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-848d4c4894-xfwgj Total loading time: 0 Render date: 2024-06-20T11:31:09.995Z Has data issue: false hasContentIssue false

Chapter 12 - Recurrent Pregnancy Loss in the First and Second Trimesters

from Section 3 - Reproductive Endocrinology and Infertility

Published online by Cambridge University Press:  24 November 2021

By
Basil C. Tarlatzis ,
Alexandros Sotiriadis  and
Grigoris F. Grimbizis
Edited by
Tahir Mahmood ,
Charles Savona-Ventura ,
Ioannis Messinis  and
Sambit Mukhopadhyay
Tahir Mahmood
Affiliation:
Victoria Hospital, Kirkcaldy
Charles Savona-Ventura
Affiliation:
University of Malta, Malta
Ioannis Messinis
Affiliation:
University of Thessaly, Greece
Sambit Mukhopadhyay
Affiliation:
Norfolk & Norwich University Hospital, UK
Get access

Summary

Recurrent pregnancy loss (RPL) is defined as the consecutive or non-consecutive loss of two or more pregnancies before viability. Established, contributory and postulated causes for RPL include advanced maternal age, anti-TPO antibodies, antiphospholipid antibodies, Müllerian anomalies, parental chromosomal aberrations, inherited thrombophilia and alloimmunity. Recommended investigations include thyroid screening, testing for antiphospholipid antibodies and imaging of the uterus. A thorough reproductive history can guide investigation to include tailored tests (e.g. metabolic and genetic profile). Despite investigation, no cause is found in about 50% of RPL cases.

Thyroid dysfunction should be treated, antiphospholipid antibodies are managed with low-dose aspirin and heparin in a subsequent pregnancy and an intrauterine septum should be resected.

Maternal age and number of prior losses are the major determinants for the prognosis of a subsequent pregnancy. Pregnancies after RPL should be managed as high-risk.

Keywords

recurrent miscarriagepregnancy lossantiphospholipid syndromelow-dose aspirinmicronized progesteroneaberrations
Type
Chapter
Information
The EBCOG Postgraduate Textbook of Obstetrics & Gynaecology
Gynaecology
 , pp. 101 - 107
Publisher: Cambridge University Press
Print publication year: 2021

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.)

