First trimester prenatal screening among women pregnant after IVF/ICSI

Human Reproduction Update

Volumn 18, Issue 4, 2012, Pages 350-359

  Gjerris, Anne Cathrine ^a   Tabor, Ann ^b   Loft, Anne ^b   Christiansen, Michael ^c   Pinborg, Anja ^b  

^a HILLERØD HOSPITAL   (Denmark)

^b Rigshospitalet   (Denmark)

^c STATENS SERUM INSTITUT   (Denmark)

Author keywords

Chromosomal anomalies; First trimester screening; IVF ICSI Down's syndrome

Indexed keywords

BIOLOGICAL MARKER;

CHROMOSOME ABERRATION; COCHRANE LIBRARY; DOWN SYNDROME; FERTILIZATION IN VITRO; GESTATIONAL AGE; HUMAN; INTRACYTOPLASMIC SPERM INJECTION; MATERNAL AGE; MEDLINE; NUCHAL TRANSLUCENCY MEASUREMENT; PRENATAL SCREENING; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; SYSTEMATIC REVIEW; TWIN PREGNANCY;

BIOLOGICAL MARKERS; CHORION; CHROMOSOME ABERRATIONS; DOWN SYNDROME; FEMALE; FERTILIZATION IN VITRO; GESTATIONAL AGE; HUMANS; MATERNAL AGE; NUCHAL TRANSLUCENCY MEASUREMENT; PREGNANCY; PREGNANCY TRIMESTER, FIRST; PREGNANCY, TWIN; PRENATAL DIAGNOSIS; SPERM INJECTIONS, INTRACYTOPLASMIC;

EID: 84863458415     PISSN: 13554786     EISSN: 14602369     Source Type: Journal    
DOI: 10.1093/humupd/dms010     Document Type: Review

References (99)

