Is There a Cumulative Effect for Congenital Heart Defects in Monochorionic Twins after Assisted Reproduction? – A Retrospective Analysis at a Tertiary Referral Center

Abstract

Introduction

The aim of our study was to compare maternal, chorionicity and neonatal complications in monochorionic (MC) twins between spontaneously conceived (SC) and assisted reproductive technologies (ART) pregnancies.

Material and Methods

This was a retrospective cohort study between January 2010 to December 2019 at a tertiary referral University center. All consecutive pregnancies with MC twins that delivered at our University hospital were included. Maternal, chorionicity and neonatal complications were recorded and compared between SC and ART pregnancies.

Results

393 MC pregnancies were included for final analysis, including 353 (89.8%) SC and 40 (10.2%) pregnancies conceived after ART. Hypothyroidism was the only maternal condition seen significantly more often in ART pregnancies (35.0% vs 12.5%, p = 0.001). There were no significant differences in chorionicity complications, such as twin-twin transfusion syndrome, selective fetal growth restriction and twin anemia-polycythemia sequence (40.0% in ART pregnancies vs 31.6% in SC pregnancies, p = 0.291). At least one congenital anomaly in one twin was seen significantly more often in ART pregnancies (18.8% vs 8.1%, p = 0.004), especially congenital heart defects (16.3% vs 6.2%, p = 0.005). There were no other significant differences in neonatal outcomes between both groups, however, there were non-significant trends in gestational age at delivery (34 weeks in ART pregnancies vs 35 weeks, p = 0.078) and birthweight (1951 g ± 747 in ART pregnancies vs 2143 g ± 579, p = 0.066).

Conclusion

This is the largest cohort study to date comparing maternal, chorionicity and neonatal complications between MC twin pregnancies after ART and after SC. Hypothyroidism was the only maternal condition occurring more frequently in pregnancies conceived after ART. There were no significant differences in chorionicity complications, in contrast to previously reported studies. While MC twins and ART pregnancies per se are known to be at risk for congenital heart defects, there seems to be a cumulative effect in MC pregnancies conceived after ART.

Zusammenfassung

Einleitung

Das Ziel dieser Studie war es, die mütterlichen, neonatalen und chorionizitätsbedingte Komplikationen von monochorialen (MC) Zwillingen bei spontan gezeugten (SG) bzw. mit Techniken der assistierten Reproduktion (ART) gezeugten Kindern zu vergleichen.

Material und Methoden

Diese retrospektive Kohortenstudie untersucht den Zeitraum von Januar 2010 bis Dezember 2019 in einem Universitätsklinikum der Maximalversorgung. Alle konsekutiven in unserem Universitätskrankenhaus entbundenen Schwangerschaften mit MC Zwillingen wurden in die Studie aufgenommen. Die mütterlichen, neonatalen und chorionizitätsbedingten Komplikationen wurden aufgezeichnet und ihr Auftreten in SG- und ART-Schwangerschaften wurde verglichen.

Ergebnisse

Insgesamt wurden 393 MC Schwangerschaften in die Endanalyse aufgenommen, davon waren 353 (89,8%) SG- und 40 (10,2%) ART-Schwangerschaften. Die Schilddrüsenunterfunktion war die einzige mütterliche Komplikation, die signifikant häufiger bei ART-Schwangerschaften auftrat (35,0% vs. 12,5%, p = 0,001). Es gab keine signifikanten Unterschiede in den chorionizitätsbedingten Komplikationen wie fetofetales Transfusionssyndrom, selektive fetale Wachstumsrestriktion und Zwillings-Anämie-Polyzythämie-Sequenz (40,0% in ART-Schwangerschaften vs. 31,6% in SG-Schwangerschaften, p = 0,291). Bei ART-Schwangerschaften trat mindestens eine angeborene Anomalie bei einem Zwilling signifikant häufiger auf (18,8% vs. 8,1%, p = 0,004), insbesondere angeborene Herzfehler (16,3% vs. 6,2%, p = 0,005). Es gab keine anderen signifikanten Unterschiede in den neonatalen Outcomes zwischen beiden Gruppen; es gab aber nichtsignifikante Trends hinsichtlich des Schwangerschaftsalters bei der Entbindung (34 Wochen für ART-Schwangerschaften vs. 35 Wochen, p = 0,078) und des Geburtsgewichts (1951 g ± 747 für ART-Schwangerschaften vs. 2143 g ± 579, p = 0,066).

