Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-swprf Total loading time: 0 Render date: 2025-05-03T16:53:12.015Z Has data issue: false hasContentIssue false

Section 2 - Early Prenatal Problems

Published online by Cambridge University Press:  15 November 2017

Edited by
David James ,
Philip Steer ,
Carl Weiner ,
Bernard Gonik  and
Stephen Robson
David James
Affiliation:
University of Nottingham
Philip Steer
Affiliation:
Imperial College London
Carl Weiner
Affiliation:
University of Kansas
Bernard Gonik
Affiliation:
Wayne State University, Detroit
Stephen Robson
Affiliation:
University of Newcastle
Get access

Summary

Complications arise more frequently during the first trimester than at any other stage of pregnancy. Most present with bleeding, pain, or both. Vaginal bleeding occurs in about 20% of clinically diagnosed pregnancies. It causes considerable anxiety for the woman and her partner. In the vast majority of cases, no intervention alters the outcome. The main aim of clinical management is a prompt and accurate diagnosis, with reassurance if the pregnancy is appropriately developed and viable, or appropriate intervention if not. This chapter focuses on the principles of diagnosis and management and three principal diagnoses: miscarriage, ectopic pregnancy, and gestational trophoblastic disease. The other differential diagnoses are shown in Table 5.1.

Type
Chapter
Information
High-Risk Pregnancy
Management Options
 , pp. 85 - 206
Publisher: Cambridge University Press
First published in: 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

References

Krause, SA, Graves, BW. Midwifery triage of first trimester bleeding. J Nurse Midwifery 1999; 44: 537–48.Google Scholar
Smith, NC. Epidemiology of spontaneous abortion. Contemp Rev Obstet Gynaecol 1988; 1: 43–8.Google Scholar
Zinaman, MJ, Clegg, DE, Brown, CC, O’Connor, J, Selevan, SG. Estimates of human fertility and pregnancy loss. Fertil Steril 1996; 65: 503–9.CrossRefGoogle ScholarPubMed
Hemminki, E. Treatment of miscarriage: Current practice and rationale. Obstet Gynecol 1988; 91: 247–53.Google Scholar
Stabile, I, Campbell, S, Grudzinskas, JG. Ultrasonic assessment of complications during first trimester of pregnancy. Lancet 1987; 2: 1237–40.Google Scholar
O’Herlihy, C. Deaths in early pregnancy. In Cantwell, R, Clutton-Brock, T, Cooper, G, et al. (eds), Saving Mothers’ Lives: Reviewing Maternal Deaths to Make Motherhood Safer 2006–08. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. London: BJOG, 2011, pp. 81–4.Google Scholar
Grimes, DA. The morbidity and mortality of pregnancy: still a risky business. Am J Obstet Gynecol 1994; 170: 1489–94.Google Scholar
Stirtzinger, R, Robinson, GE. The psychological effects of spontaneous abortion. Can Med Assn J 1989; 140: 799–806.Google Scholar
Conway, K. Miscarriage. J Psychosomatic Obstet Gynecol 1991; 12: 121–31.Google Scholar
Murphy, FA, Lipp, A, Powles, DL. Follow-up for improving psychological well being for women after a miscarriage. Cochrane Database Syst Rev 2012; (3): CD008679.Google Scholar
Huxley, RR. Nausea and vomiting in early pregnancy. Its role in placental development. Obstet Gynecol 2000; 95: 779–82.Google Scholar
Furneaux, EC, Langley-Evans, AJ, Langley-Evans, SC. Nausea and vomiting of pregnancy. Obstet Gynecol Surv 2001; 56: 775–82.CrossRefGoogle ScholarPubMed
Weigel, MM, Weigel, RM. Nausea and vomiting of pregnancy and pregnancy outcome: An epidemiological study. Br J Obstet Gynaecol 1989; 96: 1304–11.Google ScholarPubMed
Regan, L, Braude, PB, Trembath, PL. Influence of past reproductive performance on risk of spontaneous abortion. Br Med J 1989; 299: 541–5.CrossRefGoogle ScholarPubMed
Knudsen, UB, Hansen, V, Juul, S, Secher, NJ. Prognosis of a new pregnancy following previous spontaneous abortions. Europ J Obstet Gynecol Reprod Biol 1991; 39: 31–6.Google Scholar
Canis, M, Wattize, A, M. B. Multifunctional analysis or fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients. Fertil Steril 1991; 56: 453–60.Google Scholar
Pouly, JL, Chapron, C, Manhes, H. Multifactorial analysis of fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients. Fertil Steril 1991; 56: 453–60.Google Scholar
Semer, DA, Macfee, MS. Gestational trophoblastic disease: epidemiology. Semin Oncol 1995; 22: 109–12.Google Scholar
Peckham, CH. Uterine bleeding during pregnancy. Obstet Gynecol 1970; 78: 14–18.Google Scholar
Grobman, WA, Peaceman, AM. What are the rates and mechanisms of first and second trimester pregnancy loss in twins. Clin Obstet Gynecol 1998; 41: 37–45.CrossRefGoogle ScholarPubMed
Brown, DL, Doubilet, PM. Transvaginal sonography for diagnosing ectopic pregnancy: positivity criteria and performance characteristics. J Ultrasound Med 1994; 13: 259–66.Google Scholar
Condous, G, Okaro, E, Khalid, A, et al. The accuracy of transvaginal ultrasonography for the diagnosis of ectopic pregnancy prior to surgery. Hum Reprod 2005; 20: 1404–9.Google Scholar
Barnhart, KT, Gosman, G, Ashby, R, Sammel, M. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol 2003; 101: 778–84.Google Scholar
Nepomnaschy, PA, Weinberg, CR, Wilcox, AJ, Baird, DD. Urinary hCG patterns during the week following implantation. Hum Reprod 2008; 23: 271–7.Google Scholar
Mills, MS. Ultrasonography of early embryonic growth and fetal development. MD thesis, University of Bristol, 1992.Google Scholar
Hollander, HJ. Estimation of gestational age by mean gestational sac diameter. Die Ultraschalldiagnostik in der Schwangerschaft 1972: 47–53.Google Scholar
Merchiers, EH, Dhont, M, De Sutter, PA, Beghin, CJ, Vandekerckhove, DA. Predictive value of early embryonic cardiac activity for pregnancy outcome. Am J Obstet Gynecol 1991; 165: 11–14.CrossRefGoogle ScholarPubMed
Robinson, HP, Shaw-Dunn, J. Fetal heart rates as determined by sonar in early pregnancy. J Obstet Gynaecol Br Commonw 1973; 80: 805–9.Google Scholar
Bourne, T, Bottomley, C. When is a pregnancy nonviable and what criteria should be used to define miscarriage? Fertil Steril 2012; 98: 1091–6.Google Scholar
Nyberg, DA, Filly, RA, Mahony, BS, et al. Early gestation: correlation of HCG levels and sonographic identification. AJR Am J Roentgenol 1985; 144: 951–4.Google Scholar
Jouppila, P, Huhtaniemi, I, Tapanainen, J. Early pregnancy failure: study by ultrasonic and hormonal methods. Obstet Gynecol 1980; 55: 42–7.Google Scholar
Wilson, RD, Kendrick, V, Wittmann, BK, McGillivray, B. Spontaneous abortion and pregnancy outcome after normal first trimester ultrasound examination. Obstet Gynecol 1986; 67: 352–5.Google ScholarPubMed
Verhaegen, J, Gallos, ID, van Mello, NM, et al. Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: meta-analysis of cohort studies. BMJ 2012; 345: e6077.Google Scholar
Stovall, TG, Ling, FW, Carson, SA, Buster, JE. Serum progesterone and uterine curettage in differential diagnosis of ectopic pregnancy. Fertil Steril 1992; 57: 456–8.Google Scholar
Kadar, N, DeVore, G, Romero, R. Discriminatory hCG zone: its use in the sonographic evaluation for ectopic pregnancy. Obstet Gynecol 1981; 58: 156–61.Google Scholar
Barnhart, KT, Sammel, MD, Rinaudo, PF, et al. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol 2004; 104: 50–5.Google Scholar
Senapati, SB, Barnhart, KT. Biomarkers for ectopic pregnancy and pregnancy of unknown location. Fertil Steril 2013; 99: 1107–16.Google Scholar
Rausch, M, Sammel, MD, Takacs, P et al. Development of a multiple marker test for ectopic pregnancy. Obstet Gynecol 2011; 117: 573–82.Google Scholar
Regan, L, Rai, R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 839–54.Google Scholar
Hutchon, DJR, Cooper, S. Terminology for early pregnancy loss must be changed. BMJ 1998; 317: 1081.Google Scholar
World Health Organization. Spontaneous and Induced Abortions. Technical report series No. 41. Geneva: WHO, 1970.Google Scholar
Bigrigg, MA, Read, MD. Management of women referred to early pregnancy assessment unit: care and cost effectiveness. BMJ 1991; 302: 577–9.Google Scholar
Draycott, T, Read, M. The managed care of early pregnancy problems. Curr Opin Obstet Gynecol 1997; 9: 262–6.Google Scholar
Chard, T. Frequency of implantation and early pregnancy loss in natural cycles. Baillieres Clin Obstet Gynaecol 1991; 5: 179–89.CrossRefGoogle ScholarPubMed
Macklon, NS, Geraedts, JP, Fauser, BC. Conception to ongoing pregnancy: the ‘black box’ of early pregnancy loss. Hum Reprod Update 2002; 8: 333–43.CrossRefGoogle ScholarPubMed
Blohm, F, Friden, B, Milsom, I. A prospective longitudinal population based study of clinical miscarriage in an urban Swedish population. BJOG 2008; 115: 176–83.Google Scholar
Hooker, AB, Lemmers, M, Thurkow, AL, et al. Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome. Hum Reprod Update 2014; 20: 262–78.Google Scholar
Tuuli, MG, Norman, SM, Odibo, AO, Macones, GA, Cahill, AG. Perinatal outcomes in women with subchorionic hematoma: a systematic review and meta- analysis. Obstet Gynecol 2011; 117: 1205–12.Google Scholar
Wahabi, HA, Fayed, AA, Esmaeil, SA, Bahkali, KH. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev 2018; (8): CD005943. doi: 10.1002/14651858.CD005943.pub5.Google ScholarPubMed
European Society of Human Reproduction and Embryology. Guideline on the management of recurrent pregnancy loss. www.eshre.eu/Guidelines-and-Legal/Guidelines/Recurrent-pregnancy-loss (accessed June 2019).Google Scholar
Pandya, PP, Snijders, RJ, Psara, N, Hilbert, L, Nicolaides, KH. The prevalence of non-viable pregnancy at 10–13 weeks of gestation. Ultrasound Obstet Gynecol 1996; 7: 170–3.Google Scholar
Forna, F, Gülmezoglu, AM. Surgical procedures to evacuate incomplete abortion. Cochrane Database Syst Rev 2001; (1): CD001993.Google Scholar
Wieringa-de Waard, M, Hartman, EE, Ankum, WM, et al. Expectant management versus surgical evacuation in first trimester miscarriage: health-related quality of life in randomized and non-randomized patients. Hum Reprod 2002; 17: 1638–42.Google Scholar
Ankum, WM, Wieringa-de Waard, M, Bindels, PJE. Management of spontaneous miscarriage in the first trimester: an example of putting informed shared decision making into practice. BMJ 2001; 322: 1343–6.Google Scholar
Nanda, K, Lopez, LM, Grimes, DA, Peloggia, A, Nanda, G. Expectant care versus surgical treatment for miscarriage. Cochrane Database Syst Rev 2012; (3): CD003518.CrossRefGoogle Scholar
Trinder, J, Brocklehurst, P, Porter, R, et al. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ 2006; 332: 1235–40.Google Scholar
Shelley, JM, Healy, D, Grover, S. A randomised trial of surgical, medical and expectant management of first trimester spontaneous miscarriage. Aust N Z J Obstet Gynaecol 2005; 45: 122–7.Google Scholar
Petrou, S, McIntosh, E. Women’s preferences for attributes of first-trimester miscarriage management: a stated preference discrete-choice experiment. Value Health 2009; 12: 551–9.CrossRefGoogle ScholarPubMed
Petrou, S, Trinder, J, Brocklehurst, P, Smith, L. Economic evaluation of alternative management methods of first-trimester miscarriage based on results from the MIST trial. BJOG 2006; 113: 879–89.Google Scholar
Harwood, B, Nansel, T. Quality of life and acceptability of medical versus surgical management of early pregnancy failure. BJOG 2008; 115: 501–8.Google Scholar
Luise, C, Jermy, K, Collins, WP, Bourne, TH. Expectant management of incomplete, spontaneous first-trimester miscarriage: outcome according to initial ultrasound criteria and value of follow-up visits. Ultrasound Obstet Gynecol 2002; 19: 580–2.CrossRefGoogle ScholarPubMed
Gronlund, L, Gronlund, AL, Clevin, L, et al. Spontaneous abortion: expectant management, medical treatment or surgical evacuation. Acta Obstet Gynecol Scand 2002; 81: 781–2.Google Scholar
Child, TJ, Thomas, J, Rees, M, MacKenzie, IZ. A comparative study of surgical and medical procedures: 932 pregnancy terminations up to 63 days gestation. Hum Reprod 2001; 16: 67–71.Google Scholar
Nielsen, S, Hahlin, M, Platz-Christensen, J. Randomised trial comparing expectant with medical management for first trimester miscarriages. Br J Obstet Gynaecol 1999; 106: 804–7.Google Scholar
Hurd, WW, Whitfield, RR, Randolph, JF, Kercher, ML. Expectant management versus elective curettage for the treatment of spontaneous abortion. Fertil Steril 1997; 68: 601–6.Google Scholar
Royal College of Obstetricians and Gynaecologists. The Management of Early Pregnancy Loss. Green-top Guideline No. 25. London: RCOG, 2006.Google Scholar
Royal College of Obstetricians and Gynaecologists. Recommendations from the Study Group on Problems in Early Pregnancy: Advances in Diagnosis and Management. London: RCOG, 1997.Google Scholar
Schwarzler, P, Holden, D, Nielson, S, et al. The conservative management of first trimester miscarriages and the use of colour Doppler sonography for patient selection. Hum Reprod 1999; 14: 1341–5.Google Scholar
Prieto, JA, Eriksen, NL, Blanco, JD. A randomized trial of prophylactic doxycycline for curettage in incomplete abortion. Obstet Gynecol 1995; 85: 692–6.Google Scholar
Xiang, L, Wei, Z, Cao, Y. Symptoms of an intrauterine hematoma associated with pregnancy complications: a systematic review. PLoS One 2014; 9: e111676.Google Scholar
Moini, A, Hosseini, R, Jahangiri, N, Shiva, M, Akhoond, MR. Risk factors for ectopic pregnancy: a case–control study. J Res Med Sci 2014; 19: 844–9.Google Scholar
Kirk, E, Papageorghiou, AT, Condous, G, et al. The diagnostic effectiveness of an initial transvaginal scan in detecting ectopic pregnancy. Hum Reprod 2007; 22: 2824–8.CrossRefGoogle ScholarPubMed
Atri, M, Valenti, DA, Bret, PM, Gillett, P. Effect of transvaginal sonography on the use of invasive procedures for evaluating patients with a clinical diagnosis of ectopic pregnancy. J Clin Ultrasound 2003; 31: 1–8.CrossRefGoogle ScholarPubMed
Kirk, E, Daemen, A, Papageorghiou, AT, et al. Why are some ectopic pregnancies characterized as pregnancies of unknown location at the initial transvaginal ultrasound examination? Acta Obstet Gynecol Scand 2008; 87: 1150–4.Google Scholar
Condous, G, Lu, C, Van Huffel, SV, Timmerman, D, Bourne, T. Human chorionic gonadotrophin and progesterone levels in pregnancies of unknown location. Int J Gynaecol Obstet. 2004; 86: 351–7.Google Scholar
Condous, G, Timmerman, D, Goldstein, S, et al. Pregnancies of unknown location: consensus statement. Ultrasound Obstet Gynecol 2006; 28: 121–2.Google Scholar
van Mello, NM, Mol, F, Opmeer, BC, et al. Diagnostic value of serum hCG on the outcome of pregnancy of unknown location: a systematic review and meta-analysis. Hum Reprod Update. 2012; 18: 603–17.Google Scholar
Banerjee, S, Aslam, N, Woelfer, B, et al. Expectant management of early pregnancies of unknown location: a prospective evaluation of methods to predict spontaneous resolution of pregnancy. BJOG 2001; 108: 158–63.Google Scholar
Royal College of Obstetricians and Gynaecologists. The Management of Tubal Pregnancies. London: RCOG, 2010.Google Scholar
National Institute for Health and Care Excellence. Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy. Clinical Guideline CG154. London: NICE, 2012 [updated February 2015]. https://www.nice.org.uk/guidance/cg154 (accessed March 2017).Google Scholar
Trio, D, Strobelt, N, Picciolo, C, Lapinski, RH, Ghidini, A. Prognostic factors for successful expectant management of ectopic pregnancy. Fertil Steril 1995; 63: 469–72.CrossRefGoogle ScholarPubMed
Day, A, Sawyer, E, Mavrelos, D, et al. Use of serum progesterone measurements to reduce need for follow-up in women with pregnancies of unknown location. Ultrasound Obstet Gynecol 2009; 33: 704–10.Google Scholar
Korhonen, J, Stenman, UH, Ylostalo, P. Serum human chorionic gonadotropin dynamics during spontaneous resolution of ectopic pregnancy. Fertil Steril 1994; 61: 632–6.Google Scholar
Rozenberg, P, Chevret, S, Camus, E, et al. Medical treatment of ectopic pregnancies: a randomized clinical trial comparing methotrexate-mifepristone and methotrexate-placebo. Hum Reprod 2003; 18: 1802–8.CrossRefGoogle ScholarPubMed
Tanaka, T, Hayashi, H, Kutsuzawa, T, Fujimoto, S, Ichinoe, K. Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case. Fertil Steril 1982; 37: 851–2.Google Scholar
Yao, M, Tulandi, T. Current status of surgical and nonsurgical management of ectopic pregnancy. Fertil Steril 1997; 67: 421–33.Google Scholar
Hajenius, PJ, Mol, F, Mol, BW, et al. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev 2007; (1): CD000324.Google Scholar
Newbatt, E, Beckles, Z, Ullman, R, Lumsden, MA. Ectopic pregnancy and miscarriage: summary of NICE guidance. BMJ 2012; 345: e8136.Google Scholar