1. Aboulghar H, Aboulghar M, Mansour R, Serour G, Amin Y, Al-Inany H. A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection. Fertil Steril 2001; 76:249-253.
2. Abu-Musa AA, Nassar AH, Usta IM. Attitude of women with IVF and spontaneous pregnancies towards prenatal screening. Hum Reprod 2008;23:2438-2443.
3. Ahlborg L, Ek S, Fridstrom M, Kublickas M, Leijon M, Nisell H. Is fetal growth impaired after in vitro fertilization? Acta Obstet Gynecol Scand 2006;85:195-199.
4. Almog B, Al-Shalaty J, Sheizaf B, Shehata F, Son WY, Tan SL, Tulandi T. Difference between serum beta-human chorionic gonadotropin levels in pregnancies after in vitro maturation and in vitro fertilization treatments. Fertil Steril 2011;95:85-88.
5. Amor DJ, Xu JX, Halliday JL, Francis I, Healy DL, Breheny S, Baker HW, Jaques AM. Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome. Hum Reprod 2009;24:1330-1338.
6. Anckaert E, Schiettecatte J, Sleurs E, Devroey P, Smitz J. First trimester screening for Down's syndrome after assisted reproductive technology: non-male factor infertility is associated with elevated free beta-human chorionic gonadotropin levels at 10-14 weeks of gestation. Fertil Steril 2008;90:1206-1210.
7. Bar-Hava I, Yitzhak M, Krissi H, Shohat M, Shalev J, Czitron B, Ben-Rafael Z, Orvieto R. Triple-test screening in in vitro fertilization pregnancies. J Assist Reprod Genet 2001;18:226-229.
8. Barkai G, Goldman B, Ries L, Chaki R, Dor J, Cuckle H. Down's syndrome screening marker levels following assisted reproduction. Prenat Diagn 1996;16:1111-1114.
9. Bender F, Hecken J, Reinsberg J, Berg C, van d V, Gembruch U, Geipel A. Altered first-trimester screening markers after IVF/ICSI: no relationship with small-for-gestational-age and number of embryos transferred. Reprod Biomed Online 2010;20:516-522.
10. Bermudez C, Becerra CH, Bornick PW, Allen MH, Arroyo J, Quintero RA. Placental types and twin-twin transfusion syndrome. Am J Obstet Gynecol 2002; 187:489-494.
11. Bersinger NA, Noble P, Nicolaides KH. First-trimester maternal serum PAPP-A, SP1, and M-CSF levels in normal and trisomic twin pregnancies. Prenat Diagn 2003;23:157-162.
12. Bhasin S. Approach to the infertile man. J Clin Endocrinol Metab 2007;92:1995-2004.
13. Bonduelle M, Van AE, Joris H, Keymolen K, Devroey P, Van Steirteghem A, Liebaers I. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Hum Reprod 2002;17:2600-2614.
14. Casanova C, Bellver J, Garrido N, Lara C, Pellicer A, Serra V. First trimester screening for Downs syndrome in natural versus assisted conception. In: Annual Meeting of ESHRE. Abstract, July 2011.
15. 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;195:236-239.
16. Chasen ST, Perni SC, Kalish RB, Chervenak FA. First-trimester risk assessment for Trisomies 21 and 18 in twin pregnancy. Am J Obstet Gynecol 2007; 197:374.e1-374.e3.
17. Chen H, Egan JO, Ohlu JF. Regulation and activities of alpha-fetoprotein. Crit Rev Eukaryot Gene Expr 1997;7:11-41.
18. Cole LA. Immunoassay of human gonadotropin, its free subunits, and metabolites. Clin Chem 1997;43:2233-2243.
19. Cuckle H. Down's syndrome screening in twins. J Med Screen 1998;5:3-4.
20. Cuckle H, Maymon R. Down syndrome risk calculation for a twin fetus taking account of the nuchal translucency in the co-twin. Prenat Diagn 2010; 30:827-833.
21. Dugoff L, Hobbins JC, Malone FD, Vidaver J, Sullivan L, Canick JA, Lambert-Messerlian GM, Porter TF, Luthy DA, Comstock CH et al. Quad screen as a predictor of adverse pregnancy outcome. Obstet Gynecol 2005; 106:260-267.
22. Dumoulin JC, Land JA, Van Montfoort AP, Nelissen EC, Coonen E, Derhaag JG, Schreurs IL, Dunselman GA, Kester AD, Geraedts JP et al. Effect of in vitro culture of human embryos on birthweight of newborns. Hum Reprod 2010; 25:605-612.
23. Engels MA, Kooij M, Schats R, Twisk JW, Blankenstein MA, van Vugt JM. First-trimester serum marker distribution in singleton pregnancies conceived with assisted reproduction. Prenat Diagn 2010;30:372-377.
24. Frendo JL, Vidaud M, Guibourdenche J, Luton D, Muller F, Bellet D, Giovagrandi Y, Tarrade A, Porquet D, Blot P et al. Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome. J Clin Endocrinol Metab 2000;85:3700-3707.
25. Ghisoni L, Ferrazzi E, Castagna C, Levi Setti PE, Masini AC, Pigni A. Prenatal diagnosis after ART success: the role of early combined screening tests in counselling pregnant patients. Placenta 2003(Suppl. B):S99-S103.
