Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Triaging Women with Pregnancy of Unknown Location- the Performance of Protocols Based on Single Serum Progesterone, Serum hcg Ratios and M4 Model

Authors
1 Department of Gynaecology and Obstetrics, Aziz Medical Center, Karachi, Pakistan; Department of Obstetrics and Gynaecology, Karachi Medical and Dental College, Karachi, Pakistan
2 Department of Gynaecology and Obstetrics, Aziz Medical Center, Karachi, Pakistan
3 Department of Gynaecology and Obstetrics, Aziz Medical Center, Karachi, India
4 Dow University of Health Sciences (DUHS), Karachi, India
5 Department of Obstetrics and Gynaecology, Karachi Medical and Dental College, Karachi, Pakistan
6 Aga Khan University Hospital, Karachi, Pakistan
Abstract
Background: The purpose of the current study was to evaluate the ability of three protocols to triage women presenting with pregnancy of unknown location (PUL). Methods: Women with pregnancy of unknown location were recruited from Aziz Medical Centre from 1st August, 2018 to 31st July, 2020. The criterion of progesterone, human chorionic gonadotrophin (hCG) ratio, and M4 algorithm were used to predict risk of adverse pregnancy outcomes and classify women. Finally, 3 groups were established including ectopic pregnancy, failed pregnancy of unknown location, and intrauterine pregnancy (IUP). The primary outcome was to assign women to ectopic pregnancy group using these protocols. The secondary outcome was to compare the sensitivity and specificity of the three protocols relative to the final outcome. Results: Of the 288 women, 66 (22.9%) had ectopic pregnancy, 144 (50.0%) had intrauterine pregnancy, and 78 (27.1%) had failed pregnancy of unknown location. The criterion of progesterone had a sensitivity of 81.8%, specificity of 27%, negative predictive value (NPV) of 83.3%, and positive predictive value (PPV) of 25% for high risk result (ectopic pregnancy). The hCG ratio had sensitivity of 72%, specificity of 73%, NPV of 90%, and PPV of 44% for high risk result (ectopic pregnancy). However, model M4 had sensitivity of 86.4%, specificity of 91.9%, NPV of 95.8%, and PPV of 76% for high risk result. Conclusion: Based on the findings of the study, it was revealed that prediction model of M4 had the highest sensitivity, specificity, negative predictive value and positive predictive value for high risk result (ectopic pregnancy).
Keywords

Bobdiwala S, Al-Memar M, Farren J, Bourne T. Factors to consider in pregnancy of unknown loca-tion. Womens Health (Lond). 2017;13(2):27-33.
Fields L, Hathaway A. Key concepts in pregnancy of unknown location: identifying ectopic pregnancy and providing patient-centered care. J Midwifery Womens Health. 2017;62(2):172-9.
Fistouris J, Bergh C, Strandell A. Classification of pregnancies of unknown location according to four different hCG-based protocols. Hum Reprod. 2016; 31(10):2203-11.
Cordina M, Schramm-Gajraj K, Ross JA, Lautman K, Jurkovic D. Introduction of a single visit protocol in the management of selected patients with preg-nancy of unknown location: a prospective study. BJOG. 2011;118(6):693-7.
Condous G, Kirk E, Lu C, Van Huffel S, Gevaert O, De Moor B, et al. Diagnostic accuracy of varying discriminatory zones for the prediction of ectopic pregnancy in women with a pregnancy of unknown location. Ultrasound Obstet Gynecol. 2005;26(7): 770-5.
Condous G, Kirk E, Van Calster B, Van Huffel S, Timmerman D, Bourne T. Failing pregnancies of unknown location: a prospective evaluation of the human chorionic gonadotrophin ratio. BJOG. 2006; 113(5):521-7.
Condous G, Okaro E, Bourne T. Pregnancies of un-known location: diagnostic dilemmas and manage-ment. Curr Opin Obstet Gynecol. 2005;17(6):568-73.
Kirk E, Condous G, Van Calster B, Van Huffel S, Timmerman D, Bourne T. Rationalizing the follow-up of pregnancies of unknown location. Hum Re-prod. 2007;22(6):1744-50.
Condous G, Van Calster B, Kirk E, Haider Z, Tim-merman D, Van Huffel S, et al. Prediction of ectopic pregnancy in women with a pregnancy of unknown location. Ultrasound Obstet Gynecol. 2007;29(6): 680-7.
Barnhart KT, Sammel MD, Appleby D, Rausch M, Molinaro T, Van Calster B, et al. Does a prediction model for pregnancy of unknown location devel-op-ed in the UK validate on a US population? Hum Reprod. 2010;25(10):2434-40.
Bobdiwala S, Guha S, Van Calster B, Ayim F, Mitchell-Jones N, Al-Memar M, et al. The clinical performance of the M4 decision support model to triage women with a pregnancy of unknown loca-tion as at low or high risk of complications. Hum Reprod. 2016;31(7):1425-35.
Ooi S, De Vries B, Ludlow J. How do the M4 and M6 models perform in an Australian pregnancy of unknown location population? Aust N Z J Obstet Gynaecol. 2021;61(1):100-5.
Bobdiwala S, Saso S, Verbakel JY, Al-Memar M, Van Calster B, Timmerman D, et al. Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis. BJOG. 2019;126(2):190-8.
van Mello NM, Mol F, Opmeer BC, Ankum WM, Barnhart K, Coomarasamy A, 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(6):603-17.
Nadim B, Leonardi M, Infante F, Lattouf I, Reid S, Condous G. Rationalizing the management of pregnancies of unknown location: Diagnostic ac-curacy of human chorionic gonadotropin ratio-based decision tree compared with the risk pre-diction model M4. Acta Obstet Gynecol Scand. 2020;99(3):381-90.
Bignardi T, Condous G, Kirk E, Van Calster B, Van Huffel S, Timmerman D, et al. Viability of intrauterine pregnancy in women with pregnancy of unknown location: prediction using human cho-rionic gonadotropin ratio vs. progesterone. Ultra-sound Obstet Gynecol. 2010;35(6):656-61.
Christodoulou E, Bobdiwala S, Kyriacou C, Farren J, Mitchell-Jones N, Ayim F, et al. External vali-dation of models to predict the outcome of preg-nancies of unknown location: a multicentre cohort study. BJOG. 2020;128(3):552-62.
Nadim B, Leonardi M, Stamatopoulos N, Reid S, Condous G. External validation of risk prediction model M4 in an Australian population: Rationalis-ing the management of pregnancies of unknown location. Aust N Z J Obstet Gynaecol. 2020;60(6): 928-34.
Valdera Simbrón CJ, Hernández Rodríguez C, Ll-anos Jiménez L, Pérez García L, Plaza Arranz J, Albi González M. Management of early gestations with low beta-hCG levels after the use of assisted reproduction techniques: assessment of the M4 predictive model performance. Ultrasound Obstet Gynecol. 2021;58(4):616-24.