Earlier this month, a ProPublica investigation reported that deaths involving ruptured ectopic pregnancy in the United States nearly doubled between 2020–2025 compared with the prior six-year period, with a steeper rise in states enforcing strict abortion bans. 

Reporters documented cases in which patients with clear signs of ectopic pregnancy were sent home from emergency departments, sometimes repeatedly, before rupture occurred. A death from an ectopic pregnancy is preventable with early intervention and should never occur. Full stop. So, what do clinicians who interface with pregnant patients need to know about diagnosis and management, since delay—whatever its cause—is the single greatest driver of morbidity and mortality?

What is Ectopic Pregnancy?

Ectopic pregnancies implant outside of the uterine cavity and most commonly occur in the fallopian tubes, accounting for 90-95% of ectopic pregnancies.¹ As a tubal ectopic pregnancy progresses, there is no space for growth and it may rupture, resulting in potentially life-threatening intra-abdominal hemorrhage. Ruptured ectopic pregnancies remain the leading cause of first-trimester maternal death.² Significant racial disparities in outcomes have been documented in the United States: Black patients experience higher rates of major complications from ectopic pregnancy and have historically experienced substantially higher ectopic pregnancy–related mortality than White patients.² The reasons for these disparities are not fully understood and are likely multifactorial. A higher incidence of ectopic pregnancy among Black patients may contribute, while differences in access to and timing of care may also influence the risk of severe complications.³

Overall, ectopic pregnancies affect up to 2% of pregnancies.¹ At least one-half of patients have no identifiable risk factor, which is why any reproductive-age patient with a positive pregnancy test and concerning symptoms warrants evaluation.¹ The most common risk factors include: 

• Prior ectopic pregnancy

• History of tubal damage from surgery

• History of pelvic inflammatory disease causing residual inflammation or scarring of the fallopian tubes

• History of infertility

• Age over 35 years old

• Smoking

Women who use an IUD have an overall lower risk of an ectopic pregnancy than women who do not use contraception, as IUDs are highly effective at preventing pregnancy. However, if a pregnancy does occur with an IUD in place, up to 50% end up being ectopic pregnancies.*

*Among women who become pregnant using assisted reproductive technology, factors such as tubal factor infertility and multiple embryo transfers are risk factors. Ectopic pregnancies can occur within c-section scars, and so one or more prior uterine surgeries is also a risk factor.

Clinical Considerations from ReproHH

"When should I be concerned about an ectopic pregnancy?" 

The most common clinical presentation of ectopic pregnancy is first-trimester vaginal bleeding and/or abdominal pain.¹ Both symptoms do not need to be present, and ectopic pregnancy can be asymptomatic. These symptoms typically appear six to eight weeks after the last normal menstrual period, but may occur earlier or later, depending on where the pregnancy has implanted. 

Of note, a patient may have common pregnancy symptoms, such as nausea or breast tenderness, but not always. In rare circumstances, a patient may present with severe abdominal pain or symptoms of ongoing blood loss, suggesting a ruptured ectopic pregnancy, which can result in a life-threatening intra-abdominal hemorrhage.

"What should I do if a patient presents with bleeding or pain in the first trimester?" 

First, check vital signs and perform a physical exam, with specific attention to the abdomen, to ensure the patient is hemodynamically stable. In addition, confirm a positive pregnancy test if one has not been previously documented. 

Next, ensure the patient has previously had an ultrasound or order one, to assess for pregnancy location. Once a confirmed intrauterine pregnancy is visualized on ultrasound, you can be mostly reassured.* If no pregnancy is visualized on ultrasound, this is called a “pregnancy of unknown location” (PUL). 

The core challenge is that early intrauterine pregnancy, miscarriage, and ectopic pregnancy can all look identical on an initial clinical presentation. In some cases, an ultrasound can visualize signs concerning for an ectopic pregnancy, including an adnexal mass and/or free fluid in the cul-de-sac, but these signs are not diagnostic.

"What should I do if the ultrasound is non-diagnostic?"

When the ultrasound is non-diagnostic, the next step in evaluation is to obtain a quantitative serum hCG (human chorionic gonadotropin). While a single serum hCG value alone should not be used to diagnose an ectopic pregnancy, this value can help you interpret your ultrasound - an intrauterine gestational sac generally becomes visible around an hCG 2,000-3,500mIU/mL. The quality of the ultrasound machine and skill of the sonographer can also impact visualization. 