Nurmohamed, L, Moretti, ME, Schechter, T, et al. Outcome following high-dose methotrexate in pregnancies misdiagnosed as ectopic. Am J Obstet Gynecol 2011; 205: 533 e1–3.Google Scholar
Lipscomb, GH, McCord, ML, Stovall, TG, et al. Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies. N Engl J Med 1999; 341: 1974–8.Google Scholar
Fernandez, H, Yves Vincent, SC, Pauthier, S, Audibert, F, Frydman, R. Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertility. Hum Reprod 1998; 13: 3239–43.CrossRefGoogle ScholarPubMed
Sowter, MC, Farquhar, CM, Petrie, KJ, Gudex, G. A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy. BJOG 2001; 108: 192–203.Google Scholar
Nieuwkerk, PT, Hajenius, PJ, Van der Veen, F, et al. Systemic methotrexate therapy versus laparoscopic salpingostomy in tubal pregnancy. Part II. Patient preferences for systemic methotrexate. Fertil Steril 1998; 70: 518–22.Google Scholar
Vermesh, M, Presser, SC. Reproductive outcome after linear salpingostomy for ectopic gestation: a prospective 3-year follow-up. Fertil Steril 1992; 57: 682–4.Google Scholar
Murphy, AA, Nager, CW, Wujek, JJ, et al. Operative laparoscopy versus laparotomy for the management of ectopic pregnancy: a prospective trial. Fertil Steril 1992; 57: 1180–5.CrossRefGoogle ScholarPubMed
Gray, DT, Thorburn, J, Lundorff, P, Lindblom, B. Laparoscopic treatment of ectopic pregnancy. Lancet 1995; 346: 706–7.Google Scholar
Lundorff, P, Thorburn, J, Lindblom, B. Fertility outcome after conservative surgical treatment of ectopic pregnancy evaluated in a randomized trial. Fertil Steril 1992; 57: 998–1002.Google Scholar
Sau, AK, Sau, M. Can we offer completely non-surgical management for ectopic pregnancy? BMJ 2000; 322: 793.Google Scholar
Carson, SA, Buster, JE. Ectopic pregnancy. N Engl J Med 1993; 329: 1174–81.Google Scholar
Dubuisson, JB, Morice, P, Chapron, C, De Gayffier, A, Mouelhi, T. Salpingectomy: the laparoscopic surgical choice for ectopic pregnancy. Hum Reprod 1996; 11: 1199–203.Google Scholar
Mol, BW, Hajenius, PJ, Ankum, WM, van der Veen, F, Bossuyt, PM. Cut-off level–what do you want it to be? Fertil Steril 1997; 67: 980–1.CrossRefGoogle Scholar
Clausen, I. Conservative versus radical surgery for tubal pregnancy: a review. Acta Obstet Gynecol Scand 1996; 75: 8–12.Google Scholar
Mol, F, van Mello, NM, Strandell, A, et al. Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial. Lancet 2014; 383: 1483–9.Google Scholar
Ego, A, Subtil, D, Cosson, M, et al. Survival analysis of fertility after ectopic pregnancy. Fertil Steril 2001; 75: 560–6.Google Scholar
Job-Spira, N, Fernandez, H, Bouyer, J, et al. Ruptured tubal ectopic pregnancy: risk factors and reproductive outcome: results of a population-based study in France. Am J Obstet Gynecol 1999; 180: 938–44.Google Scholar
Mol, BW, Matthijsse, HC, Tinga, DJ, et al. Fertility after conservative and radical surgery for tubal pregnancy. Hum Reprod 1998; 13: 1804–9.Google Scholar
Deepa, J, Oladimeji, O, Funlayo, O. Factors that determine patient satisfaction after surgical treatment of ectopic pregnancy: improving the patient journey! Eur J Obstet Gynecol Reprod Biol 2014; 178: 60–5.CrossRefGoogle ScholarPubMed
Capmas, P, Bouyer, J, Fernandez, H. Treatment of ectopic pregnancies in 2014: new answers to some old questions. Fertil Steril 2014; 101: 615–20.Google Scholar
Skubisz, MM, Horne, AW, Johns, TG, et al. Combination gefitinib and methotrexate compared with methotrexate alone to treat ectopic pregnancy. Obstet Gynecol 2013; 122: 745–51.Google Scholar
Kirk, E, Bottomley, C, Bourne, T. Diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location. Hum Reprod Update 2014; 20: 250–61.Google Scholar
Ankum, WM, Van der Veen, F, Hamerlynck, JV, Lammes, FB. Laparoscopy: a dispensable tool in the diagnosis of ectopic pregnancy? Hum Reprod 1993; 8: 1301–6.CrossRefGoogle ScholarPubMed
Lang, PF, Makinen, JI, Irjala, KM, et al. Laparoscopic instillation of hyperosmolar glucose vs. expectant management of tubal pregnancies with serum hCG ≤ 2500 mIU/mL. Acta Obstet Gynecol Scand 1997; 76: 797–800.Google Scholar
Laatikainen, T, Tuomivaara, L, Kaar, K. Comparison of a local injection of hyperosmolar glucose solution with salpingostomy for the conservative treatment of tubal pregnancy. Fertil Steril 1993; 60: 80–4.Google Scholar
Scully, R, Bonfiglio, TA, Kurman, RJ, Silverberg, SG, Wilkinson, EJ. Histological Typing of Female Genital Tract Tumours (World Health Organization International Histological Classification of Tumours). 2nd edn. New York, NY: Springer-Verlag, 1994.Google Scholar
Rose, PG. Hydatidifrom mole: diagnosis and management. Semin Oncol 1995; 22: 149–56.Google Scholar
Bower, M, Brock, C, Fisher, RA, Newlands, ES, Rustin, GJ. Gestational choriocarcinoma. Ann Oncol 1995; 6: 503–8.Google Scholar
Lage, JM, Bagg, A, Berchem, GJ. Gestational trophoblastic diseases. Curr Opin Obstet Gynecol 1996; 8: 79–82.Google Scholar
Bagshawe, KD, Dent, J, Webb, J. Hydatidiform mole in England and Wales 1973–1983. Lancet 1986; ii: 673–7.Google Scholar
Palmer, JR. Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med 1994; 39: 155–62.Google ScholarPubMed
Kohorn, EI. The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: description and critical assessment. Int J Gynecol Cancer 2001; 11: 73–7.Google Scholar
Altieri, A, Franceschi, S, Ferlay, J, Smith, J, La Vecchia, C. Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol 2003; 4: 670–8.Google Scholar
Bracken, MB. Incidence and aetiology of hydatidiform mole: an epidemiological review. Br J Obstet Gynaecol 1987; 94: 1123–35.Google Scholar
Smith, HO, Hilgers, RD, Bedrick, EJ, et al. Ethnic differences at risk for gestational trophoblastic disease in New Mexico: A 25-year population-based study. Am J Obstet Gynecol 2003; 188: 357–66.Google Scholar
Sebire, NJ, Foskett, M, Fisher, RA, et al. Risk of partial and complete hydatidiform molar pregnancy in relation to maternal age. BJOG 2002; 109: 99–102.Google Scholar
Parazzini, F, La Vecchia, C, Pampallona, S. Parental age and risk of complete and partial hydatidiform mole. Br J Obstet Gynaecol 1986; 93: 582–5.Google Scholar
Graham, IH, Fajardo, AM, Richards, RL. Epidemiological study of complete and partial hydatidiform mole in Abu Dhabi: influence age and ethnic group. J Clin Pathol 1990; 43: 661–4.Google Scholar
Sebire, NJ, Fisher, RA, Fockett, M, et al. Risk of recurrent hydatidiform mole and subsequent pregnancy outcome following complete or partial hydatidiform molar pregnancy. Br J Obstet Gynaecol 2003; 110: 22–6.Google Scholar
Fisher, RA, Hodges, MD. Genomic imprinting in gestational trophoblastic disease–a review. Placenta 2003; 24: S111–18.Google Scholar
Sebire, NJ. Histopathological diagnosis of hydatidiform mole: contemporary features and clinical implications. Fetal Pediatr Pathol 2010; 29: 1–16.Google Scholar
Fisher, RA, Hodges, MD, Newlands, ES. Familial recurrent hydatidiform mole: a review. J Reprod Med 2004; 49: 595–601.Google Scholar
Petignat, P, Billieux, MH, Blouin, JL, Dahoun, S, Vassilakos, P. Is genetic analysis useful in the routine management of hydatidiform mole? Hum Reprod 2003; 18: 243–9.Google Scholar
Zaragoza, MV, Surti, U, Redline, RW, et al. Parental origin and phenotype of triploidy in spontaneous abortions: predominance of diandry and association with the partial hydatidiform mole. Am J Hum Genet 2000; 66: 1807–20.Google Scholar
Fryns, JP, van de Kerckhove, A, Goddeeris, P, van den Berghe, H. Unusually long survival in a case of full triploidy of maternal origin. Hum Genet 1977; 38: 147–55.Google Scholar
Seckl, MJ, Fisher, RA, Salerno, G, et al. Choriocarcinoma and partial hydatidiform moles. Lancet 2000; 356: 36–9.Google Scholar
Trophoblastic Tumour Screening and Treatment Centre. Information for clinicians. London: Department of Medical Oncology, Charing Cross Hospital, 2013. http://www.hmole-chorio.org.uk/clinicians_info.html (accessed March 2017).Google Scholar
Jauniaux, E, Kadri, R, Hustin, J. Partial mole and triploidy: screening patients with first-trimester spontaneous abortion. Obstet Gynecol 1996; 88: 616–19.Google Scholar
Niemann, I, Petersen, LK, Hansen, ES, Sunde, L. Differences in current clinical features of diploid and triploid hydatidiform mole. BJOG 2007; 114: 1273–7.Google Scholar
Soto-Wright, V, Bernstein, M, Goldstein, DP, Berkowitz, RS. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol 1995; 86: 775–9.Google Scholar
Fowler, DJ, Lindsay, I, Seckl, MJ, Sebire, NJ. Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center. Ultrasound Obstet Gynecol 2006; 27: 56–60.Google Scholar
Stone, M, Bagshawe, KD. An analysis of the influence of maternal age, gestational age, contraceptive method and mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy. Br J Obstet Gynaecol 1979; 86: 782–92.Google Scholar
Gillespie, AM, Tidy, J, Bright, N, et al. Primary gynaecological management of gestational trophoblastic tumours and the subsequent development of persistent trophoblastic disease. Br J Obstet Gynaecol 1998; 107 (suppl 17 abstr. 287): 95.Google Scholar
Royal College of Obstetricians and Gynaecologists. Gestational Trophoblastic Disease. Green-top Guideline No. 38. London: RCOG, 2010.Google Scholar
Bahar, AM, el-Ashnehi, MS, Senthilselvan, A. Hydatidiform mole in the elderly: hysterectomy or evacuation? Int J Gynaecol Obstet 1989; 29: 233–8.Google Scholar
Sebire, NJ, Foskett, M, Fisher, RA, Lindsay, I, Seckl, MJ. Persistent gestational trophoblastic disease is rarely, if ever, derived from non-molar first-trimester miscarriage. Med Hypotheses 2005; 64: 689–93.Google Scholar
Alazzam, M, Tidy, J, Hancock, BW, Osborne, R, Lawrie, TA. First-line chemotherapy in low-risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2012; (7): CD007102.Google Scholar
Sebire, NJ, Foskett, M, Short, D, et al. Shortened duration of human chorionic gonadotrophin surveillance following complete or partial hydatidiform mole: evidence for revised protocol of a UK regional trophoblastic disease unit. BJOG 2007; 114: 760–2.Google Scholar
Hancock, BW, Tidy, JA. Current management of molar pregnancy. J Reprod Med 2002; 47: 347–54.Google Scholar
Feltmate, CM, Growdon, WB, Wolfberg, AJ, et al. Clinical characteristics of persistent gestational trophoblastic neoplasia after partial hydatidiform molar pregnancy. J Reprod Med 2006; 51: 902–6.Google Scholar
Hancock, BW, Nazir, K, Everard, JE. Persistent gestational trophoblastic neoplasia after partial hydatidiform mole incidence and outcome. J Reprod Med 2006; 51: 764–6.Google Scholar
Curry, SL, Hammond, CB, Tyrey, L, Creasman, WT, Parker, RT. Hydatidiform mole: diagnosis, management, and long-term followup of 347 patients. Obstet Gynecol 1975; 45: 1–8.Google Scholar
Wang, Q, Fu, J, Hu, L, Fang, F, et al. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2017; (9): CD007289.Google Scholar
Costa, HL, Doyle, P. Influence of oral contraceptives in the development of post-molar trophoblastic neoplasia: a systematic review. Gynecol Oncol 2006; 100: 579–85.Google Scholar
Savage, P. Molar pregnancy: a review. Obstetrician and Gynaecologist 2008; 10 (10): 3–8.Google Scholar
Bagshawe, KD, Harland, S. Immunodiagnosis and monitoring of gonadotrophin-producing metastases in the central nervous system. Cancer 1976; 38: 112–18.Google Scholar
Shapter, AP, McLellan, R. Gestational trophoblastic disease. Obstet Gynecol Clin North Am 2001; 28: 805–17.Google Scholar
Pezeshki, M, Hancock, BW, Silcocks, P, et al. The role of repeat uterine evacuation in the management of persistent gestational trophoblastic disease. Gynecol Oncol 2004; 95: 423–9.Google Scholar
Savage, P, Seckl, MJ. The role of repeat uterine evacuation in trophoblast disease. Gynecol Oncol 2005; 99: 251–2.Google Scholar
FIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2009; 105: 3–4.Google Scholar
Matsui, H, Iitsuka, Y, Seki, K, Sekiya, S. Comparison of chemotherapies with methotrexate, VP-16 and actinomycin-D in low-risk gestational trophoblastic disease. Remission rates and drug toxicities. Gynecol Obstet Invest 1998; 46: 5–8.Google Scholar
Bagshawe, KD, Dent, J, Newlands, ES, Begent, RH, Rustin, GJ. The role of low-dose methotrexate and folinic acid in gestational trophoblastic tumours (GTT). Br J Obstet Gynaecol 1989; 96: 795–802.Google Scholar
Deng, L, Zhang, J, Wu, T, Lawrie, TA. Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour. Cochrane Database Syst Rev 2013; 1: CD005196.Google Scholar
Ngan, S, Seckl, MJ. Gestational trophoblastic neoplasia management: an update. Curr Opin Oncol 2007; 19: 486–91.CrossRefGoogle ScholarPubMed
Lurain, JR, Sand, PK, Carson, SA, Brewer, JI. Pregnancy outcome subsequent to consecutive hydatidiform moles. Am J Obstet Gynecol 1982; 142: 1060–1.Google Scholar
Berkowitz, RS, Goldstein, DP, Bernstein, MR, Sablinska, B. Subsequent pregnancy outcome in patients with molar pregnancy and gestational trophoblastic tumors. J Reprod Med 1987; 32: 680–4.Google ScholarPubMed
Berkowitz, RS, Goldstein, DP. Chorionic tumors. N Engl J Med 1996; 335: 1740–8.Google Scholar
Garner, EIO, Lipson, E, Bernstein, MR, Goldstein, DP, Berkowitz, RS. Subsequent pregnancy experience in patients with molar pregnancy and gestational trophoblastic tumor. J Reprod Med 2002; 47: 380–6.Google Scholar
Garrett, LA, Garner, EI, Feltmate, CM, Goldstein, DP, Berkowitz, RS. Subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia. J Reprod Med 2008; 53: 481–6.Google Scholar
Petersen, RW, Ung, K, Holland, C, Quinlivan, JA. The impact of molar pregnancy on psychological symptomatology, sexual function, and quality of life. Gynecol Oncol 2005; 97: 535–42.Google Scholar
Szulman, AE. Trophoblastic disease: clinical pathology of hydatidiform moles. Obstet Gynecol Clin North Am 1988; 15: 443–56.Google Scholar
Horn, LC, Bilek, K. Clinicopathologic analysis of gestational trophoblastic disease–report of 158 cases. Gen Diagn Pathol 1997; 143: 173–8.Google Scholar
Schlaerth, JB, Morrow, CP, Rodriguez, M. Diagnostic and therapeutic curettage in gestational trophoblastic disease. Am J Obstet Gynecol 1990; 162: 1465–70.Google Scholar
Newlands, ES, Bower, M, Holden, L, Short, D, Seckl, MJ, Rustin, GJ, et al. Management of resistant gestational trophoblastic tumors. J Reprod Med 1998; 43: 111–18.Google Scholar
Dobson, LS, Lorigan, PC, Coleman, RE, Hancock, BW. Persistent gestational trophoblastic disease: results of MEA (methotrexate, etoposide and dactinomycin) as first-line chemotherapy in high risk disease and EA (etoposide and dactinomycin) as second-line therapy for low risk disease. Br J Cancer 2000; 82: 1547–52.Google ScholarPubMed
Qureshi, H, Massey, E, Kirwan, D, et al. BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn. Transfus Med 2014; 24: 8–20.Google Scholar
Matthews, CD, Matthews, AE. Transplacental haemorrhage in spontaneous and induced abortion. Lancet 1969; 1: 694–5.Google Scholar
Schorge, JO, Goldstein, DP, Bernstein, MR, Berkowitz, RS. Gestational trophoblastic disease. Curr Treat Options Oncol 2000; 1: 169–75.Google Scholar
ACOG Practice Bulletin #53. Diagnosis and treatment of gestational trophoblastic disease. Obstet Gynecol 2004; 103: 1365–77.Google Scholar
Soothill, P, Finning, K, Latham, T, et al. Use of cffDNA to avoid administration of anti-D to pregnant women when the fetus is RhD-negative: implementation in the NHS. BJOG 2015; 122: 1682–6.Google Scholar

References

Regan, L, Rai, R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 839–54.Google Scholar
Goddijn, M, Leschot, NJ. Genetic aspects of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 855–65.Google Scholar
Marlow, N, Bennett, C, Draper, ES, et al. Perinatal outcomes for extremely preterm babies in relation to place of birth in England: the EPICure 2 study. Arch Dis Child Fetal Neonatal Ed 2014; 99: F181–8.Google Scholar
World Health Organization. Definitions and Indicators in Family Planning, Maternal and Child Health and Reproductive Health. Geneva: WHO, 2001.Google Scholar
Stephenson, MD, Awartani, KA, Robinson, WP. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002; 17: 446–51.Google Scholar
Coulam, CB, Faulk, WP, McIntyre, JA. Immunotherapy for recurrent spontaneous abortion and its analogies to treatment for cancer. Am J Reprod Immunol 1991; 25: 114–19.Google Scholar
Wilcox, AJ, Weinberg, CR, O’Connor, JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189–94.Google Scholar
Wang, X, Chen, C, Wang, L, et al. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril 2003; 79: 577–84.Google Scholar
Wyatt, PR, Owolabi, T, Meier, C, Huang, T. Age-specific risk of fetal loss observed in a second trimester serum screening population. Am J Obstet Gynecol 2005; 192: 240–6.Google Scholar
Rai, R, Regan, L. Recurrent miscarriage. Lancet 2006; 368: 601–11.Google Scholar
