■  Ectopic pregnancy is part of the differential diagnosis of bleeding in early pregnancy.

■  It is a pregnancy implanted outside the decidualised endometrium mostly in the fallopian tube (98 per cent; ampulla, 81 per cent; isthmus, 12 per cent; fimbrial end, 5 per cent; interstitial segment, 2 per cent). Other sites include the ovary, cervix, peritoneal cavity (abdominal pregnancy, 1 per cent).

■  The incidence is approximately 20 per 1000 pregnancies.

■  Reversal of sterilisation – rate of ectopic pregnancy is about 4 per cent (it is increased if the tubes have not been damaged by infection).

■  Incidence of ectopic pregnancy after in vitro fertilisation and embryo transfer (In vitro fertilisation-ET) is 4-7 per cent of clinical pregnancies. It is more common with transplantation of cryo-preserved embryos from unstimulated cycles than with fresh embryos.

Table Risk factors for ectopic pregnancy.

Past history of ectopic pregnancy
History of infertility
Use of ovulation induction agents
History of tubal reconstruction (14% of women)
Endometriosis
History of termination of pregnancy
Use of an intrauterine contraceptive device
History of sexually transmitted disease – Chlamydia (identified by antichlamydial IgG antibodies), trachomatous or Neisseria gonorrhoeae
History of salpingitis (40%)

Table Clinical features of an ectopic pregnancy.

History
Irregular menstrual cycles
Irregular bleeding
Amenorrhoea
Symptoms
Irregular vaginal bleeding
Unilateral pain
Generalised pain
Fainting and signs of abdominal tenderness
Unilateral or generalised plus/minus guarding and peritonism
Possibly pallour, shock, sweating, tachycardia, decreased blood pressure
On vaginal examination irregular bleeding, closed os, signs of pregnancy, small uterus for gestational age, adnexal mass with or without tenderness, cervical excitation

Ectopic pregnancy and a quantitative human chorionic gonadotrophin

■  A fi-human chorionic gonadotrophin level >1500IU/1 (first international reference) and no gestational sac visualised in the endometrial cavity on vaginal ultrasound suggest ectopic pregnancy.

■  In normal pregnancy, fi-human chorionic gonadotrophin should increase by 66 per cent in 48 hours.

■  fi-human chorionic gonadotrophin level should increase by 1000IU/1 in 2 days.

■  A serum progesterone level <30IU/1 suggests an abnormally developing pregnancy. Progesterone levels <10IU/1 are associated with either an ectopic or non-viable intrauterine pregnancy, compared with 50 IU/1 indicating a viable intrauterine pregnancy.

Management of ectopic pregnancy

■  With increasing diagnosis at earlier gestation, it is possible to observe the ectopic pregnancy when indicated, and await natural resolution.

■  The success rate of expectant management is up to 70 per cent.

■  Follow-up requires measurement of fi-human chorionic gonadotrophin levels twice weekly for the first 2 weeks, and thereafter weekly until it disappears.

■  Surgery is indicated if at any time there are peritoneal signs or haemodynamic instability. Resolution may take up to 50 days.

Medical management

The ectopic pregnancy may be injected under ultrasound guidance with methotrexate, prostaglandins (PGF2a) or hyperosmolar glucose.

Methotrexate is a cytotoxic agent which may be used either systemically, by intramuscular injection or by localised injection into the ectopic pregnancy.

Table A scoring system for non-surgical treatment of ectopic pregnancy.

Score
1 2 3
Gestational age, weeks, amenorrhoea >8 7-8 6
human chorionic gonadotrophin level (IU/1) >1000 1000-5000 >5000
Progesterone level <5 5-10 >10
Abdominal pain, absent, induced, spontaneous, haematosalpinx (cm) <1 1-3 >3
Haematoperitoneum 0 1-100 >100

Methotrexate is an antimetabolite that interferes with the synthesis of deoxyribonucleic acid by inhibiting the action of dihydrofolate reductase in the conversion of dihydrofolic acid into tetrahydrofolic acid. It interrupts the synthesis of the purine nucleotide thymidylate and the amino acids serine and methionine. The intramuscular dose is 50mg/m2 or lmg/kg body weight.

Methotrexate stops deoxyribonucleic acid synthesis and to some extent ribonucleic acid synthesis. The trophoblast, therefore, with its rapid cellular turnover, is very susceptible.

