19/9/2020 Ectopic pregnancy: Expectant management - UpToDate Official reprint from UpToDateđ www.uptodate.com â2020 UpToDate, Inc and/or its affiliates All Rights Reserved Ectopic pregnancy: Expectant management Author: Togas Tulandi, MD, MHCM Section Editor: Courtney A Schreiber, MD, MPH Deputy Editor: Alana Chakrabarti, MD All topics are updated as new evidence becomes available and our peer review process is complete Literature review current through: Aug 2020 | This topic last updated: Jan 23, 2020 INTRODUCTION An ectopic pregnancy is a pregnancy outside of the uterine cavity The majority of ectopic pregnancies occur in the fallopian tube (96 percent) [1], but other possible sites include cervical, interstitial (also referred to as cornual; a pregnancy located in the proximal segment of the fallopian tube that is embedded within the muscular wall of the uterus), hysterotomy scar, intramural, ovarian, or abdominal In addition, in rare cases, a multiple gestation may be heterotopic (include both a uterine and extrauterine pregnancy) Ectopic pregnancy is a potentially life-threatening condition, usually requiring expeditious surgical or medical treatment to reduce the risk of rupture of the fallopian tube or another structure and catastrophic hemorrhage However, in a small proportion of cases in which the risk of tubal rupture is minimal, expectant management may be offered [2] Women who are candidates for expectant management of ectopic pregnancy require informed consent about the risks of this strategy and close observation until the pregnancy has resolved Expectant management of ectopic pregnancy will be reviewed here Related topics regarding ectopic pregnancy are discussed in detail separately, including: ● Epidemiology, risk factors, and pathology (see "Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites") ● Clinical manifestations and diagnosis (see "Ectopic pregnancy: Clinical manifestations and diagnosis") ● Choosing a treatment (see "Ectopic pregnancy: Choosing a treatment") ● Methotrexate therapy (see "Ectopic pregnancy: Methotrexate therapy") https://www.uptodate.com/contents/ectopic-pregnancy-expectant-management/print?search=ectopic pregnancy&source=search_result&selected… 1/9 19/9/2020 Ectopic pregnancy: Expectant management - UpToDate ● Surgical management (see "Ectopic pregnancy: Surgical treatment") ● Diagnosis and management of uncommon sites of ectopic pregnancy (see "Abdominal pregnancy, cesarean scar pregnancy, and heterotopic pregnancy") INDICATIONS The most common treatments of ectopic pregnancy are pharmacologic therapy with methotrexate (MTX) or surgical treatment Only a small proportion of women are candidates for expectant management The indication for expectant management of ectopic pregnancy is a suspicion of ectopic pregnancy in a woman who meets the selection criteria for expectant management The patient must also prefer expectant management rather than MTX or surgical treatment Selection criteria — When ectopic pregnancy is suspected, in our practice, we offer expectant management only for women who meet ALL the following criteria: ● Asymptomatic ● Understand the clinical implications and risks of an ectopic pregnancy ● Ready access to a medical facility if emergency surgical treatment is needed ● Able and willing to comply with close follow-up ● Transvaginal ultrasound (TVUS) does not show an extrauterine gestational sac or demonstrate an extrauterine mass suspicious for an ectopic pregnancy ● Serum quantitative beta-human chorionic gonadotropin (hCG) concentration is low (≤200 mIU/mL) and decreasing [3] We define decreasing as a decrease of >10 percent across two consecutive measurements Some guidelines advise offering expectant management to patients who meet the above criteria and have an hCG ≤1000 mIU/mL [4] Patients with no extrauterine or intrauterine mass on TVUS are described as a pregnancy of unknown location since imaging and laboratory assessment not clearly distinguish between a failed intrauterine pregnancy and a resolving ectopic pregnancy in an early pregnancy An extrauterine mass that can be characterized as not being suspicious for an ectopic pregnancy (eg, corpus luteum) is not a contraindication for expectant management (See "Ultrasonography of pregnancy of unknown location".) There are few data to determine the threshold hCG level that allows for expectant management of ectopic pregnancy without unnecessary risk of tubal rupture The rate of tubal rupture without treatment is high This was illustrated in a population-based study in France that reported an 18 https://www.uptodate.com/contents/ectopic-pregnancy-expectant-management/print?search=ectopic pregnancy&source=search_result&selected… 2/9 19/9/2020 Ectopic pregnancy: Expectant management - UpToDate percent rate of tubal rupture among 843 women with ectopic pregnancy; women treated with MTX were excluded [5] Reported rates of rupture after MTX treatment are to 14 percent [6] (See "Ectopic pregnancy: Choosing a treatment", section on 