Carrington, B, Sacks, G, Regan, L. Recurrent miscarriage: pathophysiology and outcome. Curr Opin Obstet Gynecol 2005; 17: 591–7.Google Scholar
Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril 2013; 99: 63.Google Scholar
Stirrat, GM. Recurrent miscarriage. Lancet 1990; 336: 673–5.Google Scholar
Regan, L. Recurrent miscarriage (editorial). BMJ 1991; 302: 543–4.Google Scholar
Strobino, B, Fox, HE, Kline, J, et al. Characteristics of women with recurrent spontaneous abortions and women with favorable reproductive histories. Am J Public Health 1986; 76: 986–91.Google Scholar
Brigham, SA, Conlon, C, Farquharson, RG. A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod 1999; 14: 2868–71.Google Scholar
Jivraj, S, Anstie, B, Cheong, YC, et al. Obstetric and neonatal outcome in women with a history of recurrent miscarriage: a cohort study. Hum Reprod 2001; 16: 102–6.Google Scholar
Sullivan, AE, Silver, RM, LaCoursiere, DY, Porter, TF, Branch, DW. Recurrent fetal aneuploidy and recurrent miscarriage. Obstet Gynecol 2004; 104: 784–8.Google Scholar
Royal College of Obstetricians and Gynaecologists. The Investigation and Treatment of Couples with Recurrent First-trimester and Second-trimester Miscarriage. Green-top Guideline No. 17. London: RCOG, 2011. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg17.Google Scholar
American College of Obstetricians and Gynecologists. ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). Int J Gynaecol Obstet 2002; 78: 179–90.Google Scholar
Nakano, Y, Akechi, T, Furukawa, TA, Sugiura-Ogasawara, M. Cognitive behavior therapy for psychological distress in patients with recurrent miscarriage. Psychol Res Behav Manag 2013; 6: 37–43.Google Scholar
Vansenne, F, Goddijn, M, Redeker, B, et al. Knowledge and perceived risks in couples undergoing genetic testing after recurrent miscarriage or for poor semen quality. Reprod Biomed Online 2011; 23: 525–33.Google Scholar
Jaoul, M, Ozon, A, Marx de Fossey, I, et al. [What does a thorough personality questionnaire, the MMPI-2, tell us about psychological aspects of recurrent miscarriage?]. Gynecol Obstet Fertil 2013; 41: 297–304.Google Scholar
Jauniaux, E, Farquharson, RG, Christiansen, OB, Exalto, N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 2006; 21: 2216–22.Google Scholar
Li, W, Newell-Price, J, Jones, GL, Ledger, WL, Li, TC. Relationship between psychological stress and recurrent miscarriage. Reprod Biomed Online 2012; 25: 180–9.Google Scholar
Mevorach-Zussman, N, Bolotin, A, Shalev, H, et al. Anxiety and deterioration of quality of life factors associated with recurrent miscarriage in an observational study. J Perinat Med 2012; 40: 495–501.Google Scholar
Larsen, EC, Christiansen, OB, Kolte, AM, Macklon, N. New insights into mechanisms behind miscarriage. BMC Med 2013; 11: 154. doi: 10.1186/1741-7015-11-154; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699442.Google Scholar
Li, M, Huang, SJ. Innate immunity, coagulation and placenta-related adverse pregnancy outcomes. Thromb Res 2009; 124: 656–62.Google Scholar
Hassold, T, Chiu, D. Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy. Hum Genet 1985. 70: 11–17.Google Scholar
Ní Bhrolcháin, M, Beaujouan, E. Fertility postponement is largely due to rising educational enrolment. Popul Stud (Camb) 2012; 66: 311–27.Google Scholar
MRC/RCOG Working Party on Cervical Cerclage. Interim report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomized trial of cervical cerclage. Br J Obstet Gynaecol 1988; 95: 437–45.Google Scholar
Dechanet, C, Brunet, C, Anahory, T, et al. [Effects of cigarette smoking on embryo implantation and placentation and analysis of factors interfering with cigarette smoke effects (Part II)]. Gynecol Obstet Fertil 2011; 39: 567–74.Google Scholar
Delabaere, A, Huchon, C, Deffieux, X, et al. [Epidemiology of loss pregnancy]. J Gynecol Obstet Biol Reprod (Paris) 2014; 43: 764–75.Google Scholar
Christiansen, OB, ed. Recurrent Pregnancy Loss. London: John Wiley & Sons, 2014.Google Scholar
Bell, JC, Raynes-Greenow, C, Turner, RM, et al. Maternal alcohol consumption during pregnancy and the risk of orofacial clefts in infants: a systematic review and meta-analysis. Paediatr Perinat Epidemiol 2014; 28: 322–32.Google Scholar
Polygenis, D, Wharton, S, Malmberg, C, et al. Moderate alcohol consumption during pregnancy and the incidence of fetal malformations: a meta-analysis. Neurotoxicol Teratol 1998; 20: 61–7.Google Scholar
Boots, C, Stephenson, MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med 2011; 29: 507–13.Google Scholar
Pineles, BL, Park, E, Samet, LM. Systematic review and meta-analysis of miscarriage and maternal exposure to tobacco smoke during pregnancy. Am J Epidemiol 2014; 179: 807–23.Google Scholar
Murphy, FA, Lipp, A, Powles, DL. Follow-up for improving psychological well being for women after a miscarriage. Cochrane Database Syst Rev 2012; (3): CD008679.Google Scholar
Musters, AM, Taminiau-Bloem, EF, van den Boogaard, E, van der Veen, F, Goddijn, M. Supportive care for women with unexplained recurrent miscarriage: patients’ perspectives. Hum Reprod 2011; 26: 873–7.Google Scholar
Lathi, RB, Gray-Hazard, FK, Heerema-McKenney, A, Taylor, J, Chueh, JT. First trimester miscarriage evaluation. Semin Reprod Med 2011; 29: 463–9.Google Scholar
Clark, DA, Daya, S, Coulam, CB, Gunby, J. Implication of abnormal human trophoblast karyotype for the evidence-based approach to the understanding, investigation, and treatment of recurrent spontaneous abortion. The Recurrent Miscarriage Immunotherapy Trialists Group. Am J Reprod Immunol 1996; 35: 495–8.CrossRefGoogle Scholar
Kroon, B, Harrison, K, Martin, N, Wong, B, Yazdani, A. Miscarriage karyotype and its relationship with maternal body mass index, age, and mode of conception. Fertil Steril 2011; 95: 1827–9.Google Scholar
Sugiura-Ogasawara, M, Ozaki, Y, Katano, K, et al. Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Hum Reprod 2012; 27: 2297–303.Google Scholar
Grande, M, Borrell, A, Garcia-Posada, R, et al. The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. Hum Reprod 2012; 27: 3109–17.Google Scholar
Ogasawara, M, Aoki, K, Okada, S, Suzumori, K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril 2000; 73: 300–4.Google Scholar
Philipp, T, Philipp, K, Reiner, A, Beer, F, Kalousek, DK. Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies. Hum Reprod 2003; 18: 1724–32.Google Scholar
Menasha, J, Levy, B, Hirschhorn, K, Kardon, NB. Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med 2005; 7: 251–63.Google Scholar
Rubio, C, Pehlivan, T, Rodrigo, L, et al. Embryo aneuploidy screening for unexplained recurrent miscarriage: a minireview. Am J Reprod Immunol 2005; 53: 159–65.Google Scholar
Dukhovny, S, Zutshi, P, Abbott, JF. Recurrent second trimester pregnancy loss: evaluation and management. Curr Opin Endocrinol Diabetes Obes 2009; 16: 451–8.Google Scholar
Kwinecka-Dmitriew, B, Zakrzewska, M, Latos-Bielenska, A, Skrzypczak, J. Frequency of chromosomal aberrations in material from abortions. Ginekol Pol 2010; 81: 896–901.Google Scholar
De Braekeleer, M, Dao, TN. Cytogenetic studies in couples experiencing repeated pregnancy losses. Hum Reprod 1990; 5: 519–28.Google Scholar
Sierra, S, Stephenson, M. Genetics of recurrent pregnancy loss. Semin Reprod Med 2006; 24: 17–24.Google Scholar
Stephenson, MD, Sierra, S. Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of a structural chromosome rearrangement. Hum Reprod 2006; 21: 1076–82.Google Scholar
Meza-Espinoza, JP, Anguiano, LO, Rivera, H. Chromosomal abnormalities in couples with reproductive disorders. Gynecol Obstet Invest 2008; 66: 237–40.Google Scholar
Franssen, MT, Korevaar, JC, Leschot, NJ, et al. Selective chromosome analysis in couples with two or more miscarriages: case-control study. BMJ 2005; 331: 137–41.Google Scholar
Diedrich, U, Hansmann, I, Janke, D, et al. Chromosome anomalies in 136 couples with a history of recurrent abortions. Hum Genet 1983; 65: 48–52.Google Scholar
Brookfield, JF. Q&A: promise and pitfalls of genome-wide association studies. BMC Biol 2010; 8: 41.Google Scholar
Topalidou, M, Effraimidou, S, Farmakiotis, D, et al. Low protein Z levels, but not the intron F G79A polymorphism, are associated with unexplained pregnancy loss. Thromb Res 2009; 124: 24–7.Google Scholar
Goodman, C, Goodman, CS, Hur, J, et al. The association of apoprotein E polymorphisms with recurrent pregnancy loss. Am J Reprod Immunol 2009; 61: 34–8.Google Scholar
Finan, RR, Mustafa, FE, Al-Zaman, I, et al. STAT3 polymorphisms linked with idiopathic recurrent miscarriages. Am J Reprod Immunol 2010; 63: 22–7.Google Scholar
Baek, KH, Lee, EJ, Kim, YS. Recurrent pregnancy loss: the key potential mechanisms. Trends Mol Med 2007; 13: 310–17.Google Scholar
Su, MT, Lin, SH, Chen, YC. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update 2011; 17: 803–12.Google Scholar
Salker, M, Teklenburg, G, Molokhia, M, et al. Natural selection of human embryos: impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss. PLoS One 2010; 5: e10287.Google Scholar
Beshay, VE, Bukulmez, O. Sperm DNA damage: how relevant is it clinically? Curr Opin Obstet Gynecol 2012; 24: 172–9.Google Scholar
Robinson, L, Gallos, ID, Conner, SJ, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod 2012; 27: 2908–17.Google Scholar
Ashton, D, Amin, HK, Richart, RM, Neuwirth, RS. The incidence of asymptomatic uterine anomalies in women undergoing transcervical tubal sterilization. Obstet Gynecol 1988; 72: 28–30.Google Scholar
Lin, PC. Reproductive outcomes in women with uterine anomalies. J Womens Health (Larchmt) 2004; 13: 33–9.Google Scholar
Sugiura-Ogasawara, M, Ozaki, Y, Suzumori, N. Mullerian anomalies and recurrent miscarriage. Curr Opin Obstet Gynecol 2013; 25: 293–8.Google Scholar
Saravelos, SH, Cocksedge, KA, Li, TC. The pattern of pregnancy loss in women with congenital uterine anomalies and recurrent miscarriage. Reprod Biomed Online 2010; 20: 416–22.Google Scholar
Maneschi, F, Zupi, E, Marconi, D, et al. Hysteroscopically detected asymptomatic müllerian anomalies: prevalence and reproductive implications. J Reprod Med 1995; 40: 684–8.Google Scholar
Sugiura-Ogasawara, M, Ozaki, Y, Katano, K, et al. Uterine anomaly and recurrent pregnancy loss. Semin Reprod Med 2011; 29: 514–21.Google Scholar
Rackow, BW, Arici, A. Reproductive performance of women with müllerian anomalies. Curr Opin Obstet Gynecol 2007; 19: 229–37.Google Scholar
Kroon, B, Johnson, N, Chapman, M, et al. Fibroids in infertility: consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence). Aust N Z J Obstet Gynaecol 2011; 51: 289–95.Google Scholar
Pritts, EA, Parker, WH, Olive, DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril 2009; 91: 1215–23.Google Scholar
Saravelos, SH, Yan, J, Rehmani, H, Li, TC. The prevalence and impact of fibroids and their treatment on the outcome of pregnancy in women with recurrent miscarriage. Hum Reprod 2011; 26: 3274–9.Google Scholar
Benson, CB, Chow, JS, Chang-Lee, W, Hill, JA, Doubilet, PM. Outcome of pregnancies in women with uterine leiomyomas identified by sonography in the first trimester. J Clin Ultrasound 2001; 29: 261–4.Google Scholar
Simpson, JL. Causes of fetal wastage. Clin Obstet Gynecol 2007; 50: 10–30.Google Scholar
Bajekal, N, Li, TC. Fibroids, infertility and pregnancy wastage. Hum Reprod Update 2000; 6: 614–20.Google Scholar
Hart, R, Khalaf, Y, Yeong, CT, et al. A prospective controlled study of the effect of intramural uterine fibroids on the outcome of assisted conception. Hum Reprod 2001; 16: 2411–17.Google Scholar
Casini, ML, Rossi, F, Agostini, R, Unfer, V. Effects of the position of fibroids on fertility. Gynecol Endocrinol 2006; 22: 106–9.Google Scholar
Klatsky, PC, Tran, ND, Caughey, AB, Fujimoto, VY. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am J Obstet Gynecol 2008; 198: 357–66.Google Scholar
Pérez-Medina, T, Bajo-Arenas, J, Salazar, F, et al. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod 2005; 20: 1632–5.Google Scholar
Maheshwari, A, Gurunath, S, Fatima, F, Bhattacharya, S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update 2012; 18: 374–92.Google Scholar
Tremellen, KP, Russell, P. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. II: Adenomyosis and macrophages. J Reprod Immunol 2012; 93: 58–63.Google Scholar
Alfirevic, Z, Stampalija, T, Roberts, D, Jorgensen, AL. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev 2012; (4): CD008991.Google Scholar
Berghella, V, Pereira, L, Gariepy, A, Simonazzi, G. Prior cone biopsy: prediction of preterm birth by cervical ultrasound. Am J Obstet Gynecol 2004; 191: 1393–7.Google Scholar
Bruinsma, FJ, Quinn, MA. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. BJOG 2011; 118: 1031–41.Google Scholar
Milhan, D. DES exposure: implications for childbearing. Int J Childbirth Educ 1992; 7: 21–8.Google Scholar
Word, RA, Li, XH, Hnat, M, Carrick, K. Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. Semin Reprod Med 2007; 25: 69–79.Google Scholar
Stenlund, PM, Ekman, G, Aedo, AR, Bygdeman, M. Induction of labor with mifepristone: a randomized, double-blind study versus placebo. Acta Obstet Gynecol Scand 1999; 78: 793–8.Google Scholar
Hassan, S, Romero, R, Hendler, I, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med 2006; 34: 13–19.Google Scholar
Kiefer, DG, Keeler, SM, Rust, OA, et al. Is midtrimester short cervix a sign of intra-amniotic inflammation? Am J Obstet Gynecol 2009; 200: 374.e1–5.Google Scholar
Hein, M, Helmig, RB, Schønheyder, HC, Ganz, T, Uldbjerg, N. An in vitro study of antibacterial properties of the cervical mucus plug. Am J Obstet Gynecol 2001; 185: 586–92.Google Scholar
Becher, N, Adams Waldorf, K, Hein, M, Uldbjerg, N. The cervical mucus plug: structured review of the literature. Acta Obstet Gynecol Scand 2009; 88: 502–13.Google Scholar
Hassan, SS, Romero, R, Berry, SM, et al. Patients with an ultrasonographic cervical length ≤ 15 mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol 2000; 182: 1458–67.Google Scholar
To, MS, Skentou, C, Liao, AW, Cacho, A, Nicolaides, KH. Cervical length and funneling at 23 weeks of gestation in the prediction of spontaneous early preterm delivery. Ultrasound Obstet Gynecol 2001; 18: 200–3.Google Scholar
Alijotas-Reig, J, Garrido-Gimenez, C. Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv 2013; 68: 445–66.Google Scholar
Cocksedge, KA, Li, TC, Saravelos, SH, Metwally, M. A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage. Reprod Biomed Online 2008; 17: 151–60.Google Scholar
Kalra, SK, Ratcliffe, SJ, Dokras, A. Is the fertile window extended in women with polycystic ovary syndrome? Utilizing the Society for Assisted Reproductive Technology registry to assess the impact of reproductive aging on live-birth rate. Fertil Steril 2013; 100: 208–13.Google Scholar
Usadi, RS, Legro, RS. Reproductive impact of polycystic ovary syndrome. Curr Opin Endocrinol Diabetes Obes 2012; 19: 505–11.Google Scholar
Kinsley, B. Achieving better outcomes in pregnancies complicated by type 1 and type 2 diabetes mellitus. Clin Ther 2007; 29 (Suppl D): S153–60.Google Scholar
McGrogan, A, Snowball, J, de Vries, CS. Pregnancy losses in women with Type 1 or Type 2 diabetes in the UK: an investigation using primary care records. Diabet Med 2014; 31: 357–65.Google Scholar
Stagnaro-Green, A, Abalovich, M, Alexander, E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21: 1081–125.Google Scholar
van den Boogaard, E, Vissenberg, R, Land, JA, et al. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum Reprod Update 2011; 17: 605–19.Google Scholar
Abalovich, M, Gutierrez, S, Alcaraz, G, et al. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002; 12: 63–8.Google Scholar
Casey, BM, Dashe, JS, Wells, CE, et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol 2006; 107: 337–41.Google Scholar
Abalovich, M, Mitelberg, L, Allami, C, et al. Clinical hypothyroidism and thyroid autoimmunity in women with infertility. Gynecol Endocrinol 2007; 23: 279–83.Google Scholar
Negro, R, Formoso, G, Mangieri, T, et al. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006; 91: 2587–91.Google Scholar
De Carolis, C, Greco, E, Guarino, MD, et al. Anti-thyroid antibodies and antiphospholipid syndrome: evidence of reduced fecundity and of poor pregnancy outcome in recurrent spontaneous aborters. Am J Reprod Immunol 2004; 52: 263–6.Google Scholar
Bukulmez, O, Arici, A. Luteal phase defect: myth or reality. Obstet Gynecol Clin North Am 2004; 31: 727–44.Google Scholar
Regan, L, Owen, EJ, Jacobs, HS. Hypersecretion of luteinising hormone, infertility, and miscarriage. Lancet 1990; 336: 1141–4.Google Scholar
