Vanishing twin

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Vanishing twin syndrome

Vanishing twin syndrome is defined as the spontaneous reduction of a fetus while still in utero 1, which dissipates either partially or completely during gestation 2. Vanishing twin syndrome is estimated to occur in 50% of pregnancies that start with three or more gestational sacs, and 36% of twin pregnancies 3. In vanishing twin syndrome, there may be complete reabsorption of a fetus, formation of a fetus papyraceus (ie, a “mummified” or compressed fetus), or development of a subtle abnormality on the placenta such as a cyst, subchorionic fibrin, or amorphous material 4. The timing of this event significantly affects the outcome of the viable twin and the maternal complications. For example, if the event occurs during the second half of pregnancy, the fetus could develop cerebral palsy or cutis aplasia, and the mother could develop preterm labor, infection, puerperal hemorrhage, consumptive coagulopathy, or obstruction of labor 5.

Vanishing twin syndrome has also been demonstrated to alter the results of first trimester biochemistry testing that is used to screen for aneuploidy 6. Additionally, vanishing twin syndrome was found to be associated with an increased risk for congenital anomalies 7, malformations of cortical development in monochorionic twins 8, vaginal bleeding 9, and preterm premature rupture of membranes 10, as compared with other types of gestation.

Conversely, there is no uniform consensus as to whether any detrimental perinatal outcome concerning infants delivered after vanishing twin syndrome exists at all 11. Moreover, another study that examined only IVF (in-vitro fertilization) pregnancies compared the outcomes of singletons, twins, and vanishing twin syndrome and found that indeed vanishing twin syndrome was associated with poorer outcome when compared with singletons, although a better outcome was noted when compared with twins 12. Hence, there may be additional factors pertaining directly to the inherent underlying cause of infertile couples seeking treatment that can account for the adverse outcomes noted above, regardless of whether spontaneous fetal reduction or other potentially confounding factors have concomitantly occurred 13.

In addition to its association with adverse maternal and neonatal outcome, vanishing twin syndrome was also found to be an independent risk factor for perinatal mortality. This finding confirms conclusions reached in previous studies, which showed that vanishing twin syndrome indeed posed a substantially higher risk for perinatal mortality 14. One study even showed that vanishing twin syndrome more than tripled the risk for such an outcome, even after adjustment for maternal age and parity 14. This last study was composed of 7,757 deliveries, all conceived through assisted reproductive technology (ART), whereas our study population is more than 32 times this value and is composed mainly of spontaneously conceived gestations. In contrast, other smaller studies demonstrated no increased risk of mortality or other adverse outcomes among the vanishing twin syndrome group 15. The conflicting data noted above further emphasize the controversial views regarding the detrimental effects caused by vanishing twin syndrome.

With regard to IVF (in-vitro fertilization) or ICSI (Intracytoplasmic Sperm Injection) pregnancies, it is estimated to occur in 12–30% 16. Furthermore, vanishing twin syndrome is associated with adverse pregnancy outcomes for the remaining survivor among both spontaneously conceived 17 and assisted reproductive technology (ART) pregnancies 18. Adverse outcomes include higher risk of low birth weight, preterm birth, small for gestational age (SGA) and birth defects 19.

Vanishing twin syndrome statistics

The frequency of multiple gestations is 3.3-5.4% at 8 weeks’ gestation 20. Vanishing twin syndrome occurs in 21-30% of multifetal gestation 21.

Research from a European series of pregnancies associated with assisted reproductive technology (ART) show that 10-15% of singleton births were initially twin gestations.

What causes vanishing twin syndrome?

The cause of vanishing twin syndrome is frequently unknown; however, vanishing twin syndrome occurs more often in fetuses with genetic or chromosomal abnormalities 22. Improper cord implantation may also play a role in some cases.

Vanishing twin syndrome pathophysiology

Abnormalities that result in the disappearance of a fetus usually appear to be present from early in development rather than occurring from an acute insult. Placental or fetal analysis frequently reveals chromosome abnormalities. These abnormalities include diploidy, triploidy, and alternate sex chromosome results on placental pathology, skin biopsies, and chorionic villus sampling 23. Study findings of the viable twin chromosomes in these reports are normal. Therefore, it is thought that the vanished twin had a chromosomal abnormality resulting in disappearance.

