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Chapter 6 - Recurrent Miscarriage (Content last reviewed: 15th March 2020)

from Section 2 - Early Prenatal Problems

Published online by Cambridge University Press:  15 November 2017

By
Sadia Malick  and
Ramesh Ganapathy
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
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Summary

Recurrent miscarriage (RM) is defined conventionally as the loss of three or more consecutive pregnancies. This affects about 1–3% of women of reproductive age trying to conceive. However, there are further differences in definitions, depending on whether the miscarriages are consecutive with no live births in between. Some have amended the definition even further to include women with two miscarriages. This affects 5% of women trying to conceive. The reported incidence of 1–3% of women trying to conceive is much higher than can be explained on the basis of the likelihood of three spontaneous miscarriages occurring consecutively by chance alone.

Type
Chapter
Information
High-Risk Pregnancy
Management Options
 , pp. 113 - 147
Publisher: Cambridge University Press
First published in: 2017

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References

Regan, L, Rai, R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 839–54.CrossRefGoogle ScholarPubMed
Goddijn, M, Leschot, NJ. Genetic aspects of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 855–65.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Lathi, RB, Gray-Hazard, FK, Heerema-McKenney, A, Taylor, J, Chueh, JT. First trimester miscarriage evaluation. Semin Reprod Med 2011; 29: 463–9.CrossRefGoogle ScholarPubMed
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.Google 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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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 ScholarPubMed
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.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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

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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.

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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.

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