If you have an hCG above 3,500 (the “discriminatory zone”) and are not able to visualize an intrauterine pregnancy, be appropriately concerned for ectopic pregnancy and consider referring or consulting for treatment.⁴

If a patient with a PUL is hemodynamically stable, and the initial hCG level is less than 3,500, trending serial quantitative hCGs 48-72 hours apart can be helpful in evaluating a PUL for progression since neither ultrasound nor a single hCG can fully exclude ectopic pregnancy in isolation.** In early pregnancy, serum hCG levels increase in a curvilinear fashion until a plateau. Because of this, there is a slower increase when initial hCGs are higher. In a normally developing intrauterine pregnancy, a minimum rise is at least 35% over 48 hours with an initial hCG >3000mIU/mL, and higher percentage increases with lower initial hCGs.⁵ 

A rise below a minimum level, a plateau, or a fall is suspicious for either ectopic pregnancy or an early pregnancy loss. It is important to remember that decreasing hCG values do not confirm an early pregnancy loss or eliminate the possibility of an ectopic pregnancy, and rupture of the ectopic can occur even while levels are decreasing or very low. Once the hCG is above 2000-3500mIU/mL, an ultrasound can be repeated for more information about the location of the pregnancy. 

Finally, in some cases, repeated serial hCGs may be necessary to determine the trend of rise and fall; certain cases can be very tricky to interpret! This is a great opportunity to call ReproHH to help you interpret next steps!

*In very rare circumstances, an ectopic pregnancy can occur with an additional twin pregnancy in the uterus. While this is rare in naturally conceived pregnancies - ranging from 1 in 4,000 to 1 in 30,000 pregnancies - in those women who have undergone in vitro fertilization, the risk can be as high as 1 in 100 pregnancies.

 **A pelvic exam is not required, but may also be performed to examine for the source of bleeding and presence of any products of conception in the vagina.

Uterine Aspiration for Diagnosis

Uterine aspiration can be an additional diagnostic method to evaluate for an ectopic pregnancy.¹ In states where abortion is legal, and a patient does not desire pregnancy, uterine aspiration can help to distinguish early intrauterine pregnancy from ectopic pregnancy by identifying the presence or absence of intrauterine chorionic villi. In states where abortion is not legal, once the possibility of a progressing intrauterine gestation is excluded, uterine aspiration can be used to distinguish early intrauterine pregnancy from ectopic pregnancy in the same manner. If no chorionic villi are confirmed, hCG levels should be monitored after aspiration to determine ongoing trends.¹

It is important to recognize that a PUL should not be considered a final diagnosis and additional work-up with repeat quantitative bHCG and/or radiological assessment should occur, potentially more than once, in order to make a definitive diagnosis: is this pregnancy an intrauterine pregnancy, an early pregnancy loss, or an ectopic pregnancy? Once that diagnosis can be made, treatment can occur. 

Legal Considerations: Resources from Bridge to Treatment outline an algorithm for PUL and ectopic pregnancy work-up and management in states where abortion is permitted and where abortion is limited. However, clinical suspicion should drive appropriate urgency of evaluation and treatment, regardless of imaging. Any hemodynamically unstable patient with a positive pregnancy test needs immediate surgical evaluation.

"Once an ectopic pregnancy in a hemodynamically stable individual has been confirmed, how can I treat it?"

Once an ectopic pregnancy is confirmed, management can occur in three ways:

1. Medical management with methotrexate: This is appropriate for those with an unruptured pregnancy and no contraindications to the medication (renal, hepatic, or hematologic disease; breastfeeding; immunodeficiency).¹ 
   1. Single-dose regimens (50 mg/m² IM) are most common, with hCG checked at baseline and on days 4 and 7. 
   2. hCG will likely rise between baseline and day 4, although a decline of more than 15% between days 4 and 7 is expected for successful treatment. 
   3. If this decline is unmet, management warrants a repeat dose or reassessment; an additional dose may be required to ensure resolution in up to one-quarter of patients.¹ 
   4. Ongoing surveillance is recommended, and resolution of serum hCG levels is usually complete within 2-4 weeks, although it can take longer. 
   5. Lower baseline hCG and smaller mass size predict the success of treatment; hCG above roughly 5,000 mIU/mL is associated with meaningfully higher failure rates.⁶ 
   6. Resources from Bridge to Treatment outline absolute and relative contraindications for methotrexate therapy, protocols for use, including lab management, and patient education to provide.
2. Surgical management: This is required for patients with hemodynamic instability, indicating signs of rupture or hemoperitoneum. Surgical management can also occur when medical management is contraindicated or has failed, or as an alternative through patient-informed choice.
3. Expectant management: This should be generally avoided. Expectant management should only be considered for carefully selected, asymptomatic patients with low, declining hCG levels. These patients should be followed until their hCG is undetectable, as ruptures can occur even at low levels. Expectant management has been found to delay pregnancy resolution compared to empiric medical management with methotrexate and/or diagnostic aspiration in patients with a persistent PUL.⁷ 

