Empowering Fertility - While the Twin May Vanish, the Problems Do Not 
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While the Twin May Vanish, the Problems Do Not 

By Paul Bergh, MD

A recent report by Evron et al.,  in press that is due to be published in the journal Fertility and Sterility highlights the often unappreciated long-term risks of the vanishing twin syndrome (VTS).  With the advent of assisted reproductive technologies (ART), twins have been on the rise with almost a two-fold increase in the twin rate between 1971 and 2009.  In 2011, twins accounted for 3.3% of live births in the U.S. and the majority of these were conceived naturally.  However, the proportion of twin birth resulting from infertility treatment rose from 27% in 1998 to 36% in 2011 with two-thirds of this increase coming from IVF.  Of naturally conceived twins, approximately 69% of them are fraternal or dizygotic twins (coming from two eggs and two sperm) and the other 31%, are monozygotic or identical twins (coming from a single egg and sperm where the embryo split).   The vast majority of twins conceived as a result of infertility treatments are dizygotic twins.

Twin pregnancies are associated with a six to seven-fold increase in neonatal mortality compared to singleton pregnancies.  Risks associated with twin pregnancies include low birth weight and prematurity with their associated increase in morbidity and mortality.  The mothers of twins are also at increased risk of complications including hypertensive disorders, gestational diabetes (GDM), anemia, postpartum hemorrhage and maternal death.  Preterm delivery (PTD) is of the fetus is of major concern given that in 2011, this was one of the five leading causes of infant death in the U.S.

Vanishing twin syndrome (VTS) is a condition that is diagnosed by early ultrasound.  It occurs when a twin pregnancy identified in the first trimester spontaneously reduces to a singleton.  The lost twin typically is completely reabsorbed; however, a twin lost later in pregnancy can often be identified by remnants discovered at birth, which are referred to as fetus papyraceus.  Past studies report that approximately 30% to 40% of twins conceived by natural conception or in vitro fertilization (IVF) will spontaneously reduce.   There are numerous reports of an increase in adverse outcomes in a VTS pregnancy.  However, this topic remains controversial, and there is no consensus in the literature regarding the impact of VTS.

This study was a retrospective evaluation of a cohort of 252,994 singleton pregnancies, 1801 dizygotic twin pregnancies and 278 pregnancies with VTS.  Interestingly, pregnancy complications were the highest in the VTS group and decreased in a linear fashion to twins and were the lowest in the singleton pregnancy group.  These complications consisted of GDM, chronic hypertension, intrauterine growth restriction (IUGR), premature rupture of membranes (PROM) and cervical insufficiency.  More concerning is that the perinatal mortality was significantly higher for the VTS pregnancy group compared to both the twins and the singleton pregnancy groups.  A report by Pinborg et al. in 2005 found similar results.  Even after adjusting for maternal age and parity, compared to singletons, there was more than a three-fold increased risk of perinatal mortality in the VTS pregnancies.  Additionally, the same linear decrease (highest in VTS – lower in twins – then lowest in singleton) in risk was seen with incidence of very low birth weight (<1500g), low Apgar scores, fetal malformations, and placental abruption.

The reason for the adverse influence of VTS on pregnancy outcomes is not clear though many hypothesize that it may be due to abnormalities in placentation.  It is thought that there is likely some placental vascular compromise or imbalance that may either be a result or a cause of the loss of one twin.   While this topic remains controversial, this recent study is compelling and coupled with past reports, lends credence to having an increased vigilance in pregnancies with VTS.  It also lends support to the movement toward single embryo transfer for in vitro fertilization treatments.  It is important for patients to understand that after a two embryo transfer, the spontaneous reduction to a singleton pregnancy may not reduce their risk of an adverse outcome. It may, in fact, increase the risk compared to a sustained twin pregnancy.  It appears that in regards to risk, once a twin pregnancy, always a twin pregnancy.

References:

Evron, Evyatar, Sheiner, Eyal, Friger, Michael, Sergienko, Ruslan, and Harlev, Avi. Vanishing twin syndrome: is it associated with adverse perinatal outcome? Fertility and Sterility (0). 2015.

Kulkarni, A. D., Kissin, D. M., and Adashi, E. Y. Fertility treatments and multiple births in the United States. N Engl J Med 370(11), 1070-1071. 3-13-2014

Stock, S. and Norman, J. Preterm and term labour in multiple pregnancies. Semin.Fetal Neonatal Med. 15(6), 336-341. 2010.

Chauhan, S. P., Scardo, J. A., Hayes, E., Abuhamad, A. Z., and Berghella, V. Twins: prevalence, problems, and preterm births. Am.J.Obstet.Gynecol. 203(4), 305-315. 2010.

Hamilton, B. E., Hoyert, D. L., Martin, J. A., Strobino, D. M., and Guyer, B. Annual summary of vital statistics: 2010-2011. Pediatrics 131(3), 548-558. 2013.

Landy, H. J. and Keith, L. G. The vanishing twin: a review. Hum.Reprod.Update. 4(2), 177-183. 1998.

Dickey, Richard P. Spontaneous reduction of multiple pregnancy: Incidence and effect on outcome. Am J Obstet Gynecol 186(1), 77-83. 2002.

La Sala, G. B., Nucera, G., Gallinelli, A., Nicoli, A., Villani, M. T., and Blickstein, I. Spontaneous embryonic loss following in vitro fertilization: incidence and effect on outcomes. Am.J.Obstet.Gynecol. 191(3), 741-746. 2004.

Pinborg, A., Lidegaard, O., la Cour, Freiesleben N., and Andersen, A. N. Consequences of vanishing twins in IVF/ICSI pregnancies. Hum.Reprod. 20(10), 2821-2829. 2005

Pinborg, A., Lidegaard, O., and Andersen, A. N. The vanishing twin: a major determinant of infant outcome in IVF singleton births. Br.J.Hosp.Med.(Lond) 67(8), 417-420. 2006.

Pinborg, A., Lidegaard, O., Freiesleben, Nl, and Andersen, A. N. Vanishing twins: a predictor of small-for-gestational age in IVF singletons. Hum.Reprod. 22(10), 2707-2714. 2007.

Almog, B., Levin, I., Wagman, I., Kapustiansky, R., Lessing, J. B., Amit, A., and Azem, F. Adverse obstetric outcome for the vanishing twin syndrome. Reprod.Biomed.Online. 20(2), 256-260. 2010.

Sazonova, A., Kallen, K., Thurin-Kjellberg, A., Wennerholm, U. B., and Bergh, C. Factors affecting obstetric outcome of singletons born after IVF. Hum.Reprod. 26(10), 2878-2886. 2011

Pharoah, P. O., Glinianaia, S. V., and Rankin, J. Congenital anomalies in multiple births after early loss of a conceptus. Hum.Reprod. 24(3), 726-731. 2009

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. 195(3), 814-817. 2006.

Kinzler, W. L., Ananth, C. V., and Vintzileos, A. M. Medical and economic effects of twin gestations. J.Soc.Gynecol.Investig. 7(6), 321-327. 2000.

Sun, L. M., Chen, X. K., Wen, S. W., Fung, K. F., Yang, Q., and Walker, M. C. Perinatal outcomes of normal cotwins in twin pregnancies with one structurally anomalous fetus: a population-based retrospective study. Am.J.Perinatol. 26(1), 51-56. 2009.

Empowering Fertility: An educational blog for patients & healthcare professionals that empowers individuals to take charge of their fertility. Visit us at http://empoweringfertility.com.

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