Vanishing twin syndrome symptoms

Problems usually develop during the first trimester of pregnancy. The most common presenting complaints include bleeding, uterine cramps, and pelvic pain 24. When vanishing twin syndrome occurs during the first trimester, the mother is most likely to develop mild vaginal bleeding and cramping. If the event occurs later in the first trimester, morbidity may be similar to that of the second and third trimesters.

Maternal morbidity in the second and third trimesters

Maternal complications include premature labor, infection from a retained fetus, severe puerperal hemorrhage, consumptive coagulopathy, and obstruction of labor by a low-lying fetus papyraceus causing dystocia and leading to a cesarean delivery 25.

The diagnosis of vanishing twin in a pregnancy significantly increases both preterm (< 37 gestational weeks) and very preterm (< 32 gestational weeks) births 25.

Fetal morbidity and mortality

In addition to loss of a twin, the surviving fetus has an increased risk of cerebral palsy, particularly if vanishing twin syndrome occurred during the second half of pregnancy 26.

Other forms of morbidity reported in the surviving twin are aplasia cutis or areas of skin necrosis. In twins connected through vascular connection by placental anastomoses, temporary hypotension in the surviving twin at the time of fetal demise of the vanishing twin leads to poor perfusion and skin necrosis 27.

Vanishing twin syndrome complications

Prematurity

Singleton pregnancies that were reduced to singleton because of vanishing twin syndrome are more likely to be delivered preterm (35.1 vs 38.2 weeks). These rates of preterm delivery are similar to twin IVF pregnancies (23%) 28. In one series, singletons remaining after a vanishing twin event were associated with very premature birth (< 32 weeks estimated gestational age) 29.

Low birth weight/small for gestational age

Singleton pregnancies that were reduced to singleton because of vanishing twin syndrome are at higher risk for growth restriction (32.6% vs 16.3% of control IVF singleton pregnancies) 30. Risks associated with intrauterine growth restriction include increased morbidity and mortality in the neonatal period and increased rates of hospitalization in the neonatal intensive care unit.

Cerebral palsy

Researchers proposed that vanishing twin syndrome could result in spastic cerebral palsy in the remaining twin. Cerebral palsy is the most common hypothesized pathological clinical sequela in the viable twin 26.

A possible mechanism is the transfusion of thromboplastic proteins from the vanishing twin to the surviving twin, leading to disseminated intravascular coagulation (DIC). Researchers hypothesize that disseminated intravascular coagulation (DIC) results from reverse blood flow from the macerated twin to the viable twin, thus carrying thromboplastins into the circulation. This large thromboplastin load is hypothesized to lead to a state of disseminated intravascular coagulation (DIC) in the viable twin, which then leads to intrauterine central nervous system damage 31.

Another proposed mechanism for central nervous system damage involves large amounts of blood loss from the surviving twin to the low resistance system of the vanishing twin through placental anastomoses. This transfusion could cause wide fluctuation in intravascular pressures, leading to intraventricular hemorrhage that results in cerebral palsy 32.

Cerebral impairment in the survivor has also been linked to confirmed cases of vanishing twin with impairment on the Griffiths Mental and Developmental Scales and Optimality score 32.

Associated congenital anomalies

A link in children with cerebral palsy and other congenital anomalies is possible. In one series, the relative risk for congenital malformations, including microcephaly, isolated hydrocephaly, eye, cleft lip/palate, and cardiac anomalies, increased over baseline from relative risk 3.1-116 depending on the specific defect 33. These anomalies are postulated to be due in part to perturbations in fetal flow in the surviving twin at the time of loss of the vanishing twin 33.

Cutis aplasia

The mechanism of development of cutis aplasia is most likely vascular. There is thought to be decreased perfusion to the affected area at the time of demise of the vanished twin. Most case reports include a fetus papyraceous as the vanished twin 34.

Other complications

Preterm birth of the surviving twin has been described with a 2.3-fold increased risk and a mortality rate that is 3-fold increased 35.

The surviving singleton infant after a twin vanishes has been shown to have a lower birth weight (mean difference, 368 g) than singleton pregnancies 36.

Vanishing twin syndrome diagnosis

Recent vanishing twin has been shown to increase pregnancy associated plasma protein-A (PAPP-A) and free beta-hCG. This may affect risk assessment for aneuploidy in the surviving fetus 37.

Alpha-fetoprotein levels are elevated compared with values at similar junctures in both a singleton pregnancy and a normal twin pregnancy 38.

The rate of rise of beta-human chorionic gonadotropin is slower than in a normal twin pregnancy 39.