With methotrexate only 5 per cent of women experience minor side effects. These include stomatitis and elevated serum glutamic-oxalo-acetic transaminase levels. Intramuscular methotrexate preserves the potential for reproductive function. The rates of recurrent ectopic pregnancy in subsequent intrauterine pregnancy are very similar to those seen after laparoscopic salpingotomy. Methotrexate is widely used for the treatment of gestational trophoblastic disease in much higher doses. Follow-up of women who have received such treatment in subsequent pregnancies has identified no increase in stillbirths, premature deliveries, ectopic pregnancies or repeat molar pregnancies, or first and second trimester spontaneous miscarriages. There was no increase in major or minor congenital anomalies.

Recognising treatment complications

With methotrexate patients can have an exacerbation of low abdominal pain in up  to 60 per cent. This may confuse the pain of  impending tubal rupture. Pain is typically bloating or full feeling. If it is not relieved by anti-inflammatory medication, check the haemoglobin level to make certain there is no intra-abdominal blood loss.

Surgical treatment of ectopic pregnancy

Surgical treatment is the principal mode of treatment for ectopic pregnancy. Increasingly salpingotomy via a laproscopic approach is both effective and advantageous.

Advantages of surgical treatment

  • ■  Confirmation of the diagnosis of tubal pregnancy
  • ■  Assessment of the status of the affected and contralateral tubes and the pelvis in general
  • ■  Effective and prompt treatment irrespective of the size of gestation, tubal rupture and presence of haemoperitoneum. Treatment may be either conservative (salpingotomy) or radical, depending on the history of the patient, the pelvic findings and the patient’s wishes for future fertility.

Lapatoscopic surgery

Surgical treatment for unruptured ectopic pregnancies is essentially either linear salpingotomy or salpingectomy at laparoscopy. The advantages of laparoscopy are less blood loss, a lower requirement for analgesia and a shorter stay in hospital with subsequent cost savings. There is no difference in reproductive outcome with salpingostomy by laparoscopy or laparotomy.

The complication rate from laparoscopic salpingectomy is 0.6 per cent. Approximately 5 per cent require a second laparoscopy or laparotomy for persistent trophoblastic disease. Intramuscular methotrexate (lmg/kg) is given when asymptomatic with fi-human chorionic gonadotrophin levels rising as previously outlined.

Laparoscopic linear salpingotomy (conservation of the tubes)

A three-puncture laparoscopy technique is used with two operative port sites, placed one to the left and one to the right one third of the distance to the umbilicus. Any haematoperitoneum is aspirated.

Marcaine with adrenaline diluted in 20 ml of Plasma-Lyte is injected into the mesosalpinx through a 20-gauge spinal needle. Blanching of the fallopian tube and transient ischaemia occurs. A 10-15 mm incision is made into the antemesenteric border of the haematosalpinx with the needle electrode (15W coagulation and 30W cutting, force II diathermy). A suction/irrigation apparatus is used for evacuating the clot and trophoblast. Alternatively, if the clot and trophoblast are too organised, making suction difficult, 10 mm spoon-shaped grasping forceps (Semm spoon forceps) may be introduced through a 10 mm port to remove the trophoblast. Alternatively a combined instrument (the triton-needlepoint diathermy and suction/irrigation) is efficient for opening the tube and removing the ectopic. The salpingotomy site is left open for healing. This decreases the incidence of tubal damage and allows better healing of the circumferential mucosal fold. Bleeding points are diathermied.

Laparoscopic salpingectomy

Salpingectomy is performed laparoscopically either by using a suture loop or by coagulation with bipolar diathermy forceps (3 mm) before cutting the tube. The excised tube together with the ectopic pregnancy is removed through a 10 mm port. Laparotomy is indicated in approximately 10 per cent of cases of ectopic pregnancy.

If the patient is shocked and haemodynamically unstable, or the serum fi-human chorionic gonadotrophin is >15000 IU/1 or there are extensive intra-abdominal adhesions or conservative surgery has failed, a mini laparotomy incision is made. The salpingectomy is performed by clamping the mesosalpinx and dividing the tube at the cornual end. It is transected and sutured with vicryl. The abdomen is closed after irrigation.

