Ectopic pregnancy is the leading cause of maternal death in early pregnancy. Ectopic pregnancy is defined as implantation of a fertilized egg outside the uterine cavity. In a normal pregnancy, the fertilized egg moves from the fallopian tube into the uterus, where the pregnancy develops. In a small percentage of pregnancies, however, the embryo implants in extra uterine locations leading to an ectopic pregnancy. Most extra uterine pregnancies (97%) implant in the fallopian tube; another 3% of ectopic pregnancies implant in the cervix, ovary, peritoneal cavity, or in uterine scars. In ectopic pregnancy as the pregnancy continues, it can cause the tube to rupture with internal bleeding. This situation can be life threatening and needs to be treated as medical emergency.
Many risk factors like pelvic inflammatory disease, intrauterine device, tubal surgeries, sexually transmitted diseases, infertility are associated with ectopic pregnancy.
The incidence of ectopic pregnancy among all pregnancies is about 0.25-2.0% worldwide* and can occur in any sexually active woman of reproductive age. Ectopic pregnancy was reported in 0.91% of pregnant women (with no maternal deaths) in a study done at tertiary care centre in South India.**
Globally the incidence of ectopic pregnancy has been on the rise over the past few decades because of increased incidence of salpingitis (infection of fallopian tubes mostly due to sexually transmitted infections), induction of ovulation, and tubal surgeries; and improved ability to detect ectopic pregnancy. The incidence of ectopic pregnancy has risen from 4.5 cases per 1,000 pregnancies in 1970 to 19.7 cases per 1,000 pregnancies in 1992 in North America. Though the cases of ectopic pregnancy are on rise; the incidence of rupture of ectopic pregnancy and maternal deaths has declined because of early diagnosis and management. Ectopic pregnancy still accounts for 4% to 10% of pregnancy-related deaths and leads to a high incidence of ectopic site gestations in subsequent pregnancies. Ectopic pregnancy accounts for 3.5-7.1% of maternal deaths in India.
Suspicion of an ectopic pregnancy in women of reproductive age group presenting with lower abdominal pain or vaginal bleeding with timely case management can prevent the maternal deaths and future fertility problems in women.
It is important to be aware of the symptoms of ectopic pregnancy because it can occur in any sexually active woman whether or not she is using contraceptives or has undergone tubal sterilization (“tying the tubes”).
Symptoms of ectopic pregnancy are different in each woman. Sometimes ectopic pregnancy may be asymptomatic or women may not be aware about the pregnancy (if her menstrual periods are irregular previously or pregnancy is due to failure of contraception).
Most women get symptoms in the 6th week of pregnancy (about 2 weeks after the missed period). The most common symptoms are unilateral lower abdominal pain, a short period of amenorrhoea, and slight vaginal bleeding.
Ectopic pregnancy may cause the following symptoms:
- Vaginal bleeding often occurs (but not always). It is mostly different to the bleeding of a normal period. It may start about the time a period is due or about few weeks after the missed period. The bleeding may be heavier or lighter than a normal period. The blood may look darker.
- Abdominal or pelvic pain is felt in lower abdomen; it develops suddenly for no apparent reason or may come on gradually over several days. Pain can be sudden and sharp without relief or seems to come and go. It may occur on only one side.
(These symptoms are neither sensitive nor specific and are also associated with other pregnancy complications, such as miscarriage).
Other less common symptoms include:
- Shoulder pain can be felt because of collection of blood from ruptured tube into the abdomen under the diaphragm. Pain may be worse during lying down.
- Women may feel weakness, dizziness, or fainting because of blood loss; if the fallopian tube ruptures and causes internal bleeding.
- In rare instances, collapse may be the first sign of an ectopic pregnancy. This is an emergency situation and should seek urgent medical attention.
- Urinary symptoms.
- Rectal pressure or pain on defecation.
An ectopic pregnancy is mostly occurs in fallopian tube. A fertilized egg has difficulty passing through a damaged tube, causing the egg to implant and grow in the tube. Adnexal infections or tubal surgery can damage the fallopian tubes. Therefore women who have abnormal fallopian tubes are at higher risk of ectopic pregnancy.
Most of the ectopic pregnancies (97%) occur in ampullary part of the fallopian tube. Another 3% of ectopic pregnancies implant in the cervix, ovary, peritoneal cavity, isthmic, or interstitial portion of the fallopian tube, or in uterine scars.
Risk factors– Several factors may increase the risk of ectopic pregnancy:
- Pelvic inflammatory disease (PID): It is an infection of the uterus, fallopian tubes, and nearby pelvic structures and may be due to sexually transmitted infections.