van Hooff, M, Schoute, E, Schoemaker, J. Hypersecretion of luteinizing hormone (LH) and ovarian steroids in women with recurrent abortion. Hum Reprod 1994; 9: 179–80.Google Scholar
Clifford, K, Rai, R, Watson, H, Franks, S, Regan, L. Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomized controlled trial. BMJ 1996; 312: 1508–11.Google Scholar
Li, TC, Spuijbroek, MD, Tuckerman, E, et al. Endocrinological and endometrial factors in recurrent miscarriage. BJOG 2000; 107: 1471–9.Google Scholar
Li, TC, Tuckerman, EM, Laird, SM. Endometrial factors in recurrent miscarriage. Hum Reprod Update 2002; 8: 43–52.Google Scholar
Patel, BG, Lessey, BA. Clinical assessment and management of the endometrium in recurrent early pregnancy loss. Semin Reprod Med 2011; 29: 491–506.Google Scholar
Zenclussen, AC. Regulatory T cells in pregnancy. Semin Imunol 2006; 28: 31–9.Google Scholar
Praprotnik, S, Agmon-Levin, N, Porat-Katz, BS, et al. Prolactin’s role in the pathogenesis of the antiphospholipid syndrome. Lupus 2010; 19: 1515–19.Google Scholar
Nigro, G, Mazzocco, M, Mattia, E, et al. Role of the infections in recurrent spontaneous abortion. J Matern Fetal Neonatal Med 2011; 24: 983–9.Google Scholar
Hay, PE. Bacterial vaginosis and miscarriage. Curr Opin Infect Dis 2004; 17: 41–4.Google Scholar
Tafuri, A, Alferink, J, Möller, P, Hämmerling, GJ, Arnold, B. T cell awareness of paternal alloantigens during pregnancy. Science 1995; 270: 630–3.Google Scholar
Zenclussen, AC. CD4(+)CD25+ T regulatory cells in murine pregnancy. J Reprod Immunol 2005; 65: 101–10.Google Scholar
Alijotas-Reig, J. Immunological puzzle related to recurrent miscarriage: overview. Curr Immunol Rev 2009; 5: 175–86.Google Scholar
Zenclussen, AC, Gerlof, K, Zenclussen, ML, et al. Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model. Am J Pathol 2005; 166: 811–22.Google Scholar
Sollwedel, A, Bertoja, AZ, Zenclussen, ML, et al. Protection from abortion by heme oxygenase-1 up-regulation is associated with increased levels of Bag-1 and neuropilin-1 at the fetal-maternal interface. J Immunol 2005; 175: 4875–85.Google Scholar
Rocklin, RE, Kitzmiller, JL, Carpenter, CB, Garovoy, MR, David, JR. Maternal-fetal relation. Absence of an immunologic blocking factor from the serum of women with chronic abortions. N Engl J Med 1976; 295: 1209–13.Google Scholar
Tangri, S, Wegmann, TG, Lin, H, Raghupathy, R. Maternal anti-placental reactivity in natural, immunologically-mediated fetal resorptions. J Immunol 1994; 152: 4903–11.Google Scholar
Thellin, O, Coumans, B, Zorzi, W, Igout, A, Heinen, E. Tolerance to the foeto-placental “graft”: ten ways to support a child for nine months. Curr Opin Immunol 2000; 12: 731–7.Google Scholar
Wang, Q, Li, TC, Wu, YP, et al. Reappraisal of peripheral NK cells in women with recurrent miscarriage. Reprod Biomed Online 2008; 17: 814–19.Google Scholar
Seshadri, S, Sunkara, SK. Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Hum Reprod Update 2014; 20: 429–38.Google Scholar
Lash, GE, Bulmer, JN, Innes, BA, et al. Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage. Angiogenesis 2011; 14: 523–32.Google Scholar
Hutton, B, Sharma, R, Fergusson, D, et al. Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review. BJOG 2007; 114: 134–42.Google Scholar
Christiansen, OB, Larsen, EC, Egerup, P, et al. Intravenous immunoglobulin treatment for secondary recurrent miscarriage: a randomised, double-blind, placebo-controlled trial. BJOG 2015; 122: 500–8.Google Scholar
Katz, U, Achiron, A, Sherer, Y, Shoenfeld, Y. Safety of intravenous immunoglobulin (IVIG) therapy. Autoimmun Rev 2007; 6: 257–9.Google Scholar
Martinez-Zamora, MA, Cervera, R, Balasch, J. Recurrent miscarriage, antiphospholipid antibodies and the risk of thromboembolic disease. Clin Rev Allergy Immunol 2012; 43: 265–74.Google Scholar
Sater, MS, Finan, RR, Abu-Hijleh, FM, Abu-Hijleh, TM, Almawi, WY. Anti-phosphatidylserine, anti-cardiolipin, anti-beta2 glycoprotein I and anti-prothrombin antibodies in recurrent miscarriage at 8–12 gestational weeks. Eur J Obstet Gynecol Reprod Biol 2012; 163: 170–4.Google Scholar
Diejomaoh, MF. Recurrent spontaneous miscarriage is still a challenging diagnostic and therapeutic quagmire. Med Princ Pract 2015; 24 (Suppl 1): 38–55.Google Scholar
Alijotas-Reig, J, Vilardell-Tarres, M. Is obstetric antiphospholipid syndrome a primary nonthrombotic, proinflammatory, complement-mediated disorder related to antiphospholipid antibodies? Obstet Gynecol Surv 2010; 65: 39–45.Google Scholar
Galarza-Maldonado, C, Kourilovitch, MR, Pérez-Fernández, OM, et al. Obstetric antiphospholipid syndrome. Autoimmun Rev 2012; 11: 288–95.Google Scholar
Ludvigsson, JF, Montgomery, SM, Ekbom, A. Celiac disease and risk of adverse fetal outcome: a population-based cohort study. Gastroenterology 2005; 129: 454–63.Google Scholar
Tursi, A, Giorgetti, G, Brandimarte, G, Elisei, W. Effect of gluten-free diet on pregnancy outcome in celiac disease patients with recurrent miscarriages. Dig Dis Sci 2008; 53: 2925–8.Google Scholar
Bradley, RJ, Rosen, MP. Subfertility and gastrointestinal disease: “unexplained” is often undiagnosed. Obstet Gynecol Surv 2004; 59: 108–17.Google Scholar
Kumar, A, Meena, M, Begum, N, et al. Latent celiac disease in reproductive performance of women. Fertil Steril 2011; 95: 922–7.Google Scholar
Gleicher, N, el-Roeiy, A, Confino, E, Friberg, J. Reproductive failure because autoantibodies: unexplained infertility and pregnancy wastage. Am J Obstet Gynecol 1989; 160: 1376–80.Google Scholar
Gleicher, N. Some thoughts on the reproductive autoimmune failure syndrome (RAFS) and Th-1 versus Th-2 immune responses. Am J Reprod Immunol 2002; 48: 252–4.Google Scholar
Gleicher, N, el-Roeiy, A. The reproductive autoimmune failure syndrome. Am J Obstet Gynecol 1988; 159: 223–7.Google Scholar
Gleicher, N. Reproductive failure prior to the onset of clinical autoimmune disease. Rheumatology (Oxford) 1999; 38: 485–7.Google Scholar
de Jong, PG, Goddijn, M, Middeldorp, S. Testing for inherited thrombophilia in recurrent miscarriage. Semin Reprod Med 2011; 29: 540–7.Google Scholar
Brenner, B. Thrombophilia and pregnancy loss in first intended pregnancy. J Thromb Haemost 2005; 3: 2176–7.Google Scholar
Greer, IA. Thrombophilia: implications for pregnancy outcome. Thromb Res 2003; 109: 73–81.Google Scholar
McNamee, K, Dawood, F, Farquharson, RG. Thrombophilia and early pregnancy loss. Best Pract Res Clin Obstet Gynecol 2012; 26: 91–102.Google Scholar
Kist, WJ, Janssen, NG, Kalk, JJ, et al. Thrombophilias and adverse pregnancy outcome: a confounded problem! Thromb Haemost 2008; 99: 77–85.Google Scholar
Dutch Society for Obstetrics and Gynaecology. Habitual Abortion. Guideline No. 20. Utrecht; 1999.Google Scholar
Battinelli, EM, Marshall, A, Connors, JM. The role of thrombophilia in pregnancy. Thrombosis 2013; 2013: 516420.Google Scholar
Kovac, M, Mikovic, Z, Mitic, G, et al. Does anticoagulant therapy improve pregnancy outcome equally, regardless of specific thrombophilia type? Clin Appl Thromb Hemost 2014; 20: 184–9.Google Scholar
Rey, E, Kahn, SR, David, M, Shrier, I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 2003; 361: 901–8.Google Scholar
Laurino, MY, Bennett, RL, Saraiya, DS, et al. Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J Genet Couns 2005; 14: 165–81.Google Scholar
Carp, H, Toder, V, Aviram, A, et al. Karyotype of the abortus in recurrent miscarriage. Fertil Steril 2001; 75: 678–82.Google Scholar
Barber, JC, Cockwell, AE, Grant, E, et al. Is karyotyping couples experiencing recurrent miscarriage worth the cost? BJOG 2010; 117: 885–8.Google Scholar
Robert, JM, Macara, LM, Chalmers, EA, Smith, GC. Inter-assay variation in antiphospholipid antibody testing. BJOG 2002; 109: 348–9.Google Scholar
Miyakis, S, Lockshin, MD, Atsumi, T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306.Google Scholar
Rai, RS, Regan, L, Clifford, K, et al. Antiphospholipid antibodies and β2-glycoprotein-I in 500 women with recurrent miscarriage: results of a comprehensive screening approach. Hum Reprod 1995; 10: 2001–5.Google Scholar
de la Rochebrochard, E, Thonneau, P. Paternal age and maternal age are risk factors for miscarriage: results of a multicentre European study. Hum Reprod 2002; 17: 1649–56.Google Scholar
Clifford, K, Rai, R, Regan, L. Future pregnancy outcome in unexplained recurrent first trimester miscarriage. Hum Reprod 1997; 12: 387–9.Google Scholar
Liddell, HS, Pattison, NS, Zanderigo, A. Recurrent miscarriage: outcome after supportive care in early pregnancy. Aust N Z J Obstet Gynaecol 1991; 31: 320–2.Google Scholar
Haas, DM, Ramsey, PS. Progestogen for preventing miscarriage. Cochrane Database Syst Rev 2013; (10): CD003511.Google Scholar
Rai, R, Backos, M, Baxter, N, Chilcott, I, Regan, L. Recurrent miscarriage: an aspirin a day? Hum Reprod 2000; 15: 2220–3.Google Scholar
Tulppala, M, Marttunen, M, Söderstrom-Anttila, V, et al. Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production. Hum Reprod 1997; 12: 1567–72.Google Scholar
Kaandorp, SP, Goddijn, M, van der Post, JA, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med 2010; 362: 1586–96.Google Scholar
Clark, P, Walker, ID, Langhorne, P, et al.; Scottish Pregnancy Intervention Study (SPIN) collaborators. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood 2010; 115: 4162–7.Google Scholar
Ogilvie, CM, Braude, P, Scriven, PN. Successful pregnancy outcomes after preimplantation genetic diagnosis (PGD) for carriers of chromosome translocations. Hum Fertil (Camb) 2001; 4: 168–71.Google Scholar
Scriven, PN, Flinter, FA, Braude, PR, Ogilvie, CM. Robertsonian translocations: reproductive risks and indications for preimplantation genetic diagnosis. Hum Reprod 2001; 16: 2267–73.Google Scholar
Regan, L, Rai, R, Backos, M, El Gaddal, S. Recurrent miscarriage and parental karyotype abnormalities: prevalence and future pregnancy outcome. Abstracts of the 17th Annual Meeting of the ESHRE, Lausanne, Switzerland 2001. Hum Reprod 2001; 16 (Suppl 1): 177–8.Google Scholar
Lalioti, MD. Can preimplantation genetic diagnosis overcome recurrent pregnancy failure? Curr Opin Obstet Gynecol 2008; 20: 199–204.Google Scholar
Grimbizis, GF, Camus, M, Tarlatzis, BC, Bontis, JN, Devroey, P. Clinical implications of uterine malformations and hysteroscopic treatment results. Hum Reprod Update 2001; 7: 161–74.Google Scholar
Porcu, G, Cravello, L, D’Ercole, C, et al. Hysteroscopic metroplasty for septate uterus and repetitive abortions: reproductive outcome. Eur J Obstet Gynecol Reprod Biol 2000; 88: 81–4.Google Scholar
Pace, S, Cipriano, L, Pace, G, Catania, R, Montanino, G. Septate uterus: reproductive outcome after hysteroscopic metroplasty. Clin Exp Obstet Gynecol 2006; 33: 110–12.Google Scholar
Tang, AW, Quenby, S. Recent thoughts on management and prevention of recurrent early pregnancy loss. Curr Opin Obstet Gynecol 2010; 22: 446–51.Google Scholar
Roy, KK, Singla, S, Baruah, J, et al. Reproductive outcome following hysteroscopic myomectomy in patients with infertility and recurrent abortions. Arch Gynecol Obstet 2010; 282: 553–60.Google Scholar
Campo, S, Campo, V, Gambadauro, P. Reproductive outcome before and after laparoscopic or abdominal myomectomy for subserous or intramural myomas. Eur J Obstet Gynecol Reprod Biol 2003; 110: 215–19.Google Scholar
Kodaman, PH, Arici, A. Intra-uterine adhesions and fertility outcome: how to optimize success? Curr Opin Obstet Gynecol 2007; 19: 207–14.Google Scholar
Jacobsen, LJ, DeCherney, A. Results of conventional and hysteroscopic surgery. Hum Reprod 1997; 12: 1376–81.Google Scholar
Homer, HA, Li, TC, Cooke, ID. The septate uterus: a review of management and reproductive outcome. Fertil Steril 2000; 73: 1–14.Google Scholar
Sugiura-Ogasawara, M, Lin, BL, Aoki, K, et al. Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies? J Obstet Gynaecol 2015; 35: 155–8.Google Scholar
Jaslow, CR, Kutteh, WH. Effect of prior birth and miscarriage frequency on the prevalence of acquired and congenital uterine anomalies in women with recurrent miscarriage: a cross-sectional study. Fertil Steril 2013; 99: 1916–22.e1.Google Scholar
Boivin, J, Lancastle, D. Medical waiting periods: imminence, emotions and coping. Womens Health 2010; 6: 59–69.Google Scholar
Royal College of Obstetricians and Gynaecologists. Cervical Cerclage. Green-top Guideline No. 60. London: RCOG, 2011.Google Scholar
Drakeley, AJ, Roberts, D, Alfirevic, Z. Cervical cerclage for prevention of preterm delivery: meta-analysis of randomized trials. Obstet Gynecol 2003; 102: 621–7. Erratum in: Obstet Gynecol 2004; 103: 201.Google Scholar
MRC/RCOG Working Party on Cervical Cerclage. Final report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomised trial of cervical cerclage. Br J Obstet Gynaecol 1993; 100: 516–23.Google Scholar
Berghella, V, Odibo, AO, To, MS, Rust, OA, Althuisius, SM. Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data. Obstet Gynecol 2005; 106: 181–9.Google Scholar
Gibb, DM, Salaria, DA. Transabdominal cervicoisthmic cerclage in the management of recurrent second trimester miscarriage and preterm delivery. Br J Obstet Gynaecol 1995; 102: 802–6.Google Scholar
Anthony, GS, Walker, RG, Cameron, AD, et al. Transabdominal cervico-isthmic cerclage in the management of cervical incompetence. Eur J Obstet Gynecol Reprod Biol 1997; 72: 127–30.Google Scholar
Debbs, RH, De La Vega, GA, Pearson, S, et al. Transabdominal cerclage after comprehensive evaluation of women with previous unsuccessful transvaginal cerclage. Am J Obstet Gynecol 2007; 197: 317.e1–4.Google Scholar
Zaveri, V, Aghajafari, F, Amankwah, K, Hannah, M. Abdominal versus vaginal cerclage after a failed transvaginal cerclage: a systematic review. Am J Obstet Gynecol 2002; 187: 868–72.Google Scholar
Thuesen, LL, Diness, BR, Langhoff-Roos, J. Pre-pregnancy transabdominal cerclage. Acta Obstet Gynecol Scand 2009; 88: 483–6.Google Scholar
Drakeley, AJ, Roberts, D, Alfirevic, Z. Cervical stitch (cerclage) for preventing pregnancy loss in women. Cochrane Database Syst Rev 2003; (1): CD003253.Google Scholar
McDonald, IA. Suture of the cervix for inevitable miscarriage. J Obstet Gynaecol Br Emp 1957; 64: 346–50.Google Scholar
Birmingham Clinical Trials Unit. Cerclage Suture Type for an Insufficient Cervix and its effect on Health (C-STICH). http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/C-Stich (accessed March 2017).Google Scholar
Shirodkar, VN. A new method of operative treatment for habitual abortions in the second trimester of pregnancy. Antiseptic 1955; 52: 299–300.Google Scholar
Benson, RC, Durfee, RB. Transabdominal cervico-uterine cerclage during pregnancy for the treatment of cervical incompetency. Obstet Gynecol Clin North Am 1965; 25: 145–55.Google Scholar
Umstad, MP, Quinn, MA, Ades, A. Transabdominal cervical cerclage. Aust N Z J Obstet Gynaecol 2010; 50: 460–4.Google Scholar
Tulandi, T, Alghanaim, N, Hakeem, G, Tan, XJ. Pre- and post-conceptional abdominal cerclage by laparoscopy or laparotomy. Minim Invasive Gynecol 2014; 21: 987.Google Scholar
Burger, NB, Einarsson, JI, Brölmann, HA, Vree, FE, McElrath, TF, Huirne, JA. Preconceptional laparoscopic abdominal cerclage: a multicenter cohort study. Am J Obstet Gynecol 2012; 207: 273.e1.Google Scholar
Burger, NB, Brölmann, HA, Einarsson, JI, Langebrekke, A, Huirne, JA. Effectiveness of abdominal cerclage placed via laparotomy or laparoscopy: systematic review. J Minim Invasive Gynecol 2011; 18: 696–704.Google Scholar
Althuisius, S, Dekker, G, Hummel, P, et al. Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): effect of therapeutic cerclage with bed rest vs. bed rest only on cervical length. Ultrasound Obstet Gynecol 2002; 20: 163–7.Google Scholar
Noori, M, Helmig, RB, Hein, M, Steer, PJ. Could a cervical occlusion suture be effective at improving perinatal outcome? BJOG 2007; 114: 532–6.Google Scholar
Khan, KS, Hills, R. Can we trust the results of trials that are stopped early? BJOG 2006; 113: 766–8.Google Scholar
Wahabi, HA, Alzeidan, RA, Bawazeer, GA, Alansari, LA, Esmaeil, SA. Preconception care for diabetic women for improving maternal and fetal outcomes: a systematic review and meta-analysis. BMC Pregnancy Childbirth 2010; 10: 63.Google Scholar
Abbassi-Ghanavati, M. Thyroid autoantibodies and pregnancy outcomes. Clin Obstet Gynecol 2011; 54: 499–505.Google Scholar
Negro, R, Schwartz, A, Gismondi, R, et al. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab 2010; 95: 1699–707.Google Scholar
Garber, JR, Cobin, RH, Gharib, H, et al. Clinical practice guidelines for hypothyroidism in adults: co-sponsored by American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012; 18: 988–1028.Google Scholar
