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RARE TYPES OF ECTOPIC PREGNANCY

Abdominal Pregnancy

The incidence of abdominal pregnancy is estimated at 1 in 8,000 births and represents 1.4% of all ectopic pregnancies. The prognosis is poor, with an estimated

maternal mortality rate of 5.1 per 1,000 cases. The risk of dying from an abdominal pregnancy is 7.7 times higher than from other forms of ectopic pregnancy. The high rate of morbidity and mortality from abdominal pregnancy often results from a delay in diagnosis.

Abdominal pregnancies can be categorized as primary or secondary. These ectopic pregnancies may become apparent throughout gestation, from the first trimester to fetal viability. Symptoms may vary from those considered normal for pregnancy to severe abdominal pain, intraabdominal hemorrhage, and hemodynamic instability.

Primary abdominal pregnancies are rare and are thought to occur as a result of primary peritoneal implantation. They usually abort early in the first trimester due to hemorrhagic disruption of the implantation site and hemoperitoneum. Secondary abdominal pregnancies occur with reimplantation after a partial tubal abortion or

intraligamentary extension following tubal rupture. Historical criteria to distinguish between primary and secondary abdominal pregnancies are moot, because treatment is directed by the clinical picture.

Ultrasonography is the diagnostic tool of choice and usually can identify the empty uterus along with the extrauteral products of conception. If the fetus is near viability, hospitalization is recommended. If time permits, bowel preparation, administration of prophylactic antibiotics, and adequate blood replacement should be made

available prior to an operative delivery. Unless the placenta is implanted on major vessels or vital structures, it should be removed. Although complications may occur, including sepsis, abscess formation, secondary hemorrhage, intestinal obstruction, wound dehiscence, amniotic fluid cyst formation, hypofibrinogenemia, and

preeclampsia, the placenta can be left in place to prevent further hemorrhage at the time of surgery. In contrast to the typical tubal ectopic pregnancy, methotrexate is unlikely to accelerate retained placental absorption, because the trophoblastic cells are no longer actively dividing.

Ovarian Pregnancy

Ovarian pregnancy, the most common form of abdominal pregnancy, is rare, accounting for less than 3% of all ectopic gestations. Clinical findings are similar to those of tubal ectopic gestations: abdominal pain, amenorrhea, and abnormal vaginal bleeding. In addition, hemodynamic instability as a result of rupture occurs in 30% of patients.

Women with ovarian pregnancies are usually young and multiparous, but the factors leading to ovarian pregnancies are not clear.

The diagnosis usually is made by the pathologist, because many ovarian pregnancies are mistaken for a ruptured corpus luteum or other ovarian tumors. Only 28% of cases were diagnosed correctly at time of laparotomy. The recommended treatment is cystectomy, wedge resection, or oophorectomy during laparotomy, although laparoscopic removal has been successful.

Cornual Pregnancy

Cornual or interstitial pregnancy accounts for 4.7% of ectopic gestations and carries a 2.2% maternal mortality. Almost all cases are diagnosed after the patient is symptomatic. The most frequent symptoms are menstrual aberration, abdominal pain, abnormal vaginal bleeding, and shock, resulting from the brisk hemorrhage associated with uterine rupture. Due to myometrial distensibility, rupture is usually delayed, occurring at 9 to 12 weeks gestation.

A unique risk factor for interstitial pregnancy is previous salpingectomy, present in about 25% of patients.

Only a high index of suspicion and repeated ultrasonographic examination with Doppler flow studies allows early diagnosis. With a timely early diagnosis, alternatives to the traditional cornual resection during laparotomy have been performed successfully. These include laparoscopic cornual resection, systemic methotrexate

administration, local injection of methotrexate, potassium chloride injection, and removal by hysteroscopy. Regardless of the initial treatment attempted, if uncontrolled hemorrhage occurs, immediate hysterectomy is warranted.

Cervical Pregnancy

The incidence of cervical pregnancy ranges from 1 in 2,500 to 1 in 12,422 pregnancies. The most common predisposing factor is a prior dilation and curettage, present in 68.6% of patients. Interestingly, 31% of these were performed for termination of pregnancy. Other predisposing factors implicated in cervical pregnancies are

previous cesarean delivery and IVF.

