 times higher than in singletons.4 Moreover, chorionicity determines the ultrasound surveillance patterns during gestation and also the techniques for selective fetal reduction. Therefore, accurate determination of chorionicity is essential to improve the pregnancy outcome of twins.

The accuracy of chorionicity determination before 14 weeks is 99% as the amnion and chorion are not fused at this stage, but it decreases to only 77% for MC after 14 weeks.5,6 Herein, FIGO guidelines7 suggest that chorionicity should be determined and documented clearly in the first trimester using the membrane thickness at the site of insertion of the amniotic membrane into the placenta, identifying the T sign or lambda (λ) sign. For women presenting for the first time after 14 weeks, chorionicity can still be determined by using the same signs as well as the discordant fetal sex. However, clinicians should be aware that there are still some limitations to ultrasound-guided assessment of chorionicity.8 First, various reasons such as advancing gestation and regressing yolk sac can result in both false-negative and false-positive λ signs. In very rare situations, both T and λ signs can coexist. Second, sometimes intrauterine synechia can be considered as a thick intrauterine septum, leading to the misdiagnosis of DC twins. The thickness of intertwin membrane is not always a reliable marker for chorionicity. When using 2-dimensional ultrasound, an intertwin membrane thickness of 1.5 to 2.0 mm may be inconclusive for MC twins. Bracero et al.9 reported that a cutoff value of 1.9 mm of the dividing membrane thickness is found to be the best predictor of chorionicity with the ultrasound beam parallel. However, there is still no consensus about the optimal cutoff value. Besides, approximately 3% of placentas in MC twins may be bilobar and appear as two placental masses.10 Although the positive predictive value of sex discordance is almost 100%, the existence of MC dizygosity twins, sex chromosomal abnormality, and monogenetic disorders can lead to sex discordance in MC twins. Genital malformation such as hypospadias or cloacal malformation can result in confusion. Moreover, the ascertaining of amnionicity by the number of yolk sacs is not always true. Sometimes it is difficult to visualize the intertwin amniotic membrane if it is too thin or has collapsed because of severe oligohydramnios in the donor twin in twin-to-twin transfusion syndrome (TTTS).

Therefore, we should use a combination of the number of placental masses, λ and T signs, and intertwin membrane thickness to improve the accuracy of ultrasound assessment in clinical practice.11,12 Furthermore, if sonographers cannot obtain a satisfied transabdominal ultrasound image, transvaginal sonography is recommended for a retroverted uterus or in patients with high body mass index in the ISUOG guidelines.12 Patients should preferably be referred to the tertiary center. If it is still difficult to determine the chorionicity, it is safer to be treated as MC twins, which require additional fetal surveillance for specific complications.

The dilemma of ultrasound surveillance in twin pregnancy

The FIGO guidelines suggest7 that in general ultrasound examination of twins, the following parameters should be assessed in cotwins in serial ultrasound scans: fetal biometry, estimated fetal weight (EFW), and amniotic fluid volume (AFV). In addition, peak systolic velocity of middle cerebral artery (MCA-PSV) should be assessed intensively from the second trimester screening for twin anemia polycythemia sequence (TAPS). In MC twins, ultrasound scan should be performed at least every two weeks since 16 weeks’ gestation for assessment of the aforementioned parameters. In uncomplicated DC twins, it should be performed at approximately 20 weeks’ gestation for detailed anomalies and thereafter every month. If there are any abnormal ultrasound findings, the scan should be more intensive. Besides, in all twin pregnancies, the 20-week scan should include measurement of cervical length to identify women at increased risk of extreme premature delivery.

A high degree of growth discordance is known to be associated with adverse perinatal outcomes regardless of chorionicity. Regular monitoring for intertwin-size discordance is therefore essential for antenatal care. A systematic review reported that twin pregnancy with discordant EFW is associated with the increased risk of intrauterine demise, whereas the risk of IUD is higher when at least one twin is small for gestational age.13 However, another study showed that for DC twins, the discordance of fetal growth increased across gestation, and there was no consensus regarding the appropriate cutoff point to predict adverse perinatal outcome.14 More research about variation of fetal growth discordance during gestation is necessary to define an appropriate cutoff point for prediction of adverse outcomes.

It is widely acknowledged that the growth patterns of twin and singleton pregnancies are different during the third trimester, and therefore, the growth charts should be distinct for more accurate assessment. Several studies have proven that use of twin-specific growth charts can reduce the diagnosis of FGR and unnecessary interventions in twins.15,16 Therefore, twin-specific growth charts have been developed in different regions and populations, but its clinical application needs further improvement.15–19 Moreover, per the FIGO guidelines, umbilical artery (UA) Doppler should only be carried out in high-risk pregnancies, but according to the ISUOG and RCOG guidelines and the consensus in China,10,12,20 the UA Doppler is recommended at each scan to detect the complications in a timely manner and improve perinatal outcomes. Another study shows that abnormal UA Doppler in the midtrimester indicates poor outcome, and therefore, close surveillance is warranted in all MC twins.21 However, another prospective study shows that abnormal UA is presented in a small part of uncomplicated twins in the second trimester, and most of them can achieve normalization, which seems that the routine monitoring for UA is not necessary.22 Hence, the assessment of UA Doppler is still unclear. However, it is known that complications such as TTTS result from long-lasting transfusion and hemodynamic imbalance; hence, it is possible that the UA Doppler waveforms deteriorate before TTTS can be diagnosed, and routine monitoring thus seems reasonable in this situation.