26. Giudice LC, Conover CA, Bale L, Faessen GH, Ilg K, Sun I, Imani B, Suen LF, Irwin JC, Christiansen M et al. Identification and regulation of the IGFBP-4 protease and its physiological inhibitor in human trophoblasts and endometrial stroma: evidence for paracrine regulation of IGF-II bioavailability in the placental bed during human implantation. J Clin Endocrinol Metab 2002; 87:2359-2366.
27. Gjerris AC, Loft A, Pinborg A, Christiansen M, Tabor A. Prenatal testing among women pregnant after assisted reproductive techniques in Denmark 1995-1000: a national cohort study. Hum Reprod 2008a;23:1545-1552.
28. Gjerris AC, Loft A, Pinborg A, Tabor A, Christiansen M. First-trimester screening in pregnancies conceived by assisted reproductive technology: significance of gestational dating by oocyte retrieval or sonographic measurement of crown-rump length. Ultrasound Obstet Gynecol 2008b;32:612-617.
29. Gjerris AC, Loft A, Pinborg A, Christiansen M, Tabor A. First-trimester screening markers are altered in pregnancies conceived after IVF/ICSI. Ultrasound Obstet Gynecol 2009a;33:8-17.
30. 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 2009b;24:55-62.
31. Goncé A, Borrell A, Fortuny A, Casals E, Martínez MA, Mercadé I, Cararach V, Vanrell JA. First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement? Prenat Diagn 2005; 25:1156-1161.
32. Govaerts I, Devreker F, Koenig I, Place I, Van den BM, Englert Y. Comparison of pregnancy outcome after intracytoplasmic sperm injection and in-vitro fertilization. Hum Reprod 1998;13:1514-1518.
33. Grinsted J, Avery B. A sporadic case of delayed implantation after in-vitro fertilization in the human? Hum Reprod 1996;11:651-654.
34. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002; 346:725-730.
35. Hui PW, Lam YH, Tang MH, Ng EH, Yeung WS, Ho PC. Maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin in pregnancies conceived with fresh and frozen-thawed embryos from in vitro fertilization and intracytoplasmic sperm injection. Prenat Diagn 2005a;25:390-393.
36. Hui PW, Tang MH, Lam YH, Yeung WS, Ng EH, Ho PC. Nuchal translucency in pregnancies conceived after assisted reproduction technology. Ultrasound Obstet Gynecol 2005b;25:234-238.
37. Hui PW, Tang MHY, Ng EHY, Yeung WSB, Ho PC. Nuchal translucency in dichorionic twins conceived after assisted reproduction. Prenat Diagn 2006; 26:510-513.
38. Jozwiak EA, Ulug U, Mesut A, Erden HF, Bahceci M. Prenatal karyotypes of fetuses conceived by intracytoplasmic sperm injection. Fertil Steril 2004;82:628-633.
39. Kirkegaard I, Petersen OB, Uldbjerg N, Tørring N. Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks. Prenat Diagn 2008;28:839-844.
40. Krantz DA, Larsen JW, Buchanan PD, Macri JN. First-trimester Down syndrome screening: free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. Am J Obstet Gynecol 1996;174:612-616.
41. Lambert-Messerlian G, Dugoff L, Vidaver J, Canick JA, Malone FD, Ball RH, Comstock CH, Nyberg DA, Saase G, Eddleman K et al. First- and second-trimester Down syndrome screening markers in pregnancies achieved through assisted reproductive technologies (ART): a FASTER trial study. Prenatal Diagn 2006;26:672-678.
42. Lee YM, Cleary-Goldman J, Thaker HM, Simpson LL. Antenatal sonographic prediction of twin chorionicity. Am J Obstet Gynecol 2006;195:863-867.
43. Liao AW, Heath V, Kametas N, Spencer K, Nicolaides KH. First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction. Hum Reprod 2001;16:1501-1504.
44. Linskens IH, Spreeuwenberg MD, Blankenstein MA, van Vugt JM. Early first-trimester free beta-hCG and PAPP-A serum distributions in monochorionic and dichorionic twins. Prenat Diagn 2009;29:74-78.
45. Madsen HN, Ball S, Wright D, Tørring N, Petersen OB, Nicolaides KH, Spencer K. A reassessment of biochemical marker distributions in trisomy 21-affected and unaffected twin pregnancies in the first trimester. Ultrasound Obstet Gynecol 2011;37:38-47.
46. Mashiach R, Orr-Urtreger A, Yaron Y. A comparison between maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels in first-trimester twin and singleton pregnancies. Fetal Diagn Ther 2004; 19:174-177.
47. Matilainen M, Peuhkurinen S, Laitinen P, Jarvela I, Morin-Papunen L, Ryynanen M. In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies. Fertil Steril 2011;95:378-381.
48. Maymon R, Jauniaux E. Down's syndrome screening in pregnancies after assisted reproductive techniques: an update. Reprod Biomed Online 2002;4:285-293.
49. Maymon R, Shulman A. Integrated first- and second-trimester Down syndrome screening test among unaffected IVF pregnancies. Prenat Diagn 2004;24:125-129.
50. Meyers C, Adam R, Dungan J, Prenger V. Aneuploidy in twin gestations: when is maternal age advanced? Obstet Gynecol 1997;89:248-251.