Schlussfolgerung

Es handelt sich hier um die bislang größte Kohortenstudie, die mütterliche, neonatale und chorionizitätsbedingte Komplikationen in MC Zwillingsschwangerschaften untersucht und das Auftreten von Komplikationen in ART-Schwangerschaften mit denen in SG-Schwangerschaften vergleicht. Die Schilddrüsenunterfunktion war die einzige mütterliche Komplikation, die häufiger bei ART-Schwangerschaften auftat. Im Gegensatz zu früheren Studien gab es keine signifikanten Unterschiede in den chorionizitätsbedingten Komplikationen. Während MC Zwillinge und ART-Schwangerschaften bekanntlich ein höheres Risiko für angeborene Herzfehler haben, scheint es einen kumulativen Effekt bei mit ART gezeugten MC Schwangerschaften zu geben.

Keywords

assisted reproductive technologies - congenital heart defect - congenital anomalies - monochorionic twins - sFGR - TAPS - TTTS

Schlüsselwörter

Techniken der assistierten Reproduktion - angeborener Herzfehler - kongenitale Anomalien - monochoriale Zwillinge - sFGR - TAPS - fetofetales Transfusionssyndrom - TTTS

Publication History

Received: 20 November 2023

Accepted after revision: 27 December 2023

Article published online:
06 March 2024

• References

• 1 De Geyter C, Calhaz-Jorge C, Kupka MS. et al. ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod 2018; 33: 1586-1601
• 2 Pandey S, Shetty A, Hamilton M. et al. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update 2012; 18: 485-503
• 3 Vermey BG, Buchanan A, Chambers GM. et al. Are singleton pregnancies after assisted reproduction technology (ART) associated with a higher risk of placental anomalies compared with non-ART singleton pregnancies? A systematic review and meta-analysis. BJOG 2019; 126: 209-218
• 4 Jiang F, Gao J, He J. et al. Obstetric outcomes for twins from different conception methods – A multicenter cross-sectional study from China. Acta Obstet Gynecol Scand 2021; 100: 1061-1067
• 5 Korb D, Schmitz T, Seco A. et al. Risk factors and high-risk subgroups of severe acute maternal morbidity in twin pregnancy: A population-based study. PLoS One 2020; 15: e0229612
• 6 von Kaisenberg C, Klaritsch P, Ochsenbein-Kölble N. et al. Screening, Management and Delivery in Twin Pregnancy. Ultraschall Med 2021; 42: 367-378
• 7 Groene SG, Tollenaar LSA, Middeldorp JM. et al. Neonatal management and outcome in complicated monochorionic twins: What have we learned in the past decade and what should you know?. Best Pract Res Clin Obstet Gynaecol 2022; 84: 218-228
• 8 Slaghekke F, Kist WJ, Oepkes D. et al. Twin anemia-polycythemia sequence: Diagnostic criteria, classification, perinatal management and outcome. Fetal Diagn Ther 2010; 27: 181-190
• 9 Gratacós E, Lewi L, Muñoz B. et al. A classification system for selective intrauterine growth restriction in monochorionic pregnancies according to umbilical artery Doppler flow in the smaller twin. Ultrasound Obstet Gynecol 2007; 30: 28-34
• 10 Tavares de Sousa M, Fonseca A, Hecher K. Role of fetal intertwin difference in middle cerebral artery peak systolic velocity in predicting neonatal twin anemia–polycythemia sequence. Ultrasound Obstet Gynecol 2019; 53: 794-797
• 11 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: 47-54
• 12 Khalil A, Rodgers M, Baschat A. et al. ISUOG Practice Guidelines: role of ultrasound in twin pregnancy. Ultrasound Obstet Gynecol 2016; 47: 247-263
• 13 Hartge DR, Weichert J. Prenatal diagnosis and outcome of multiple pregnancies with reversed arterial perfusion (TRAP-sequence). Arch Gynecol Obstet 2012; 286: 81-88
• 14 Bennasar M, Eixarch E, Martinez JM. et al. Selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies. Semin Fetal Neonatal Med 2017; 22: 376-382
• 15 Bamberg C, Hecher K. Twin-to-twin transfusion syndrome: Controversies in the diagnosis and management. Best Pract Res Clin Obstet Gynaecol 2022; 84: 143-154
• 16 ACOG. Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies: ACOG Practice Bulletin, Number 231. Obstet Gynecol 2021; 137: e145-e162
• 17 Cheong-See F, Schuit E, Arroyo-Manzano D. et al. Prospective risk of stillbirth and neonatal complications in twin pregnancies: Systematic review and meta-analysis. BMJ (Online) 2016; 354: i4353