The cervical-length screening in the second trimester is also a controversial issue. Given that the risk of preterm birth in twin pregnancies is 10 times higher than in singletons,23 most experts in China recommend routine measurement of cervical length during the 18 to 24 weeks’ ultrasound scan, which is consistent with the ISUOG and FIGO guidelines.7,12,24 These guidelines suggest that a short cervix in asymptomatic women is a risk factor for preterm delivery, but its predictive value is poor in symptomatic women.7 However, routine cervical length screening is not recommended in asymptomatic women per the NICE and American College of Obstetricians and Gynecologists guidelines,24,25 because the sensitivity of cervical-length screening in twins is lower than that in singletons, and there are no effective interventions to prevent spontaneous preterm delivery.26 Rehal et al.23 conducted a randomized clinical trial among 1194 unselected twin pregnancies to explore the effect of early use of high-dose vaginal progesterone and found that it did not reduce the incidence of preterm birth before 34 weeks. Some cohort studies have also found that pessary and cerclage had no contribution in decreasing the risk of preterm birth before 32 weeks in twin pregnancies with short cervix.27,28 Although data showed that pessary can reduce the rate of morbidity in neonate and the economic costs when compared with progesterone, more data are needed to reach a consensus for prevention of preterm birth in twins.29 Therefore, the use of cervical-length screening is still contentious.5,16

There is still relatively little evidence-based guidance about the frequency of ultrasound examination in DC twins.24 A recent large-scale prospective study reported excellent fetal outcomes in DC twins, in their fortnightly ultrasound scan research.30 The study shows that this strategy may increase the detection rate (DR) for FGR cases. Although a longer scan interval is likely to miss abnormal cases and may cause higher risk of poor outcomes, shortening the screening interval will lead to cost issues and unnecessary iatrogenic preterm delivery. More evidence is needed for appropriate ultrasound surveillance frequency in DC twins.

Therefore, the optimal cutoff points of EFW discordance, the use of twin-specific growth charts, and a consensus about ultrasound surveillance parameters are needed for better management in twin pregnancy.

Screening for chromosome abnormalities and invasive prenatal procedures in twin pregnancy

The FIGO guidelines state that the combined test (serum biochemistry screening and nuchal translucency) or the combination of maternal age, nuchal translucency, and cell-free DNA (cfDNA) test should be offered to screen chromosomal abnormalities in twins in the first trimester.7,12,15,31 However, the patient should be informed that serum tests in twin pregnancies are less accurate than in singleton pregnancies. If necessary, combined screening for sonographic markers of chromosomal aneuploidy such as the nasal bone, tricuspid regurgitation, and ductus venosus is recommended.31

Cell-free DNA is the most sensitive and specific screening test for common fetal aneuploidies in twin pregnancies.15,32 In singleton pregnancies, cfDNA analysis of maternal blood provides effective screening for trisomy 21, 18, and 13. A recent meta-analysis reported that the DR of cfDNA was >99%, and the false-positive rate was 0.04% in singleton pregnancies.15,33 By contrast, noninvasive prenatal testing has a higher failure rate in twin pregnancies owing to many factors such as maternal body mass index, placenta-confined mosaicism, conception by in vitro fertilization, dichorionicity, and single-twin demise, and data on cfDNA tests in twin pregnancies are still limited.15 Gil et al.33 conducted a meta-analysis to describe the performance of cfDNA analysis in twin pregnancy. The results showed that the performance of cfDNA analysis for trisomy 21 may be similar to that in singleton pregnancy, with a DR of 99.7% and a false-positive rate of 0.04%.33 However, the sample size of trisomy 18 and 13 was very limited to accurately assess the predictive performance of the cfDNA test. Currently, the application of cfDNA screening is advised in twin pregnancies. If the cfDNA results are positive and indicate a high risk for trisomy 21, chorionic villus sampling (CVS) should be carried out for a more accurate confirmation. Regarding the high risk of trisomy 13 and 18, if fetal defects are detected in the follow-up ultrasound scan, amniocentesis can be considered.

