Ectopic Pregnancy


Article Author:
Tyler Mummert


Article Editor:
David Gnugnoli


Editors In Chief:
Casey Ciresi


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
3/10/2019 5:53:15 PM

Introduction

Ectopic pregnancy is a known complication of pregnancy that can carry a high rate of morbidity and mortality when not recognized and treated promptly.  It is essential that providers maintain a high index of suspicion for an ectopic in their pregnant patients as they may present with pain, vaginal bleeding, or more vague complaints such as nausea and vomiting. Fertilization and embryo implantation involve an interplay of chemical, hormonal, and anatomical interactions and conditions to allow for a viable intrauterine pregnancy.  Much of this system is outside the scope of this article but the most relevant anatomical components to our discussion on the ovaries, fallopian tubes, uterus, egg, and sperm.  Ovaries are the female reproductive organs located to both lateral aspects of the uterus in the lower pelvic region. Ovaries serve multiple functions, one of which is to release an egg each month for potential fertilization. The fallopian tubes are tubular structures that serve as a conduit to allow transport of the female egg from the ovaries to the uterus. When sperm is introduced, it will fertilize the egg forming an embryo. The embryo will then implant into endometrial tissue within the uterus. An ectopic pregnancy occurs when this fetal tissue implants somewhere outside of the uterus or attaching to an abnormal or scarred portion of the uterus.

Etiology

Ectopic pregnancy, in essence, is the implantation of an embryo outside of the uterine cavity most commonly in the fallopian tube. Smooth muscle contraction and ciliary beat within the fallopian tubes to assist the transport of an oocyte and embryo. Damage to the fallopian tubes, usually secondary to inflammation, induces tubal dysfunction which can result in retention of an oocyte or embryo. There are several local factors, such as toxic, infectious, immunologic, and hormonal, that can induce inflammation.[1] There is upregulation of pro-inflammatory cytokines following tubal damage; this subsequently promotes embryo implantation, invasion, and angiogenesis within the fallopian tube.[1] Chlamydia trachomatis infection results in the production of interleukin 1 by tubal epithelial cells; this happens to be a vital indicator for embryo implantation within the endometrium[1] Interleukin 1 also has a role in downstream neutrophil recruitment which would further contribute to fallopian tubal damage.[1] Cilia beat frequency is negatively affected by smoking and infection. Hormonal variations throughout the menstrual cycle additionally have demonstrated effects on cilia beat frequency.[1].

Ectopic implantation can occur in the cervix, uterine cornea, myometrium, ovaries, abdominal cavity, etc.[2] Women with tubal ligation or other post-surgical alterations to their fallopian tubes are at risk for ectopic pregnancies as the native function of the fallopian tube would be altered. The patient additionally can have an ectopic pregnancy with a concurrent intrauterine pregnancy, as known as a heterotopic pregnancy.[1]

Epidemiology

The estimated rate of ectopic pregnancy in the general population is 1 to 2% and 2 to 5% among patients who utilized assisted reproductive technology [1]. Ectopic pregnancies with implantation occurring outside of the fallopian tube account for less than 10% of all ectopic pregnancies.[1] Cesarean scar ectopic pregnancies occur in 4% of all ectopic pregnancies, as well as 1 in 500 pregnancies in women who underwent at least one prior c-section.[3] Interstitial ectopic pregnancies are reported in up to 4% of all ectopic implantation sites and have morbidity with mortality rates up to 7 times higher than other ectopic implantation sites.  This increased morbidity and mortality are due to a high rate of hemorrhage in interstitial ectopic pregnancies.[1] Intramural ectopic pregnancies, those implanted in the myometrium, were reported in 1% of ectopic pregnancies.[1] Ectopic pregnancies implanting in the abdominal cavity account for 1.3% of ectopic implantation sites, of which adhere most commonly in the pouches anterior and posterior to the uterus as well as on the serosa of the adnexa and uterus.[1] Reports also exist of implantation sites in omental, retroperitoneal, splenic, and hepatic locations.[1]

Risk factors associated with ectopic pregnancies include advanced maternal age, smoking, history of ectopic pregnancy, tubal damage or tubal surgery, prior pelvic infections, DES exposure, IUD use, and assisted reproductive technologies.[1] Older age does bear risk with ectopic pregnancy; aged fallopian tubes likely have relatively decreased function predisposing to delay of oocyte transport. Women with prior ectopic pregnancies have up to ten times risk compared to the general population. Women pursuing in vitro fertilization have increased risk with developing an ectopic pregnancy with a concurrent intrauterine pregnancy, as known as heterotypic pregnancy. The risk is estimated as high as 1:100 women pursuing in vitro fertilization. The risk of developing a  heterotopic pregnancy has been estimated as high as 1:100 in women seeking in vitro fertilization.[1]