References

Rai, R, Regan, L. Recurrent miscarriage. Lancet 2006;368:601–611.CrossRefGoogle ScholarPubMed
Kolte, AM, Bernardi, LA, Christiansen, OB, et al. Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group. Hum Reprod 2015;30:495–498.CrossRefGoogle ScholarPubMed
ESHRE EPGDG. Recurrent pregnancy loss: guideline of the European Society of Human Reproduction and Embryology. 2017.Google Scholar
Nybo Andersen, AM, Wohlfahrt, J, Christens, P, Olsen, J, Melbye, M. Maternal age and fetal loss: population based register linkage study. BMJ 2000;320:1708–1712.Google Scholar
Puscheck, EE, Jeyendran, RS. The impact of male factor on recurrent pregnancy loss. Curr Opin Obstet Gynecol 2007;19:222–228.Google Scholar
Habbema, JDF, Eijkemans, MJC, Leridon, H, Te Velde, ER. Realizing a desired family size: when should couples start? Hum Reprod 2015;30:2215–2221.CrossRefGoogle ScholarPubMed
Franssen, MTM, Korevaar, JC, van der Veen, F, et al. Reproductive outcome after chromosome analysis in couples with two or more miscarriages: index [corrected]-control study. BMJ 2006;332:759–763.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;21:1076–1082.CrossRefGoogle ScholarPubMed
Thangaratinam, S, Tan, A, Knox, E, et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 2011;342:1–8.Google Scholar
Bhandari, HM, Tan, BK, Quenby, S. Superfertility is more prevalent in obese women with recurrent early pregnancy miscarriage. BJOG 2016;123:217–222.CrossRefGoogle ScholarPubMed
Cavalcante, MB, Sarno, M, Peixoto, AB, Araujo Júnior, E, Barini, R. Obesity and recurrent miscarriage: a systematic review and meta-analysis. J Obstet Gynaecol Res 2018;45:30–38.CrossRefGoogle ScholarPubMed
Ticconi, C, Pietropolli, A, Borelli, B, et al. Antinuclear autoantibodies and pregnancy outcome in women with unexplained recurrent miscarriage. Am J Reprod Immunol 2016;76:396–399.Google Scholar
RCOG. The role of natural killer cells in human fertility. Scientific Impact Paper No. 53. 2016.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;20:429–438.Google Scholar
Saravelos, SH, Cocksedge, KA, Li, T. Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal Hum Reprod Update 2008;14:415–429.CrossRefGoogle ScholarPubMed
Wold, ASD, Pham, N, Arici, A. Anatomic factors in recurrent pregnancy loss. Semin Reprod Med 2006;24:25–32.Google Scholar
Rey, E, Kahn, SR, David, M, Shrier, I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 2003;361:901–908.CrossRefGoogle ScholarPubMed
Sotiriadis, A, Makrigiannakis, A, Stefos, T, Paraskevaidis, E, Kalantaridou, SN. Fibrinolytic defects and recurrent miscarriage: a systematic review and meta-analysis. Obstet Gynecol 2007;109:1146–1155.Google Scholar
Mekinian, A, Cohen, J, Alijotas-Reig, J, et al. Unexplained recurrent miscarriage and recurrent implantation failure: is there a place for immunomodulation? Am J Reprod Immunol 2016;76:8–28.CrossRefGoogle Scholar
Antovic, A, Sennström, M, Bremme, K, Svenungsson, E. Obstetric antiphospholipid syndrome. Lupus Sci Med 2018;5:e000197.CrossRefGoogle ScholarPubMed
Grimbizis, GF, Di Spiezio Sardo, A, Saravelos, SH, et al. The Thessaloniki ESHRE/ESGE consensus on diagnosis of female genital anomalies. Gynecol Surg 2016;13:1–16.Google Scholar
Royal College Obstetricians and Gynaecologists (RCOG). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. Green-top guideline No. 17. 2011;17:1–18.Google Scholar
Pauta, M, Grande, M, Rodriguez-Revenga, L, Kolomietz, E, Borrell, A. Added value of chromosomal microarray analysis over karyotyping in early pregnancy loss: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018;4:453–462.CrossRefGoogle Scholar
Iews, M, Tan, J, Taskin, O, et al. Does preimplantation genetic diagnosis improve reproductive outcome in couples with recurrent pregnancy loss owing to structural chromosomal rearrangement? A systematic review. Reprod Biomed Online 2018;36:677–685.Google Scholar
Maraka, S, Mwangi, R, McCoy, RG, et al. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment. BMJ 2017;356:1–12.Google Scholar
Venetis, CA, Papadopoulos, SP, Campo, R, et al. Clinical implications of congenital uterine anomalies: a meta-analysis of comparative studies. Reprod Biomed Online 2014;29:665–683.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;35:155–158.Google Scholar
Skeith, L, Carrier, M, Kaaja, R, et al. A meta-analysis of low-molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia. Blood 2016;127:1650–1655.CrossRefGoogle ScholarPubMed
Yang, X-L, Chen, F, Yang, X-Y, Du, G-H, Xu, Y. Efficacy of low-molecular-weight heparin on the outcomes of in vitro fertilization/intracytoplasmic sperm injection pregnancy in non-thrombophilic women: a meta-analysis. Acta Obstet Gynecol Scand 2018;97:1061–1072.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;115:1256–1262.CrossRefGoogle Scholar
Mak, A, Cheung, MWL, Cheak, AA, Ho, RC-M. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology 2010;49:281–288.Google Scholar
Achilli, C, Duran-Retamal, M, Saab, W, Serhal, P, Seshadri, S. The role of immunotherapy in in vitro fertilization and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril 2018;110:1089–1100.Google Scholar
Popescu, F, Jaslow, CR, Kutteh, WH. Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients. Hum Reprod 2018;33:579–587.Google Scholar
Haas, DM, Hathaway, TJ, Ramsey, PS. Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Syst Rev 2018;10:CD003511.Google Scholar
Coomarasamy, A, Williams, H, Truchanowicz, E, et al. Progesterone in women with recurrent miscarriages. N Engl J Med 2016;374:894–894.Google ScholarPubMed
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
Wang, NF, Kolte, AM, Larsen, EC, Nielsen, HS, Christiansen, OB. Immunologic abnormalities, treatments, and recurrent pregnancy loss: what is real and what is not? Clin Obstet Gynecol 2016;59:509–523.Google Scholar
Boomsma, CM, Keay, SD, Macklon, NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev 2012;6:CD005996.Google Scholar
Zhang, L, Xu, WH, Fu, XH, et al. Therapeutic role of granulocyte colony-stimulating factor (G-CSF) for infertile women under in vitro fertilization and embryo transfer (IVF-ET) treatment: a meta-analysis. Arch Gynecol Obstet 2018;298:861–871.CrossRefGoogle ScholarPubMed
Eapen, A, Joing, M, Kwon, P, et al. Recombinant human granulocyte- colony stimulating factor in women with unexplained recurrent pregnancy losses: a randomized clinical trial. Hum Reprod 2019;34:424–432.CrossRefGoogle ScholarPubMed
Kling, C, Magez, J, Hedderich, J, von Otte, S, Kabelitz, D. Two-year outcome after recurrent first trimester miscarriages: prognostic value of the past obstetric history. Arch Gynecol Obstet 2016;293:1113–1123.Google Scholar
Lund, M, Kamper-Jørgensen, M, Nielsen, HS, et al. Prognosis for live birth in women with recurrent miscarriage. Obstet Gynecol 2012;119:37–43.CrossRefGoogle ScholarPubMed
Brigham, SA, Conlon, C, Farquharson, RG. A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod 1999;14:2868–2871.Google Scholar
Van Oppenraaij, RHF, Jauniaux, E, Christiansen, OB, et al. Predicting adverse obstetric outcome after early pregnancy events and complications: a review. Hum Reprod Update 2009;15:409–421.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org 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
×