If vanishing twin syndrome is diagnosed at the time of nuchal translucency ultrasound, biochemical screening markers may not be as precise as in singleton-assisted reproductive technique pregnancies 40.

The use of biochemical markers may be indicated if, at the time of nuchal translucency, a vanishing twin is confirmed to have an empty gestational sac; however, if a dead fetus remains, biochemical markers are not accurate for screening 41.

Other tests

Amniocentesis after diagnosis of a vanishing twin by prior ultrasonography has been reported to detect an XY cell by both FISH and real-time PCR in the sustained XX 20 weeks’ gestation pregnancy. Take caution about interpretation of amniocentesis results because a vanishing twin fetus could lead to false-positive results 42.

Imaging Studies

Ultrasonography is used to confirm the diagnosis of early twin pregnancy. Follow-up ultrasonography reveals the pregnancy loss (vanishing twin) 43. In addition, after diagnosing first-trimester bleeding, using ultrasonography before dilation and curettage is important. This ensures that bleeding does not signal the loss of just one fetus.

Procedures

Chorionic villus sampling may be helpful if the placenta has a mosaic makeup and there is a singleton at birth.

Histologic Findings

Obtain histological samples of the placenta at birth since they may be the only evidence of vanishing twin syndrome with a reabsorbed fetus 23.

Vanishing twin syndrome management

Uncomplicated vanishing twin syndrome requires no special medical care.

If a fetus papyraceus remains, the pregnancy should be followed closely with serial ultrasonographic evaluation of the live fetus. Risks include premature labor, obstruction of labor, or death of the surviving fetus due to placental abruption or chorioamnionitis 44. This fetus is also at risk for low birth weight and small for gestational age (SGA) with increasing risk in the surviving twin for vanishing twin occurring later in gestation 45.

Your doctor should watch carefully for infection and consumptive coagulopathy.

Instruct pregnant women to seek medical care for vaginal bleeding, cramping, and pelvic pain.

The viable twin should receive specialized medical care as indicated by initial physical examination and subsequent mental and physical development.

Anand et al 46 reported in 2007 that surviving cotwins had poorer scores on the Griffiths Mental and Development Scales when compared with singleton pregnancies.

Surgical Care

Only perform dilation and curettage after ultrasonographic confirmation that a viable embryo or fetus does not exist 42.