Histopathology

The most common site for ectopic pregnancy adherence is in the ampullary region of the fallopian tube.[1] Reportedly 95% of ectopic pregnancies develop in the ampulla, infundibular, and isthmic portions of the fallopian tubes.[4] With cesarean scar pregnancies, there is a migration of blastocyst into the myometrium due to residual scarring defect from prior c-section.[3] The depth of implantation determines the type of cesarean scar pregnancy with type 1 having proximity to the uterine wall and type 2 implanting closer to the urinary bladder.[3]

History and Physical

Women presenting with an ectopic pregnancy will often complain of pelvic pain; however, not all ectopic pregnancies manifest with pain. Women of childbearing age who complain of pelvic pain/discomfort, abdominal pain/discomfort, nausea/vomiting, syncope, lightheadedness, vaginal bleeding, etc. should merit consideration for the possibility of pregnancy. Providers need to identify when the patient's last menstrual period occurred and whether they have monthly routine menstrual periods. If patients have missed their last period or have abnormal uterine bleeding, and are sexually active, then they may be pregnant and thus need further testing with a pregnancy test. Providers should identify any known risk factors for ectopic pregnancy in their patient's history, such as if a patient has had a prior confirmed ectopic pregnancy, known fallopian tube damage (history of pelvic inflammatory disease, tubal surgery, known obstruction), or achieved pregnancy through infertility treatment.[2]

After obtaining a thorough history, an attentive physical exam is the next step. Evaluation of vital signs to assess for tachycardia and hypotension is pivotal in determining the patient’s hemodynamic stability. When examining the abdomen and suprapubic regions, attention should focus on the location of tenderness as well as any exacerbating factors. If voluntary/involuntary guarding of the abdominal musculature is elicited on palpation, this should raise concern for possible free fluid or other cause of peritoneal signs. Palpating a gravid uterus may suggest pregnancy, however, does not exclude other pathologies such as progressed ectopic pregnancy or heterotopic pregnancy. Patient’s presenting with vaginal bleeding would likely benefit from a pelvic exam to assess for infections as well as assess the cervical os. Bimanual pelvic exams additionally allow for palpation of bilateral adnexa to assess for any abnormal masses/structures or to elicit adnexal tenderness. A thorough history and physical exam will lend better certainty with testing obtained when evaluating for possible ectopic pregnancy.

Evaluation

Transvaginal ultrasound imaging is pivotal in diagnosing suspected ectopic pregnancy. Serial exams with transvaginal imaging, serum hCG level measurements, or both are necessary to confirm the diagnosis. The first marker of an intrauterine pregnancy on ultrasound is a small sac eccentrically located within the decidua.[2] Two rings of tissue will form around the sac thus terming it the “double decidual” sign.[2] The double decidual sign usually becomes visible during the 5th week of pregnancy seen on abdominal ultrasound imaging.[2] The yolk sac will become apparent at this time but will require transvaginal ultrasound imaging for identification.[2] An embryonic pole will become visible on transvaginal imaging at around six weeks of pregnancy.[2] Uterine fibroids or highly elevated body mass index can limit the accuracy of ultrasound imaging to identify an early intrauterine pregnancy. MRI imaging can be helpful in extreme circumstances, such as those with large obstructing uterine fibroids; however, its sensitivity and specificity require further research and the potential risks with gadolinium contrast exposure merit consideration.[2]

The best diagnostic confirmation of an ectopic pregnancy comes through identifying a fetal heartbeat outside of the uterine cavity on ultrasound imaging.  The absence of a discernable fetal heartbeat can be misleading; however, as a fetal heartbeat does not develop throughout all ectopic pregnancies.[2] Additional signs of ectopic pregnancy include identification of a gestational sac with or without a yolk sac within an ectopic location or having identified a complex adnexal mass that strays from the typical presentations of hemorrhagic corpus luteum.[2] When radiologic imaging fails to confirm the presence of an ectopic pregnancy adequately, direct visualization of the suspicious mass can occur via diagnostic laparoscopy.[2] Direct laparoscopy may not identify very small ectopic gestations, cervical pregnancies, or those located in cesarean scars.[2]

