Early pregnancy pain and bleeding, including pregnancy of unknown location

It is Saturday morning in the early pregnancy assessment unit. Your first patient is 25, six weeks by dates, bleeding lightly and aching low on the left. She looks well. The scan shows an empty uterus, a normal left ovary and no free fluid. Her hCG is 940 IU/L. You now hold the single most dangerous label in gynaecology — a pregnancy you cannot find — and the whole of this topic is how you hold it safely.[1][4]

Overview and definition

Pain and bleeding in the first trimester is the commonest reason a woman meets a gynaecologist. Most of those pregnancies are fine, some are miscarrying, and a small but lethal minority are ectopic. Your job is not to guess which; it is to run a protocol that makes guessing unnecessary.[1][4]

The word "unknown" is doing real work. It does not mean "probably fine". In the largest prospective implementation cohort, 320 of 2625 women classified as PUL (roughly 12%) ultimately had an ectopic pregnancy.[6]

References17Show ledgerHide ledger

1. [1]Royal College of Obstetricians and Gynaecologists Diagnosis and Management of Ectopic Pregnancy: Green-top Guideline No. 21 BJOG, 2016.PMID 27813249
2. [2]American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Gynecology ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy Obstet Gynecol, 2018.PMID 29470343
3. [3]Barnhart K, van Mello NM, Bourne T, et al. Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome Fertil Steril, 2011.PMID 20947073
4. [4]Barnhart KT Clinical practice. Ectopic pregnancy N Engl J Med, 2009.PMID 19625718
5. [5]Van Calster B, Bobdiwala S, Guha S, et al. Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol Ultrasound Obstet Gynecol, 2016.PMID 26776599
6. [6]Bobdiwala S, Christodoulou E, Farren J, et al. Triaging women with pregnancy of unknown location using two-step protocol including M6 model: clinical implementation study Ultrasound Obstet Gynecol, 2020.PMID 31385381
7. [7]Bobdiwala S, Saso S, Verbakel JY, et al. Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis BJOG, 2019.PMID 30129999
8. [8]Bobdiwala S, Kyriacou C, Christodoulou E, et al. Evaluating cut-off levels for progesterone, β human chorionic gonadotropin and β human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study Acta Obstet Gynecol Scand, 2022.PMID 34817062
9. [9]Kyriacou C, Ledger A, Bobdiwala S, et al. Updating M6 pregnancy of unknown location risk-prediction model including evaluation of clinical factors Ultrasound Obstet Gynecol, 2024.PMID 37842861
10. [10]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.PMID 23045257
11. [11]Barnhart KT, Sammel MD, Rinaudo PF, et al. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined Obstet Gynecol, 2004.PMID 15229000
12. [12]Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable pregnancy early in the first trimester N Engl J Med, 2013.PMID 24106937
13. [13]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.PMID 31067371
14. [14]Farren J, Jalmbrant M, Falconieri N, et al. Posttraumatic stress, anxiety and depression following miscarriage and ectopic pregnancy: a multicenter, prospective, cohort study Am J Obstet Gynecol, 2020.PMID 31953115
15. [15]Ankum WM, Mol BW, Van der Veen F, Bossuyt PM Risk factors for ectopic pregnancy: a meta-analysis Fertil Steril, 1996.PMID 8641479
16. [16]Preisler J, Kopeika J, Ismail L, et al. Defining safe criteria to diagnose miscarriage: prospective observational multicentre study BMJ, 2015.PMID 26400869
17. [17]Connolly A, Ryan DH, Stuebe AM, Wolfe HM Reevaluation of discriminatory and threshold levels for serum β-hCG in early pregnancy Obstet Gynecol, 2013.PMID 23262929