Vissenberg, R, van den Boogaard, E, van Wely, M, et al. Treatment of thyroid disorders before conception and in early pregnancy: a systematic review. Hum Reprod Update 2012; 18: 360–73.Google Scholar
Sieiro Netto, L, Medina Coeli, C, Micmacher, E, et al. Influence of thyroid autoimmunity and maternal age on the risk of miscarriage. Am J Reprod Immunol 2004; 52: 312–16.Google Scholar
Dal Lago, A, Vaquero, E, Pasqualetti, P, et al. Prediction of early pregnancy maternal thyroid impairment in women affected with unexplained recurrent miscarriage. Hum Reprod 2011; 26: 1324–30.Google Scholar
Milewicz, T, Spałkowska, M, Wasyl, B, et al. [The role of thyroid antibodies in the pathogenesis of the infertility and miscarriage]. Przegl Lek 2011; 68: 284–6.Google Scholar
Thangaratinam, S, Tan, A, Knox, E, et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 2011; 342: d2616.Google Scholar
Liu, H, Shan, Z, Li, C, et al. Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study. Thyroid 2014; 24: 1642–9.Google Scholar
Gallot, V, Nedellec, S, Capmas, P, et al. [Early recurrent miscarriage: evaluation and management.]. J Gynecol Obstet Biol Reprod (Paris) 2014; 43: 812–41.Google Scholar
Dhillon-Smith, RK, Middleton, LJ, Sunner, KK, et al. Levothyroxine in women with thyroid peroxidase antibodies before conception. N Engl J Med 2019; 380 (14): 1316–25. https://doi.org/10.1056/NEJMoa1812537.Google Scholar
Xiao, J, Chen, S, Zhang, C, Chang, S. The effectiveness of metformin ovulation induction treatment in patients with PCOS: a systematic review and meta-analysis. Gynecol Endocrinol 2012; 28: 956–60.Google Scholar
Nardo, LG, El-Toukhy, T, Stewart, J, Balen, AH, Potdar, N. British Fertility Society Policy and Practice Committee: adjuvants in IVF: evidence for good clinical practice. Hum Fertil (Camb) 2015; 18: 2–15.Google Scholar
Palomba, S, Falbo, A, Orio, F, Zullo, F. Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2009; 92: 1646–58.Google Scholar
Jakubowicz, DJ, Iuorno, MJ, Jakubowicz, S, Roberts, KA, Nestler, JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 524–9.Google Scholar
Nawroth, F. Hyperprolactinaemia and the regular menstrual cycle in asymptomatic women: should it be treated during therapy for infertility? Reprod Biomed Online 2005; 11: 581–8.Google Scholar
Souter, I, Baltagi, LM, Toth, TL, Petrozza, JC. Prevalence of hyperprolactinemia and abnormal magnetic resonance imaging findings in a population with infertility. Fertil Steril 2010; 94: 1159–62.Google Scholar
Raghupathy, R, Al-Mutawa, E, Al-Azemi, M, et al. Progesterone-induced blocking factor (PIBF) modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery. J Reprod Immunol 2009; 80: 91–9.Google Scholar
Oates-Whitehead, RM, Haas, DM, Carrier, JA. Progestogen for preventing miscarriage. Cochrane Database Syst Rev 2003; (4): CD003511.Google Scholar
Szekeres-Bartho, J, Balasch, J. Progestagen therapy for recurrent miscarriage. Hum Reprod Update 2008; 14: 27–35.Google Scholar
Coomarasamy, A, Truchanowicz, EG, Rai, R. Does first trimester progesterone prophylaxis increase the live birth rate in women with unexplained recurrent miscarriages? BMJ 2011; 18: 342.d1914.Google Scholar
Conde-Agudelo, A, Romero, R, Nicolaides, K, et al. Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol 2013; 208: 42.e1–42.e18.Google Scholar
Carp, H. A systematic review of dydrogesterone for the treatment of recurrent miscarriage. Gynecol Endocrinol 2015; 31: 422–30.Google Scholar
El-Zibdeh, MY. Dydrogesterone in the reduction of recurrent spontaneous abortion. J Steroid Biochem Mol Biol 2005; 97: 431–4.Google Scholar
Kumar, A, Begum, N, Prasad, S, Aggarwal, S, Sharma, S. Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial. Fertil Steril 2014; 102: 1357–63Google Scholar
Freedman, RS, Berry, A. Progesterone deficiency in pregnancy. S Afr J Obstet Gynaecol 1970; 46: 72–6.Google Scholar
Coomarasamy, A, Williams, H, Truchanowicz, E, et al. A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med 2015; 373: 2141–8. doi: 10.1056/NEJMoa1504927.Google Scholar
Saccone, G, Schoen, C, Franasiak, JM, Scott, RT, Berghella, V. Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Fertil Steril 2017; 107: 430–8.Google Scholar
Coomarasamy, A, Devall, AJ, Cheed, V, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. N Engl J Med 2019; 380: 1815–24. https://doi.org/10.1056/NEJMoa1813730.Google Scholar
Coomarasamy, A, Devall, AJ, Brosens, JJ, et al. Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence. Am J Obstet Gynecol 2020; S0002-9378(19)32762–0. Online ahead of print. https://doi.org/10.1016/j.ajog.2019.12.006.Google Scholar
Okeke Ogwulu, CB, Goranitis, I, Devall, AJ, et al. The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial. BJOG 2020; 127: 757–67. https://doi.org/10.1111/1471-0528.16068.Google Scholar
Newbatt, E, Beckles, Z, Ullman, R, Lumsden, MA; Guideline Development Group. Ectopic pregnancy and miscarriage: summary of NICE guidance. BMJ 2012; 345: e8136. https://doi.org/10.1136/bmj.e8136.Google Scholar
Peterson, CM. Progestogens, progesterone antagonists, progesterone, and androgens: synthesis, classification, and uses. Clin Obstet Gynecol 1995; 38: 813–20.Google Scholar
Romero, R, Stanczyk, FZ. Progesterone is not the same as 17a-hydroxyprogesterone caproate: implications for obstetrical practice. Am J Obstet Gynecol 2013; 208: 421–6. https://doi.org/10.1016/j.ajog.2013.04.027.Google Scholar
Harrison, RF. Human chorionic gonadotrophin (hCG) in the management of recurrent abortion; results of a multi-centre placebo-controlled study. Eur J Obstet Gynecol Reprod Biol 1992; 47: 175–9.Google Scholar
Quenby, S, Farquharson, RG. Human chorionic gonadotropin supplementation in recurring pregnancy loss: a controlled trial. Fertil Steril 1994; 62: 708–10.Google Scholar
Wilkowska-Trojniel, M, Zdrodowska-Stefanow, B, Ostaszewska-Puchalska, I, et al. The influence of Chlamydia trachomatis infection on spontaneous abortions. Adv Med Sci 2009; 54: 86–90.Google Scholar
Akande, V, Turner, C, Horner, P, et al. Impact of Chlamydia trachomatis in the reproductive setting: British Fertility Society Guidelines for practice. Hum Fertil (Camb) 2010; 13: 115–25.Google Scholar
Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2010. http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf.Google Scholar
Howie, SE, Horner, PJ, Horne, AW. Chlamydia trachomatis infection during pregnancy: known unknowns. Discov Med 2011; 12: 57–64.Google Scholar
Ugwumadu, A, Manyonda, I, Reid, F, Hay, P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial. Lancet 2003; 361: 983–8.Google Scholar
Lamont, RF, Taylor-Robinson, D. The role of bacterial vaginosis, aerobic vaginitis, abnormal vaginal flora and the risk of preterm birth. BJOG 2010; 117: 119–20.Google Scholar
Empson, M, Lassere, M, Craig, J, Scott, J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev 2005; (2): CD002859.Google Scholar
Noble, LS, Kutteh, WH, Lashey, N, Franklin, RD, Herrada, J. Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective,multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin. Fertil Steril 2005; 83: 684–90.Google Scholar
Stephenson, MD, Ballem, PJ, Tsang, P, et al. Treatment of antiphospholipid antibody syndrome (APS) in pregnancy: a randomized pilot trial comparing low molecular weight heparin to unfractionated heparin. J Obstet Gynaecol Can 2004; 26: 729–34.Google Scholar
Farquharson, RG, Quenby, S, Greaves, M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 2002; 100: 408–13.Google Scholar
Laskin, CA, Spitzer, KA, Clark, CA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. J Rheumatol 2009; 36: 279–87.Google Scholar
Duley, L, Henderson-Smart, DJ, Meher, S, King, JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2007; (2): CD004659.Google Scholar
Backos, M, Rai, R, Thomas, E, et al. Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study. Hum Reprod 1999; 14: 2876–80.Google Scholar
Carlin, AJ, Farquharson, RG, Quenby, SM, Topping, J, Fraser, WD. Prospective observational study of bone mineral density during pregnancy: low molecular weight heparin versus control. Hum Reprod 2004; 19: 1211–14.Google Scholar
Greer, IA, Nelson-Piercy, C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005; 106: 401–7.Google Scholar
Backos, M, Rai, R, Baxter, N, et al. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 1999; 106: 102–7.Google Scholar
Branch, DW, Silver, RM, Blackwell, JL, Reading, JC, Scott, JR. Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience. Obstet Gynecol 1992; 80: 614–20.Google Scholar
Ziakas, PD, Pavlou, M, Voulgarelis, M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis. Obstet Gynecol 2010; 115: 1256–62.Google Scholar
Lassere, M, Empson, M. Treatment of antiphospholipid syndrome in pregnancy: a systematic review of randomized therapeutic trials. Thromb Res 2004; 114: 419–26.Google Scholar
de Jong, PG, Kaandorp, S, Di Nisio, M, Goddijn, M, Middeldorp, S. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev 2014; (7): CD004734.Google Scholar
Geerts, WH, Pineo, GF, Heit, JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 338S–400S.Google Scholar
Bates, SM, Greer, IA, Pabinger, I, et al. Venous thromboembolism, thrombophilias, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edn). Chest 2008; 133: 844S–886S.Google Scholar
Triolo, G, Ferrante, A, Ciccia, F, et al. Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis Rheum 2003; 48: 728–31.Google Scholar
Dendrinos, S, Sakkas, E, Makrakis, E. Low-molecular-weight heparin versus intravenous immunoglobulin for recurrent abortion associated with antiphospholipid antibody syndrome. Int J Gynaecol Obstet 2009; 104: 223–5.Google Scholar
Royal College of Obstetricians and Gynaecologists. Reducing the Risk of Venous Thromboembolism During Pregnancy and the Puerperium. Green-top Guideline No. 37a. London: RCOG, 2015. http://www.rcog.org.uk/womens-health/clinical-guidance/reducing-risk-of-thrombosis-greentop37a.Google Scholar
Carp, H, Dolitzky, M, Inbal, A. Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia. J Thromb Haemost 2003; 1: 433–8.Google Scholar
Brenner, B, Hoffman, R, Carp, H, Dulitsky, M, Younis, J; LIVE-ENOX Investigators. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost 2005; 3: 227–9.Google Scholar
Ogueh, O, Chen, MF, Spurll, G, Benjamin, A. Outcome of pregnancy in women with hereditary thrombophilia. Int J Gynaecol Obstet 2001; 74: 247–53.Google Scholar
Gris, JC, Mercier, E, Quéré, I, et al. Low-molecular weight heparin versus low-dose aspirin in women with one fetal loss and constitutional thrombophilic disorder. Blood 2004; 103: 3695–9.Google Scholar
Porter, TF, LaCoursiere, Y, Scott, JR. Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev 2006; (2): CD000112.Google Scholar
Stephenson, MD, Kutteh, WH, Purkiss, S, et al. Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial. Hum Reprod 2010; 25: 2203–9.Google Scholar
Platteau, P, Staessen, C, Michiels, A, et al. Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages. Fertil Steril 2005; 83: 393–7.Google Scholar
Munné, S, Chen, S, Fischer, J, et al. Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages. Fertil Steril 2005; 84: 331–5.Google Scholar
Garrisi, JG, Colls, P, Ferry, KM, et al. Effect of infertility, maternal age, and number of previous miscarriages on the outcome of preimplantation genetic diagnosis for idiopathic recurrent pregnancy loss. Fertil Steril 2009; 92: 288–95.Google Scholar

References

Garne, E, Loane, M, Dolk, H, et al. Prenatal diagnosis of severe structural congenital malformations in Europe. Ultrasound Obstet Gynecol 2005; 25: 6–11.Google Scholar
Souka, AP, Snidjers, RJM, Novakov, A, Soares, W, Nicolaides, KH. Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10–14 weeks of gestation. Ultrasound Obstet Gynecol 1988; 11: 391–400.Google Scholar
Sonek, J. First trimester ultrasonography in screening and detection of fetal anomalies. Am J Med Genet C Semin Med Genet 2007; 145C: 45–61.Google Scholar
Gracia, CR, Barnhart, KT. Diagnosing ectopic pregnancy: decision analysis comparing six strategies. Obstet Gynecol 2001; 97: 464–70.Google Scholar
Seeber, BE, Barnhart, KT. Suspected ectopic pregnancy (review). Obstet Gynecol 2006; 107: 399–413. Erratum in Obstet Gynecol 2006; 107: 955.Google Scholar
Ahmed, AA, Tom, BD, Calabrese, P. Ectopic pregnancy diagnosis and the pseudo-sac. Fertil Steril 2004; 81: 1125–8.Google Scholar
Barnhart, K, Mennuti, MT, Benjamin, I, et al. Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet Gynecol 1994; 84: 1010–15.Google Scholar
Barnhart, K, Esposito, M, Coutifaris, C. An update on the medical treatment of ectopic pregnancy. Obstet Gynecol Clin North Am 2000; 27: 653–67.Google Scholar
Pandya, PP, Snijders, RJ, Psara, N, Hilbert, L, Nicolaides, KH. The prevalence of nonviable pregnancy at 10–13 weeks of gestation. Ultrasound Obstet Gynecol 1996; 7: 170–3.Google Scholar
Chen, BA, Creinin, MD. Contemporary management of early pregnancy failure (review). Clin Obstet Gynecol 2007; 50: 67–88.Google Scholar
Sawyer, E, Jurkovic, D. Ultrasonography in the diagnosis and management of abnormal early pregnancy. Clin Obstet Gynecol 2007; 50: 31–54.Google Scholar
Goldstein, SR. Sonography in early pregnancy failure. Clin Obstet Gynecol 1994; 37: 681–92.Google Scholar
Levi, CS, Lyons, EA, Lindsay, DJ. Early diagnosis of nonviable pregnancy with endovaginal US. Radiology 1988; 167: 383–5.Google Scholar
Hately, W, Case, J, Campbell, S. Establishing the death of an embryo by ultrasound: report of a public inquiry with recommendations. Ultrasound Obstet Gynecol 1995; 5: 353–7.Google Scholar
Pennell, RG, Needleman, L, Pajak, T, et al. Prospective comparison of vaginal and abdominal sonography in normal early pregnancy. J Ultrasound Med 1991; 10: 63–7.Google Scholar
Abaid, LN, As-Sanie, S, Wolfe, HM. Relationship between crown–rump length and early detection of cardiac activity. J Reprod Med 2007; 52: 375–8.Google Scholar
Acharya, G, Morgan, H. First-trimester, three-dimensional transvaginal ultrasound volumetry in normal pregnancies and spontaneous miscarriages. Ultrasound Obstet Gynecol 2002; 19: 575–9.Google Scholar
Choong, S, Rombauts, L, Ugoni, A, Meagher, S. Ultrasound prediction of risk of spontaneous miscarriage in live embryos from assisted conceptions. Ultrasound Obstet Gynecol 2003; 22: 571–7.Google Scholar
Chittacharoen, A, Herabutya, Y. Slow fetal heart rate may predict pregnancy outcome in first-trimester threatened abortion. Fertil Steril 2004; 82: 227–9.Google Scholar
Merchiers, EH, Dhont, M, De Sutter, PA, Beghin, CJ, Vandekerckhove, DA. Predictive value of early embryonic cardiac activity for pregnancy outcome. Am J Obstet Gynecol 1991; 165: 11–14.Google Scholar
Doubilet, PM, Benson, CB, Bourne, T, Blaivas, M; Society of Radiologists in Ultrasound Multispecialty Panel on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 2013; 369: 1443–51.Google Scholar
Spencer, K, Souter, V, Tul, N, Snijders, R, Nicolaides, KH. A screening program for trisomy 21 at 10–14 weeks using fetal nuchal translucency, maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 1999; 13: 231–7.Google Scholar
Campbell, S, Warsof, SL, Little, D, Cooper, DJ. Routine ultrasound screening for the prediction of gestational age. Obstet Gynecol 1985; 65: 613–20.Google Scholar
Dietz, PM, England, LJ, Callaghan, WM, et al. A comparison of LMP-based and ultrasound-based estimates of gestational age using linked California livebirth and prenatal screening records. Paediatr Perinat Epidemiol 2007; 21 (Suppl 2): 62–71.Google Scholar
Robinson, HP, Fleming, JE. A critical evaluation of sonar “crown–rump length” measurements. Br J Obstet Gynaecol 1975; 82: 702–10.Google Scholar
Bottomley, C, Bourne, T. Dating and growth in the first trimester. Best Pract Res Clin Obstet Gynaecol 2009; 23: 439–52.Google Scholar
Daya, S, Woods, S, Ward, S, Lappalainen, R, Caco, C. Early pregnancy assessment with transvaginal ultrasound scanning. CMAJ 1991; 144: 441–6.Google Scholar
Lasser, DM, Peisner, DB, Vollebergh, J, Timor-Tritsch, I. First-trimester fetal biometry using transvaginal sonography. Ultrasound Obstet Gynecol 1993; 3: 104–8.Google Scholar
Wisser, J, Dirscheld, P. Estimation of gestational age by transvaginal sonographic measurement of greatest embryonic length in dated human embryos. Ultrasound Obstet Gynecol 1994; 4: 457–62.Google Scholar
Hadlock, FP. Sonographic estimation of fetal age and weight. Radiol Clin North Am 1990; 28: 39–50.Google Scholar
Papageorghiou, AT, Kennedy, SH, Salomon, LJ, et al.; International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown–rump length in the first trimester of pregnancy. Ultrasound Obstet Gynecol 2014; 44: 641–8.Google Scholar
