Doing enough without doing everything: evidence-based management of recurrent first-trimester miscarriage in resource-limited settings

Olatokunbo O. Kolawole; Funmilola S. Odukoya; Prisca O. Ogide; Favour Sylva-Oriji

doi:10.18203/2320-1770.ijrcog20264039

Authors

Olatokunbo O. Kolawole Department of Obstetrics and Gynaecology, Nigerian Air Force Hospital, Abuja, Nigeria
Funmilola S. Odukoya Department of Obstetrics and Gynaecology, Nigerian Air Force Hospital, Abuja, Nigeria
Prisca O. Ogide Department of Obstetrics and Gynaecology, Garki Hospital, Abuja, Nigeria
Favour Sylva-Oriji Department of Obstetrics and Gynaecology, Garki Hospital, Abuja, Nigeria

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20264039

Keywords:

Recurrent miscarriage, Recurrent pregnancy loss, First trimester, Resource-limited settings, Progesterone, Antiphospholipid syndrome

Abstract

Recurrent first-trimester miscarriage is a common but difficult problem in obstetric and gynaecological practice. The difficulty is greater in resource-limited settings, where genetic testing, specialised coagulation assays and advanced imaging may be unavailable or unaffordable. This narrative review examines a practical question: which investigations and treatments are sufficiently useful to justify their cost and burden in women with recurrent early pregnancy loss? A focused literature search of PubMed/MEDLINE, the Cochrane Library and major professional guidelines was updated to October 2026. The evidence supports a careful reproductive and medical history, assessment of maternal age and modifiable risk factors, evaluation of uterine anatomy, thyroid function testing and appropriately prioritised testing for antiphospholipid syndrome. Glycaemic assessment should be risk-directed. Genetic analysis of miscarriage tissue is informative when available, but routine inherited thrombophilia, natural-killer-cell, broad immunological and infection screening have limited first-line value. Folic acid remains appropriate preconception care but is not a specific treatment for recurrent miscarriage. Aspirin and heparin should principally be used for appropriately diagnosed antiphospholipid syndrome. Vaginal micronized progesterone has the clearest evidence in women with previous miscarriage who develop bleeding in a subsequent intrauterine pregnancy; evidence for routine progestogen use in otherwise unexplained recurrent miscarriage is weaker. Routine prednisolone is not supported. Resource limitation should therefore favour selective investigation, cause-directed treatment and structured early-pregnancy supportive care.

References

Practice Committee of the American Society for Reproductive Medicine. Recurrent pregnancy loss: a committee opinion. Fertil Steril. 2026;125(6):1023-41.

Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, et al. ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023;2023(1):hoad002.

Regan L, Rai R, Saravelos S, Li TC. Recurrent miscarriage: Green-top Guideline No. 17. BJOG. 2023;130(12):e9-e39.

Motan T, Cockwell H, Elliott J, Antaki R, White J. Guideline No. 464: recurrent pregnancy loss. J Obstet Gynaecol Can. 2025;47(12):103167.

Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, et al. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. 2021;397(10285):1658-67.

Inversetti A, Perna G, Lalli G, Grande G, Di Simone N. Depression, stress and anxiety among women and men affected by recurrent pregnancy loss (RPL): a systematic review and meta-analysis. Life (Basel). 2023;13(6):1268.

Eleje GU, Ugwu EO, Igbodike EP, Malachy DE, Nwankwo EU, Ugboaja JO, et al. Prevalence and associated factors of recurrent pregnancy loss in Nigeria according to different national and international criteria (ASRM/ESHRE vs. WHO/RCOG). Front Reprod Health. 2023;5:1049711.

Bosire A, Kosgei R, Gathara D, Madadi M, Osoti A. Burden, causes, and treatment approaches of recurrent pregnancy loss: a scoping review. Pan Afr Med J. 2025;52:109.

Carvalho T, Ângelo-Dias M, Moutinho F, Serra SS, Costa T, Martins JP, et al. Recurrent pregnancy loss: systematic review and meta-analysis of overall prevalence and the distribution of major etiological categories. Front Med (Lausanne). 2026;13:1805994.

Lei D, Zhang XY, Zheng PS. Recurrent pregnancy loss: fewer chromosomal abnormalities in products of conception? a meta-analysis. J Assist Reprod Genet. 2022;39(3):559-72.

Eliwa J, Papas RS, Kutteh WH. Expanding the role of chromosomal microarray analysis in the evaluation of recurrent pregnancy loss. J Reprod Immunol. 2024;161:104188.

Kim MA, Kim HS, Kim YH. Reproductive, obstetric and neonatal outcomes in women with congenital uterine anomalies: a systematic review and meta-analysis. J Clin Med. 2021;10(21):4797.

Barbhaiya M, Zuily S, Naden R, Hendry A, Manneville F, Amigo MC, et al. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol. 2023;75(10):1687-702.

World Health Organization. Periconceptional folic acid supplementation to prevent neural tube defects. Geneva: World Health Organization; 2023. Available at: https://www.who.int/tools/elena/interventions/folate-periconceptional. Accessed on 02 September 2026.

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.

Quenby S, Booth K, Hiller L, Coomarasamy A, de Jong PG, Hamulyák EN, et al. Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial. Lancet. 2023;402(10395):54-61.

Hamulyák EN, Scheres LJJ, Marijnen MC, Goddijn M, Middeldorp S. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Cochrane Database Syst Rev. 2020;(5):CD012852.

Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, et al. A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med. 2015;373(22):2141-8.

Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. N Engl J Med. 2019;380(19):1815-24.

National Institute for Health and Care Excellence. Ectopic pregnancy and miscarriage: diagnosis and initial management. NICE guideline NG126. London: NICE; 2019. Available at: https://www.nice.org.uk/guidance/ng126.Accessed on 02 September 2026.

Haas DM, Bofill Rodriguez M, Hathaway TJ, Ramsey PS. Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Syst Rev. 2025 Jun 11;6(6):CD003511.

Carp H. A systematic review of dydrogesterone for the treatment of recurrent miscarriage. Gynecol Endocrinol. 2015;31(6):422-30.

Katalinic A, Noftz MR, Garcia-Velasco JA, Shulman LP, van den Anker JN, Strauss JF 3rd. No additional risk of congenital anomalies after first-trimester dydrogesterone use: a systematic review and meta-analysis. Hum Reprod Open. 2024;2024(1):hoae004.

Coomarasamy A, Dhillon-Smith RK, Papadopoulou A, Al-Memar M, Brewin J, Abrahams VM, et al. Recurrent miscarriage: evidence to accelerate action. Lancet. 2021;397(10285):1675-82.