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  » Infertility  »  Ectopic and Tubal pregnancy
Ultrasound image of ectopic pregnancy
Ultrasound showing uterus and tubal pregnancy Same image. Uterus outlined in red, uterine lining in green, ectopic pregnancy yellow. Fluid in uterus at blue circle - sometimes called a "pseudosac"
Same case as above. Detailed view of ectopic. Same image. Tubal pregnancy circled in red, 4.5 mm fetal pole (between cursors) in green, pregnancy yolk sac blue.

Background

Definition of ectopic: Pregnancy in which the fertilized ovum implants on any tissue other than the endometrial lining of the uterus.

95% occur in the tube. 1.5% are abdominal, 0.5% are ovarian and 0.03% are cervical.

The death rate is about 1 per 2000 ectopics in this country. About 40-50 women die each year from ectopic pregnancy in the U.S.

There has been a large drop in the death/ectopic rate since 1970. In other words, it is much safer to have an ectopic than it was in 1970.

Risk factors for ectopic pregnancy

Pelvic inflammatory disease (PID)

Rate of ectopic pregnancy in women with previous known PID is increased 6-10 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 conceive showed that 16% were infertile from tubal occlusion. Of those that conceived, 6.4% had ectopic pregnancies.

Pelvic inflammatory disease is usually caused by invasion of either 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 combats the infection. Eventually, the body wins and the bacteria are controlled and destroyed. However, during the healing process the delicate inner lining of the tubes (tubal mucosa) 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 conception in the future. If pelvic inflammatory disease is treated very early and aggressively with IV antibiotics, the tubal damage might be minimized, and fertility maintained.

Progestin contraceptives

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

Pregnancy after tubal ligation

Tubal sterilization and ectopics: After non-laparoscopic tubal ligation about 12% of pregnancies are ectopic.

After laparoscopic tubal coagulation about 51% of pregnancies are ectopic.

Previous tubal surgery

See table with ectopic rates by procedure on tubal infertility page.

Ovulation induction or ovarian stimulation

Risk of ectopic increased.

In vitro fertilization

About 2-5% of clinical pregnancies are ectopic with IVF. The figure is higher for women with a history of previous ectopic pregnancy or tubal infertility.

Previous ectopic: Details discussed below.

Heterotopic pregnancy: Combined intra- and extra-uterine pregnancy

Old (1940's) literature says the rate is 1/30,000 pregnancies.

Current rate is about 1/4000 pregnancies.

Rate is increased with the use of ovarian stimulation.

With IVF, rate is about 1/35-1/100 clinical pregnancies.

Diagnosis of ectopic pregnancy

Although we talk a lot about 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.

HCG levels

Initial hCG level: One titer is not of much use unless it is above the discriminatory zone (about 1000-2000 mIU/ml).

Peak hCG level in 47 ectopics

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%

36

Normally rising 6.4%

6.4

Reference for these 2 tables: Daus et al, Journal of Reproductive Medicine, February, 1989, p.162

General rules often used for hCG levels:

Tables with normal values for HCG levels in early pregnancy (single and twins listed).

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 have to be careful to give pregnancies with slow hCG rises every chance possible because they may turn out to be normal.

Progesterone levels and ectopics

Progesterone levels are usually not of much use 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, 11% of normal intrauterine pregnancies.

Less than 2% of ectopics and less than or equal to 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 of some kind.

A single value over 25 is probably a normal pregnancy. If the woman had ovarian stimulation with medication this value may not be applicable.

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 5.5-6 weeks of pregnancy (1.5-2 weeks after the missed period) all normal pregnancies should be seen by vaginal ultrasound.

20-30% of ectopics have no detectable sonographic abnormality.

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 fetus or fetal cardiac motion is seen outside the uterus. This is only seen in about 20% of ectopics with vaginal probe ultrasound.

Sac in uterus: 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 initially. We need to see a yolk sac, a fetal pole or cardiac motion to be sure it is a normal pregnancy.

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).

Usually, if the tube is not ruptured it is done by laparoscopy. Cases of rupture with significant hemorrhage into the abdomen are almost always done by laparotomy because it can be done much faster.

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 will be salpingectomy if future fertility is of no concern, if the tube is ruptured, if there is significant anatomic distortion, or if there is overt hemorrhage.