The most common initial symptom of cervical pregnancy is painless vaginal bleeding. These ectopics usually are diagnosed incidentally during routine ultrasonography or at the time of surgery for a suspected abortion in progress. In reported cases, 91% of patients sought treatment for vaginal bleeding, and 29.2% had massive

bleeding. Not surprisingly, abdominal pain occurred with vaginal bleeding in only 25.8% of cases. The cervix is usually enlarged, globular, or distended. On occasion, it appears cyanotic, hyperemic, and soft in consistency. Sonography and magnetic resonance imaging have improved diagnosis of cervical pregnancy. Up to 81.8% of patients have been diagnosed correctly with ultrasonographic identification of the gestational sac in the cervix below a closed internal cervical os, with trophoblastic invasion into the endocervical tissue.

When the patient is hemodynamically stable, conservative therapy commonly is employed. There are no large studies, only several case series. These have shown that use of methotrexate and uterine artery embolization are safe and effective for treatment in the stable patient with a cervical pregnancy. Systemic and local treatment with various agents carries an overall success rate of 81.3%. Unfortunately, massive hemorrhage may occur despite conservative measures, and hysterectomy is warranted.

Heterotopic Pregnancy

Heterotopic pregnancy is the coexistence of an intrauterine and ectopic gestation. In 1948, the spontaneous heterotopic pregnancy rate was calculated as 1 in 30,000 pregnancies, based on an ectopic pregnancy incidence of 0.37% and dizygous twinning rate of 0.8%. In the 1980s, the calculation rose to 1 in 10,000 due to an

increased ectopic pregnancy rate. Today, heterotopic pregnancies occur in 1 in 3,889 to 1 in 6,778 pregnancies. In a review of 66 heterotopic pregnancies by Reece et al., 93.9% were tubal and 6.1% ovarian.

Simultaneous existence of intra- and extrauterine pregnancies poses several diagnostic pitfalls. Heterotopic pregnancies are diagnosed in most cases after clinical signs and symptoms develop, and 50% of patients are admitted for emergency surgery following rupture. The delay in diagnosis is secondary to the finding of an intrauterine pregnancy, with the assumption that any symptoms will be self-limited.

Similar to tubal ectopic pregnancies, the most common complaint is lower abdominal pain. Routine ultrasonography detects only about 50% of tubal heterotopic

pregnancies, and the remainder are diagnosed during laparoscopy or laparotomy when patients become symptomatic. Serial levels of the ß subunit of hCG are not helpful due to the effect of the intrauterine pregnancy.

If patients are hemodynamically unstable, exploratory laparotomy is warranted. If the diagnosis is suspected or the patient is symptomatic but hemodynamically stable, laparoscopy can be performed. Expectant management is not recommended, because ß-hCG levels cannot be monitored adequately. Systemic methotrexate is

contraindicated if a viable intrauterine pregnancy is present and desired. Local injection of methotrexate with potassium chloride has been noted successful in a small case series.

SUMMARY POINTS

In most circumstances, ectopic pregnancy can be diagnosed before symptoms develop and treated definitively with few complications.

Quantitative ß-hCG testing, ultrasonography, and curettage allow early diagnosis of ectopic pregnancy and use of medical therapy as the initial therapy option.

Conservative surgical therapy and medical therapy for ectopic pregnancy are comparable in terms of success rates and subsequent fertility. Medical therapy is the preferred choice because of the freedom from surgical complications and lower cost.

Surgery is the treatment of choice for hemorrhage, medical failures, neglected cases, and when medical therapy is contraindicated.

Multiple-dose methotrexate is preferable to single-dose methotrexate, direct injection, or tubal cannulation and is the first choice for unruptured, uncomplicated ectopic pregnancy.

Laparoscopic salpingostomy or salpingectomy is favored for cases of intraabdominal hemorrhage, medical failure, neglected cases, and complex cases when medical therapy is contraindicated.

Prophylactic postoperative systemic methotrexate (a single dose) can prevent virtually all cases of persistent ectopic pregnancy following salpingostomy.

Salpingectomy prior to IVF decreases ectopic pregnancy incidence while increasing pregnancy rates in select patients with preexisting tubal disease.