  1. The vanishing twin: a major determinant of infant outcome in IVF singleton births. Pinborg A, Lidegaard O, Andersen AN. Br J Hosp Med (Lond). 2006 Aug; 67(8):417-20. https://www.magonlinelibrary.com/doi/pdf/10.12968/hmed.2006.67.8.21976[↩]
  2. Landy, H.J. and Keith, L.G. The vanishing twin: a review. Hum Reprod Update. 1998; 4: 177–183[↩]
  3. Spontaneous reduction of multiple pregnancy: incidence and effect on outcome. Dickey RP, Taylor SN, Lu PY, Sartor BM, Storment JM, Rye PH, Pelletier WD, Zender JL, Matulich EM. Am J Obstet Gynecol. 2002 Jan; 186(1):77-83.[↩]
  4. Landy HJ, Keith LG. The vanishing twin: a review. Hum Reprod Update. 1998 Mar-Apr. 4(2):177-83.[↩]
  5. Yoshida K, Matayoshi K. A study on prognosis of surviving cotwin. Acta Genet Med Gemellol (Roma). 1990. 39(3):383-8.[↩]
  6. Spencer, K., Staboulidou, I., and Nicolaides, K.H. First trimester aneuploidy screening in the presence of a vanishing twin: implications for maternal serum markers. Prenat Diagn. 2010; 30: 235–240[↩]
  7. Pharoah, P.O., Glinianaia, S.V., and Rankin, J. Congenital anomalies in multiple births after early loss of a conceptus. Hum Reprod. 2009; 24: 726–731[↩]
  8. Brodtkorb, E., Myhr, G., and Gimse, R. Is monochorionic twinning a risk factor for focal cortical dysgenesis?. Acta Neurol Scand. 2000; 102: 53–59[↩]
  9. Oloyede, O.A., Iketubosin, F., and Bamgbopa, K. Spontaneous fetal reduction and early pregnancy complications in multiple pregnancies following in vitro fertilization. Int J Gynaecol Obstet. 2012; 119: 57–60[↩]
  10. Rodriguez-Gonzalez, M., Serra, V., Garcia-Velasco, J.A., Pellicer, A., and Remohi, J. The “vanishing embryo” phenomenon in an oocyte donation programme. Hum Reprod. 2002; 17: 798–802[↩]
  11. La Sala, G.B., Villani, M.T., Nicoli, A., Gallinelli, A., Nucera, G., and Blickstein, I. Effect of the mode of assisted reproductive technology conception on obstetric outcomes for survivors of the vanishing twin syndrome. Fertil Steril. 2006; 86: 247–249[↩]
  12. Chasen, S.T., Luo, G., Perni, S.C., and Kalish, R.B. Are in vitro fertilization pregnancies with early spontaneous reduction high risk?. Am J Obstet Gynecol. 2006; 195: 814–817[↩]
  13. Basso, O. and Baird, D.D. Infertility and preterm delivery, birthweight, and Caesarean section: a study within the Danish National Birth Cohort. Hum Reprod. 2003; 18: 2478–2484[↩]
  14. Pinborg, A., Lidegaard, O., la Cour Freiesleben, N., and Andersen, A.N. Consequences of vanishing twins in IVF/ICSI pregnancies. Hum Reprod. 2005; 20: 2821–2829[↩][↩]
  15. Shebl, O., Ebner, T., Sommergruber, M., Sir, A., and Tews, G. Birth weight is lower for survivors of the vanishing twin syndrome: a case-control study. Fertil Steril. 2008; 90: 310–314[↩]
  16. First trimester prenatal screening among women pregnant after IVF/ICSI. Gjerris AC, Tabor A, Loft A, Christiansen M, Pinborg A. Hum Reprod Update. 2012 Jul; 18(4):350-9.[↩]
  17. Vanishing twin syndrome: is it associated with adverse perinatal outcome? Evron E, Sheiner E, Friger M, Sergienko R, Harlev A. Fertil Steril. 2015 May; 103(5):1209-14. https://www.ncbi.nlm.nih.gov/pubmed/25772775[↩]
  18. Analysis of pregnancy outcomes for survivors of the vanishing twin syndrome after in vitro fertilization and embryo transfer. Zhou L, Gao X, Wu Y, Zhang Z. Eur J Obstet Gynecol Reprod Biol. 2016 Aug; 203():35-9. https://www.ncbi.nlm.nih.gov/pubmed/27236603[↩]
  19. Magnus MC, Ghaderi S, Morken NH, et al. Vanishing twin syndrome among ART singletons and pregnancy outcomes. Hum Reprod. 2017;32(11):2298–2304. doi:10.1093/humrep/dex277 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850786[↩]
  20. Landy HJ, Weiner S, Corson SL, et al. The “vanishing twin”: ultrasonographic assessment of fetal disappearance in the first trimester. Am J Obstet Gynecol. 1986 Jul. 155(1):14-9.[↩]
  21. Sampson A, de Crespigny LC. Vanishing twins: the frequency of spontaneous fetal reduction of a twin pregnancy. Ultrasound Obstet Gynecol. 1992 Mar 1. 2(2):107-9[↩]
  22. Landy HJ, Keith LG. The vanishing twin: a review. Hum Reprod Update. 1998 Mar-Apr. 4(2):177-83[↩]