Overall rates for subsequent intrauterine pregnancy following linear salpingostomy are about 50 per cent. Approximately 12 per cent will have a further ectopic and 5 per cent require treatment for persisting trophoblastic tissue. After total or partial salpingectomy, the intrauterine pregnancy rate was 38.1 per cent in 3584 patients desiring fertility, with a recurrent ectopic rate of 9.8 per cent.

Table Intrauterine pregnancy rates and recurrent ectopic pregnancy rates with past history of ectopic pregnancy.

n Intrauterine pregnancy rate Recurrent ectopic pregnancy rate
Future pregnancy 1514 61.4 15.4
Partial or total salpingectomy 3584 38.1 9.8

Among 176 women attempting to conceive with one tube, the intrauterine pregnancy rate was 54.5 per cent with a recurrent ectopic rate of 20.5 per cent. Previous infertility is by far the most important factor for subsequent pregnancy outcome. Successful conception is four times more likely without such a history. Subsequent intrauterine pregnancy rates are lowered and there is an increase in the recurrent ectopic rate with:

  • ■  ipsilateral periadnexal adhesions
  • ■  a history of infertility
  • ■  damage to the contralateral tube.

Most spontaneous pregnancies occur within 18 months of surgical treatment of an ectopic pregnancy. Even with a history of two repeat ectopic pregnancies, approximately 66 per cent will have a further ectopic. However, between 10 and 20 per cent will have an intrauterine pregnancy.

Results of fertility after conservative laparoscopic treatment of ectopic pregnancy in 223 patients are shown in Table General fertility results per cases and per patients. Twelve per cent had a recurrent ectopic pregnancy, nearly 85 per cent recurred in the ipsilateral tube; 33 per cent failed to conceive. Parity did not make a difference to recurrence risk. If infertility has not been a prior problem, the rate of intrauterine pregnancy following an ectopic is 85 per cent, with 7.5 per cent recurrent, and 7.5 per cent infertile. Future fertility is unrelated to the characteristics of the ectopic pregnancy, i.e. the size of the haematosalpinx, the volume of haemoperitoneum and tubal rupture had no significant influence on the rates of intrauterine pregnancy, ectopic pregnancy recurrence or infertility.

Table General fertility results per cases and per patients.

Ectopic pregnancy
1st 2nd 3rd Total per case Total per patient
No. 223 24 11 258 223
Ectopic pregnancy 27 (12%) 11 (46%) 1 (9%) 39 (15%)
Intrauterine pregnancy 143 (64%) 5 (21%) 1 (9%) 149 (58%) 149 (67%)
Infertility 53 (24%) 8 (33%) 9 (82%) 70 (27%) 74 (33%)

Similarly, the location of ectopic pregnancy in a tube was of no predictive value in terms of future intrauterine pregnancy, ectopic pregnancy, recurrence or infertility.

Future fertility is dramatically affected by the incidence of ipsi-lateral periadnexal adhesions. With no adhesions present, 67.5 per cent had an intrauterine pregnancy, compared with 45.7 per cent with ipsilateral adhesions. The prognosis is worse for those where the function of the contralateral tube is compromised. In 21.1 per cent the contralateral tube was non-functional. For these patients the rates found for intrauterine pregnancy, recurrent ectopic and infertility were 21.3, 21.3, and 5 7.4 per cent respectively.

If there was a patent contralateral tube, 75.5 per cent achieved an intrauterine pregnancy, 9.7 per cent had an ectopic recurrence and 14.8 per cent were infertile. If the contralateral tube was patent but with periadnexal adhesions, the rate of intrauterine pregnancy was 41.9 per cent, the rate of infertility 38.7 per cent. If there were no adhesions and a patent contralateral tube, the intrauterine pregnancy rate was 82.8 per cent with 9.6 per cent infertility.

Previous history

If there was no history of prior abdominal surgery, Intrauterine Device use or prior history of ectopic pregnancy, infertility or salpingitis, subsequent intrauterine pregnancy was 88.7 per cent with 3.8 per cent infertile versus 56 per cent intrauterine pregnancy and 30 per cent infertility in those with that history. There is no difference in rates of recurrence, 7.5 per cent without a history, compared to 13.5 per cent with. Fifty per cent intrauterine pregnancy rates occur in the first year, and 70 per cent within 2 years, of the management of the ectopic pregnancy. Conservative surgical treatment may be contraindicated when the probability of an intrauterine pregnancy is lower than that of a recurrent ectopic pregnancy.

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