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Medical Management of Ectopic Pregnancy

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Ectopic pregnancy refers to the pregnancy occurring outside the uterine cavity, predominantly i.e. 90% of them in the fallopian tube. Ectopic pregnancy affects 11 in 1000 pregnancies and is a …

Ectopic pregnancy refers to the pregnancy occurring outside the uterine cavity, predominantly i.e. 90% of them in the fallopian tube. Ectopic pregnancy affects 11 in 1000 pregnancies and is a significant cause of morbidity and at times mortality in the first trimester of pregnancy. In a 20-year longitudinal study on ectopic pregnancy in a defined
population of women aged 15e39 years the rate of ectopic pregnancy per 1000 diagnosed conceptions increased
from 5.8 during 1960e4 to 11.1 during 1975e9. The mean annual incidence of ectopic pregnancy per 1000 women
increased from 0.6 to 1.2 during the same period. The numbers of ectopic pregnancies per 1000 diagnosed
conceptions increased with increasing age of the women and were 4.1 in the teenage group, 6.9 in women aged
20e29 years, and 12.9 in women aged 30e39.

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  • 1. Medical Management of Ectopic Pregnancy
  • 2. Apollo Medicine 2012 September Volume 9, Number 3; pp. 198e201 Review Article Medical management of ectopic pregnancy Preeti Shettya,*, Aparajitab, Neha Sharmab ABSTRACT Ectopic pregnancy refers to the pregnancy occurring outside the uterine cavity, predominantly i.e. 90% of them in the fallopian tube. Ectopic pregnancy affects 11 in 1000 pregnancies and is a significant cause of morbidity and at times mortality in the first trimester of pregnancy. In a 20-year longitudinal study on ectopic pregnancy in a defined population of women aged 15e39 years the rate of ectopic pregnancy per 1000 diagnosed conceptions increased from 5.8 during 1960e4 to 11.1 during 1975e9. The mean annual incidence of ectopic pregnancy per 1000 women increased from 0.6 to 1.2 during the same period. The numbers of ectopic pregnancies per 1000 diagnosed conceptions increased with increasing age of the women and were 4.1 in the teenage group, 6.9 in women aged 20e29 years, and 12.9 in women aged 30e39. Copyright © 2012, Indraprastha Medical Corporation Ltd. All rights reserved. Keywords: Tubal pregnancy, Age, Hemoperitoneum, Laparoscopy, Methotrexate INTRODUCTION MEDICAL MANAGEMENT Ectopic pregnancy presents a major health problem for women of childbearing age. It is the result of a flaw in human reproductive physiology that allows the conceptus to implant and mature outside the endometrial cavity, which ultimately ends in death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a life-threatening situation and it may adversely affect the woman’s future ability to reproduce.1 The most common place that ectopic pregnancy occurs is in one of the Fallopian tubes (a so-called tubal pregnancy). These are the tubes that transport the egg from the ovary to the uterus. Ectopic pregnancies also can be found on the outside of the uterus, on the ovaries, or attached to the bowel. The most serious complication of an ectopic pregnancy is intra-abdominal hemorrhage (severe bleeding). In the case of a tubal pregnancy, for example, as the products of conception continue to grow in the Fallopian tube, the tube expands and eventually ruptures. This can be very dangerous because a large artery runs on the outside of each Fallopian tube. If the artery ruptures, the woman can bleed severely.2 As health care costs continue to rise. It has become increasingly important to develop new approaches which have the potential to reduce cost. It is equally important for any of these newer methods to provide equal or better clinical outcomes. In the case of ectopic pregnancy treatment, these clinical outcomes are fairly well defined and include treatment success rate, tubal patency following treatment, treatment cost, treatment side effects, subsequent intrauterine pregnancy rates and recurrent ectopic pregnancy rates.3 a RISK FACTORS Risk factors for ectopic pregnancy include: d Age: The overall risk of ectopic pregnancy was 2.3%. The incidence of ectopic pregnancy showed a steady increase with the increase in maternal age at conception from 1.4% of all pregnancies at the age of 21 years to 6.9% of pregnancies in women aged 44 years or more (Fig. 1).4 Consultant, Apollo Hospital, Bannerghatta Road, Bangalore 560076, bTrainee, AHERF, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi 110076, India. * Corresponding author. Tel.: þ91 8041106422, email: preetipshetty@yahoo.co.in Received: 29.5.2012; Accepted: 29.6.2012; Available online: 5.7.2012 Copyright Ó 2012, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2012.06.009