According to the FIGO guidelines, CVS is preferred in DC twins, because it can be performed earlier than amniocentesis, and genetic disorders can be identified earlier to reduce the risk of fetal loss.7 The rate of fetal loss after invasive procedure is approximately 2% to 3.8% for CVS and 1.5% to 3.1% for amniocentesis in twins, which is higher than in singletons.5,12,31,34–36 A recent meta-analysis showed that there is no significant difference between twin pregnancies undergoing and those not undergoing invasive procedure regarding the risk of fetal loss within four weeks after the procedure.36 Another retrospective study showed that the risk of fetal loss was twofold higher in twin pregnancies undergoing CVS than those not undergoing CVS, but such an increased risk was reportedly associated with the maternal characteristic rather than the procedure itself.37 Agarwal and Alfirevic35 proposed that chorionicity should also be considered with respect to fetal loss rate because it presents with different perinatal outcomes, and few studies describe the outcome according to chorionicity. Other complications such as amniotic fluid leakage, chorioamnionitis, and severe fetal injury are very rare; thus, invasive prenatal diagnosis is still a safe procedure. These findings are helpful when counseling parents about the safety of the procedure, but there is a need for further large-scale studies to verify the actual rate of fetal loss.

There are some distinct differences between MC and DC twins.38 Because DC twins have different genetic information, analysis of the estimated risks of chromosomal abnormalities, for example, Down syndrome, is different according to chorionicity. The assessment of estimated risk is equivalent with singletons in MC twins, whereas it should be calculated independently in each of the DC twins. It is also recognized that both amniotic sacs should be sampled regardless of chorionicity, unless the MC twins are concordant for growth and AFV and have no fetal abnormality.

Diagnosis of selective FGR (sFGR) in twins

sFGR occurs in 10% to 15% of twin pregnancies.39 The diagnostic standard of sFGR is still heterogeneous in different countries for both MC and DC twins. According to the FIGO and ISUOG guidelines,7,12 the diagnostic standards of sFGR are that one fetus has an EFW below the 10th percentile in DC twins and an intertwin EFW discordance of ≥25% in MC twins.7 In the NICE guidelines, it is suggested that a fetal weight discordance >25% is a clinical indicator of sFGR. Khalil et al. established a consensus definition of sFGR through the Delphi procedure in 2019.31,40

Nikolaos thought that the Delphi diagnostic criteria may lead to less diagnosis of sFGR, less iatrogenic preterm birth, and no significant influence in perinatal outcomes in DC twins.41 It is believed that sFGR in DC twins can be managed similar to FGR in singletons, but recent studies have found that the abnormal flow of umbilical and cerebral arteries seem to have different prognostic value between DC twins and singletons.42 Therefore, the management strategy of sFGR in DC twins still needs further studies. Given that sFGR in MC twins is more common and considered to have a worse perinatal mortality and morbidity rate, most published studies have focused on the clinical characteristics and prognosis of selective intrauterine growth restriction (sIUGR) in MC twin pregnancies. However, a wide heterogeneity in the definition of sIUGR applied in different studies hinders the comparison and summarization of these new findings. The consensus definition of sFGR through the Delphi procedure takes vascular indices into account. This criteria were also adopted by the Chinese guidelines.43 Interestingly, a recent study44 that compared different diagnostic criteria of sIUGR claimed that when intertwin EFW discordance of ≥25% was used as the diagnostic standard, the incidence of sIUGR is similar regardless of whether abdominal circumference or EFW <10th percentile is included. A combination with UA PI of the small fetus >95th percentile may indicate a more severe case. Donepudi et al.45 reported that the use of this new definition could help to detect more sFGR cases and that it was a sensitive predictor of donor demise after fetoscopic laser surgery when complicated with TTTS. More trials are needed to validate Khalil and colleagues’40 consensus before they can be widely used in clinical practice to make advances in fetal surveillance, counseling, and management.

Management of the co-twin in single intrauterine demise (sIUD)

sIUD can be caused by TTTS, maternal disorders, abnormal umbilical cord and placenta, or congenital abnormalities. It affects 6% of twin pregnancy46 and leads to adverse outcomes such as cotwin demise, preterm delivery, and neurological impairment. The impact on the cotwin following sIUD is usually worse in MC twins because of the independent fetoplacental circulation, especially when the sIUD occurs within 28 weeks of gestation or is complicated by sFGR.12,46–48 The data show that the risk of cotwin demise is 5 times higher (15% and 3%), and the neurodevelopmental impairment is 13 times higher (26% and 2%) in MC twins than in DC twins.46,47 However, the aforementioned complications can still occur in DC twins, in which case the patient should be referred to a tertiary center. According to the international guidelines,7,12,31 when sIUD occurs before the surviving cotwin is viable, immediate delivery of the surviving fetus is not advised because the brain damage has probably occurred. A serial fetal Doppler examination should be performed to assess for fetal anemia, in particular MCA-PSV in the surviving fetus. If necessary, magnetic resonance imaging (MRI) should be performed 4 to 6 weeks later after fetal demise.12,31 However, Shinar et al.49 found that although increased MCA-PSV may be a poor predictor of cerebral injury, early MRI within 2 weeks of sIUD is valuable to identify any cerebral injury with additional diffusion-weighted imaging. Thus, conservative surveillance is suggested when sIUD occurs prematurely, but the utility of MRI with diffusion-weighted imaging to detect brain injury needs more clinical trials.