Treatment / Management

Administration of intramuscular methotrexate or performance of laparoscopic surgery is safe and effective treatment modalities in hemodynamically stable women with a non-ruptured ectopic pregnancy. The decision of which modality to pursue is guided by the patient’s clinical picture, their laboratory findings, and radiologic imaging as well as the patient’s well-informed choice after having reviewed the risks and benefits with each procedure. Patients with relatively low hCG levels would benefit from the single-dose methotrexate protocol. Patients with higher hCG levels may necessitate two-dose regimens. There is literature suggestive that methotrexate treatment does not have adverse effects on ovarian reserve or fertility.[5] hCG levels should be trended until a non-pregnancy level exists post-methotrexate administration.[6]  Surgical management is necessary when the patients demonstrate any of the following: an indication of intraperitoneal bleeding, symptoms suggestive of ongoing ruptured ectopic mass, or hemodynamically instability.[6]

Surgical management including salpingostomy or salpingectomy should be guided by clinical status, the extent of fallopian tube compromise, and desire for future fertility. In simplest form salpingectomy involves removing the fallopian tube partially or in full.[1] Salpingostomy, or salpingotomy, involves removal of the ectopic pregnancy via tubal incision while leaving the fallopian tube in situ.[1]

Differential Diagnosis

One should begin to formulate a differential diagnosis when taking into account the patient’s history and physical exam findings.  Important differential diagnoses to consider with ectopic pregnancies are ovarian torsion, tuba-ovarian abscess, appendicitis, hemorrhagic corpus luteum, ovarian cyst rupture, threatened miscarriage, incomplete miscarriage, pelvic inflammatory disease, and ureteral calculi. The patient's history and hemodynamic status on clinical presentation will influence the order of these differentials, as well as the testing necessary to rule out said differentials. 

Prognosis

Patients with a relatively low beta hCG level will likely have a better prognosis regarding treatment success with single-dose methotrexate.[6] The further the ectopic pregnancy has advanced, the less likely single-dose methotrexate therapy will suffice. The patients that present in extremis or with hemodynamically instability have more risk of deterioration such as from hemorrhagic shock or other perioperative complications. Prognosis will thus hinge on early recognition and timely intervention. Fertility outcomes with tubal conservation surgeries remain debatable as some data suggests no significant difference in intrauterine pregnancy rates when comparing salpingectomy versus conservative tubal management.[7]

Complications

Women who present early in pregnancy and have testing suggestive of an ectopic pregnancy would jeopardize the viability of an intrauterine pregnancy if given Methotrexate.[4] Women who receive the single-dose Methotrexate regimen are at high risk of treatment failure if the hCG level does not decrease by 15% from day 4 to day 7 thus prompting second-dose regimen.[6] Women presenting with vaginal bleeding and pelvic pain may be misdiagnosed as an abortion in progress if the ectopic pregnancy is at the cervical os. The patient may have a cervical ectopic pregnancy and would thus run the risk of hemorrhage and potential hemodynamic instability if a dilation and curettage are performed.[4] Complications from management extend to treatment failure, in that women may present with/or develop hemodynamic instability which can result in death despite early operative interventions.  

Deterrence and Patient Education

Patients who seek medical treatment for ectopic pregnancy may need to discuss with their obstetrician which foods, supplements, and drugs to avoid when taking methotrexate as there may be decreased efficacy due to adverse interactions with the drug. Methotrexate may increase immunosuppression when paired with other medications, among other potential adverse side effects. Patient’s that undergo surgical interventions will need to adhere to the recommendations by their surgeon as to limit the risk of infection as well as other post-operative complications.

Enhancing Healthcare Team Outcomes

When faced with the possibility of an ectopic pregnancy, the health care team needs to work collectively and efficiently to diagnose accurately and treat the susceptible patient. Women typically will present to the ER with this ailment, accurate and timely identification starts from the initial encounter when triaged by the nursing or provider in triage staff. It is the provider's responsibility to include/consider ectopic pregnancy as a potential differential diagnosis in all sexually active women of childbearing age. A systematic review and meta-analysis were performed to compare and test the performance of current protocols used when managing women with a pregnancy of unknown location [8]. This study found that a logistic regression model, termed the M4 model, outperformed the comparison management protocols thus providing guidance for clinicians when treating patients with the pregnancy of unknown location [8]. This model may increase efficiency when considering unnecessary testing or treatment. Communication remains vital when the discussion takes place with consultants such as between obstetricians, emergency department physician, nurses, and pharmacists. Patient safety and patient-centered care must be implemented when discussing the patient's treatment plan with the obstetrician and when utilizing treatment/management protocols.