51. Monni G, Zoppi MA, Ibba RM, Putzolu M, Floris M. Nuchal translucency in multiple pregnancies. Croat Med J 2000;41:266-269.
52. Monteaugudo A, Timor-Tritsch I, Sharma S. Early and simple determination of chorionic and amniotic type in multifetal gestations in the first 14 weeks by high frequency transvaginal ultrasound. Am J Obstet Gynecol 1994;170:824-829.
53. Morales C, Sanchez A, Bruguera J, Margarit E, Borrell A, Borobio V, Soler A. Cytogenetic study of spontaneous abortions using semi-direct analysis of chorionic villi samples detects the broadest spectrum of chromosome abnormalities. Am J Med Genet A 2008;146:66-70.
54. Mujezinovic F, Alfirevic Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet Gynecol 2007;110:687-694.
55. Naaktgeboren N, Devroey P, Wisanto A, Traey E, Van Steirteghem AC. Endocrine profiles in early pregnancies with delayed implantation. Hum Reprod 1986;1:9-14.
56. Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004;191:45-67 (Review).
57. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn 2011;31:7-15.
58. Niemimaa M, Suonpaa M, Heinonen S, Seppala M, Bloigu R, Ryynanen M. Maternal human serum chorionic gonadotrophin and pregnancy-associated plasma protein A in twin pregnancies in the first trimester. Prenatal Diagn 2002;22:183-185.
59. Orlandi F, Rossi C, Allegra A, Krantz D, Hallahan T, Orlandi E, Macri J. First trimester screening with free beta-hCG, PAPP-A and nuchal translucency in pregnancies conceived with assisted reproduction. Prenat Diagn 2002; 22:718-721.
60. Pandya PP, Snijders RJ, Johnson SP, De Lourdes Brizot M, Nicolaides KH. Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation. Br J Obstet Gynaecol 1995;102:957-962.
61. Pihl K, Larsen T, Krebs L, Christiansen M. First trimester maternal serum PAPP-A, beta-hCG and ADAM12 in prediction of small-for-gestational-age fetuses. Prenat Diagn 2008;28:1131-1135.
62. Pinborg A, Lidegaard O, la Cour FN, Andersen AN. Consequences of vanishing twins in IVF/ICSI pregnancies. Hum Reprod 2005;20:2821-2829.
63. Pinborg A, Loft A, Aaris Henningsen AK, Rasmussen S, Andersen AN. Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995-2006. Fertil Steril 2010;94:1320-1327.
64. Radojcic BA, Buretic-Tomljanovic A, Starcevic N, Kapovic M, Vlastelic I, Randic L. Chromosome studies in patients with defective reproductive success. Am J Reprod Immunol 2000;44:279-283.
65. Ranta JK, Raatikainen K, Romppanen J, Pulkki K, Heinonen S. Increased time-to-pregnancy and first trimester Down's syndrome screening. Hum Reprod 2010;25:412-417.
66. Raty R, Virtanen A, Koskinen P, Laitinen P, Forsstûñm J, Salonen R, Mûñrsky P, Ekblad U. Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies. Prenat Diagn 2000;20:221-223.
67. Robinson WP, McFadden DE, Stephenson MD. The origin of abnormalities in recurrent aneuploidy/polyploidy. Am J Hum Genet 2001;69:1245-1254.
68. Rubio C, Simon C, Blanco J, Vidal F, Minguez Y, Egozcue J, Crespo J, Remohi J, Pellicer A. Implications of sperm chromosome abnormalities in recurrent miscarriage. J Assist Reprod Genet 1999;16:253-258.
69. Samli H, Solak M, Imirzalioglu N, Beyatli Y, Simsek S, Kahraman S. Fetal chromosomal analysis of pregnancies following intracytoplasmic sperm injection with amniotic tissue culture. Prenat Diagn 2003;23:847-850.
70. Santolaya-Forgas J, De Leon JA, Cullen HR, Castracane VD, Kauffman RP, Sifuentes GA. Low pregnancy-associated plasma protein-a at 10(+1) to 14(+6) weeks of gestation and a possible mechanism leading to miscarriage. Fetal Diagn Ther 2004;19:456-461.
71. Sebire NJ, Snijders RJ, Hughes K, SepulvedaW, Nicolaides KH. Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. Br J Obstet Gynaecol 1996;103:999-1003.
72. Sepulveda W, Sebire NJ, Hughes K, Odibo A, Nicolaides KH. The lambda sign at 10-14 weeks of gestation as a predictor of chorionicity in twin pregnancies. Ultrasound Obstet Gynecol 1996;7:421-423.
73. Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, Hankins GD, Eddleman K, Dolan S, Dugoff L et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 2005;106:1039-1045.
74. Shih W, Rushford DD, Bourne H, Garrett C, McBain JC, Healy DL, Baker HW. Factors affecting low birthweight after assisted reproduction technology: difference between transfer of fresh and cryopreserved embryos suggests an adverse effect of oocyte collection. Hum Reprod 2008;23:1644-1653.
75. Skiadas CC, Missmer SA, Benson CB, Gee RE, Racowsky C. Risk factors associated with pregnancies containing a monochorionic pair following assisted reproductive technologies. Hum Reprod 2008;23:1366-1371.