Staging and management of TTTS

TTTS occurs in 10% to 15% of all MC diamniotic (MCDA) twins.4 It is a severe complication leading to hypovolemia, oliguria, and oligohydramnios in the donor and hypervolemia, polyuria, and polyhydramnios in the recipient. The general consensus about the diagnostic criteria is based on the discordance of AFV: the donor twin has the deepest vertical pocket (DVP) of <2 cm (oligohydramnios) at any gestational age, and the recipient twin has a DVP of ≥8 cm (polyhydramnios) at ≤20 weeks and ≥10 cm after 20 weeks of gestation.12 A recent study investigated DVP in MCDA twins throughout the gestation and established a reference range for AFV. The authors sought out that the DVP in MCDA twins varies with gestational age and increases between 16 and 26 gestational weeks.50 The data show that the 97.5th centile of the DVP is 7 cm before 16 weeks’ gestation, which increases to 8 cm after 18 weeks. Therefore, Khalil51 recommends a lower DVP cutoff value (≥6 cm) to identify polyhydramnios before 18 weeks.

As is well known, the Quintero staging system is the most commonly used classification system of TTTS in the last two decades. However, this system is not a representation of the chronological evolution of the disease, and its prognostic value is contentious. A recent retrospective analysis showed a stage-related perinatal outcome. The rates of double survival and at least one survivor are significantly higher in cases of stage I and II when compared with those in cases of stage III and IV. But the overall survival rates between stages I vs. II and those in stages III vs. IV is not significant different. The study concluded that the staging system may have no necessity to differentiate between stages I and II vs. stages III and IV.52

Because unbalanced blood flows through placenta vascular anastomoses, cardiovascular dysfunction may occur in TTTS because of severe fetal hemodynamic instability, especially in the recipient. The Children’s Hospital of Philadelphia (CHOP) has developed a score to evaluate fetal cardiac function. Gapp-Born et al.53 found that higher CHOP scores (≥3) and myocardial performance index z score (>1.645) may be the predictors of recipient fetal loss. However, the studies investigating the CHOP cardiovascular score are still limited.53,54 More observational and prospective studies are needed to validate the prediction value of cardiovascular parameters and improve Quintero’s classification.

TTTS is a severe condition, and patients with TTTS should be referred promptly to a fetal medicine center. The treatment methods include laser coagulation, amniodrainage, selective fetal reduction, and conservative management. A randomized controlled trial has proven that the Solomon technique can significantly reduce postlaser TAPS and recurrence of TTTS, but the survival rate after the procedure is similar to standard laser coagulation.55 Recently, an international randomized trial suggested that expectant management with heightened weekly surveillance is a reasonable option compared with immediate surgery for asymptomatic women with a long cervix in stage I TTTS before 26 weeks’ gestation.56

More large-scale clinical trials are needed to validate a lower DVP to diagnose polyhydramnios in early pregnancy and the cardiovascular function in TTTS to modify the diagnostic standards and classification of TTTS. Laser therapy is the best available option for TTTS at Quintero staging II and greater; however, unexpected progression of TTTS stage I leads to challenges in fetal therapy and laser therapy in TTTS stage I is hence still controversial.15

Diagnosis and management of TAPS

TAPS is caused by the slow and chronic unbalanced fetofetal transfusion through minuscule placenta anastomoses, leading to anemia in the donor and polycythemia in the recipient, without differences between AFVs.57 Because prenatal ultrasound has a good predictive value, the antenatal diagnosis of TAPS is based on the discordant fetal Doppler measurements.58 According to the ISUOG guidelines,10 the criteria are recommended as MCA-PSV >1.5 multiples of the median (MoM) in the donor and MCA-PSV <1.0 MoM in the recipient. In a recent study, a group of maternal-fetal medicine specialists proposed a consensus-based diagnostic criteria through the Delphi procedure. They agreed on the combination of MCA-PSV ≥1.5 MoM in the donor and MCA-PSV ≤0.8 MoM in the recipient or MCA-PSV discordance ≥1.0 MoM to diagnose TAPS.59 Because ΔMCA-PSV is related to the intertwin hemoglobin difference, it seems a better antenatal indicator of TAPS. Several cohort studies show that an intertwin MCA-PSV discordance >0.5 MoM may be more sensitive to identify TAPS and proposed a new classification system of TAPS according to ΔMCA-PSV.57,60 However, the evidence of modified prenatal diagnostic criteria is still insufficient, given the relatively low incidence of TAPS.

