Ectopic Pregnancy: Causes, Diagnosis and Treatment

An ectopic pregnancy is defined as a gestation that implants outside of the uterus. The most common site is in the fallopian tube, but it can also occur in the ovary, the cervix, outer surface of the uterus or elsewhere with the abdomen. An exrauterine, intraabdominal ectopic pregnancy can even develop into an advanced and even full term gestati. However, such fetuses are usually severely developmentally compromized and rarely, if ever survive.

About 1:200 naturally conceived pregnancies and 1:30 IVF gestations are ectopic. On very rare occasions (1:2,000), a tubal ectopic pregnancy occurs in combination with another pregnancy (usually in the uterus. Timely, early ssurgical removal of the tubal component often is followed by the intrauterine pregnancy progressing normally to delivery at term.

Ectopic pregnancy is one of the most dangerous complications of gestation. If undetected, the pregnancy will continue to grow and will typically rupture; resulting in calamitous intra-abdominal bleeding. If not treated quickly, such an event could be fatal.

Monitoring pregnancies both hormonally and with ultrasound technology now makes it possible to completely prevent catastrophic events associated with ectopic pregnancies. Within the last two decades, treatment of ectopic pregnancies has evolved from emergency surgery with tubal removal and blood transfusion, to out-patient surgery with tubal repair or even treatment with medication. The key with ectopic pregnancy is to diagnose early and manage the outcome instead of waiting for events to unfold.

The fertilization of the human egg normally takes place within the fallopian tube. The embryo then takes about 5 to 6 days to complete its journey to the uterus, where it implants into the endometrium. Anything that delays the passage of the embryo down the fallopian tube can result in the embryo hatching and sending its “root system” into the wall of the fallopian tube and initiating growth within the tube. One of the most common predisposing factors is pelvic inflammatory disease (PID) in which microorganisms, such as Chlamydia and Gonococcus, damage the inner lining (endosalpinx) and eventually also the muscular walls of the tube(s) by creating scar tissue.

The endosalpinx has a very complex and delicate internal architecture, with small hairs and secretions that help to propel the embryo toward the uterine cavity. Once damaged, this lining does not regenerate. This is one of the reasons why women who manage to conceive following surgery to unblock fallopian tubes damaged by PID, have about a 1 in 4 chance of a subsequent pregnancy developing within the fallopian tube. Another cause of ectopic pregnancies are congenital malformations of the fallopian tube associated with shortening of, or small pockets and side channels within, the tube. These can interrupt the smooth passage of the embryo down the fallopian tube. There has even been some suggestion that premature appearance of hormones like progesterone, which relax muscle contractions within the fallopian tube, may also create an increased risk of ectopic pregnancy.

A woman who has had one ectopic pregnancy has an almost four-fold higher risk of another ectopic implantation in a future pregnancy. With every subsequent ectopic, this risk increases dramatically. Since the lining of the fallopian tube does not represent an optimal site for healthy implantation, a large percentage of pregnancies that gain early attachment to its inner lining will be absorbed before the woman even knows that she is pregnant. This is often referred to as a tubal abortion.

When an ectopic pregnancy occurs after ART, it is most likely the result of a uterine contraction causing a carefully placed embryo to be ejected into the fallopian tube. Various strategies to reduce the risk of this occurring are typically employed. The use of ultrasound guidance to place embryos and the use of minimal fluid to transfer them helps. There is some evidence that transferring blastocysts that are ready to implant instead of earlier embryos may also reduce the incidence. Sometimes however, despite the best laid plans, ectopic pregnancies do occur.

Diagnosis of an Ectopic Pregnancy
The easiest and most common method of diagnosing an ectopic pregnancy is by tracking the rate of rise in the blood levels of the “hormone of pregnancy,” human chorionic gonadotropin (hCG). With a normal intrauterine pregnancy, blood levels of hCG will usually double every two days throughout the first nine to ten weeks. However, an increase of at least 60% is still reassuring. A slower rate of increase in hCG more commonly suggests an impending miscarriage of one or more of the embryos that have implanted. However, it might be a sign of an ectopic pregnancy. Thus, the hCG levels should be followed serially until a clear pattern emerges.