  • Image 8714 Not availableImage 8714 Not available
    Image courtesy S Bhimji MD
Attributed To: Image courtesy S Bhimji MD

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Ectopic Pregnancy - Questions

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Where do most ectopic pregnancies occur?



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A 17-year-old female presents with abdominal pain and nausea. Close examination reveals that she has extensive bruising on the flanks. This bruising started 24 hours ago. Which of the following disorders may explain these findings?



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A 16-year-old female, accompanied by her parents, presents to the emergency department with a chief complaint of lower abdominal pain and lightheadedness. In triage, she was found to be tachycardic with otherwise appropriate vital signs. The patient reports uncertainty when asked to date her last menstrual period. Her mother quickly interjects stating concern for appendicitis and that her daughter is not sexually active, is requesting a CT scan be obtained. The patient only reports nausea in addition to the pain and lightheadedness, is denying any fevers, urinary symptoms, or vaginal discharge. She is instructed to lie down supine on the stretcher to begin the exam. Upon laying flat, she begins to complain of a sudden sharp pain to her left shoulder. She also demonstrates some voluntary guarding with abdominal palpation. Which of the following is the most appropriate next step?



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An 18-year-old female, roughly eight weeks pregnant, presents for a scheduled visit. She discloses having vaginal bleeding and lower abdominal pain which began a few days ago. She is concerned she may be having a miscarriage. However, immediate ultrasound is done to determine the location of the pregnancy. Her vital signs at the time of presentation are within normal limits. Which finding would warrant consideration to treat with methotrexate?



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A woman has an ultrasound of the abdomen and pelvis. It reveals a living 16-week gestation located posterior to a normal-appearing 10 x 6 x 5.5 cm uterus. Both ovaries appear normal. No free fluid is noted. Which of the following is the most likely cause of these findings?



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A female presents with abdominal pain, tachycardia, and hypotension. Patient reports last menstrual period occurred eight weeks ago. Initial testing reveals human chorionic gonadotropin is present. A bedside ultrasound was performed demonstrating fluid in the peritoneum and the abdominal cavity. What is her most likely diagnosis?



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What advantage does a laparoscopic salpingostomy have over salpingectomy via laparotomy for an unruptured ectopic pregnancy?



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Which of the following would be the most likely factor to predispose a female to ectopic pregnancy?



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A woman who is 10 weeks pregnant presents with lower abdominal pain, shoulder pain, heavy cramping and vaginal bleeding. What is your diagnosis?



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What is the most common cause of ectopic pregnancy?



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Which of the following is the diagnostic test of choice for ectopic pregnancy?



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Which of the following can be used as medical treatment for small ectopic pregnancies that have not ruptured?



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Select the true statement about ectopic pregnancy.



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Which of the following is not a risk factor for ectopic pregnancy?



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What is the rate of ectopic pregnancy when all pregnancies are considered?



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What is a risk factor for a repeat ectopic pregnancy?



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What is not a factor associated with a high risk for an ectopic pregnancy?



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What is not associated with a moderately increased risk for ectopic pregnancy?



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Which of the following is not associated with a slightly increased risk for ectopic pregnancy?



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What is the possible etiology of smoking increasing the risk of an ectopic pregnancy?



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What is the percentage of women presenting with an ectopic pregnancy who do not give a history of any risk factors?



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Which of the following sequences of beta HCG levels would increase suspicion of an ectopic?



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What is true about distinguishing between an intrauterine pregnancy and an ectopic pregnancy?



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If a beta HCG is rising and is above 1800 mIU/mL, what would confirm an ectopic pregnancy?



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What is not a possible treatment for an ectopic pregnancy?



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What is the most common site of implantation of an ectopic pregnancy?



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A 24-year-old female has a sudden onset of low abdominal pain. She passes a clot per vagina and collapses. She is brought to the emergency department where fluid resuscitation is initiated. The abdomen is slightly distended and the left adnexa shows a tender soft mass. Ultrasound only is remarkable for fluid in the pouch of Douglas. The clot is examined and only shows decidua and coagulated blood without trophoblastic tissue or chorionic villi. What is the most probable diagnosis?



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A patient with a ruptured ectopic pregnancy and is going to surgery. Which of the following should be the highest nursing priority?



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A 17-year-old female presents to the with lower abdominal pain and vaginal bleeding. She states that she just missed her period and has been sexually active. She has a past medical history of gonorrhea and trichomonas, which have been treated successfully. She is allergic to penicillin. The physical exam reveals mild tenderness to palpation in the right lower quadrant. The pelvic exam reveals the presence of blood but no masses are felt. Her urinary human chorionic gonadotropin (hCG) is positive. Blood hCG level is 1,000 IU. The patient remains stable while waiting for an ultrasound. If this is an ectopic pregnancy, what blood hCG level will be seen in 24 hours?