REFERENCES Incidence

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Pathogenesis

Bone NL, Greene RR. Histological study of uterine tube with tubal pregnancy: a search for evidence of previous injection. Am J Obstet Gynecol 1961;82:1166.

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Risk Factors

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Signs and Symptoms

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Diagnosis

Buster JE, Carson SA. Ectopic pregnancy: new advances in diagnosis and treatment. Curr Opin Obstet Gynecol 1995;7:168–176.

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Shalev E, Yarom I, Bustan M, et al. Transvaginal sonography as the ultimate diagnostic tool for the management of ectopic pregnancy: experience with 840 cases. Fertil Steril 1998;69:62–65.

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Treatment for Ectopic Pregnancy Medical Management

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Surgical Treatment

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Ectopic Pregnancy and Assisted Reproductive Technology

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Camus E, Poncelet C, Goffinet F, et al. Pregnancy rates after in-vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a meta-analysis of published comparative studies. Hum Reprod 1999;14:1243–1249.

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Expectant Management

Fernandez H, Lelaidier C, Baton C, et al. Return of reproductive performance after expectant management and local treatment for ectopic pregnancy. Hum Reprod 1991;6:1474–1477.

Garcia AJ, Aubert JM, Sama J, et al. Expectant management of presumed ectopic pregnancies. Fertil Steril 1987;48:395–400.

Shalev E, Peleg D, Tsabari A, et al. Spontaneous resolution of ectopic tubal pregnancy: natural history. Fertil Steril 1995;63:15–19.

Ylöstalo P, Cacciatore B, Korhonen J, et al. Expectant management of ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol 1993;49:83–84.

Cost Analysis

Alexander JM, Rouse DJ, Varner E, et al. Treatment of the small unruptured ectopic pregnancy: a cost analysis of methotrexate versus laparoscopy. Obstet Gynecol 1996;88:123–127.

Mol BW, Hajenius PJ, Engelsbel S, et. al. Treatment of tubal pregnancy in the Netherlands: an economic comparison of systemic methotrexate administration and laparoscopic salpingostomy. Am J Obstet Gynecol 1999;181:945–951.

Mol BWJ, Hajenius PJ, Engelsbel S, et al. An economic evaluation of laparoscopy and open surgery in the treatment of tubal pregnancy. Acta Obstet Gynecol Scand 1997;76:1–5.

Stovall TG, Bradham DD, Ling FW, et al. Cost of treatment of ectopic pregnancy: single-dose methotrexate versus surgical treatment. J Womens Health 1994;3:445–450.

Washington AE, Katz P. Ectopic pregnancy in the United States: economic consequences and payment source trends. Obstet Gynecol 1993;81:287–292.

Yao M, Tulandi T, Kaplow M, et al. A comparison of methotrexate versus laparoscopic surgery for treatment of ectopic pregnancy: a cost analysis. Hum Reprod 1996;11:2762–2766.

Rare Types of Ectopic Pregnancy

Atrash HK, Friede A, Hogue CJR. Abdominal pregnancy in the United States: frequency and maternal mortality. Obstet Gynecol 1987;69:333–337.

Goldenberg M, Bider D, Oelsner G, et al. Treatment of interstitial pregnancy with methotrexate via hysteroscopy. Fertil Steril 1992;58:1234–1236.

Grimes HG, Nosal RA, Gallagher JC. Ovarian pregnancy: a series of 24 cases. Obstet Gynecol 1983;61:174–180.

Hallatt JG. Primary ovarian pregnancy: a report of twenty-five cases. Am J Obstet Gynecol 1982;143:55–60.

Reece EA, Petrie RH, Sirmans MF, et al. Combined intrauterine and extrauterine gestations: a review. Am J Obstet Gynecol 1983;146:323–330.

Timor-Tritsch IE, Monteagudo A, Mandeville EO, et al. Successful management of viable cervical pregnancy by local injection of methotrexate. Am J Obstet Gynecol 1994;170:737–739.

Ushakov FB, Elchalal U, Aceman PJ, et al. Cervical pregnancy: past and future. Obstet Gynecol 1996;52:45–59.

Chapter 6 Genetics and Prenatal Diagnosis

Danforth’s Obstetrics and Gynecology

Chapter 6

Kenneth Ward