Morin, I, Morin, L, Zhang, X, et al. Determinants and consequences of discrepancies in menstrual and ultrasonographic gestational age estimates. BJOG 2005; 112: 145–52.Google Scholar
Bottomley, C, Daemen, A, Mukri, F, et al. Functional linear discriminant analysis: a new longitudinal approach to the assessment of embryonic growth. Hum Reprod 2009; 24: 278–83.Google Scholar
Bukowski, R, Smith, GC, Malone, FD, et al.; FASTER Research Consortium. Human sexual size dimorphism in early pregnancy. Am J Epidemiol 2007; 165: 1216–18.Google Scholar
Salomon, LJ, Bernard, JP, Nizard, J, Ville, Y. First-trimester screening for fetal triploidy at 11 to 14 weeks: a role for fetal biometry. Prenat Diagn 2005; 25: 479–83.Google Scholar
Bahado-Singh, RO, Lynch, L, Deren, O, et al. First-trimester growth restriction and fetal aneuploidy: the effect of type of aneuploidy and gestational age. Am J Obstet Gynecol 1997; 176: 976–80.Google Scholar
Goldstein, SR, Kerenyi, T, Scher, J, Papp, C. Correlation between karyotype and ultrasound findings in patients with failed early pregnancy. Ultrasound Obstet Gynecol 1996; 8: 314–17.Google Scholar
Smith, GC, Smith, MF, McNay, MB, Fleming, JE. First-trimester growth and the risk of low birth weight. N Engl J Med 1998; 339: 1817–22.Google Scholar
Rossi, C, Prefumo, F. Accuracy of ultrasonography at 11–14 weeks of gestation for detection of fetal structural anomalies: a systematic review. Obstet Gynecol 2013; 122: 1160–7.Google Scholar
Souka, AP, Pilalis, A, Kavalakis, Y, et al. Assessment of fetal anatomy at the 11–14-week ultrasound examination. Ultrasound Obstet Gynecol 2004; 24: 730–4.Google Scholar
Timor-Tritsch, IE, Fuchs, KM, Monteagudo, A, D’Alton, ME. Performing a fetal anatomy scan at the time of first-trimester screening. Obstet Gynecol 2009; 113: 402–7.Google Scholar
Green, JJ, Hobbins, JC. Abdominal ultrasound examination of the first trimester fetus. Am J Obstet Gynecol 1988; 159: 165–175.Google Scholar
Lazanakis, M, Whitlow, BJ, Economides, DL. The significance of choroids plexus cysts, “golf ball” sign and pyelectasis in the first trimester of pregnancy. J Obstet Gynecol 1997; 17: S32.Google Scholar
Bromley, B, Lieberman, R, Benacerraf, BR. Choroid plexus cysts: not associated with Down syndrome. Ultrasound Obstet Gynecol 1996; 8: 232–5.Google Scholar
Blaas, HG, Eik-Nes, SH. Sonoembryology and early prenatal diagnosis of neural anomalies. Prenat Diagn 2009; 29: 312–25.Google Scholar
Blaas, HG, Eik-Nes, SH, Berg, S, Torp, H. In-vivo three dimensional ultrasound reconstructions of embryos and early fetuses. Lancet 1998; 352: 1182–6.Google Scholar
Tache, V, Tarsa, M, Romine, L, Pretorius, DH. Three-dimensional obstetric ultrasound (review). Semin Ultrasound CT MR 2008; 29: 147–55.Google Scholar
Kim, MS, Jeanty, P, Turner, C, Benoit, B. Three-dimensional sonographic evaluation of embryonic brain development. J Ultrasound Med 2008; 27: 119–24.Google Scholar
Smrcek, JM, Berg, C, Geipel, A, et al. Early fetal echocardiography: heart biometry and visualization of cardiac structures between 10–15 weeks’ gestation. J Ultrasound Med 2006; 25: 173–82.Google Scholar
Huggon, IC, Ghi, T, Cook, AC, et al. Fetal cardiac abnormalities identified prior to 14 weeks’ gestation. Ultrasound Obstet Gynecol 2002; 20: 22–9.Google Scholar
Braithwaite, JM, Armstrong, MA, Economides, DL. Assessment of fetal anomaly at 12 to 13 weeks of gestation by transabdominal and transvaginal sonography. Br J Obstet Gynaecol 1996; 103: 82–5.Google Scholar
Whitlow, BJ, Economides, DL. The optimal gestational age to examine fetal anatomy and measure nuchal translucency in the first trimester. Ultrasound Obstet Gynecol 1998; 11: 258–61.Google Scholar
Lombardi, CM, Bellotti, M, Fesslova, V, Cappellini, A. Fetal echocardiography at the time of the nuchal translucency scan. Ultrasound Obstet Gynecol 2007; 29: 249–57.Google Scholar
Pajkrt, E, Weisz, B, Firth, HV, Chitty, LS. Fetal cardiac anomalies and genetic syndromes. Prenat Diagn 2004; 24: 1104–15.Google Scholar
Allan, LD, Santos, R, Pexieder, T. Anatomical and echocardiographic correlates of normal cardiac morphology in the late first trimester fetus. Heart 1997; 77: 68–72.Google Scholar
Cook, AC, Yates, RW, Anderson, RH. Normal and abnormal fetal cardiac anatomy. Prenat Diagn 2004; 24: 1032–48.Google Scholar
McAuliffe, FM, Hornberger, LK, Winsor, S, et al. Fetal cardiac defects and increased nuchal translucency thickness: a prospective study. Am J Obstet Gynecol 2004; 19: 1486–90.Google Scholar
Makrydimas, G, Sotiriadis, A, Ioannidis, JP. Screening performance of first-trimester nuchal translucency for major cardiac defects: a meta-analysis. Am J Obstet Gynecol 2003; 189: 1330–5.Google Scholar
Makrydimas, G, Sotiriadis, A, Huggon, IC, et al. Nuchal translucency and fetal cardiac defects: a pooled analysis of major echocardiography centers. Am J Obstet Gynecol 2005; 192: 89–95.Google Scholar
Blaas, HG, Eik-Nes, SH, Kiserud, T, Hellevik, LR. Early development of the abdominal wall, stomach and heart from 7 to 12 weeks of gestation: a longitudinal ultrasound study. Ultrasound Obstet Gynecol 1995; 6: 240–9.Google Scholar
Diamant, NE. Development of esophageal function. Am Rev Respir Dis 1985; 131: S29–S32.Google Scholar
Rosati, P, Guariglia, L. Transvaginal sonographic assessment of the fetal urinary tract in early pregnancy. Ultrasound Obstet Gynecol 1996; 7: 95–100.Google Scholar
Sebire, NJ, Von Kaisenberg, C, Rubio, C, Snijders, RJ, Nicolaides, KH. Fetal megacystis at 10–14 weeks of gestation. Ultrasound Obstet Gynecol 1996; 8: 387–90.Google Scholar
Zorzoli, A, Kusterman, E, Carvelli, E, et al. Measurements of fetal limb bones in early pregnancy. Ultrasound Obstet Gynecol 1994; 4: 29–33.Google Scholar
Efrat, Z, Perri, T, Ramati, E, Tugendreich, D, Meizner, I. Fetal gender assignment by first- trimester ultrasound. Ultrasound Obstet Gynecol 2006; 27: 619–21.Google Scholar
Mazza, V, Di Monte, I, Pati, M, et al. Sonographic biometrical range of external genitalia differentiation in the first trimester of pregnancy: analysis of 2593 cases. Prenat Diagn 2004; 24: 677–84.Google Scholar
Whitlow, BJ, Lazanakis, MS, Economides, DL. The sonographic identification of fetal gender from 11 to 14 weeks of gestation. Ultrasound Obstet Gynecol 1999; 13: 301–4.Google Scholar
Pedreira, DA. In search for the “third point.” Ultrasound Obstet Gynecol 2000; 15: 262–3.Google Scholar
Michailidis, GD, Papageorgiou, P, Morris, RW, Economides, DL. The use of three-dimensional ultrasound for fetal gender determination in the first trimester. Br J Radiol 2003; 76: 448–51.Google Scholar
Snijders, RJ, Noble, P, Sebire, N, Souka, A, Nicolaides, KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation. Lancet 1998; 352: 343–6.Google Scholar
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: 957–62.Google Scholar
Braithwaite, JM, Morris, RW, Economides, DL. Nuchal translucency measurements: frequency distribution and changes with gestation in a general population. Br J Obstet Gynaecol 1996; 103: 1201–4.Google Scholar
The Fetal Medicine Centre. www.fetalmedicine.com (accessed March 2017).Google Scholar
Pandya, PP, Altman, DG, Brizot, ML, Pettersen, H, Nicolaides, KH. Repeatability of measurement of fetal nuchal translucency thickness. Ultrasound Obstet Gynecol 1995; 5: 334–7.Google Scholar
Pajkrt, E, Mol, BW, Boer, K, et al. Intra- and interoperator repeatability of the nuchal translucency measurement. Ultrasound Obstet Gynecol 2000; 15: 297–301.Google Scholar
Pandya, PP, Goldberg, H, Walton, B, et al. The implementation of first-trimester scanning at 10–13 weeks’ gestation and the measurement of fetal nuchal translucency thickness in two maternity units. Ultrasound Obstet Gynecol 1995; 5: 20–5.Google Scholar
Nicolaides, KH. A unified approach to risk assessment for fetal aneuploidies. Ultrasound Obstet Gynecol 2015; 45: 48–54.Google Scholar
Szabo, J, Gellen, J, Sizemere, G. First-trimester ultrasound screening for fetal aneuploidies in women over 35 and under 35 years of age. Ultrasound Obstet Gynecol 1995; 5: 161–3.Google Scholar
Carmichael, JB, Liu, HP,Janik, D, et al. Expanded conventional first trimester screening. Prenat Diagn 2017; 37: 802–7.Google Scholar
Taipale, P, Hiilesmaa, V, Salonen, R, Ylostalo, P. Increased nuchal translucency as a marker for fetal chromosomal defects. N Engl J Med 1997; 337: 1654–8.Google Scholar
Hafner, E, Schuchter, K, Liebhart, E, Philipp, K. Results of routine fetal nuchal translucency measurement at 10–13 weeks in 4,233 unselected pregnant women. Prenat Diagn 1998; 18: 29–34.Google Scholar
Pajkrt, E, van Lith, JM, Mol, BW, Bleker, OP, Bilardo, CM. Screening for Down’s syndrome by fetal nuchal translucency measurement in a general obstetric population. Ultrasound Obstet Gynecol 1998; 12: 163–9.Google Scholar
Economides, DL, Whitlow, BJ, Kadir, R, Lazanakis, M, Verdin, SM. First trimester sonographic detection of chromosomal abnormalities in an unselected population. Br J Obstet Gynaecol 1998; 105: 58–62.Google Scholar
Schwärzler, P, Carvalho, JS, Senat, MV, et al. Screening for fetal aneuploidies and fetal cardiac abnormalities by nuchal translucency thickness measurement at 10–14 weeks of gestation as part of routine antenatal care in an unselected population. Br J Obstet Gynaecol 1999; 106: 1029–34.Google Scholar
Theodoropoulos, P, Lolis, D, Papageorgiou, C, et al. Evaluation of first-trimester screening by fetal nuchal translucency and maternal age. Prenat Diagn 1998; 18: 133–7.Google Scholar
Zoppi, MA, Ibba, RM, Floris, M, Monni, G. Fetal nuchal translucency screening in 12,495 pregnancies in Sardinia. Ultrasound Obstet Gynecol 2001; 18: 649–51.Google Scholar
Gasiorek-Wiens, A, Tercanli, S, Kozlowski, P, et al. Screening for trisomy 21 by fetal nuchal translucency and maternal age: a multicenter project in Germany, Austria and Switzerland. Ultrasound Obstet Gynecol 2001; 18: 645–8.Google Scholar
Brizot, ML, Carvalho, MH, Liao, AW, et al. First-trimester screening for chromosomal abnormalities by fetal nuchal translucency in a Brazilian population. Ultrasound Obstet Gynecol 2001; 18: 652–5.Google Scholar
Audibert, F, Dommergues, M, Benattar, C, et al. Screening for Down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: a prospective longitudinal study. Ultrasound Obstet Gynecol 2001; 18: 26–31.Google Scholar
Wayda, K, Kereszturi, A, Orvos, H, et al. Four years experience of first-trimester nuchal translucency screening for fetal aneuploidies with increasing regional availability. Acta Obstet Gynecol Scand 2001; 80: 1104–9.Google Scholar
Nicolaides, KH. Screening for chromosomal defects. Ultrasound Obstet Gynecol 2003; 21: 313–21.Google Scholar
Cuckle, H. Integrating Down’s syndrome screening. Curr Opin Obstet Gynaecol 2001; 13: 175–81.Google Scholar
Snijders, RJ, Nicolaides, KH. Assessment of risks. In Ultrasound Markers for Fetal Chromosomal Defects. Carnforth: Parthenon, 1996, pp. 63–120.Google Scholar
Sherrod, C, Sebire, NJ, Soares, W, Snijders, RJ, Nicolaides, KH. Prenatal diagnosis of trisomy 18 at the 10–14-week ultrasound scan. Ultrasound Obstet Gynecol 1997; 10: 387–90.Google Scholar
Snijders, RJ, Sebire, NJ, Nayar, R, Souka, A, Nicolaides, KH. Increased nuchal translucency in trisomy 13 fetuses at 10–14 weeks of gestation. Am J Med Genet 1999; 86: 205–7.Google Scholar
Sebire, NJ, Snijders, RJ, Brown, R, Southall, T, Nicolaides, KH. Detection of sex chromosome abnormalities by nuchal translucency screening at 10–14 weeks. Prenat Diagn 1998; 18: 581–4.Google Scholar
Jauniaux, E, Brown, R, Snijders, RJ, Noble, P, Nicolaides, KH. Early prenatal diagnosis of triploidy. Am J Obstet Gynecol 1997; 176: 550–4.Google Scholar
Benacerraf, BR, Frigoletto, FD. Soft tissue nuchal fold in the second-trimester fetus: standards for normal measurements compared with those in Down syndrome. Am J Obstet Gynecol 1987; 157: 1146–9.Google Scholar
Senat, MV, De Keersmaecker, B, Audibert, F, et al. Pregnancy outcome in fetuses with increased nuchal translucency and normal karyotype. Prenat Diagn 2002; 22: 345–9.Google Scholar
Souka, AP, Krampl, E, Bakalis, S, Heath, V, Nicolaides, KH. Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester. Ultrasound Obstet Gynecol 2001; 18: 9–17.Google Scholar
Hyett, JA, Perdu, M, Sharland, G, Snijders, R, Nicolaides, KH. Increased nuchal translucency at 10–14 weeks of gestation as a marker for major cardiac defects. Ultrasound Obstet Gynecol 1997; 10: 242–6.Google Scholar
Hyett, JA, Perdu, M, Sharland, G, Snijders, R, Nicolaides, KH. Using fetal nuchal translucency to screen for major congenital cardiac defects at 10–14 weeks of gestation: population based cohort study. BMJ 1999: 318: 81–5.Google Scholar
Mavrides, E, Cobian-Sanchez, F, Tekay, A, et al. Limitations of using first-trimester nuchal translucency measurement in routine screening for major congenital heart defects. Ultrasound Obstet Gynecol 2001; 17: 106–10.Google Scholar
Michailidis, GD, Economides, DL. Nuchal translucency measurement and pregnancy outcome in karyotypically normal fetuses. Ultrasound Obstet Gynecol 2001; 17: 102–5.Google Scholar
Nicolaides, KH, Heath, V, Cicero, S. Increased fetal nuchal translucency at 11–14 weeks. Prenat Diagn 2002; 22: 308–15.Google Scholar
Hiippala, A, Eronen, M, Taipale, P, Salonen, R, Hiilesmaa, V. Fetal nuchal translucency and normal chromosomes: a long-term follow-up study. Ultrasound Obstet Gynecol 2001; 18: 18–22.Google Scholar
Michailidis, GD, Papageorgiou, P, Economides, DL. Assessment of fetal anatomy in the first trimester using two- and three-dimensional ultrasound. Br J Radiol 2002; 75: 215–19.Google Scholar
Van Vugt, JM, Tinnemans, BW, van Zalen-Sprock, RM. Outcome and early childhood follow-up of chromosomally normal fetuses with increased nuchal translucency at 10–14 weeks’ gestation. Ultrasound Obstet Gynecol 1998; 11: 407–9.Google Scholar
Adekunle, O, Gopee, A, el-Sayed, M, Thilaganathan, B. Increased first trimester nuchal translucency: pregnancy and infant outcomes after routine screening for Down’s syndrome in an unselected antenatal population. Br J Radiol 1999; 72: 457–60.Google Scholar
Curry, CJ, Stevenson, RE, Aughton, D, et al. Evaluation of mental retardation: recommendations of a consensus conference: American College of Medical Genetics. Am J Med Genet 1997; 72: 468–77.Google Scholar
Ville, Y. Nuchal translucency in the first trimester of pregnancy: ten years on and still a pain in the neck? Ultrasound Obstet Gynecol 2001; 18: 5–8.Google Scholar
Cha’ban, FK, Van Splunder, P, Los, FJ, Wladimiroff, JW. Fetal outcome in nuchal translucency with emphasis on normal fetal karyotype. Prenat Diagn 1996; 16: 537–41.Google Scholar
Hillman, SC, Pretlove, S, Coomarasamy, A, et al. Additional information from array comparative genomic hybridization technology over conventional karyotyping in prenatal diagnosis: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2011; 37: 6–14.Google Scholar
Shaffer, LG, Coppinger, J, Alliman, S, et al. Comparison of microarray-based detection rates for cytogenetic abnormalities in prenatal and neonatal specimens. Prenat Diagn 2008; 28: 789–95.Google Scholar
American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol 2009; 114: 1161–3.Google Scholar
Cicero, S, Curcio, P, Papageorghiou, A, Sonek, J, Nicolaides, K. Absence of nasal bone in fetuses with trisomy 21 at 11–14 weeks of gestation: an observational study. Lancet 2001; 358: 1665–7.Google Scholar
Cicero, S, Longo, D, Rembouskos, G, Sacchini, C, Nicolaides, KH. Absent nasal bone at 11–14 weeks of gestation and chromosomal defects. Ultrasound Obstet Gynecol 2003; 22: 31–5.Google Scholar
Cicero, S, Rembouskos, G, Vandecruys, H, Hogg, M, Nicolaides, KH. Likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11–14-week scan. Ultrasound Obstet Gynecol 2004; 23: 218–23.Google Scholar
Senat, MV, Bernard, JP, Boulvain, M, Ville, Y. Intra- and interoperator variability in fetal nasal bone assessment at 11–14 weeks of gestation. Ultrasound Obstet Gynecol 2003; 22: 138–41.Google Scholar
Otaño, L, Aiello, H, Igarzábal, L, Matayoshi, T, Gadow, EC. Association between first trimester absence of fetal nasal bone on ultrasound and Down syndrome. Prenat Diagn 2002; 22: 930–2.Google Scholar
Zoppi, MA, Ibba, RM, Axiana, C, et al. Absence of fetal nasal bone and aneuploidies at first-trimester nuchal translucency screening in unselected pregnancies. Prenat Diagn 2003; 23: 496–500.Google Scholar
Orlandi, F, Bilardo, CM, Campogrande, M, et al. Measurement of nasal bone length at 11–14 weeks of pregnancy and its potential role in Down syndrome risk assessment. Ultrasound Obstet Gynecol 2003; 22: 36–9.Google Scholar