Treatment options for TAPS include expectant management, preterm delivery, intrauterine blood transfusion, selective feticide, and fetoscopic laser surgery. Intrauterine blood transfusion can be considered for severe anemia, but the possible adverse effect is deterioration of the polycythemia-hyperviscosity syndrome in the recipient twin.57 Selective feticide can be the option in severe early-onset TAPS.57 Laser surgery is the only causal treatment, but the recurrence rate after the procedure is 15%, which is higher than that for TTTS (1%).57 There is still no consensus about the outcome and optimal management of TAPS.57 Therefore, treatment choices should be individualized and discussed with the parents.

Strengths and limitations

This review aimed to refine the problems based on the latest FIGO guidelines and compared and summarized the international guidelines and clinical studies, for example, the pitfalls of chorionicity determination, essential parameters for monitoring and management of twin pregnancy, and the inconsistent diagnosis or intervention protocol for specific complications. At present, these issues remain unsolved in China. This prompts clinicians and researchers to propose stronger evidence and convincing opinions to improve specific clinical guidelines. It can benefit clinicians not only in China but also across the world.

The main weakness is that this review should be viewed using a dialectical perspective, as it is mainly based on the studies and guidelines around the word, especially in Western developed countries.


The FIGO practice guidelines highlight the importance of the accurate and early determination of gestational age and chorionicity, demonstrate the prenatal screening for chromosomal abnormalities, and provide routine ultrasound assessment and optimal management for pregnancy complications in twin pregnancy. The referral to a tertiary center is necessary.61 However, there are still many challenges and controversies that remain unaddressed. For example, the cutoff value of cervical length to define increased risk of preterm delivery still requires validation, and the effective preventive strategy for preterm birth warrants further confirmation. Furthermore, increased efforts are needed to find a better way of ultrasound surveillance in twin pregnancy to identify the abnormalities in a timely and effective manner. The standard diagnostic criteria and superior management of specific complications remain controversial. The studies about the predictive indices for specific complications in an early gestational age are also important. More randomized controlled trials, cohort studies, or consensuses are needed to resolve these issues and establish consistent international protocol to improve the outcome of twin pregnancies.


This study was supported by the National Key Research and Development Plan (2018YFC1002900) and the Research and Development Projects in Key Areas of Guangdong Province (2019B020227001).

Author Contributions

Jingyu Liu: Conceptualization, Methodology, Evidence collection, Data/Evidence Analysis, Writing-Original Draft; Quanrui Liu: Data/Evidence collection, Writing - Original Draft; Jingya Zhao: Validation, Writing – Review & Editing; Danlun Li: Data/evidence collection; Yi Zhou: Idea & Conceptualization, Funding Acquisition, Supervision, Project Administration, Writing - Review & Editing.