76. Snijders RJ, Sebire NJ, Nicolaides KH. Maternal age and gestational age-specific risk for chromosomal defects. Fetal Diagn Ther 1995;10:356-367.
77. Spencer K. Evaluation of an assay of the free beta-subunit of choriogonadotropin andits potential value in screening for Down's syndrome. Clin Chem 1991;37:809-814.
78. Spencer K. Second-trimester prenatal screening for Down syndrome and the relationship of maternal serum biochemical markers to pregnancy complications with adverse outcome. Prenat Diagn 2000a;20:652-656.
79. Spencer K. Screening for trisomy 21 in twin pregnancies in the first trimester using free beta-hCG and PAPP-A, combined with foetal nuchal translucency thickness. Prenat Diagn 2000b;20:91-95.
80. Spencer K. Screening for trisomy 21 in twin pregnancies in the first trimester: does chorionicity impact on maternal serum free beta-hCG or PAPP-A levels? Prenat Diagn 2001a;21:715-717.
81. Spencer K. Between pregnancy biological variability of first trimester markers of Down syndrome: implications for screening in subsequent pregnancies. Prenat Diagn 2001b;21:445-447.
82. Spencer K, Nicolaides KH. Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years experience. BJOG 2003;110:276-280.
83. Spencer K, Salonen R, Muller F. Down's syndrome screening in multiple pregnancies using alpha-fetoprotein and free beta hCG. Prenat Diagn 1994;14:537-542.
84. Spencer K, Crossley JA, Aitken DA, Nix AB, Dunstan FD, Williams K. The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient-specific risks and detection rates for Down's syndrome. Ann Clin Biochem 2003; 40:219-231.
85. Spencer K, Kagan KO, Nicolaides KH. Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers. Prenat Diagn 2008;28:49-52.
86. Spencer K, Staboulidou I, Nicolaides KH. First trimester aneuploidy screening in the presence of a vanishing twin: implications for maternal serum markers. Prenat Diagn 2010;30:235-240.
87. Tabor A, Alfirevic Z. Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther 2010;27:1-7.
88. Tabor A, Vestergaard CH, Lidegaard Ø. Fetal loss rate after chorionic villus sampling and amniocentesis: an 11-year national registry study. Ultrasound Obstet Gynecol 2009;34:19-24.
89. Tul N, Novak-Antolic Z. Serum PAPP-A levels at 10-14 weeks of gestation are altered in women after assisted conception. Prenat Diagn 2006; 26:1206-1211.
90. Van Opstal D, Los FJ, Ramlakhan S, Van Hemel JO, Van Den Ouweland AM, Brandenburg H, Pieters MH, Verhoeff A, Vermeer MC, Dhont M et al. Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection. Hum Reprod 1997;12:682-686.
91. Wald NJ, White N, Morris JK, Huttly WJ, Canick JA. Serum markers for Down's syndrome in women who have had in vitro fertilisation: implications for antenatal screening. Br J Obstet Gynaecol 1999;106:1304-1306.
92. Wald NJ, Rish S, Hackshaw AK. Combining nuchal translucency and serum markers in prenatal screening for Down syndrome in twin pregnancies. Prenat Diagn 2003; 23:588-592.
93. Wennerholm UB, Bergh C, Hamberger L, Lundin K, Nilsson L, Wikland M, Källen B. Incidence of congenital malformations in children born after ICSI. Hum Reprod 2000;15:944-948.
94. Wenstrom KD, Syrop CH, Hammitt DG, Van Voorhis BJ. Increased risk of monochorionic twinning associated with assisted reproduction. Fertil Steril 1993; 60:510-514.
95. Wøjdemann KR, Larsen SO, Shalmi A, Sundberg K, Christiansen M, Tabor A. First trimester screening for Down syndrome and assisted reproduction: no basis for concern. Prenat Diagn 2001;21:563-565.
96. Wøjdemann KR, Shalmi AC, Christiansen M, Larsen SO, Sundberg K, Brocks V, Bang J, Nørgaard-Pedersen B, Tabor A. Improved first-trimester Down syndrome screening performance by lowering the false-positive rate: a prospective study of 9941 low-risk women. Ultrasound Obstet Gynecol 2005; 25:227-233.
97. Wøjdemann KR, Larsen SO, Shalmi A-C, Sundberg K, Tabor A, Christiansen M. Nuchal translucency measurements are highly correlated in both mono- and dichorionic twin pairs. Prenat Diagn 2006;26:218-220.
98. Zegers-Hochschild F, Altieri E, Fabres C, Fernandez E, Mackenna A, Orihuela P. Predictive value of human chorionic gonadotrophin in the outcome of early pregnancy after in-vitro fertilization and spontaneous conception. Hum Reprod 1994;9:1550-1555.
99. Zheng MM, Hu YL, Zhang CY, Ru T, Liu QL, Xu BY, Chen QG, Xu ZF, Zhang Y, Zhong XL. Comparison of second-trimester maternal serum free-beta-human chorionic gonadotrophin and alfa-fetoprotein between normal singleton and twin pregnancies: a population-based study. Chin Med J (Engl) 2010; 123:555-558.