There is no evidence that suturing the incision on the tube closed or leaving it open is better.

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.

Incidence of 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 therapy is usually the treatment of choice.

Medical therapy: Methotrexate

First tubal pregnancy treated 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 MTX therapy have been mild and transient.

Selection criteria for methotrexate:

1. Hemodynamically stable
2. No evidence of tubal rupture or significant intra-abdominal hemorrhage
3. Tube < 3-4 cm diameter
4. No contraindications to MTX
5. Informed consent
6. Patient will be available for protracted follow-up.

Good results with very few side effects are seen with use of a single IM 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.

Tubal patency rates by hysterosalpingogram have been 70-85% on the same side as the ectopic.

Repeat ectopic and pregnancy rates are comparable to those after conservative surgery.

Future reproductive performance after ectopic pregnancy

Conservative surgery for small unruptured ectopics restores tubal patency in over 80% of cases.

In general the ratio of intrauterine to recurrent ectopic is about 6:1 but it rises to about 10:1 if the other tube appears normal.

After one ectopic and a tubal sparing surgery:

The subsequent delivery rate is about 55-60%.

The recurrent ectopic rate is about 15% (so about 20% of pregnancies are ectopics).

The infertility rate is about 25-30%.

If the other tube is absent or blocked:

The subsequent delivery rate is about 45-50%.

The recurrent ectopic rate is about 20% (so about 30% of pregnancies are ectopics).

The infertility rate is about 30-35%.

After 2 or more ectopics and conservative surgery:

The subsequent delivery rate is about 30%.

The recurrent ectopic rate is about 20-30% (so about 50% of pregnancies are ectopics).

The infertility rate is about 40-50%.

As a woman has more and more ectopics, the chances for a delivery (without treatment) become less and less.

In vitro fertilization (IVF) will be the best option for attaining a successful pregnancy for many women with a history of tubal damage and one or more ectopic pregnancies. 

Pregnancy rates with IVF are very good in (young) women with tubal problems, and a tubal pregnancy results from IVF in only about 2-4% of cases.

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 than would salpingectomy.

It is very important for the doctor and the woman to discuss issues regarding future reproductive desires before surgery (if possible). She should be aware of the risks of infertility, recurrent ectopic and persistent ectopic pregnancy if a tubal-saving procedure is done.

Who should be treated with egg donation?

Egg donation (also called oocyte donation or ovum donation) can be used as an effective treatment for infertility of all causes except for women with infertility caused by an anatomic problem with the uterus, such as severe intrauterine adhesions.

Pregnancy rates with egg donation are high, particularly as compared to pregnancy rates in women with poor egg quality and quantity.

Donor ovum IVF is generally used only in women with significantly diminished egg quantity and quality (poor ovarian reserve). This includes women with:

Premature ovarian failure (menopause)
Very poor egg quality
Poor response to ovarian stimulation
Significantly elevated day 3 follicle stimulating hormone (FSH)  level
Advanced female age , suc h as over about 39-40

How is egg donation performed?

1. An appropriate egg donor is chosen by the infertile couple and thoroughly screened for infectious diseases and genetically transmissible conditions. Donors are generally given some monetary compensation for going through the treatment.

2. Consents are signed by all parties.

3. The donor is stimulated with injected medications to develop multiple egg development. This allows us to perform in vitro fertilization with her eggs and the sperm of the infertile woman's male partner.

Details about the subcutaneous injectable medications that are used for IVF

Sample calendar of a "typical" egg donation cycle that shows the days of medications, procedures, etc.

4. The infertile woman (recipient) is placed on medications that suppress her own menstrual cycle and stimulate development of a receptive uterine lining.

Ultrasound images of a properly prepared receptive uterine lining - endometrium
In this case the endometrial lining is 11.5 mm thick
Image on right shows uterus outlined in blue and "triple stripe" endometrial lining outlined in yellow
 The endometrium is the landing pad and implantation zone for the embryos

5. When the donor's follicles are mature, an egg aspiration procedure is performed to remove the eggs from her ovaries. The eggs are then fertilized in the laboratory with the sperm of the infertile woman's male partner.

6. The embryos develop in the laboratory for 3 days. Then, an embryo transfer procedure is done which places the embryos in the infertile woman's uterus where they will hopefully implant and develop to result in the birth of a baby.