Viora, E, Masturzo, B, Errante, G, et al. Ultrasound evaluation of fetal nasal bone at 11 to 14 weeks in a consecutive series of 1906 fetuses. Prenat Diagn 2003; 23: 784–7.Google Scholar
Nicolaides, KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004; 191: 45–67.Google Scholar
Maiz, N, Valencia, C, Kagan, KO, Wright, D, Nicolaides, KH. Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11–13 weeks of gestation. Ultrasound Obstet Gynecol 2009; 33: 512–17.Google Scholar
Matias, A, Gomes, C, Flack, N, Montenegro, N, Nicolaides, KH. Screening for chromosomal abnormalities at 11–14 weeks: the role of ductus venosus blood flow. Ultrasound Obstet Gynecol 1998; 2: 380–4.Google Scholar
Antolin, E, Comas, C, Torrents, M, et al. The role of ductus venosus blood flow assessment in screening for chromosomal abnormalities at 10–16 weeks of gestation. Ultrasound Obstet Gynecol 2001; 17: 295–300.Google Scholar
Mavrides, E, Sairam, S, Hollis, B, Thilaganathan, B. Screening for aneuploidy in the first trimester by assessment of blood flow in the ductus venosus. BJOG 2002; 109: 1015–19.Google Scholar
Murta, CG, Moron, AF, Avila, MA, Weiner, CP. Application of ductus venosus Doppler velocimetry for the detection of fetal aneuploidy in the first trimester of pregnancy. Fetal Diagn Ther 2002; 1: 308–14.Google Scholar
Zoppi, MA, Putzolu, M, Ibba, RM, Floris, M, Monni, G. First trimester ductus venosus velocimetry in relation to nuchal translucency thickness and fetal karyotype. Fetal Diagn Ther 2002; 17: 52–7.Google Scholar
Borrell, A, Martinez, JM, Seres, A, et al. Ductus venosus assessment at the time of nuchal translucency measurement in the detection of fetal aneuploidy. Prenat Diagn 2003; 23: 921–6.Google Scholar
Huggon, IC, DeFigueiredo, DB, Allan, LD. Tricuspid regurgitation in the diagnosis of chromosomal anomalies in the fetus at 11–14 weeks of gestation. Heart 2003; 89: 1071–3.Google Scholar
Faiola, S, Tsoi, E, Huggon, IC, Allan, LD, Nicolaides, KH. Likelihood ratio for trisomy 21 in fetuses with tricuspid regurgitation at the 11 to 13+6-week scan. Ultrasound Obstet Gynecol 2005; 26: 22–7.Google Scholar
Sonek, J, Borenstein, M, Dagklis, T, Persico, N, Nicolaides, KH. Frontomaxillary facial angle in fetuses with trisomy 21 at 11–13(6) weeks. Am J Obstet Gynecol 2007; 196: 271.e1–e4.Google Scholar
Liao, AW, Snijders, R, Geerts, L, Spencer, K, Nicolaides, KH. Fetal heart rate in chromosomally abnormal fetuses. Ultrasound Obstet Gynecol 2000; 16: 610–13.Google Scholar
Cicero, S, Curcio, P, Rembouskos, G, Sonek, J, Nicolaides, KH. Maxillary length at 11–14 weeks of gestation in fetuses with trisomy 21. Ultrasound Obstet Gynecol 2004; 24: 19–22.Google Scholar
Sacchini, C, El-Sheikhah, A, Cicero, S, Rembouskos, G, Nicolaides, KH. Ear length in trisomy 21 fetuses at 11–14 weeks of gestation. Ultrasound Obstet Gynecol 2003; 22: 460–3.Google Scholar
Longo, D, DeFigueiredo, D, Cicero, S, Sacchini, C, Nicolaides, KH. Femur and humerus length in trisomy 21 fetuses at 11–14 weeks of gestation. Ultrasound Obstet Gynecol 2004; 23: 143–7.Google Scholar
Schuchter, K, Hafner, E, Stangl, G, Ogris, E, Philipp, K. Sequential screening for trisomy 21 by nuchal translucency measurement in the first trimester and maternal serum biochemistry in the second trimester in a low-risk population. Ultrasound Obstet Gynecol 2001; 18: 23–5.Google Scholar
Cuckle, H. Biochemical screening for Down syndrome. Eur J Obstet Gynecol Reprod Biol 2000; 92: 97–101.Google Scholar
Rozenberg, P, Malagrida, L, Cuckle, H, et al. Down’s syndrome screening with nuchal translucency at 12(+0)–14(+0) weeks and maternal serum markers at 14(+1)–17(+0) weeks: a prospective study. Hum Reprod 2002; 17: 1093–8.Google Scholar
Spencer, K, Spencer, CE, Power, M, Dawson, C, Nicolaides, KH. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one stop clinic: a review of three years’ prospective experience. BJOG 2003; 110: 281–6.Google Scholar
Thilaganathan, B, Slack, A, Wathen, NC. Effect of first-trimester nuchal translucency on second-trimester maternal serum biochemical screening for Down’s syndrome. Ultrasound Obstet Gynecol 1997; 10: 261–4.Google Scholar
Wapner, R, Thom, E, Simpson, JL, et al. First-trimester screening for trisomies 21 and 18. N Engl J Med 2003; 349: 1405–13.Google Scholar
Malone, F, Wald, N, Canick, J, et al. First and second trimester evaluation of risk (FASTER) trial: principal results of the NICHD multicenter Down syndrome screening study (abstract 1). Am J Obstet Gynecol 2003; 189: S56.Google Scholar
Ekelund, CK, Jørgensen, FS, Petersen, OB, Sundberg, K, Tabor, A. Impact of a new national screening policy for Down’s syndrome in Denmark: population based cohort study. BMJ 2008; 337: a2547. doi: 10.1136/bmj.a2547.Google Scholar
Norton, ME, Jacobsson, B, Swamy, GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 2015; 372: 1589–97.Google Scholar
Zhang, H, Gao, Y, Jiang, F, et al. Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146,958 pregnancies. Ultrasound Obstet Gynecol 2015; 45: 530–8.Google Scholar
Taylor-Phillips, S, Freeman, K, Geppert, J, et al. Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ Open 2016; 6 (1): e010002.Google Scholar
Canick, JA, Palomaki, GE, Kloza, EM, Lambert-Messerlian, GM, Haddow, JE. The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies. Prenat Diagn 2013; 33: 667–74.Google Scholar
McCullough, RM, Almasri, EA, Guan, X, et al. Non-invasive prenatal chromosomal aneuploidy testing – clinical experience: 100,000 clinical samples. PLoS ONE 2014; 9 (10): e109173.Google Scholar
Hall, AL, Drendel, HM, Verbrugge, JL, et al. Positive cell-free fetal DNA testing for trisomy 13 reveals confined placental mosaicism. Genet Med 2013; 15: 729–32.Google Scholar
Gil, MM, Accurti, V, Santacruz, B, Plana, MN, Nicolaides, KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol 2017; 50: 302–14.Google Scholar
Liao, H, Liu, S, Wang, H. Performance of non-invasive prenatal screening for fetal aneuploidy in twin pregnancies: a meta-analysis. Prenat Diagn 2017; 37: 874–82.Google Scholar
Agenzia Sanitaria e Sociale Regionale. Is non-invasive genetic prenatal testing ready for use? The evidence, the costs and the ethics addressed in a HTA with recommendations for practice and for research. June 2015. http://assr.regione.emilia-romagna.it/it/servizi/pubblicazioni/corsi-convegni/non-invasive-genetic-prenatal-testing (accessed January 2018).Google Scholar
Health Council of the Netherlands. Prenatal screening, 2016. Publication no. 2016/19. https://www.gezondheidsraad.nl/en/task-and-procedure/areas-of-activity/prevention/prenatal-screening (accessed January 2018).Google Scholar
Gregg, AR, Skotko, BG, Benkendorf, JL, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med 2016; 18: 1056–65.Google Scholar
Belgian Society for Human Genetics. Good practice guidelines. www.beshg.be/index.php?page=guidelines (accessed January 2018).Google Scholar
Haute Autorité de Santé. Place des tests ADN libre circulant dans le sang maternel dans le dépistage de la trisomie 21 foetale. www.has-sante.fr/portail/jcms/c_2768510/fr/place-des-tests-adn-libre-circulant-dans-le-sang-maternel-dans-le-depistage-de-la-trisomie-21-foetale (accessed January 2018).Google Scholar
International, FIGO Federation of Gynecology and Obstetrics. www.figo.org (accessed January 2018).Google Scholar
Nordic Federation of Societies of Obstetrics and Gynecology. https://nfog.org (accessed January 2018).Google Scholar
Schmid, M, Klaritsch, P, Arzt, W, et al. Cell-free DNA testing for fetal chromosomal anomalies in clinical practice: Austrian–German–Swiss recommendations for non-invasive prenatal tests (NIPT). Ultraschall Med 2015; 36: 507–10.Google Scholar
Salomon, LJ, Alfirevic, Z, Audibert, F, et al. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound Obstet Gynecol 2014; 44: 122–3.Google Scholar
Benn, P, Borrell, A, Chiu, RWK, et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn 2015; 35: 725–34.Google Scholar
NHS RAPID project. NIPT for Down syndrome. www.rapid.nhs.uk/guides-to-nipd-nipt/nipt-for-down-syndrome (accessed January 2018).Google Scholar
Yagel, S, Achiron, R, Ron, M, Revel, A, Anteby, E. Transvaginal ultrasonography at early pregnancy cannot be used alone for targeted organ ultrasonographic examination in a high–risk population. Am J Obstet Gynecol 1995; 172: 971–5.Google Scholar
Rottem, S, Bronshtein, M. Transvaginal sonographic diagnosis of congenital anomalies between 9 weeks and 16 weeks, menstrual age. J Clin Ultrasound 1990; 18: 307–14.Google Scholar
Rottem, S. Early detection of structural anomalies and markers of chromosomal aberrations by transvaginal ultrasonography. Curr Opin Obstet Gynecol 1995; 7: 122–5.Google Scholar
Taipale, P, Ammala, M, Salonen, R, Hiilesmaa, V. Learning curve in ultrasonographic screening for selected fetal structural anomalies in early pregnancy. Obstet Gynecol 2003; 101: 273–8.Google Scholar
Bernard, JP, Cuckle, HS, Bernard, MA, et al. Combined screening for open spina bifida at 11–13 weeks using fetal biparietal diameter and maternal serum markers. Am J Obstet Gynecol 2013; 209: 223.e1–5.Google Scholar
Bernard, JP, Suarez, B, Rambaud, C, Muller, F, Ville, Y. Prenatal diagnosis of neural tube defect before 12 weeks’ gestation: direct and indirect ultrasonographic semeiology. Ultrasound Obstet Gynecol 1997; 10: 406–9.Google Scholar
Karl, K, Benoit, B, Entezami, M, Heling, KS, Chaoui, R. Small biparietal diameter in fetuses with spina bifida on 11–13-week and mid-gestation ultrasound. Ultrasound Obstet Gynecol 2012; 40: 140–4.Google Scholar
Chaoui, RI, Benoit, B, Mitkowska-Wozniak, H, Heling, KS, Nicolaides, KH. Assessment of intracranial translucency (IT) in the detection of spina bifida at the 11–13-week scan. Ultrasound Obstet Gynecol 2009; 34: 249–52.Google Scholar
Loureiro, T, Ushakov, F, Montenegro, N, Gielchinsky, Y, Nicolaides, KH. Cerebral ventricular system in fetuses with open spina bifida at 11–13 weeks’ gestation. Ultrasound Obstet Gynecol 2012; 39: 620–4.Google Scholar
Achiron, R, Tadmor, O. Screening for fetal anomalies during the first trimester of pregnancy: transvaginal versus transabdominal sonography. Ultrasound Obstet Gynecol 1991; 1: 186–91.Google Scholar
Hernadi, L, Töröcsik, M. Screening for fetal anomalies in the 12th week of pregnancy by transvaginal sonography in an unselected population. Prenat Diagn 1997; 17: 753–9.Google Scholar
Economides, DL, Braithwaite, JM. First trimester ultrasonographic diagnosis of fetal structural abnormalities in a low risk population. Br J Obstet Gynaecol 1998; 105: 53–7.Google Scholar
D’Ottavio, G, Meir, YJ, Rustico, MA, et al. Screening for fetal anomalies by ultrasound at 14 and 21 weeks. Ultrasound Obstet Gynecol 1997; 10: 375–80.Google Scholar
Guariglia, L, Rosati, P. Transvaginal sonographic detection of embryonic-fetal abnormalities in early pregnancy. Obstet Gynecol 2000; 96: 328–32.Google Scholar
Drysdale, K, Ridley, D, Walker, K, Higgins, B, Dean, T. First-trimester pregnancy scanning as a screening tool for high-risk and abnormal pregnancies in a district general hospital setting. J Obstet Gynaecol 2002; 22: 159–65.Google Scholar
den Hollander, NS, Wessels, MW, Niermeijer, MF, Los, FJ, Wladimiroff, JW. Early fetal anomaly scanning in a population at increased risk of abnormalities. Ultrasound Obstet Gynecol 2002; 19: 570–4.Google Scholar
Carvalho, MH, Brizot, ML, Lopes, LM, et al. Detection of fetal structural abnormalities at the 11–14 week ultrasound scan. Prenat Diagn 2002; 22: 1–4.Google Scholar
Chen, M, Lam, YH, Lee, CP, Tang, MH. Ultrasound screening of fetal structural abnormalities at 12 to 14 weeks in Hong Kong. Prenat Diagn 2004; 24: 92–7.Google Scholar
Taipale, P, Ammala, M, Salonen, R, Hiilesmaa, V. Two-stage ultra-sonography in screening for fetal anomalies at 13–14 and 18–22 weeks of gestation. Acta Obstet Gynecol Scand 2004; 83: 1141–6.Google Scholar
Markov, D, Chernev, T, Dimitrova, V, et al. [Ultrasound screening and diagnosis of fetal structural abnormalities between 11–14 gestational weeks] (Bulgarian). Akush Ginekol (Sofiia) 2004; 43: 3–10.Google Scholar
McAuliffe, FM, Fong, KW, Toi, A, et al. Ultrasound detection of fetal anomalies in conjunction with first-trimester nuchal translucency screening: a feasibility study. Am J Obstet Gynecol 2005; 193: 1260–5.Google Scholar
Becker, R, Wegner, RD. Detailed screening for fetal anomalies and cardiac defects at the 11–13-week scan. Ultrasound Obstet Gynecol 2006; 27: 613–18.Google Scholar
Souka, AP, Pilalis, A, Kavalakis, I, et al. Screening for major structural abnormalities at the 11- to 14-week ultrasound scan. Am J Obstet Gynecol 2006; 194: 393–6.Google Scholar
Saltvedt, S, Almström, H, Kublickas, M, Valentin, L, Grunewald, C. Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation: a randomised controlled trial in 39,572 pregnancies. BJOG 2006; 113: 664–74.Google Scholar
Cedergren, M, Selbing, A. Detection of fetal structural abnormalities by an 11–14 week ultrasound dating scan in an unselected Swedish population. Acta Obstet Gynecol Scand 2006; 85: 912–15.Google Scholar
Weiner, Z, Goldstein, I, Bombard, A, Applewhite, L, Itzkovits-Eldor, J. Screening for structural fetal anomalies during the nuchal translucency ultrasound examination. Am J Obstet Gynecol 2007; 197: 181.e1–e5.Google Scholar
Dane, B, Dane, C, Sivri, D, et al. Ultrasound screening for fetal major abnormalities at 11–14 weeks. Acta Obstet Gynecol Scand 2007; 86: 666–70.Google Scholar
Chen, M, Lee, CP, Lam, YH, et al. Comparison of nuchal and detailed morphology ultrasound examinations in early pregnancy for fetal structural abnormality screening: a randomized controlled trial. Ultrasound Obstet Gynecol 2008; 31: 136–46.Google Scholar
Chatzipapas, IK, Whitlow, BJ, Economides, DL. The “Mickey Mouse” sign and the diagnosis of anencephaly in early pregnancy. Ultrasound Obstet Gynecol 1998; 13: 196–9.Google Scholar
Johnson, SP, Sebire, NJ, Snijders, RJ, Tunkel, S, Nicolaides, KH. Ultrasound screening for anencephaly at 10–14 weeks of gestation. Ultrasound Obstet Gynecol 1997; 9: 14–16.Google Scholar
Sepulveda, W, Dezerega, V, Be, C. First-trimester sonographic diagnosis of holoprosencephaly: value of the “butterfly” sign. J Ultrasound Med 2004; 23: 761–5.Google Scholar
Bronshtein, M, Zimmer, EZ. Transvaginal sonographic follow-up on the formation of fetal cephalocele at 13–19 weeks’ gestation. Obstet Gynecol 1991; 78: 528–30.Google Scholar
van Zalen-Sprock, M, van Vugt, JMG, van der Harten, HJ, van Geijn, HP. Cephalocele and cystic hygroma: diagnosis and differentiation in the first trimester of pregnancy with transvaginal sonography. Report of two cases. Ultrasound Obstet Gynecol 1992; 2: 289– 92.Google Scholar
Turner, CD, Silva, S, Jeanty, P. Prenatal diagnosis of alobar holoprosencephaly at 10 weeks of gestation. Ultrasound Obstet Gynecol 1999; 13: 360–2.Google Scholar
Wong, HS, Lam, YH, Tang, MH, et al. First-trimester ultrasound diagnosis of holoprosencephaly: three case reports. Ultrasound Obstet Gynecol 1999; 13: 356–9.Google Scholar
Timor-Tritsch, IE, Monteagudo, A, Santos, R. Three-dimensional inversion rendering in the first- and early second-trimester fetal brain: its use in holoprosencephaly. Ultrasound Obstet Gynecol 2008; 32: 744–50.Google Scholar
Buisson, O, De Keersmaecker, B, Sénat, MV, et al. Sonographic diagnosis of spina bifida at 12 weeks: heading towards indirect signs. Ultrasound Obstet Gynecol 2002; 19: 290–2.Google Scholar
Blaas, HG, Eik-Nes, SH, Isaksen, C. The detection of spina bifida before 10 gestational weeks using two- and three dimensional ultrasound. Ultrasound Obstet Gynecol 2000; 16: 25–29.Google Scholar
Carvalho, JS, Senat, MV, Schwärzler, P, Ville, Y. Increased nuchal translucency and ventricular septal defect in the fetus. Circulation 1999; 99: E10.Google Scholar
Timor-Tritsch, IE, Warren, W, Peisner, DB, Pirrone, E. First-trimester midgut herniation: a high frequency transvaginal sonographic study. Am J Obstet Gynecol 1989; 161: 831–3.Google Scholar
van Zalen-Sprock, RM, van Vugt, JMG, van Geijn, HP. First-trimester sonography of physiological midgut herniation and early diagnosis of omphalocele. Prenat Diagn 1997; 17: 511–18.Google Scholar
Maymon, R, Jauniaux, E, Cohen, O, et al. Pregnancy outcome and infant follow-up of fetuses with abnormally increased first trimester nuchal translucency. Hum Reprod 2000; 15: 2023–7.Google Scholar
Pagliano, M, Mossetti, M, Ragno, P. Echographic diagnosis of omphalocele in the first trimester of pregnancy. J Clin Ultrasound 1990; 18: 658–60.Google Scholar