Conflicts of Interest



1. Santana DS, Surita FG, Cecatti JG. Multiple pregnancy: epidemiology and association with maternal and perinatal morbidity. Rev Bras Ginecol Obstet 2018;40(9):554–562. doi:10.1055/s-0038-1668117.
2. Tchirikov M. Monochorionic twin pregnancy: screening, pathogenesis of complications and management in the era of microinvasive fetal surgery. J Perinat Med 2010;38(5):451–459. doi:10.1515/jpm.2010.069.
3. Hack KE, Derks JB, Elias SG, et al. Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study. BJOG 2008;115(1):58–67. doi:10.1111/j.1471-0528.2007.01556.x.
4. Micheletti T, Eixarch E, Bennasar M, et al. Complications of monochorionic diamniotic twins: stepwise approach for early identification, differential diagnosis, and clinical management. Matern Fetal Med 2021;3(1):42–52. doi:10.1097/fm9.0000000000000076.
5. Townsend R, Khalil A. Ultrasound surveillance in twin pregnancy: an update for practitioners. Ultrasound 2018;26(4):193–205. doi:10.1177/1742271X18794013.
6. Stenhouse E, Hardwick C, Maharaj S, et al. Chorionicity determination in twin pregnancies: how accurate are we?Ultrasound Obstet Gynecol 2002;19(4):350–352. doi:10.1046/j.1469-0705.2002.00679.x.
7. FIGO Working Group on Good Clinical Practice in Maternal-Fetal Medicine. Good clinical practice advice: management of twin pregnancy. Int J Gynaecol Obstet 2019;144(3):330–337. doi:10.1002/ijgo.12742.
8. Lu J, Cheng YKY, Ting YH, et al. Pitfalls in assessing chorioamnionicity: novel observations and literature review [published correction appears in Am J Obstet Gynecol 2019;220(5):499]. Am J Obstet Gynecol 2018;219(3):242–254. doi:10.1016/j.ajog.2018.02.010.
9. Bracero LA, Huff C, Blitz MJ, et al. Ultrasound and histological measurements of dividing membrane thickness in twin gestations. Ultrasound Obstet Gynecol 2017;50(4):470–475. doi:10.1002/uog.17337.
10. Management of monochorionic twin pregnancy: green-top guideline no. 51. BJOG 2017;124(1):e1–e45. doi:10.1111/1471-0528.14188.
11. Carroll SG, Soothill PW, Abdel-Fattah SA, et al. Prediction of chorionicity in twin pregnancies at 10–14 weeks of gestation. BJOG 2002;109(2):182–186. doi:10.1111/j.1471-0528.2002.01172.x.
12. Khalil A, Rodgers M, Baschat A, et al. ISUOG Practice Guidelines: role of ultrasound in twin pregnancy. Ultrasound Obstet Gynecol 2016;47(2):247–263. doi:10.1002/uog.15821.
13. D’Antonio F, Odibo AO, Prefumo F, et al. Weight discordance and perinatal mortality in twin pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018;52(1):11–23. doi:10.1002/uog.18966.
14. Amyx MM, Albert PS, Bever AM, et al. Intrauterine growth discordance across gestation and birthweight discordance in dichorionic twins. Am J Obstet Gynecol 2020;222(2):174.e1–174.e10. doi:10.1016/j.ajog.2019.08.027.
15. Khalil A, Liu B. Controversies in the management of twin pregnancy. Ultrasound Obstet Gynecol 2021;57(6):888–902. doi:10.1002/uog.22181.
16. Giorgione V, Briffa C, Di Fabrizio C, et al. Perinatal outcomes of small for gestational age in twin pregnancies: twin vs. singleton charts. J Clin Med 2021;10(4):643–652. Published February 8, 2021. doi:10.3390/jcm10040643.
17. Chen J, Zhang J, Liu Y, et al. Fetal growth standards for Chinese twin pregnancies. BMC Pregnancy Childbirth 2021;21(1):436–449. Published June 22, 2021. doi:10.1186/s12884-021-03926-y.
18. Kalafat E, Sebghati M, Thilaganathan B, et al. Predictive accuracy of Southwest Thames Obstetric Research Collaborative (STORK) chorionicity-specific twin growth charts for stillbirth: a validation study. Ultrasound Obstet Gynecol 2019;53(2):193–199. doi:10.1002/uog.19069.
19. Briffa C, Stirrup O, Huddy C, et al. Twin chorionicity-specific population birth-weight charts adjusted for estimated fetal weight. Ultrasound Obstet Gynecol 2021;58(3):439–449. doi:10.1002/uog.23606.
20. Fetal Medicine Subgroup, Chinese Society of Perinatal Medicine, Chinese Medical Association; Obstetrics Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Guideline for management of twin pregnancy (part I): monitoring and management of twin pregnancy [in Chinese]. Chinese J Perinatal Med 2015;18(8):561–567. doi:10.3760/cma.j.issn.1007-9408.2015.08.001.
21. Pan M, Chen M, Leung TY, et al. Outcome of monochorionic twin pregnancies with abnormal umbilical artery Doppler between 16 and 20 weeks of gestation. J Matern Fetal Neonatal Med 2012;25(3):277–280. doi:10.3109/14767058.2011.573830.
22. Nakanishi K, Muto H, Yamamoto R, et al. Prevalence of umbilical artery Doppler waveform abnormality during the early second trimester and the subsequent variation of waveforms in monochorionic diamniotic twin pregnancies: a prospective cohort study. J Obstet Gynaecol Res 2021;47(7):2338–2346. doi:10.1111/jog.14799.
23. Rehal A, Benkő Z, De Paco Matallana C, et al. Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: a randomized, double-blind trial. Am J Obstet Gynecol 2021;224(1):86.e1–86.e19. doi:10.1016/j.ajog.2020.06.050.