All management decisions should be guided by the initial clinical, laboratory, and ultrasound data and discussed with the patient, with decisions made in a manner that promotes patient autonomy and shared decision-making. Patients should be fully informed of the risks of rupture with an ectopic pregnancy, which can occur even after methotrexate administration, the need for surveillance with non-surgical management, and what symptoms to return to care for. 

Evidence-Based Standard of Care

The recent Propublica article reminds us that clinical management doesn't happen in a vacuum. While these stories do not prove that abortion restrictions cause these outcomes, in states with abortion restrictions, clinicians describe delaying treatment until an ultrasound can conclusively demonstrate an extrauterine mass—even when hCG trends and symptoms already support high clinical suspicion for ectopic pregnancy. This is because of concern that early intervention could be construed as an abortion. 

That hesitation, documented in several lawsuits, has coincided in delays of days or even weeks and, in some states, a measurable rise in complications and mortality. 

Regardless of where someone lives, they should get the same, evidence-based clinical standard of care. Ectopic pregnancy is not a viable pregnancy; treating it is not elective, and delay for medicolegal reassurance carries real risk to the individuals affected. Clinicians practicing in restrictive states may benefit from institutional protocols, documentation templates, and advanced legal consultation, so that clinical decisions in the moment are guided by evidence rather than by uncertainty about liability. 

On the clinical side, if you are wondering if your patient has an ectopic pregnancy, how to manage laboratory interpretation or ultrasounds, or how to counsel a patient about their treatment choices, give us a call at ReproHH for on-demand help!

References

1. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol. 2018 Mar;131(3):e91-e103. doi: 10.1097/AOG.0000000000002560. Erratum in: Obstet Gynecol. 2019 May;133(5):1059. doi: 10.1097/AOG.0000000000003269.
2. Creanga AA, Shapiro-Mendoza CK, Bish CL, et al. Trends in ectopic pregnancy mortality in the United States: 1980–2007. Obstet Gynecol. 2011;117(4):837-843. doi:10.1097/AOG.0b013e3182113c10. PMID: 21422853.
3. Stulberg DB, Cain L, Dahlquist IH, Lauderdale DS. Ectopic pregnancy morbidity and mortality in low-income women, 2004-2008. Hum Reprod. 2016 Mar;31(3):666-71. doi: 10.1093/humrep/dev332. Epub 2016 Jan 2. PMID: 26724794; PMCID: PMC4755444. 
4. Connolly A, Ryan DH, Stuebe AM, Wolfe HM. Reevaluation of discriminatory and threshold levels for serum β-hCG in early pregnancy. Obstet Gynecol. 2013 Jan;121(1):65-70. doi: 10.1097/aog.0b013e318278f421. PMID: 23262929. 
5. Barnhart KT, Guo W, Cary MS, et al. Differences in Serum Human Chorionic Gonadotropin Rise in Early Pregnancy by Race and Value at Presentation. Obstet Gynecol. 2016 Sep;128(3):504-511. doi: 10.1097/AOG.0000000000001568. PMID: 27500326; PMCID: PMC4993627. 
6. Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril. 2007 Mar;87(3):481-4. doi: 10.1016/j.fertnstert.2006.10.007. Epub 2006 Dec 14. PMID: 17173905. 
7. Barnhart KT, Hansen KR, Stephenson MD, et al. Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location: The ACT or NOT Randomized Clinical Trial. JAMA. 2021 Aug 3;326(5):390-400. doi: 10.1001/jama.2021.10767. PMID: 34342619; PMCID: PMC8335579.