'Outcomes'.) Several studies have evaluated use of a hCG threshold up to 1000 to 2000 mIU/mL [3,7,8] The two randomized trials that have evaluated expectant management of suspected ectopic pregnancy used hCG thresholds up to 200 mIU/mL (at any time during this pregnancy) and/or increasing We define increasing as an increase of >10 percent across two consecutive measurements and decreasing as a decrease of >10 percent across two consecutive measurements There are few data to support how to define an increase or decrease in serial hCG levels, but 10 percent is based on the interassay coefficient of variation, which can be in that range ● Unwilling or unable to comply with monitoring, including if the patient does not have timely access to a medical institution https://www.uptodate.com/contents/ectopic-pregnancy-expectant-management/print?search=ectopic pregnancy&source=search_result&selected… 3/9 19/9/2020 Ectopic pregnancy: Expectant management - UpToDate CLINICAL PROTOCOL The clinical protocol for expectant management of ectopic pregnancy includes (algorithm 1): ● Diagnosis of pregnancy of unknown location with suspicion of ectopic pregnancy – (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Diagnosis'.) ● Counseling of patient regarding treatment options – If expectant management is offered, the patient must be aware of and accept the risks as well as be willing and able to comply with follow-up She must also be aware of precautions and reasons to call for medical help She must be close enough to a medical center that can surgically treat ectopic pregnancy for timely care if impending or ongoing tubal rupture is suspected (See "Ectopic pregnancy: Choosing a treatment", section on 'Medical versus surgical treatment'.) ● Close monitoring – Tubal rupture has been reported in women with low and declining human chorionic gonadotropin (hCG) levels [11] We follow the hCG level every two days for three measurements to confirm that the hCG level continues to decrease (decrease of >10 percent across two consecutive measurements), and then weekly until it is undetectable • Expectant management should be abandoned if a patient experiences a significant increase in abdominal pain or the serum hCG starts to increase (increase of >10 percent across two consecutive measurements) or fails to decrease (decrease of >10 percent across two consecutive measurements) These patients should be treated with surgery or methotrexate (MTX), as appropriate for the clinical situation • Asymptomatic women who are managed expectantly and have hCG levels that are slowly declining may be offered continuation of expectant management or MTX injection In general, in our practice, if the hCG has not reached undetectable within 10 weeks, we offer MTX therapy • If the hCG level has plateaued (increase or decrease of ≤10 percent across two consecutive measurements) or is increasing, the patient should be treated with MTX (See "Ectopic pregnancy: Methotrexate therapy".) OUTCOME Efficacy — Successful expectant management of ectopic pregnancy is defined as reaching an undetectable level of beta-human chorionic gonadotropin (hCG, at most laboratories that is less than to 10 mIU/mL) with no complications and no conversion to methotrexate (MTX) or surgical treatment Success rates for expectant management of ectopic pregnancy of 47 to 100 percent have been reported [2] The wide variation is due, in part, to differences in inclusion criteria as well as the definition of success [3,8,12-14] https://www.uptodate.com/contents/ectopic-pregnancy-expectant-management/print?search=ectopic pregnancy&source=search_result&selected… 4/9 19/9/2020 Ectopic pregnancy: Expectant management - UpToDate Several randomized trials have evaluated expectant management of ectopic pregnancy and have demonstrated success rates comparable to MTX therapy The amount of time to reach an undetectable hCG was also comparable to MTX Few patients managed expectantly had complications or had to convert to MTX or surgery The available randomized trials included patients with hCG levels higher than the 200 mIU/mL threshold we use in our practice, but most did not include an analysis of success rates at different threshold levels of hCG below 1000 mIU/mL Thus, these data not give information regarding choice of an hCG threshold of 200, 400, 600 mIU/mL, or higher Thus, we prefer to use a low hCG level as a criterion to avoid unnecessary risk of unsuccessful treatment or tubal rupture These trials often included women with ultrasound evidence of an ectopic gestation, which is also a contraindication based on our practice Similarly, we prefer to be conservative when offering expectant management The two largest randomized trials that compared expectant management with standard MTX therapy (standard dose and intramuscular [IM] route of administration) were: ● One trial (n = 80) assigned women with a conclusive ultrasound diagnosis (those with an embryonic heartbeat or hemoperitoneum were excluded) of tubal ectopic pregnancy and a serum hCG