24. Committee on Practice Bulletins—Obstetrics, Society for Maternal-Fetal Medicine. Practice bulletin no. 169: multifetal gestations: twin, triplet, and higher-order multifetal pregnancies. Obstet Gynecol 2016;128(4):e131–e146. doi:10.1097/AOG.0000000000001709.
25. National Collaborating Centre for Women’s and Children’s Health (UK). Multiple Pregnancy: The Management of Twin and Triplet Pregnancies in the Antenatal Period. London: RCOG Press; 2011.
26. D’Antonio F, Berghella V, Di Mascio D, et al. Role of progesterone, cerclage and pessary in preventing preterm birth in twin pregnancies: a systematic review and network meta-analysis. Eur J Obstet Gynecol Reprod Biol 2021;261:166–177. doi:10.1016/j.ejogrb.2021.04.023.
27. França MS, Hatanaka AR, Andrade Junior VL, et al. Cervical pessary plus progesterone for twin pregnancy with short cervix compared to unselected and non-treated twin pregnancy: a historical equivalence cohort study (EPM Twin Pessary Study). Pessário cervical associado a progesterona em gestações gemelares com colo curto comparado a gestações gemelares não selecionadas e não tratadas: estudo de coorte histórica de equivalência (Estudo de Pessário em Gêmeos EPM). Rev Bras Ginecol Obstet 2020;42(10):621–629. doi:10.1055/s-0040-1713806.
28. Han MN, O’Donnell BE, Maykin MM, et al. The impact of cerclage in twin pregnancies on preterm birth rate before 32 weeks. J Matern Fetal Neonatal Med 2019;32(13):2143–2151. doi:10.1080/14767058.2018.1427719.
29. Le KD, Nguyen LK, Nguyen L, et al. Cervical pessary vs vaginal progesterone for prevention of preterm birth in women with twin pregnancy and short cervix: economic analysis following randomized controlled trial. Ultrasound Obstet Gynecol 2020;55(3):339–347. doi:10.1002/uog.20848.
30. Corcoran S, Breathnach F, Burke G, et al. Dichorionic twin ultrasound surveillance: sonography every 4 weeks significantly underperforms sonography every 2 weeks: results of the Prospective Multicenter ESPRiT Study. Am J Obstet Gynecol 2015;213(4):551.e1–5. doi:10.1016/j.ajog.2015.07.049.
31. von Kaisenberg C, Klaritsch P, Ochsenbein-Kölble N, et al. Screening, management and delivery in twin pregnancy. Ultraschall Med 2021;42(4):367–378. doi:10.1055/a-1248-8896.
32. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for fetal chromosomal abnormalities: ACOG practice bulletin, number 226. Obstet Gynecol 2020;136(4):e48–69. doi:10.1097/AOG.0000000000004084.
33. Gil MM, Galeva S, Jani J, et al. Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of the Fetal Medicine Foundation results and meta-analysis. Ultrasound Obstet Gynecol 2019;53(6):734–742. doi:10.1002/uog.20284.
34. Ghi T, Sotiriadis A, Calda P, et al. ISUOG Practice Guidelines: invasive procedures for prenatal diagnosis. Ultrasound Obstet Gynecol 2016;48(2):256–268. doi:10.1002/uog.15945.
35. Agarwal K, Alfirevic Z. Pregnancy loss after chorionic villus sampling and genetic amniocentesis in twin pregnancies: a systematic review. Ultrasound Obstet Gynecol 2012;40(2):128–134. doi:10.1002/uog.10152.
36. Di Mascio D, Khalil A, Rizzo G, et al. Risk of fetal loss following amniocentesis or chorionic villus sampling in twin pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2020;56(5):647–655. doi:10.1002/uog.22143.
37. Elger T, Akolekar R, Syngelaki A, et al. Fetal loss after chorionic villus sampling in twin pregnancy. Ultrasound Obstet Gynecol 2021;58(1):48–55. doi:10.1002/uog.23694.
38. Audibert F, Gagnon A. No. 262—prenatal screening for and diagnosis of aneuploidy in twin pregnancies. J Obstet Gynaecol Can 2017;39(9):754–767. doi:10.1016/j.jogc.2017.06.015.
39. Townsend R, D’Antonio F, Sileo FG, et al. Perinatal outcome of monochorionic twin pregnancy complicated by selective fetal growth restriction according to management: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2019;53(1):36–46. doi:10.1002/uog.20114.
40. Khalil A, Beune I, Hecher K, et al. Consensus definition and essential reporting parameters of selective fetal growth restriction in twin pregnancy: a Delphi procedure. Ultrasound Obstet Gynecol 2019;53(1):47–54. doi:10.1002/uog.19013.
41. Antonakopoulos N, Pateisky P, Liu B, et al. Selective fetal growth restriction in dichorionic twin pregnancies: diagnosis, natural history, and perinatal outcome. J Clin Med 2020;9(5):1404. doi:10.3390/jcm9051404.
42. Vanlieferinghen S, Anselem O, Le Ray C, et al. Prognostic value of umbilical and cerebral Doppler in fetal growth restriction: comparison of dichorionic twins and singletons. PLoS One 2015;10(4):e0123067. doi:10.1371/journal.pone.0123067.
43. Fetal Medicine Subgroup, Chinese Society of Perinatal Medicine, Chinese Medical Association; Obstetrics Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Guideline for management of twin pregnancy (2020 update)(in Chinese). Chinese J Perinatal Med 2020,23(8):505–516. doi:10.3760/cma.j.cn113903-20200812-00793.