  • 3. Medical management of ectopic pregnancy Fig. 1 Risk of ectopic pregnancy according to maternal age at conception. d d d d d d d d d Use of an intrauterine device (IUD), a form of birth control, at the time of conception. History of pelvic inflammatory disease (PID). Sexually-transmitted diseases such as chlamydia and gonorrhea. Congenital abnormality (problem present at birth) of the fallopian tube. History of pelvic surgery (since scarring may block the fertilized egg from leaving the fallopian tube). History of ectopic pregnancy. Unsuccessful tubal ligation (surgical sterilization) or tubal ligation reversal. Fertility drugs. Infertility treatments such as in vitro fertilization (IVF). SYMPTOMS Common symptoms include: d Light vaginal bleeding d Nausea and vomiting d Lower abdominal pain d Sharp abdominal cramps d Pain on one side of the body d Dizziness or weakness d Pain in the shoulder, neck, or rectum If the fallopian tube ruptures, the pain and bleeding could be severe enough to cause fainting.5 Review Article 199 rupture allows for outpatient treatment, reducing the risk of major complications and future infertility. Delay in diagnosis might lead to rupture, resulting in intra-abdominal hemorrhage, need for laparotomy, blood transfusion, and death. Abdominal pain or vaginal bleeding in the first trimester is the only clinical signs and symptoms of ectopic pregnancy, but they are not sensitive or specific. Most women with such symptoms have normal intrauterine pregnancies; therefore, diagnosis of ectopic pregnancy must be accurate and timely, but should use methods that do not interrupt viable intrauterine pregnancies. Several published protocols for diagnosing women at risk for ectopic pregnancy use clinical examination, transvaginal ultrasonography, serum quantitative hCG, and serum progesterone selectively and in various permutations, but no approach has been established to be superior to others. Identification of ectopic pregnancy can be difficult by ultrasound, so the most efficient way to rule out ectopic pregnancy is to diagnose intrauterine pregnancy. The sensitivity of ultrasound for diagnosing intrauterine pregnancy approaches 100% in gestations greater than 5.5 weeks. Often, exact gestational age is not known at evaluation and serum hCG is used as a surrogate marker for it. The discriminatory zone is defined as the serum hCG level above which ultrasound is expected to detect a viable intrauterine pregnancy. Often used in the evaluation of early pregnancy, the hCG discriminatory zone is based on the assumption that a serum b-hCG level exceeding 1000e2000 mIU/mL in a woman who has a normal intrauterine pregnancy should be accompanied by a gestational sac that is visible via transvaginal Ultra Sonography.6 When an intrauterine pregnancy is not visualized on ultrasound with hCG above the discriminatory zone, we presume the gestation is nonviable or ectopic. In those circumstances, a D&C is done to confirm intrauterine pregnancy. Without endometrial curettings with chorionic villi, ectopic pregnancy is presumed. Transvaginal ultrasound and quantitative hCGs are routinely used in diagnostic strategies, but there is debate about which should be done first. There has been much literature suggesting serum progesterone might aid diagnosis of ectopic pregnancy. A single serum progesterone level above 25 ng/mL is strongly associated with a normal intrauterine pregnancy, whereas levels below 5 ng/mL are associated with abnormal gestations (ectopic or abnormal intrauterine pregnancy).7 TREATMENT DIAGNOSIS Surgical treatment Despite increasing incidence, the mortality rate associated with ectopic pregnancy has fallen dramatically, Thanks to improved diagnostic methods. Early detection before tubal If you have an ectopic pregnancy that is causing severe symptoms, bleeding, or high hCG levels, surgery is usually
  • 4. 200 Apollo Medicine 2012 September; Vol. 9, No. 3 needed. This is because medicine is not likely to work and a rupture becomes more likely as time passes. When possible, laparoscopic surgery that uses a small incision is done. For a ruptured ectopic pregnancy, emergency surgery is needed.8 The current gynecology supports the use of a laparoscopic approach prospective (Fig. 2) and randomized clinical trials demonstrate that the laparoscopic approach when compared with laparotomy is associated with less estimated blood loss, shorter postoperative hospitalization and reduced cost. The two approaches are similar with respect to tubal patency rates and intrauterine pregnancy rates.3 Medical treatment Until the mid 1980s treatment for ectopic pregnancy was exclusively surgical. During that decade medical management with drugs like methotrexate was first introduced to avoid the need for surgical intervention. The decision about whether to use medical therapy for ectopic, which patients should be treated, which protocol to be used and when to convert to surgery during medical treatment can be difficult choices. In determining whether a patient is a candidate for medical therapy, a number of factors must be considered. She must be hemodynamically stable, with no signs or symptoms of active bleeding or hemoperitoneum. Furthermore, she must be reliable, compliant, and able to return for follow-up. Another factor is size of the gestation, which should not exceed 3.5 cm at its greatest dimension on US measurement. She should not have any contraindications to the use of methotrexate.9 Initial protocols required prolonged hospitalization and multiple doses of methotrexate. They were associated with significant side effects. Refinement in protocols have allowed outpatient therapy that often require only single dose of methotrexate and are associated with fewer side Shetty et al. effects. Protocols using other agents like potassium chloride, Dactinomycin, prostaglandins and RU 486 for medical management have also been developed. These agents may be administered by direct injection into the ectopic