The diagnosis of an ectopic is most often determined by a vaginal ultrasound examination. Performed by someone with sufficient expertise using a modern ultrasound machine, this test should reveal an ectopic pregnancy before it ruptures and becomes a surgical emergency. If the tube has already ruptured or internal bleeding has occurred, ultrasound examination will detect the presence of free fluid in the abdominal cavity, which is a more ominous sign.

If there has been a significant amount of intra-abdominal bleeding, irritation of the peritoneal membrane will cause the abdominal wall to become tense and, depending on the amount of blood in the abdomen, to distend. In such cases, any pressure on the abdominal wall will evoke significant pain and when a vaginal examination is done, movement of the cervix can be excruciatingly painful – especially on the side of the affected fallopian tube.

The most common conditions that must be ruled out when an ectopic pregnancy is suspected are:

• A hemorrhagic cyst of the ovary
• Appendicitis
• Acute pelvic inflammatory disease (PID)
• An inevitable miscarriage

Solutions: Surgical and Medical Management

Surgical: In some situations, laparoscopy is performed for diagnostic purposes. This may be necessary if a woman has a heterotopic pregnancy; one embryo implanted in the uterus and one in the fallopian tube. If an ectopic pregnancy is in fact detected, a small longitudinal incision over the tubal pregnancy will allow for its removal, without necessitating removal of the tube. In such situations, it may be possible to save the normally implanted embryo. Bleeding points on the fallopian tube can usually be accessed directly and bleeding can often be stopped through the laparoscope. Sometimes the damage to the fallopian tube has been so extensive that the entire tube will require removal. On occasions where very severe intra-abdominal bleeding heralds a potential catastrophe, a laparotomy is performed to stop the bleeding more rapidly. In such cases, a blood transfusion is usually required and may be life saving.

Medical: The introduction of Methotrexate (MTX) therapy for the treatment of ectopic pregnancy has profoundly reduced the need for surgery in most patients. MTX is a chemotherapeutic that kills rapidly dividing cells, such as those present in the “root system” of a developing fetus. Low doses of MTX are used to treat ectopic pregnancy since the fetal tissue is very sensitive. Accordingly, the side effects for the treatment are minimal. It is important to confirm that the ectopic pregnancy has not yet ruptured prior to administering MTX and is not too far along to be treated safely in this fashion.

The administration of MTX is by intramuscular injection. Prior to its administration, blood is drawn to get a baseline blood hCG level. After the injection of MTX the patient is allowed to return home with strict instructions that she should always have someone with her and never be alone in the ensuing week. The concern is that if she was to be on her own and internal bleeding occurred, she might not be able to get to the hospital quickly enough. In reality, this situation rarely occurs, but it is wise to be cautious. Instructions are also given to look for early signs that might point towards a worsening situation such as the sudden onset of severe pain, light-headedness or fainting. The patient returns to the doctor’s office four days later to check the blood HCG level, noting that it may have risen a bit. Three days later (7 days after MTX), the level is checked again. By this time, the HCG level should have dropped at least 15% from the value on day 4. If not, a second MTX injection is given and the blood levels are tested twice weekly until HCG level is undetectable. Once this occurs, vaginal bleeding will usually begin within a week or two.

Recent advances in the field of ultrasound diagnosis along with the introduction of MTX therapy have revolutionized the treatment of ectopic pregnancy and have significantly reduced both the high morbidity and mortality rates previously associated with this condition. When an ectopic pregnancy occurs following infertility treatment, there is the added advantage that the physician will be on the lookout for the earliest possible signs of trouble. The performance of a vaginal ultrasound within two weeks of a positive blood pregnancy (hCG) test following IVF allows for early detection of the unruptured pregnancy and timely intervention with MTX and/or laparoscopy.

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