44. Curado J, Sileo F, Bhide A, et al. Early- and late-onset selective fetal growth restriction in monochorionic diamniotic twin pregnancy: natural history and diagnostic criteria. Ultrasound Obstet Gynecol 2020;55(5):661–666. doi:10.1002/uog.20849.
45. Donepudi R, Espinoza J, Nassr AA, et al. Prediction of post-laser fetal death in selective growth restriction complicating twin-twin transfusion syndrome using standardized definitions. Ultrasound Obstet Gynecol 2021;58(5):738–743. doi:10.1002/uog.23519.
46. Mackie FL, Rigby A, Morris RK, et al. Prognosis of the co-twin following spontaneous single intrauterine fetal death in twin pregnancies: a systematic review and meta-analysis. BJOG 2019;126(5):569–578. doi:10.1111/1471-0528.15530.
47. Hillman SC, Morris RK, Kilby MD. Co-twin prognosis after single fetal death: a systematic review and meta-analysis. Obstet Gynecol 2011;118(4):928–940. doi:10.1097/AOG.0b013e31822f129d.
48. Jain D, Purohit RC. Review of twin pregnancies with single fetal death: management, maternal and fetal outcome. J Obstet Gynaecol India 2014;64(3):180–183. doi:10.1007/s13224-013-0500-5.
49. Shinar S, Harris K, van Mieghem T, et al. Early imaging predictors of fetal cerebral ischemic injury in monochorionic twin pregnancy complicated by spontaneous single intrauterine death. Ultrasound Obstet Gynecol 2022;59(4):497–505. doi:10.1002/uog.24844.
50. Dekoninck P, Deprest J, Lewi P, et al. Gestational age-specific reference ranges for amniotic fluid assessment in monochorionic diamniotic twin pregnancies. Ultrasound Obstet Gynecol 2013;41(6):649–652. doi:10.1002/uog.12387.
51. Khalil A. Modified diagnostic criteria for twin-to-twin transfusion syndrome prior to 18 weeks’ gestation: time to change? Ultrasound Obstet Gynecol 2017;49(6):804–805. doi:10.1002/uog.17443.
52. Bamberg C, Diehl W, Diemert A, et al. Differentiation between TTTS stages I vs II and III vs IV does not affect probability of double survival after laser therapy. Ultrasound Obstet Gynecol 2021;58(2):201–206. doi:10.1002/uog.23131.
53. Gapp-Born E, Sananes N, Weingertner AS, et al. Predictive value of cardiovascular parameters in twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2014;44(4):427–433. doi:10.1002/uog.13351.
54. Stirnemann JJ, Nasr B, Proulx F, et al. Evaluation of the CHOP cardiovascular score as a prognostic predictor of outcome in twin-twin transfusion syndrome after laser coagulation of placental vessels in a prospective cohort. Ultrasound Obstet Gynecol 2010;36(1):52–57. doi:10.1002/uog.7713.
55. Slaghekke F, Lopriore E, Lewi L, et al. Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-to-twin transfusion syndrome: an open-label randomised controlled trial. Lancet 2014;383(9935):2144–2151. doi:10.1016/S0140-6736(13)62419-8.
56. Stirnemann J, Slaghekke F, Khalek N, et al. Intrauterine fetoscopic laser surgery versus expectant management in stage 1 twin-to-twin transfusion syndrome: an international randomized trial. Am J Obstet Gynecol 2021;224(5):528.e1–528.e12. doi:10.1016/j.ajog.2020.11.031.
57. Tollenaar LSA, Lopriore E, Oepkes D, et al. Twin anemia polycythemia sequence: knowledge and insights after 15 years of research. Matern Fetal Med 2021;3(1):33–41. doi:10.1097/fm9.0000000000000065.
58. Wei X, Wei Y, Gong L, et al. The diagnostic value of prenatal ultrasound in the twin anemia-polycythemia sequence (in Chinese). Chinese J Ultrasound Med 2021;37(11):1316–1319.
59. Khalil A, Gordijn S, Ganzevoort W, et al. Consensus diagnostic criteria and monitoring of twin anemia-polycythemia sequence: Delphi procedure. Ultrasound Obstet Gynecol 2020;56(3):388–394. doi:10.1002/uog.21882.
60. Tollenaar L, Lopriore E, Middeldorp JM, et al. Improved prediction of twin anemia-polycythemia sequence by delta middle cerebral artery peak systolic velocity: new antenatal classification system. Ultrasound Obstet Gynecol 2019;53(6):788–793. doi:10.1002/uog.20096.
61. Zou G, Sun L. Prenatal screening, diagnosis and intrauterine therapy for twin pregnancy: referral is the key (in Chinese). Chinese J Pract Gynecol Obstet 2020;36(9):814–817. doi:10.19538/j.fk2020090107.

Edited By Yang Pan

How to cite this article: Liu J, Liu Q, Zhao J, Li D, Zhou Y. The Controversies and Challenges in theManagement of Twin Pregnancy: From the Perspective of International Federation of Gynecology and Obstetrics Guidelines. Maternal Fetal Med 2022;4(4):255–261. doi: 10.1097/FM9.0000000000000170.


Ultrasonography; Pregnancy, twin; Selective intrauterine growth restriction; Intertwin discordance; Twin-to-twin transfusion syndrome; Twin anemia polycythemia sequence; Controversies

Copyright © 2022 The Chinese Medical Association, published by Wolters Kluwer Health, Inc.