- Previous ectopic pregnancy: There is increased risk of ectopic pregnancy with previous ectopic pregnancy because it reflects the underlying tubal pathology which is almost always bilateral. Previous ectopic pregnancy becomes a more significant risk factor with each successive occurrence. The average rate of repeat ectopic pregnancies after one ectopic pregnancy is 12%.
- Pelvic or abdominal surgery
- Prior tubal surgery (such as tubal sterilization)
- Endometriosis- Endometriosis, tubal surgery and pelvic surgery result in pelvic and tubal adhesions and abnormal tubal function.
- Infertility and infertility treatment
- Intrauterine devices (IUD): It prevents intrauterine pregnancy but not tubal and ovarian pregnancy.
Other factors that increase a woman’s risk of ectopic pregnancy include the following
- Cigarette smoking- Cigarette smoking is known to affect ciliary action within the fallopian tubes.
- Exposure to the drug diethylstilbestrol (DES) during her mother’s pregnancy: (DES) is associated with uterotubal anomalies.
- Increased age
Heterotopic pregnancy is a rare situation when there is an intra-uterine and extra-uterine pregnancy occurring simultaneously.
The diagnosis of ectopic pregnancy is not always easy; and a delay in diagnosis and treatment can have serious consequences. Early diagnosis can be made before appearance of sign and symptoms.
The possibility of ectopic pregnancy should be excluded in women of child bearing age, even in the absence of risk factors (such as previous ectopic pregnancy, PID), because about a third of women with an ectopic pregnancy have no known risk factors. Clinical suspicion is the key to identifying women who need prompt and careful evaluation.
The symptoms and signs of ectopic pregnancy can resemble the common symptoms and signs of other conditions such as gastrointestinal conditions or urinary tract infection.
A detailed history, clinical examination and various tests help in diagnosing ectopic pregnancy.
(a) History– A proper history and physical examination are the initial steps for initiating an appropriate work-up that will result in the accurate and timely diagnosis of an ectopic pregnancy.
- Abdominal pain with spotting, usually occurring six to eight weeks after the last normal menstrual period is the common symptoms of tubal pregnancy in symptomatic patients. Other presentations depend on the location of the ectopic pregnancy.
- Less commonly ectopic pregnancy presents with pain radiating to the shoulder, vaginal bleeding, syncope and/ or signs of hypovolemic shock.
- Findings such as hypotension and marked abdominal tenderness with guarding and rebound tenderness suggest a leaking or ruptured ectopic pregnancy.
(b)Speculum and bimanual examination have a limited diagnostic value and findings may be nonspecific. Findings include:
- Slightly enlarged and soft uterus (enlargement of the uterus is less than expected for a pregnancy duration)
- Presence of uterine or cervical motion tenderness
- An adnexal mass may be palpated on one side
- Uterine contents may be present in the vagina, due to shedding of endometrial lining stimulated by an ectopic pregnancy
(c) Pregnancy test- A urine pregnancy test is positive in ectopic pregnancy.
(d)Ultrasonography-It is the most important tool for diagnosing an extrauterine pregnancy.
- Transvaginal ultrasonography, or endovaginal ultrasonography, can be used to visualize an intrauterine pregnancy by 24 days post ovulation or 38 days after the last menstrual period (about 1 week earlier than transabdominal ultrasonography).
- Visualization of an intrauterine sac, with or without fetal cardiac activity, is often adequate to exclude ectopic pregnancy.
- On endovaginal ultrasonographic scan, absence of an intrauterine pregnancy (or an empty uterus) with a serum β-human chorionic gonadotrophin (b-hCG) greater than discriminatory cut-off value may be an ectopic pregnancy or a recent abortion.
- Ultrasound is also an essential tool in the diagnosis of non-tubal ectopic pregnancies.
Color-flow Doppler Ultrasonography may be helpful in cases in which a gestational sac is doubtful or absent.
(e)Test to detect serum β-human chorionic gonadotrophin (b-hCG) – b-hCG is predictable during the early weeks of a normal intrauterine pregnancy (IUP). This is usually checked every 48 hours because, with a pregnancy in the uterus, the hormone level rises by 63% every 48 hours (known as the ‘doubling time’) whereas, with ectopic pregnancies, the levels are usually lower and rise more slowly or stay the same. b-hCG level less than 1,500 mIU/mL is predictive for ectopic pregnancy.
The b-hCG level is more useful in distinguishing abnormal from normal pregnancies than it is for distinguishing ectopic from intrauterine pregnancies.
(f) Laparoscopy-It is indicated for patients who are hemodynamically unstable with multiple signs and symptoms of ectopic pregnancy.
The combination of sensitive urinary pregnancy tests, transvaginal ultrasound and serum hCG estimations enables the early diagnosis of ectopic pregnancy.
