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Medication

Medication Summary

The standard medical treatment for unruptured ectopic pregnancy is methotrexate therapy. Methotrexate is an antineoplastic agent that inhibits cell proliferation by destroying rapidly dividing cells. It acts as a folate antagonist.^[71]The decision to use this agent should be made in conjunction with, if not by, the consulting obstetric specialist.

The ideal candidate for medical treatment should have the following:

Hemodynamic stability
No severe or persisting abdominal pain
The ability to follow up multiple times
Normal baseline liver and renal function test results.

Contraindications

Absolute contraindications to methotrexate therapy include the following:

Existence of an intrauterine pregnancy
Immunodeficiency
Moderate to severe anemia, leukopenia, or thrombocytopenia
Sensitivity to methotrexate
Active pulmonary or peptic ulcer disease
Clinically important hepatic or renal dysfunction
Breastfeeding
Evidence of tubal rupture

Relative contraindications that indicate likely failure of methotrexate therapy include the following:

Sonogram findings of an ectopic gestational sac greater than 4cm in size (or 3.5cm, if the ectopic pregnancy has fetal heart motion)
An initial beta–human chorionic gonadotropin (β-HCG) concentration of greater than 5000 mIU/mL
Significant free fluid
Fetal cardiac activity

Regimen

The multiple-dose regimen for methotrexate consists of the administration of daily IM doses of 1 mg/kg, with leucovorin (folinic acid, which reduces side effects) given on alternating days, until there is a 15% decline in β-HCG over 2 days.

The single-dose regimen consists of 1 dose of methotrexate 50 mg/m², followed by a repeat β-HCG measurement at day 4, and another dose of methotrexate 50 mg/m² if the β-HCG has declined less than 15% between days 4 and 7.

Efficacy and adverse effects

Both treatment regimens show an efficacy similar to that of surgical management for unruptured ectopic pregnancies in the ideal patient population. Common side effects include an increase in abdominal girth, vaginal bleeding or spotting, abdominal pain, gastrointestinal (GI) symptoms, stomatitis, and dizziness. Rare side effects include severe neutropenia, reversible alopecia, and pneumonitis.^[71]

Class Summary

Antimetabolite agents are used to terminate pregnancy.

Methotrexate (Trexall, Rheumatrex)

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Methotrexate is used for the treatment of unruptured tubal pregnancy and for persistent disease after salpingostomy

Class Summary

Vitamins are used to correct folic acid deficiency resulting from use of folic acid antagonists.

Leucovorin

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Leucovorin is used with folic acid antagonists, such as methotrexate. It is a reduced form of folic acid that does not require enzymatic reduction reaction for activation. It allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis. It is an important cofactor for the enzymes used in production of red blood cells. Leucovorin (folinic acid, which reduces adverse effects) is given alternating with methotrexate days, until there is a 15% decline in β-HCG over 2 days.

Class Summary

Vasopressors are used for their alpha1 and beta1 properties and for stimulating vasoconstriction in peripheral circulation.

Vasopressin (Pitressin)

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Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. In linear salpingostomy, the involved tube is identified and freed from surrounding structures. To minimize bleeding, a dilute solution containing 20 U of vasopressin in 20 mL of isotonic sodium chloride solution may be injected into the mesosalpinx just below the ectopic pregnancy. Make sure that the needle is not in a blood vessel by aspirating before injecting, because intravascular injection of vasopressin may precipitate acute arterial hypertension and bradycardia.

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Media Gallery

Sites and frequencies of ectopic pregnancy. By Donna M. Peretin, RN. (A) Ampullary, 80%; (B) Isthmic, 12%; (C) Fimbrial, 5%; (D) Cornual/Interstitial, 2%; (E) Abdominal, 1.4%; (F) Ovarian, 0.2%; and (G) Cervical, 0.2%.
Laparoscopic picture of an unruptured right ampullary tubal pregnancy; bleeding out of the fimbriated end has resulted in hemoperitoneum.
A 12-week interstitial gestation, which eventually resulted in a hysterectomy. Courtesy of Deidra Gundy, MD, Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU).
A 12-week interstitial gestation, which eventually resulted in a hysterectomy. Courtesy of Deidra Gundy, MD, Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU).
An endovaginal sonogram reveals an intrauterine pregnancy at approximately 6 weeks. A yolk sac (ys), gestational sac (gs), and fetal pole (fp) are depicted.
Linear incision being made at the antimesenteric side of the ampullary portion of the fallopian tube.
Laparoscopic picture of an ampullary ectopic pregnancy protruding out after a linear salpingostomy was performed.
Schematic of a tubal gestation being teased out after linear salpingostomy.

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Author

Vicken P Sepilian, MD, MSc Medical Director, Reproductive Endocrinology and Infertility, CHA Fertility Center

Vicken P Sepilian, MD, MSc is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Ellen Wood, DO, FACOG Voluntary Assistant Professor, University of Miami, Leonard M Miller School of Medicine

Ellen Wood, DO, FACOG is a member of the following medical societies: American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Frances E Casey, MD, MPH Associate Professor, Director of Family Planning Services, Department of Obstetrics and Gynecology, VCU Medical Center

Frances E Casey, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Reproductive Health Professionals, National Abortion Federation, Physicians for Reproductive Health, Society of Family Planning

Disclosure: Nothing to disclose.

Chief Editor

Michel E Rivlin, MD Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, Royal College of Surgeons of Edinburgh, Royal College of Obstetricians and Gynaecologists

Disclosure: Nothing to disclose.

Acknowledgements

A David Barnes, MD, PhD, MPH, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)

A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Robert K Zurawin, MD Associate Professor, Director of Baylor College of Medicine Program for Minimally Invasive Gynecology, Director of Fellowship Program, Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Baylor College of Medicine

Robert K Zurawin, MD is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Harris County Medical Society, North American Society for Pediatric and Adolescent Gynecology, and Texas Medical Association

Disclosure: Johnson and Johnson Honoraria Speaking and teaching; Conceptus Honoraria Speaking and teaching; ConMed Consulting fee Consulting

Ectopic Pregnancy Medication

Medication Summary

Antineoplastics, Antimetabolite