Liao, AW, Sebire, NJ, Geerts, L, Cicero, S, Nicolaides, KH. Megacystis at 10–14 weeks of gestation: chromosomal defects and outcome according to bladder length. Ultrasound Obstet Gynecol 2003; 21: 338–41.Google Scholar
Favre, R, Kohler, M, Gasser, B, Muller, F, Nisand, I. Early fetal megacystis between 11 and 15 weeks of gestation. Ultrasound Obstet Gynecol 1999; 14: 402–6.Google Scholar
Carroll, SG, Soothill, PW, Tizard, J, Kyle, PM. Vesicocentesis at 10–14 weeks of gestation for treatment of fetal megacystis. Ultrasound Obstet Gynecol 2001; 18: 366–70.Google Scholar
Bronshtein, M, Amit, A, Achiron, R, Noy, I, Blumenfeld, Z. The early prenatal sonographic diagnosis of renal agenesis: techniques and possible pitfalls. Prenat Diagn 1994; 14: 291–7.Google Scholar
Bronshtein, M, Bar-Hava, I, Blumenfeld, Z. Clues and pitfalls in the early prenatal diagnosis of “late onset” infantile polycystic kidney. Prenat Diagn 1992; 12: 293–8.Google Scholar
Fisk, NM, Vaughan, J, Smidt, M, Wigglesworth, J. Transvaginal ultrasound recognition of nuchal edema in the first-trimester diagnosis of achondrogenesis. J Clin Ultrasound 1991; 19: 586–90.Google Scholar
Soothill, PW, Vuthiwong, C, Rees, H. Achondrogenesis type 2 diagnosed by transvaginal ultrasound at 12 weeks’ gestation. Prenat Diagn 1993; 13: 523–8.Google Scholar
Rembouskos, G, Cicero, S, Longo, D, Sacchini, C, Nicolaides, KH. Single umbilical artery at 11–14 weeks: relation to chromosomal defects. Ultrasound Obstet Gynecol 2003; 22: 567–70.Google Scholar
Wigglesworth, JS, Singer, DB, eds. Textbook of Fetal and Perinatal Pathology. Amsterdam: Blackwell, 1991.Google Scholar
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: 421–3.Google Scholar
Carroll, SG, Soothill, PW, Abdel-Fattah, SA, et al. Prediction of chorionicity in twin pregnancies at 10–14 weeks of gestation. BJOG 2002; 109: 182–6.Google Scholar
Stenhouse, E, Hardwick, C, Maharaj, S, et al. Chorionicity in twin pregnancies: how accurate are we? Ultrasound Obstet Gynecol 2002; 19: 350–2.Google Scholar
Bora, SA, Papageorghiou, AT, Bottomley, C, Kirk, E, Bourne, T. Reliability of transvaginal ultrasonography at 7–9 weeks’ gestation in the determination of chorionicity and amnionicity in twin pregnancies. Ultrasound Obstet Gynecol 2008; 32: 618–21.Google Scholar
Sepulveda, W, Sebire, NJ, Hughes, K, Kalogeropoulos, A, Nicolaides, KH. Evolution of the lambda or twin/chorionic peak sign in dichorionic twin pregnancies. Obstet Gynecol 1997; 89: 439–41.Google Scholar
Shetty, A, Smith, AP. The sonographic diagnosis of chorionicity. Prenat Diagn 2005; 25: 735–9.Google Scholar
Moon, MH, Park, SY, Song, MJ, et al. Diamniotic twin pregnancies with a single placental mass: Prediction of chorionicity at 11 to 14 weeks of gestation. Prenat Diagn 2008; 28: 1011–15.Google Scholar
Sebire, NJ, Snijders, RJ, Hughes, K, Sepulveda, W, Nicolaides, KH. Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal translucency at 10–14 weeks of gestation. Br J Obstet Gynaecol 1996; 103: 999–1003.Google Scholar
Sepulveda, W, Wong, AE, Casasbuenas, A. Nuchal translucency and nasal bone in first-trimester ultrasound screening for aneuploidy in multiple pregnancies. Ultrasound Obstet Gynecol 2009; 33: 152–6.Google Scholar
Vandecruys, H, Faiola, S, Auer, M, Sebire, N, Nicolaides, KH. Screening for trisomy 21 in monochorionic twins by measurement of fetal nuchal translucency thickness. Ultrasound Obstet Gynecol 2005; 25: 551–3.Google Scholar
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.Google Scholar
Spencer, K. Screening for trisomy 21 in twin pregnancies in the first trimester: does chorionicity impact on maternal serum free β-hCG or PAPP-A levels? Prenat Diagn 2001; 21: 715–17.Google Scholar
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: 588–92.Google Scholar
Sebire, NJ, D’Ercole, C, Hughes, K, Carvalho, M, Nicolaides, KH. Increased fetal nuchal translucency at 10–14 weeks as a predictor of severe twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 1997; 10: 86–9.Google Scholar
Sebire, NJ, Souka, A, Skentou, H, Geerts, L, Nicolaides, KH. Early prediction of severe twin-to-twin transfusion syndrome. Hum Reprod 2000; 15: 2008–10.Google Scholar
Kagan, KO, Gazzoni, A, Sepulveda-Gonzalez, G, Sotiriadis, A, Nicolaides, KH. Discordance in nuchal translucency thickness in the prediction of severe twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2007; 29: 527–32.Google Scholar
El Kateb, A, Nasr, B, Nassar, M, Bernard, JP, Ville, Y. First-trimester ultrasound examination and the outcome of monochorionic twin pregnancies. Prenat Diagn 2007; 27: 922–5.Google Scholar
Kenneson, A, Cannon, MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007; 17: 253–76.Google Scholar
Faure-Bardon, V, Magny, JF, Parodi, M, et al. Sequelae of congenital cytomegalovirus (cCMV) following maternal primary infection are limited to those acquired in the first trimester of pregnancy. Clin Infect Dis 2018 Dec 31. doi: 10.1093/cid/ciy1128. [Epub ahead of print]Google Scholar
Pass, RF, Fowler, KB, Boppana, SB, Britt, WJ, Stagno, S. Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol 2006; 35: 216–20.Google Scholar
Comité Nationale Technique de l’Echographie de Dépistage Prénatal. Rapport du Comité national technique de l’échographie de dépistage prénatal. http://www.ladocumentationfrancaise.fr/rapports-publics/054000356/index.shtml (accessed March 2017).Google Scholar
South Africa Society of Ultrasound in Obstetrics and Gynaecology (SASUOG). The anomaly scan, 2015 http://sasuog.org.za/TheAnomalyScan.asp (accessed March 2017).Google Scholar
Australasian Society for Ultrasound in Medicine. ASUM Guidelines For The Mid Trimester Obstetric Scan. 2012. http://www.asum.com.au/newsite/Files/Documents/Policies/updated/D2_Policy.pdf (accessed March 2017).Google Scholar
Association Belge Francophone d’Ultrasonologie Médicale (ABeFUM) http://www.abefum.be/FR/Home.aspx (accessed March 2017).Google Scholar
Cargill, Y, Morin, L, Content of a complete routine second trimester obstetrical ultrasound examination and report. J Obstet Gynaecol Can 2017; 39(8): e144 –9.Google Scholar
American Institute of Ultrasound in Medicine. AIUM Practice Parameter for the Performance of Obstetric Ultrasound Examinations Obstetric Ultrasound, 2013. http://www.aium.org/resources/guidelines/obstetric.pdf (accessed March 2017).Google Scholar
Nederlandse Vereniging voor Obsteterie & Gynaecologie (NVOG). Modelprotocol 3 – Structureel Echoscopisch Onderzoek (SEO). 2005. www.nvog.nl (accessed March 2017).Google Scholar
Società Italiana di Ecografia Ostetrico Ginecologica (SIEOG). Linee Guida SIEOG, 2015. http://www.sigo.it/wp-content/uploads/2015/12/LineeGuidaSieog_2015.pdf (accessed March 2017).Google Scholar
International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG). Practice guidelines for performance of the routine mid-trimester fetal ultrasound scan, 2010. http://www.isuog.org/NR/rdonlyres/EA865840-6CA3-45AC-9E99-FBAF775119A9/0/ISUOGGuidelinesmidtriscan20101210.pdf (accessed March 2017).Google Scholar
Royal College of Obstetricians and Gynaecologists. Routine ultrasound screening in pregnancy, protocols, standards and training. Supplement to ultrasound screening for fetal abnormalities, 2010. https://www.rcog.org.uk/en/careers-training/specialty-training-curriculum/ultrasound-training/ultrasound-module-intermediate-ultrasound-of-normal-fetal-anatomy (accessed March 2017).Google Scholar
NHS Screening Programmes. Fetal Anomaly Screening Programme. Programme Handbook June 2015. London: NHS, 2015. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/456654/FASP_programme_handbook_August_2015.pdf (accessed March 2017).Google Scholar
Schwärzler, P, Senat, MV, Holden, D, et al. Feasibility of the second-trimester fetal ultrasound examination in an unselected population at 18, 20 or 22 weeks of pregnancy: a randomized trial. Ultrasound Obstet Gynecol 1999; 14: 92–7.Google Scholar
Ewigman, BG, Crane, JP, Frigoletto, FD, et al. Effect of prenatal ultrasound screening on perinatal outcome. RADIUS Study Group. N Engl J Med 1993; 329: 821–7.Google Scholar
Fuchs, IB, Müller, H, Abdul-Khaliq, H, et al. Immediate and long-term outcomes in children with prenatal diagnosis of selected isolated congenital heart defects. Ultrasound Obstet Gynecol 2007; 29: 38–43.Google Scholar
Bonnet, D, Coltri, A, Butera, G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation 1999; 99: 916–18.Google Scholar
Franklin, O, Burch, M, Manning, N, et al. Prenatal diagnosis of coarctation of the aorta improves survival and reduces morbidity. Heart 2002; 87: 67–9.Google Scholar
Calderon, J, Angeard, N, Moutier, S, et al. Impact of prenatal diagnosis on neurocognitive outcomes in children with transposition of the great arteries. J Pediatr 2012; 161: 94–98.e1.Google Scholar
Tracy, ET, Mears, SE, Smith, PB, et al. Protocolized approach to the management of congenital diaphragmatic hernia: benefits of reducing variability in care. J Pediatr Surg 2010; 45: 1343–8.Google Scholar
Antonoff, MB, Hustead, VA, Groth, SS, Schmeling, DJ. Protocolized management of infants with congenital diaphragmatic hernia: effect on survival. J Pediatr Surg 2011; 46: 39–46.Google Scholar
Lazar, DA, Cass, DL, Rodriguez, MA, et al. Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes. J Pediatr Surg 2011; 46: 808–13.Google Scholar
Wald, NJ, Cuckle, H, Densem, JW, et al. Maternal serum screening for Down’s syndrome in early pregnancy. BMJ 1988; 297: 883–7.Google Scholar
Phillips, OP, Elias, S, Shulman, LP, et al. Maternal serum screening for fetal Down syndrome in women less than 35 years of age using alpha-fetoprotein, hCG, and unconjugated estriol: a prospective 2-year study. Obstet Gynecol 1992; 80: 353–8.Google Scholar
Malone, FD, Canick, J, Ball, RH, et al. First-trimester or second-trimester screening, or both, for Down’s syndrome. N Engl J Med 2005; 353: 2001–11.Google Scholar
Wald, NJ, Rodeck, C, Hackshaw, AK, et al. First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). Health Technol Assess 2003; 7 (11): 1–77.Google Scholar
Vora, NL, Powell, B, Brandt, A, et al. Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges. Genet Med 2017; 19: 1207–16. doi: 10.1038/gim.2017.33.Google Scholar
Yang, Y, Muzny, DM, Reid, JG, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013; 369: 1502–11. doi: 10.1056/NEJMoa1306555.Google Scholar
Shaffer, LG, Rosenfeld, JA, Dabell, MP, et al. Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound. Prenat Diagn 2012; 32: 986–95. doi: 10.1002/pd.3943.Google Scholar
Talkowski, ME, Ordulu, Z, Pillalamarri, V, et al. Clinical diagnosis by whole-genome sequencing of a prenatal sample. N Engl J Med 2012; 367: 2226–32. doi: 10.1056/NEJMoa1208594.Google Scholar
Lord, J, McMullan, DJ, Eberhardt, RY, et al. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet 2019; 393: 747–57. doi: 10.1016/S0140-6736(18)31940-8.Google Scholar
International Society for Prenatal Diagnosis; Society for Maternal and Fetal Medicine; Perinatal Quality Foundation. Joint position statement … on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn 2018; 38: 6–9. doi: 10.1002/pd.5195.Google Scholar

References

Fetal Anomaly Screening Programme. Cut off changes to Down’s syndrome screening. 2008. http://fetalanomaly.screening.nhs.uk/programmestatements#fileid11755 (accessed 01 January 2015).Google Scholar
Royal College of Obstetricians and Gynaecologists. Advanced Training Skills Module: Fetal Medicine. London: RCOG, 2010. https://www.rcog.org.uk/en/careers-training/specialty-training-curriculum/atsms/atsm-fetal-medicine/ (accessed March 2017).Google Scholar
Royal College of Obstetricians and Gynaecologists. Amniocentesis and Chorionic Villus Sampling. Green-top Guideline No. 8. London: RCOG, 2010. https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_8.pdf (accessed March 2017).Google Scholar
Blessed, WB, Lacoste, H, Welch, RA. Obstetrician-gynecologists performing genetic amniocentesis may be misleading themselves and their patients. Am J Obstet Gynecol 2001; 1784: 1340–2.Google Scholar
Lane, S, Weeks, A, Scholefield, H, Alfirevic, Z. Monitoring obstetricians’ performance with statistical process control charts. BJOG 2007; 114: 614–18.Google Scholar
Royal College of Obstetricians and Gynaecologists. Amniocentesis. Consent Advice 6. London: RCOG, 2006.Google Scholar
Weiner, CP, Okamura, K. Diagnostic fetal blood sampling-technique related losses. Fetal Diagn Ther 1996; 11: 169–75.Google Scholar
Royal College of Obstetricians and Gynaecologists. Use of Anti D Immunoglobulin for Rh prophylaxis. Green-top Guideline No. 22. London: RCOG, 2002.Google Scholar
Fung Kee Fung, K, Eason, E. Prevention of Rh alloimmunization. J Obstet Gynaecol Can 2003; 25: 765–73.Google Scholar
Gordon, MC, Narula, K, O’Shaughnessy, R, Barth, WH. Complications of third-trimester amniocentesis using continuous ultrasound guidance. Obstet Gynecol 2002; 99: 255–9.Google Scholar
Cahill, AG, Macones, GA, Stamilio, DM, et al. Pregnancy loss rate after mid-trimester amniocentesis in twin pregnancies. Am J Obstet Gynecol 2009; 200: 257.e1–e6.Google Scholar
Yi, W, Pan, CQ, Hao, J, et al. Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers. J Hepatol 2014; 60: 523–9.Google Scholar
Maiques, V, Garcia-Tejedor, A, Perales, A, Cordoba, J, Esteban, RJ. HIV detection in amniotic fluid samples. Amniocentesis can be performed in HIV pregnant women? Eur J Obstet Gynecol Reprod Biol 2003; 108: 137–41.Google Scholar
Alfirevic, Z, Navaratnam, K, Mujezinovic, F. Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Database Syst Rev 2017; (9): CD003252.Google Scholar
Mujezinovic, F, Alfirevic, Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet Gynecol 2007; 110: 687–94.Google Scholar
Akolekar, R, Beta, J, Picciarelli, G, Ogilvie, C, D’Antonio, F. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis.Ultrasound Obstet Gynecol 2015; 45: 16–26.Google Scholar
Giorlandino, C, Cignini, P, Cini, M, et al. Antibiotic prophylaxis before second-trimester genetic amniocentesis (APGA): a single-centre open randomised controlled trial. Prenat Diagn 2009; 29: 606–12.Google Scholar
Thirkelson, A. Cell culture and cytogenetic technique. In Murken, JD, Stengel-Rutdowski, S, Schwinger, E (eds), Third European Conference on Prenatal Diagnosis of Genetic Disorders. Stuttgart: Ferdinand Enke, 1979, pp. 258–70.Google Scholar
Wolstenholme, J. Confined placental mosaicism for trisomies 2, 3, 7, 8, 9, 16 and 22: their incidence, likely origins, and mechanisms for cell lineage compartmentalization. Prenat Diagn 1996; 16: 511–24.Google Scholar
Firth, HV, Boyd, PA, Chamberlain, P, et al. Severe limb abnormalities after chorionic villus sampling at 56–66 days’ gestation. Lancet 1991; 337: 762–3.Google Scholar
Carlin, AJ, Alfirevic, Z. Techniques for chorionic villus sampling and amniocentesis: a survey of practice in specialist UK centres. Prenat Diagn 2008; 28: 914–19.Google Scholar
Young, C, Von Dadelszen, P, Alfirevic, Z. Instruments for chorionic villus sampling for prenatal diagnosis. Cochrane Database Syst Rev 2013; (1): CD000114.Google Scholar
Gordon, MC, Narula, K, O’Shaughnessy, R, Barth, WH. Complications of third-trimester amniocentesis using continuous ultrasound guidance. Obstet Gynecol 2002; 99: 255–9.Google Scholar
Van Schoubroeck, D, Verhaeghel, J. Does local anesthesia at mid-trimester amniocentesis decrease pain experience? A randomized trial in 220 patients. Ultrasound Obstet Gynecol 2000; 16: 536–8.Google Scholar
Mujezinovic, F, Alfirevic, Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet Gynecol 2007; 110: 687–94.Google Scholar
Tabor, A, Philip, J, Madsen, M, et al. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986; 1: 1287–93.Google Scholar
Daffos, F, Cappella-Pavlovsky, M, Forestier, F: A new procedure for fetal blood sampling in utero: preliminary results of fifty-three cases. Am J Obstet Gynecol 1983; 146: 985–7.Google Scholar
Orlandi, F, Damiani, G, Jaklil, C, Lauricella, S, Bertolino, O, Maggio, A. The risks of early cordocentesis (12–21 weeks): analysis of 500 procedures. Prenat Diagn 1990; 10: 425–8.Google Scholar
Bovicelli, L, Orsini, LF, Grannum, PA. A new funipuncture technique: two-needle ultrasound and needle-biopsy guided procedure. Obstet Gynecol 1989; 73: 428–31.Google Scholar
Fassihi, H, Eady, RA, Mellerio, JE, et al. Prenatal diagnosis of severe inherited skin disorders: 25 years experience. Br J Dermatol 2006; 154: 106–13.Google Scholar
Hoffman, EP. Genotype/phenotype correlations in Duchenne/Becker dystrophy. Mol Cell Biol Hum Dis Ser 1993; 3: 12–36.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×