  23. Verstraete L, Costa JM, Chantot-Bastaraud S, Siffroi JP, Fiori O, Uzan S. Finding a single XY cell among XX cells in amniotic fluid by FISH: a possible consequence of a vanishing male twin?. Prenat Diagn. 2007 Jan. 27(1):85-6.[↩][↩]
  24. Jauniaux E, Elkazen N, Leroy F, et al. Clinical and morphologic aspects of the vanishing twin phenomenon. Obstet Gynecol. 1988 Oct. 72(4):577-81.[↩]
  25. Yoshida K, Soma H. Outcome of the surviving cotwin of a fetus papyraceus or of a dead fetus. Acta Genet Med Gemellol (Roma). 1986. 35(1-2):91-8.[↩][↩]
  26. Pharoah PO, Cooke RW. A hypothesis for the aetiology of spastic cerebral palsy–the vanishing twin. Dev Med Child Neurol. 1997 May. 39(5):292-6[↩][↩]
  27. Classen DA. Aplasia cutis congenita associated with fetus papyraceous. Cutis. 1999 Aug. 64(2):104-6.[↩]
  28. Almog B, Levin I, Wagman I, Kapustiansky R, Lessing JB, Amit A, et al. Adverse obstetric outcome for the vanishing twin syndrome. Reprod Biomed Online. 2010 Feb. 20(2):256-260[↩]
  29. Sazonova A, Kallen K, Thurin-Kjellberg A, Wennerholm UB, Bergh C. Factors affecting obstetric outcome of singletons born after IVF. Hum Reprod. 2011 Oct. 26(10):2878-86[↩]
  30. Shebl O, Ebner T, Sommergruber M, Sir A, Tews G. Birth weight is lower for survivors of the vanishing twin syndrome: a case-control study. Fertil Steril. 2008 Aug. 90(2):310-4[↩]
  31. Benirschke K. Intrauterine death of a twin: mechanisms, implications for surviving twin, and placental pathology. Semin Diagn Pathol. 1993 Aug. 10(3):222-31[↩]
  32. Anand D, Platt MJ, Pharoah PO. Vanishing twin: a possible cause of cerebral impairment. Twin Res Hum Genet. 2007 Feb. 10(1):202-9[↩][↩]
  33. Pharoah PO. Prevalence and pathogenesis of congenital anomalies in cerebral palsy. Arch Dis Child Fetal Neonatal Ed. 2007 Nov. 92(6):F489-93[↩][↩]
  34. Maccario S, Fasolato V, Brunelli A, Martinelli S. Aplasia cutis congenita: an association with vanishing twin syndrome. Eur J Dermatol. 2009 Jul-Aug. 19(4):372-4.[↩]
  35. Evron E, Sheiner E, Friger M, Sergienko R, Harlev A. Vanishing twin syndrome: is it associated with adverse perinatal outcome?. Fertil Steril. 2015 May. 103 (5):1209-14.[↩]
  36. Sarhan A, Beydoun H, Jones HW Jr, Bocca S, Oehninger S, Stadtmauer L. Gonadotrophin ovulation induction and enhancement outcomes: analysis of more than 1400 cycles. Reprod Biomed Online. 2011 Aug. 23(2):220-6.[↩]
  37. Chasen ST, Perni SC, Predanic M, Kalish RB, Chervenak FA. Does a “vanishing twin” affect first-trimester biochemistry in Down syndrome risk assessment?. Am J Obstet Gynecol. 2006 Jul. 195(1):236-9[↩]
  38. Abbas A, Johnson M, Bersinger N, Nicolaides K. Maternal alpha-fetoprotein levels in multiple pregnancies. Br J Obstet Gynaecol. 1994 Feb. 101(2):156-8[↩]
  39. Kelly MP, Molo MW, Maclin VM, Binor Z, Rawlins RG, Radwanska E. Human chorionic gonadotropin rise in normal and vanishing twin pregnancies. Fertil Steril. 1991 Aug. 56(2):221-4[↩]
  40. Gjerris AC, Loft A, Pinborg A, Christiansen M, Tabor A. The effect of a ‘vanishing twin’ on biochemical and ultrasound first trimester screening markers for Down’s syndrome in pregnancies conceived by assisted reproductive technology. Hum Reprod. 2009 Jan. 24(1):55-62[↩]
  41. Gjerris AC, Tabor A, Loft A, Christiansen M, Pinborg A. First trimester prenatal screening among women pregnant after IVF/ICSI. Hum Reprod Update. 2012 Jul. 18(4):350-9.[↩]
  42. Rudnicki M, Vejerslev LO, Junge J. The vanishing twin: morphologic and cytogenetic evaluation of an ultrasonographic phenomenon. Gynecol Obstet Invest. 1991. 31(3):141-5.[↩][↩]
  43. Blumenfeld Z, Dirnfeld M, Abramovici H, et al. Spontaneous fetal reduction in multiple gestations assessed by transvaginal ultrasound. Br J Obstet Gynaecol. 1992 Apr. 99(4):333-7[↩]
  44. Lau WC, Rogers MS. Fetus papyraceous: an unusual cause of obstructed labour. Eur J Obstet Gynecol Reprod Biol. 1999 Sep. 86(1):109-11[↩]
  45. Pinborg A, Lidegaard O, Freiesleben NC, Andersen AN. Vanishing twins: a predictor of small-for-gestational age in IVF singletons. Hum Reprod. 2007 Oct. 22(10):2707-14[↩]
  46. Shebl O, Ebner T, Sommergruber M, Sir A, Tews G. Birth weight is lower for survivors of the vanishing twin syndrome: a case-control study. Fertil Steril. 2007 Oct 9.[↩]

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