sac or in the cases of Dactinomycin, prostaglandins and RU 486 given systemically by oral, intramuscular or intravenous routes. However due to limited experience with these agents their use must be considered experimental till additional data are available. Evidence shows little difference in the psychological outcomes when comparing surgical and medical methods of management of ectopic pregnancy treatment with single dose methotrexate in ectopic pregnancy is associated with sparing on treatment costs.10 Monitoring and follow-up of patients Following treatment (medical or surgical) patients are examined weekly and serial hCG levels should be taken until the levels are undetectable. If the levels do not decline, the patient can be treated with a second course of methotrexate or with a post-surgical course of methotrexate; in this case subsequent monitoring is with weekly serial hCG and transvaginal ultrasound until hCG is <10 U/L (<10 mU/mL). Increasing levels thereafter are treated surgically. Once the serum hCG levels are undetectable, no further monitoring is needed. While some experts recommend follow-up hCG only after medical management or salpingostomy, persistent trophoblastic tissue has been reported after salpingectomy as well. Therefore, it is good practice to follow-up hCG even after salpingectomy, although it might not be as crucial as after salpingostomy or medical management. Patients with a history of a previous ectopic pregnancy should be encouraged to present and be evaluated early with subsequent pregnancies to rule out the recurrence of an ectopic pregnancy. Surgery v/s medicine d d d Fig. 2 Ectopic pregnancy laparoscopic picture of an unruptured right ampullary tubal pregnancy with bleeding out of the fimbriated end resulting in hemoperitoneum.1 Methotrexate is usually the first treatment choice for ending an early ectopic pregnancy. Regular follow-up blood tests are needed for days to weeks after the medicine is injected. There are different types of surgery for a tubal ectopic pregnancy-when possible, only a slit is made in the fallopian tube (salpingostomy), rather than removing a section of the tube (salpingectomy). On average, salpingostomy is equal to methotrexate (for an early ectopic pregnancy) in terms of being effective and preserving a woman’s ability to become pregnant in the future.
  • 5. Medical management of ectopic pregnancy d Although surgery is a faster treatment, it can cause scar tissue that could cause future pregnancy problems. Tubal surgery may damage the fallopian tube, depending on where and how big the embryo is and the type of surgery needed.8 CONCLUSION Data shows that change in life style, late marriages, increases in maternal age at conception are the main causes of Ectopic pregnancies. Diagnosis of ectopic pregnancy must be accurate and timely, but should use methods that do not interrupt viable intrauterine pregnancies, diagnosing women at risk for ectopic pregnancy use clinical examination, transvaginal ultrasonography, serum quantitative hCG, and serum progesterone selectively.7 Ectopic Pregnancy can be treated both surgically and medically. Women should be carefully advised when ever possible of the advantages and disadvantages associated with each approach used for treatment of ectopic pregnancy and participate fully in selection of the appropriate treatment. CONFLICTS OF INTEREST All authors have none to declare. REFERENCES 1. Vicken P Sepilian, MD, MSc, Medical Director. Reproductive Endocrinology and Infertility, CHA Fertility Center. Ectopic pregnancy. http://emedicine.medscape.com/article/258768overview. Review Article 201 2. Stephen Metz, MD. Ectopic pregnancy. http://www. emedicinehealth.com/ectopic_pregnancy/article_em.htm. 3. Stovall Thomas G. Medical Management of Ectopic Pregnancy, http://journals.lww.com/co-obgyn/Abstract/1994/12000/ Medical_management_of_ectopic_pregnancy.7.aspx; 1994. 4. Maternal age and fetal loss: population based register linkage study. BMJ, http://www.bmj.com/content/320/7251/1708? ijkey¼2dc682363be59c50da8c3d644e26de349ec20aa7&key type2¼tf_ipsecsha&linkType¼ABST&journalCode¼bmj& resid¼320/7251/1708; 2000. 5. Web MD. Health and Ectopic Pregnancy, http://www.webmd. com/baby/pregnancy-ectopic-pregnancy; 2012. 6. Is the hCG discriminatory zone a reliable indicator of intrauterine or Ectopic Pregnancy Doubilet PM, Benson CB. Further evidence against the reliability of the human chorionic gonadotropin discriminatory level. J Ultrasound Med. 2011;30(12):1637e1642. http://www.obgmanagement.com/ article_pages.asp?aid¼10193&uid¼. 7. Gracia Clarisa R MD, Barnhart Kurt T MD, MSCE. Diagnosing Ectopic Pregnancy: Decision Analysis Comparing Six Strategies, http://journals.lww.com/greenjournal/Abstract/ 2001/03000/Diagnosing_Ectopic_Pregnancy__Decision_ Analysis.28.aspx; 2001. 8. Health and Pregnancy. Ectopic Pregnancy e Treatment Overview, http://www.webmd.com/baby/tc/ectopic-pregnancy-treatmentoverview; June 21, 2012. 9. Medscape Sepilian Vicken P. Ectopic Pregnancy Treatment & Management, http://emedicine.medscape.com/article/258768treatment; Mar 26, 2012. 10. American Society for Reproductive Health. Medical Treatment of Ectopic Pregnancy, http://www.asrm.org/uploadedFiles/ ASRM_Content/News_and_Publications/Practice_Guide lines/Technical_Bulletins/Medical_treatment(1).pdf; 2008.
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