ectopic pregnancy

ectopic pregnancy

• Pregnancy with the fertilized embryo implanted on any tissue other than the uterine lining
• 95% of ectopics are in the tube, 1.5% abdominal, 0.5% ovarian and 0.03% are in the cervix

Risk factors for ectopic pregnancy 

Previous ectopic pregnancy

 is a major risk factor for having another tubal pregnancy

Pelvic inflammatory disease, PID

• The rate of ectopic pregnancy in women with previous known PID is about 10 times higher than in women with no previous history of PID.
  
• A published study of 745 women with one or more episodes of PID that attempted to get pregnant showed that 16% were infertile from blocked tubes. For those that got pregnant, 6.4% had ectopics.

Pelvic inflammatory disease is usually caused by invasion of gonorrhea or chlamydia from the cervix up to the uterus and tubes

• The infection in these tissues causes an intense inflammatory response. Bacteria, white blood cells and other fluids (pus) fill the tubes as the body fights infection.
• Eventually, the body wins and the bacteria are destroyed. However, during the healing process the delicate inner lining of the tubes is permanently scarred.
• The end of the tube by the ovaries may become partially or completely blocked, and scar tissue often forms on the outside of the tubes and ovaries.
• All of these factors can impact ovarian or tubal function and the chances for successful pregnancy in the future.
• If pelvic inflammatory disease is treated early and aggressively with IV antibiotics, the tubal damage can be minimized, and fertility can be maintained.

Other risk factors for ectopic pregnancies

Pregnancy after tubal ligation

• After non-laparoscopic tubal ligation about 12% of pregnancies are ectopic
• After laparoscopic tubal coagulation about 50% of pregnancies are ectopic

Previous tubal surgery

• See table with ectopic rates by surgical procedure on the tubal infertility page

Ovulation induction or ovarian stimulation

• Risk of ectopic is somewhat increased

In vitro fertilization

• About 2% of IVF pregnancies are ectopic
• It is higher in women with a history of damaged tubes or previous ectopic pregnancy

Progestin only contraceptives

Progesterone-bearing IUD's and ectopics: About 16% of pregnancies are ectopics.

 

Ultrasound showing uterus and tubal pregnancy 

 Same image as above
Uterus outlined red, uterine lining green
Tubal ectopic pregnancy yellow
Fluid in uterus at blue circle is a "pseudosac"
Looks like early pregnancy sac, but is not

Same case as above
Detailed close-up of tubal pregnancy

 Same picture as above
Tubal ectopic pregnancy sac circled in red
4.5 mm fetal pole (between cursors) in green
Pregnancy yolk sac blue

 

Diagnosis of ectopic pregnancy

Although much is made of blood hCG levels and ultrasound studies, the clinical impression of the gynecologist or reproductive endocrinologist is the most important factor in making a timely diagnosis of ectopic pregnancy.

Peak HCG level	% of ectopics
<1000	45%
1000-3000	21%
3000-5000	15%
5000-10,000	10%
> 10,000	9%

Trend of hCG titers with ectopic pregnancies

Trend of HCG levels	% of cases
Falling	57%
Abnormally rising	36%
Normally rising	7%

 

General rules often used for hCG levels

• See tables with normal values for HCG levels in early pregnancy (single and twins)
• The hCG level should rise at least 66% in 48 hours, and at least double in 72 hours
• Plateauing hCG levels with either a half-life of > or = 7 days or a doubling time of > or = 7 days have the highest predictive value for ectopic pregnancy of any hCG pattern

An important point is that the lower limit in these "formulas" for hCG doubling times, etc., is usually the 15th percentile for symptomatic but viable pregnancies. Therefore, we must be careful to give pregnancies with slow hCG rise every chance possible - they may turn out to be normal.

General rules often used for hCG levels

• See tables with normal values for HCG levels in early pregnancy (single and twins)
• The hCG level should rise at least 66% in 48 hours, and at least double in 72 hours
• Plateauing hCG levels with either a half-life of > or = 7 days or a doubling time of > or = 7 days have the highest predictive value for ectopic pregnancy of any hCG pattern

An important point is that the lower limit in these "formulas" for hCG doubling times, etc., is usually the 15th percentile for symptomatic but viable pregnancies. Therefore, we must be careful to give pregnancies with slow hCG rise every chance possible - they may turn out to be normal.

Progesterone levels and ectopics

• Progesterone levels are usually not much help in making the diagnosis of ectopic pregnancy, but they can be another clue
• A progesterone level of less than 15 ng/ml is seen in 81% of ectopics, 93% of abnormal intrauterine pregnancies, and 11% of normal intrauterine pregnancies
• Less than 2% of ectopics and less than 4% of abnormal intrauterine pregnancies will have a progesterone level greater than or equal to 25 ng/ml
• Therefore, a single progesterone value less than 15 is probably an abnormal pregnancy
• A single value over 25 is probably a normal pregnancy - unless the woman had ovarian stimulation with fertility medications in which case this number might not be valid.