In order to minimize the risks to woman’s health/or to the save the woman’s life treatment of ectopic pregnancy is necessary. Options of treatment depend on duration of pregnancy, clinical condition, fertility status, scan results and level of b-hCG.
Various treatment options are-
(a) Expectant management: The term expectant management is usually defined as watchful waiting or close monitoring by a physician instead of immediate treatment. In expectant management, no treatment is given and the patient is followed closely with weekly transvaginal ultrasonography and weekly blood measurements of b-hCG until the level is less than10 mIU/mL. Expectant management may be advised when:
- An ultrasound scan shows a small ectopic pregnancy with no bleeding into the abdomen, low, declining β-hCG values and patient is willing to come for close follow-up.
- An ectopic pregnancy is suspected, but clinically fails to show an ectopic pregnancy.
(b) Medication– Sometimes drug (systemic methotrexate) is used for the treatment of very early stages of ectopic pregnancy, when tube is not ruptured. The drug stops the further development of the pregnancy and it is gradually reabsorbed by the body leaving the fallopian tube intact.
- Success rates of medical treatment vary (65-95%) depending on the circumstances in which methotrexate is given.
- Follow up visits for few weeks are required to ensure the pregnancy has completely ended.
- A reliable contraception should be used for at least 3 months.
(c) Surgery– Surgical management is performing an operation to remove the ectopic pregnancy and it is the most established form of treatment. Surgery may also be performed if expectant management or medical management has failed.
An ectopic pregnancy can be removed from the fallopian tube by using two types of surgical procedures called salpingostomy and salpingectomy. These procedures can be performed by either Laparoscopy or Laparotomy.
- Laparoscopy (keyhole surgery) -An advantage of laparoscopic surgery is that the operation is less invasive, thus recovery time is quicker and less painful as compared to a laparotomy.
- Laparotomy (open surgery) is usually done when there is heavy internal bleeding/rupture or presence of previous scar tissue and in an emergency situation.
Salpingostomy– If rupture has not occurred; the products of conception are removed through a small length wise incision in the fallopian tube (linear salpingostomy). There is a very small risk that some of the products of pregnancy may remain in the tube after salpingostomy. Therefore patient is advised to have weekly blood tests to monitor hCG levels and decreased levels of hCG shows that the pregnancy is fully resolved.
Salpingectomy– If the tube has already ruptured or damaged as a result of an ectopic pregnancy, salpingectomy is performed to remove the damaged fallopian tube. In this procedure a segment of fallopian tube is removed. The remaining healthy fallopian tube may be reconnected. Salpingectomy is appropriate for women who have a healthy contralateral tube.
Total salpingectomy is done in a patient who has completed childbearing and no longer desires fertility.
Tissue removed at the time of surgery can be sent for testing in the laboratory if facilities are there.
- The chances of having a successful pregnancy in the future are good. If only one fallopian tube is present, chances of conceiving are only slightly reduced.
- Women who have had a previous ectopic pregnancy are at higher risk of reoccurrence.
- Salpingostomy and salpingectomy have the same effect on future fertility of the women when one healthy fallopian tube is present.
- Salpingostomy may be preferred; if other tube is damaged. This may improve the chances of getting pregnant in the future.
- Laparoscopy and medical therapy have now emerged as the widely used therapeutic procedures with great success in terms of reduced morbidity, shorter hospital stay and conservation of fertility.
Rh (rhesus) factor-
All pregnant women (including ectopic pregnancies) who are Rh-negative (determined by a blood test) should receive Rh immunoglobulin (antibodies directed against the Rh).
The most common complication is rupture with internal bleeding which may lead to hypovolemic shock. In the first trimester, ectopic pregnancy is the most common cause of pregnancy-related deaths and 10% of maternal deaths may be due to ectopic pregnancy.
An ectopic pregnancy is assuming greater importance because of its increasing incidence and its impact on women’s fertility and mortality.
Lack of knowledge regarding sexual health predisposes women to sexually transmitted diseases. Health education regarding safe sexual practices, to get quick treatment for sexually transmitted infections (STIs), avoidance of risk behaviors such as smoking and provision of family planning services is very much needed for the prevention of ectopic pregnancy.
Occurrence of ectopic pregnancy cannot be prevented but complications can be reduced/ prevented with early diagnosis and treatment. Increased awareness in physicians and use of ultrasonography in early pregnancy may lead to early diagnosis and a conservative management.
Women should seek early advice from a healthcare professional when she is pregnant. She should be advised an ultrasound scan between 6 and 8 weeks of pregnancy to confirm that the pregnancy is developing in the uterus.