TY - JOUR
T1 - Methotrexate vs expectant management for treatment of tubal ectopic pregnancy
T2 - An individual participant data meta-analysis
AU - Solangon, Sarah Annie
AU - van Wely, Madelon
AU - van Mello, Norah
AU - Mol, Ben W.
AU - Ross, Jackie A.
AU - Jurkovic, Davor
N1 - Funding Information: The NL study ran between April 2007 and January 2012 and included 73 women with conclusive ultrasound diagnosis of tubal EP with hCG <1500 IU/L or suspected tubal EP (PUL with plateauing serum hCG) <2000 IU/L. This was funded by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154). The UK study ran between August 2005 and June 2014 and included 80 women with conclusive ultrasound diagnosis of tubal EP and a serum hCG <1500 IU/L. This did not receive external funding. Baseline characteristics of intervention and comparison groups were similar and all prespecified outcomes were reported in both studies. Further characteristics of both studies are outlined in Table 1 . 9 11 Funding Information: The authors thank Amsterdam University Medical Center, Amsterdam, Netherlands, King's College Hospital, London, UK and the authors of the original studies for their collaboration and provision of IPD. Funding Information: BWM is supported by a NHMRC Investigatorgrant (GNT1176437). BWM reports consultancy for ObsEva and Merck and travel support from Merck. The other authors do not have any conflict of interests to declare. Publisher Copyright: © 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).
PY - 2023/9
Y1 - 2023/9
N2 - Introduction: Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment. Material and methods: We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times. Trial registration number: PROSPERO: CRD42021214093. Results: 1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95–1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23–1.14). Mean time to success was 19.7 days (95% CI 17.4–22.3) after MTX and 21.2 days (95% CI 17.8–25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group. Conclusions: Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
AB - Introduction: Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment. Material and methods: We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times. Trial registration number: PROSPERO: CRD42021214093. Results: 1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95–1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23–1.14). Mean time to success was 19.7 days (95% CI 17.4–22.3) after MTX and 21.2 days (95% CI 17.8–25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group. Conclusions: Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
KW - expectant management
KW - medical treatment
KW - methotrexate
KW - pregnancy ectopic
KW - pregnancy tubal
UR - http://www.scopus.com/inward/record.url?scp=85163202348&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/aogs.14617
DO - https://doi.org/10.1111/aogs.14617
M3 - Review article
C2 - 37345445
SN - 0001-6349
VL - 102
SP - 1159
EP - 1175
JO - Acta obstetricia et gynecologica Scandinavica
JF - Acta obstetricia et gynecologica Scandinavica
IS - 9
ER -