• 18 Van Mieghem T, De Heus R, Lewi L. et al. Prenatal management of monoamniotic twin pregnancies. Obstet Gynecol 2014; 124: 498-506
• 19 Marleen S, Dias C, Nandasena R. et al. Association between chorionicity and preterm birth in twin pregnancies: a systematic review involving 29 864 twin pregnancies. BJOG 2021; 128: 788-796
• 20 Bamberg C, Fotopoulou C, Neissner P. et al. Maternal characteristics and twin gestation outcomes over 10 years: impact of conception methods. Fertil Steril 2012; 98: 95-101
• 21 Goeckenjan M, Madej D, Klimova A. et al. Are two children at once better than one? Risk analysis of twin pregnancies and births after assisted reproduction. Eur J Obstet Gynecol Reprod Biol 2021; 264: 76-82
• 22 Caserta D, Bordi G, Stegagno M. et al. Maternal and perinatal outcomes in spontaneous versus assisted conception twin pregnancies. Eur J Obstet Gynecol 2014; 174: 64-69
• 23 Duy Anh N, Thu Ha NT, Khac Toan N. et al. Obstetric and Perinatal Outcomes of Dichorionic-Diamniotic Twin Pregnancies Conceived by IVF/ICSI Compared with Those Conceived Spontaneously. Clin Ter 2022; 173: 155-163
• 24 Lehnen H, Schäfer S, Reineke T. et al. Twin Pregnancies Conceived Spontaneously and by ART (Assisted Reproductive Technologies) – a Retrospective Analysis and Review. Geburtshilfe Frauenheilkd 2011; 71: 669-676
• 25 ACOG. Committee Opinion No 671: Perinatal Risks Associated With Assisted Reproductive Technology. Obstet Gynecol 2016; 128: e61-e68
• 26 Schlembach D, Mörtl MG, Girard T. et al. [Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany – Austria – Switzerland)]. Anaesthesist 2014; 63: 234-242
• 27 ACOG. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 2020; 135: e237-e260
• 28 Brown MA, Magee LA, Kenny LC. et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension 2018; 72: 24-43
• 29 Poppe K. Management of endocrine disease: thyroid and female infertility: more questions than answers?!. Eur J Endocrinol 2021; 184: R123-R135
• 30 Qin J, Wang H, Sheng X. et al. Pregnancy-related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: a meta-analysis of cohort studies. Fertil Steril 2015; 103: 1492-1508.e1–7
• 31 Wang M, Chai J. Comparison of outcomes of monochorionic twin pregnancies conceived by assisted reproductive technology vs. spontaneous conceptions: A systematic review and meta-analysis. Front Pediatr 2022; 10: 962190
• 32 Ben-Ami I, Molina FS, Battino S. et al. Monochorionic diamniotic in vitro fertilization twins have a decreased incidence of twin-to-twin transfusion syndrome. Fertil Steril 2016; 105: 729-733
• 33 Hansen M, Kurinczuk JJ, Milne E. et al. Assisted reproductive technology and birth defects: A systematic review and meta-analysis. Hum Reprod Update 2013; 19: 330-353
• 34 Wennerholm UB, Bergh C. Perinatal outcome in children born after assisted reproductive technologies. Ups J Med Sci 2020; 125: 158-166
• 35 Panagiotopoulou O, Fouzas S, Sinopidis X. et al. Congenital heart disease in twins: The contribution of type of conception and chorionicity. Int J Cardiol 2016; 218: 144-149
• 36 Giorgione V, Parazzini F, Fesslova V. et al. Congenital heart defects in IVF/ICSI pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018; 51: 33-42
• 37 Galdini A, Fesslova VME, Gaeta G. et al. Prevalence of Congenital Heart Defects in Pregnancies Conceived by Assisted Reproductive Technology: A Cohort Study. J Clin Med 2021; 10: 5363
• 38 Trojner Bregar A, Blickstein I, Verdenik I. et al. Outcome of monochorionic-biamniotic twins conceived by assisted reproduction: a population-based study. J Perinat Med 2016; 44: 881-885
• 39 Sun L, Zou G, Wei X. et al. Clinical outcomes after assisted reproductive technology in twin pregnancies: chorionicity-based comparison. Sci Rep 2016; 6: 26869
• 40 McDonald SD, Han Z, Mulla S. et al. Preterm birth and low birth weight among in vitro fertilization twins: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol 2010; 148: 105-113
• 41 Reichelt J, Kyvernitakis I, Misselwitz B. et al. A population based evaluation of the mode of delivery in association with infertility treatment from 1990–2012. Z Geburtshilfe Neonatol 2015; 219: 37-44
• 42 Richmond E, Ray JG, Pudwell J. et al. Caesarean birth in women with infertility: population-based cohort study. BJOG 2022; 129: 908-916