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What is the most common cause of ectopic tubal gestation?



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How can ectopic pregnancy be fatal to the mother?



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Which abnormality of implantation is not dangerous (or deadly) for the fetus and/or mother?



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A 28-year-old woman notes irregular vaginal bleeding and pelvic pain. Pelvic examination suggest a "fullness" in the right oviduct. Which diagnosis must be excluded?



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A 20-year old female presents with vague lower abdominal pain and vaginal bleeding. She says she has not been feeling well for the past 3 days. She had unprotected sexual intercourse 6 weeks ago. She has a past history of pelvic inflammatory disease. The physical exam reveals a diffusely tender abdomen and a positive pregnancy test. A quick ultrasound reveals an empty uterus. With these findings, where is the second most common site for such a pregnancy?



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A 25-year-old female presents with vague lower abdominal pain and bleeding per vagina. She says she has not been feeling well for the past 3 days. She had unprotected sexual intercourse 6 weeks ago. The physical reveals a diffusely tender abdomen and a positive pregnancy test. An ultrasound scan reveals an empty uterus. Which of the following is known to be a risk factor for her condition?



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A 15-year-old female presents with persistent nausea, weight loss, fatigue, nipple soreness, and amenorrhea. The vomiting is worse on awakening. Both the mother and patient deny a history of any sexual activity. Today the patient has severe right lower quadrant (RLQ) abdominal pain and referred shoulder pain. Her blood pressure is 80/50 mmHg, heart rate 148 beats/min, respiratory rate 26, and pulse oximetry 98% on room air. On exam, her RLQ abdominal pain is 9/10, the abdomen is distended with diffuse tenderness, and her skin is pasty, pale, and cool to the touch. Her radial pulses are weak and thready. How should a nurse proceed in the care of this patient? Select all that apply.



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A female patient is admitted with a diagnosis of an ectopic pregnancy. What symptoms do these patients usually exhibit? Select all that apply.



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A 17-year old female patient presents to the emergency department with lower abdominal pain and vaginal bleeding. She states that she just missed her period for 14 days and has been sexually active. She has a past medical history of gonorrhea and trichomonas and has been successfully treated. The physical exam reveals mild tenderness to palpation in the right lower quadrant. The pelvic exam reveals the presence of vaginal blood, but no masses are felt. Her urinary HCG is positive. An abdominal ultrasound is ordered. Based on this figure, in which location is this pathology most commonly present?

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  • Image 6639 Not availableImage 6639 Not available
    Image courtesy S Bhimji MD
Attributed To: Image courtesy S Bhimji MD



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Ectopic Pregnancy - References

References

Panelli DM,Phillips CH,Brady PC, Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review. Fertility research and practice. 2015;     [PubMed]
Carusi D, Pregnancy of unknown location: Evaluation and management. Seminars in perinatology. 2018 Dec 20;     [PubMed]
Maheux-Lacroix S,Li F,Bujold E,Nesbitt-Hawes E,Deans R,Abbott J, Cesarean Scar Pregnancies: A Systematic Review of Treatment Options. Journal of minimally invasive gynecology. 2017 Sep - Oct;     [PubMed]
Chukus A,Tirada N,Restrepo R,Reddy NI, Uncommon Implantation Sites of Ectopic Pregnancy: Thinking beyond the Complex Adnexal Mass. Radiographics : a review publication of the Radiological Society of North America, Inc. 2015 May-Jun;     [PubMed]
ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstetrics and gynecology. 2018 Mar;     [PubMed]
Hsu JY,Chen L,Gumer AR,Tergas AI,Hou JY,Burke WM,Ananth CV,Hershman DL,Wright JD, Disparities in the management of ectopic pregnancy. American journal of obstetrics and gynecology. 2017 Jul;     [PubMed]
Bobdiwala S,Saso S,Verbakel JY,Al-Memar M,Van Calster B,Timmerman D,Bourne T, Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis. BJOG : an international journal of obstetrics and gynaecology. 2019 Jan;     [PubMed]
Boots CE,Hill MJ,Feinberg EC,Lathi RB,Fowler SA,Jungheim ES, Methotrexate does not affect ovarian reserve or subsequent assisted reproductive technology outcomes. Journal of assisted reproduction and genetics. 2016 May     [PubMed]

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