Ultrasound and Ectopics

• With good vaginal probe ultrasound (vag probe is best for imaging the uterus), a normal singleton pregnancy can be seen by the time the hCG level reaches 2000 mIU/ml
• By 5 to 6 weeks of pregnancy (1 to 2 weeks after the missed period) all normal pregnancies in the uterus should be seen by vaginal ultrasound
• 20-30% of ectopics have no detectable abnormality on ultrasound
• The usual finding for ectopic is a mass on one side, some fluid in the pelvis, and no normal pregnancy structures in the uterus
• Conclusive diagnosis of ectopic by ultrasound can only be made if a fetus or fetal cardiac motion is seen outside the uterus
  • This is only seen in about 20% of ectopics with vaginal ultrasound

Pseudo sac with tubal pregnancy

• A "pseudosac" is seen in 10-20% of ectopics. This is a sac in the uterus that is not a pregnancy but can look like one very early on.
• We need to see a yolk sac, fetal pole or cardiac motion to know it is a gestational sac.

Surgical treatment of ectopic pregnancy

• The possible procedures for ectopic pregnancy can all be done by laparoscopy (same day surgery) or by laparotomy (bigger incision).
• If the tube is not ruptured it is usually done by laparoscopy
• Cases of rupture with significant bleeding into the abdomen are usually done by laparotomy since it can be done faster.

Surgical procedures

• Salpingotomy (or -ostomy): Making an incision on the tube and removing the pregnancy
• Salpingectomy: Cutting the tube out
• Segmental resection: Cutting out the affected portion of the tube
• Fimbrial expression: "Milking" the pregnancy out the end of the tube
• In general, the procedure of choice is salpingectomy if future fertility is of no concern, if the tube is ruptured, or if there is significant distortion of the anatomy.

Persistent ectopic pregnancy

If the tube is saved at surgery, there is some risk that some of the pregnancy remains in the tube. This tissue can persist and resume growing.

• A mass can form with subsequent rupture and hemorrhage
• Case reports of patients who developed symptoms after conservative surgery have generally been at least 10 days after surgery

How common is persistent ectopic?

• After laparotomy: 3-5% of cases
• After laparoscopy: 3-20% of cases (most reports at 5-10%)
• Best approach is to follow the woman with weekly hCG levels until negative
• If a persistent ectopic is diagnosed, methotrexate is usually the best treatment

Medical therapy: Methotrexate

• First tubal pregnancy treated with methotrexate and reported was in 1985
• Methotrexate inhibits rapidly growing cells such as a pregnancy or some cancer cells
• Most side effects seen with low-dose methotrexate therapy have been very mild

Selection criteria for methotrexate

1. Hemodynamically stable (normal pulse rate and blood pressure)
2. No evidence of tubal rupture or significant intra-abdominal hemorrhage
3. Mass in tube is less than 3-4 cm diameter
4. No contraindications to methotrexate
5. Patient will be available for protracted follow-up
6. Informed consent from the patient

• Good results with very few side effects are seen with use of a single intra-muscular dose of 50 mg/square meter
• Resolution of the ectopic has been reported in about 70-95% of cases treated. This depends somewhat on selection criteria for the study.
• Tubes are later found to be open on the same side as the ectopic by a "dye test" or hysterosalpingogram in 70-85% of cases
• Pregnancy rates and repeat ectopics are comparable to those after conservative surgery

Decision making at the time of surgery for ectopic pregnancy

• After a tubal-saving procedure, ectopic pregnancy is equally likely to recur in the operated tube as in the other tube
• Overall, delivery rates are very similar after salpingostomy or salpingectomy if there is no history of infertility and the other tube appears normal
• However, if the other tube appears diseased and she has a history of infertility, salpingostomy gives a higher delivery rate (76% vs. 44% in one study) and also a higher risk of recurrent ectopic as compared to removing the tube
• It is important for the doctor to discuss future pregnancy concerns before surgery (if possible). The woman should be aware of the risks of future infertility, recurrent ectopic and persistent ectopic if her tube is saved.

Heterotopic pregnancy: Combined intra- and extra-uterine (ectopic) pregnancy

• Old (1940's) literature says the rate is 1/30,000 pregnancies
• Current heterotopic pregnancy rate is about 1/4000 pregnancies
• Rate is increased with the use of ovarian stimulation
• With IVF, the heterotopic rate is about 1/100 clinical pregnancies

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