Understanding Ectopic Pregnancy

What is ectopic pregnancy? 

Ectopic pregnancy is when an embryo (an egg that has been fertilised by sperm) implants outside of the uterine cavity.1 Most often, the location of ectopic pregnancy is inside the fallopian tube, which is the tube that transfers the egg from the ovary to the uterus. Other locations of ectopic pregnancy can be interstitial, the part of the tube that passes above the endometrial cavity, cervical; neck of the uterus, ovaries, peritoneum, and fimbriae; finger-like projections situated at the end of fallopian tubes. 

How common is ectopic pregnancy?

The incidence of ectopic pregnancy is 1 in 90 women, in the UK  Annually, 12,000 ectopic pregnancies are diagnosed. The incidence of ectopic pregnancy after assisted reproduction is between 0.8 to 8.6%.³ In women who have been through at least one ectopic pregnancy, 1 in 500 women suffer from another ectopic pregnancy. Less than 10% of ectopic pregnancies occur outside fallopian tube and 4% of those are interstitial.² However, Interstitial pregnancies are seven times higher in morbidity and mortality rates.¹ 

Understanding ectopic pregnancy

Ectopic pregnancy poses a risk to the mother’s physical health and mental well-being. Losing a pregnancy can cause immense grief and can be a very difficult time for parents. For those affected, understanding ectopic pregnancy is important to ensure the most appropriate healthcare and support is sought quickly. 

Important factors to consider in the event of ectopic pregnancy 

1. Early detection and management: ectopic pregnancies can be life-threatening, and early diagnosis is important for timely intervention to prevent complications. Early detection and knowledge of the risk factors for ectopic pregnancy can help doctors and patients in its prevention and help them to make informed decisions. 
2. Risk to mothers’ health: because ectopic pregnancy commonly occurs within the fallopian tube, there is a risk of rupture and subsequent bleeding inside the body. Importantly, this can be life-threatening to the mother and must be treated as an emergency. 
3. Risk to future pregnancies: if an ectopic pregnancy ruptures, it may cause damage, or blockage, to the fallopian tube, and this may pose a risk to the patient’s fertility and subsequent pregnancies.  

Risk factors of an ectopic pregnancy

Factors leading to ectopic implantation 

1. Fallopian Tube Abnormalities

Factors may physically inhibit the passage of a fertilised ovum (female reproductive cell, egg), or situations may arise when tubal implantation is more favourable due to factors intrinsic to the embryo.⁴  

• Hormonal Imbalances 

In a “normal” pregnancy, smooth muscle contraction and ciliary movements facilitate the transfer of the embryo from the fallopian tube to the uterus for implantation. This is carefully orchestrated by adrenergic nerve stimulation and sex steroid hormones. Within the ovarian follicular fluid, sex hormones prostaglandin and prostacyclin, alongside biological factors nitric oxide, cAMP, and IL-6, simulate tubal ciliary rhythm, moving the embryo into the uterus. Close collaboration between these biological factors contributes to the movement of the embryo from the fallopian tube to the uterus, but cilia provide the physical transport. Therefore, it is understood that a diminished count in maternal ciliated cells can increase the possibility of a tubal pregnancy.⁴

• Previous ectopic pregnancy 

Unfortunately, women who have experienced previous ectopic implantation are more likely to have another pregnancy in similar conditions - estimated chances are around 10-27%.⁵ In the event of repeated ectopic pregnancies, your healthcare provider may wish to investigate the possibility of tubal abnormalities.⁶

• History of pelvic infections 

The direct association between pelvic infections and ectopic pregnancies is not yet clear.6 A study comparing ectopic pregnancy incidence among women with and without chlamydial infection found no increased likelihood of ectopic implantation at the time of infection.⁴ 

• In-vitro Fertilisation (IVF) and Assisted Reproductive Technologies (ART)

The incidence of ectopic implantation in patients who have conceived via IVF is relatively low,  less than 5 %. However, for patients with additional tubal factor infertility, the incidence of ectopic pregnancy following IVF is more than double the risk, at 11%.⁷ 

Patients who have previously undergone IVF also have a higher chance of EP,  even following natural conception. Reasons for this are that they are more likely to have experienced tubal procedures, pelvic inflammatory disease, and other infertility-related interventions, and this may increase their overall risk for ectopic implantation. 

IVF may also result in heterotopic pregnancy. In these cases, one embryo will have a normal, intrauterine implantation and, at the same time, another embryo may have implanted within the fallopian tube (or elsewhere, ectopically). This can happen for a number of reasons, often relating to the health of the fallopian tubes, together with the procedure of IVF itself.⁷ Reassuringly, with due care and prompt attention, a favourable outcome for the intrauterine embryo is still possible.

• Other risk factors for ectopic pregnancy 

Patients may have an increased risk of ectopic pregnancy if they have a history of: 

• Fallopian tube surgery, 
• Caesarean section(s), 
• Infertility 
• Endometriosis 
• Sexually Transmitted Infections (STIs) 
• Intrauterine contraceptive devices (at the time of conception)
• Smoking  

Signs and symptoms

Early signs and indications

Symptoms of an ectopic pregnancy can start anytime between the 4th and 12th week of pregnancy. Often, vaginal bleeding is the earliest indication. If the patient is unaware of the pregnancy, this can be easily mistaken for regular menstrual bleeding.  Pain in the lower abdomen, pelvic region and lower back could also be a symptom, as well as dizziness or weakness.

Progression of symptoms

As an ectopic pregnancy progresses, there is an increased risk of rupture, and at this stage, the patient may begin to feel pressure on the bowel and/or bladder.  If you experience intense pain and internal bleeding, it may result in a loss of consciousness due to low blood pressure (hypotension). Shoulder tip pain (pain referred via nerves in the peritoneum), is a strong indicator of internal bleeding and rupture of an ectopic pregnancy - this is an emergency and requires immediate medical attention. 

Differentiating an ectopic pregnancy from a normal pregnancy

Unlike a normal pregnancy, if an embryo has implanted ectopically, you may experience constant lower abdominal pain. As the embryo continues to develop, there is a chance of internal rupture and intense bleeding, making it a life-threatening condition that requires urgent medical attention. It is important to contact your nearest healthcare provider in the event of any of these symptoms, even if you are unsure.

Diagnosis

Medical history and physical examination

Medical history regarding your signs and symptoms, sexual activity and history of contraception is important in the diagnosis of ectopic pregnancy. The date of your last menstrual period (LMP) will help determine if any bleeding may be a result of early pregnancy because the symptoms may be apparent from four to eight weeks after LMP. Determining all other risk factors and the date on which a pregnancy test was taken are also important.⁴

In the case of a ruptured ectopic pregnancy, a physical examination may show low blood pressure (hypotension) and an irregular maternal heartbeat (tachycardia). In an unruptured ectopic pregnancy, the patient may have adnexal or cervical motion tenderness upon physical examination. Ectopic pregnancy can be palpated (felt), and the patient can also experience tenderness on the lateral part of the uterus.^8,9  

Pregnancy tests and hormone levels

Beta human chorionic gonadotropin (β-hCG) can be detected in very early pregnancy, just eight days after conception. Monitoring the rate of β-hCG increase every 48 hours helps to differentiate a normal pregnancy from an abnormal one. In a viable, intrauterine pregnancy, with an initial β-hCG level under 1,500mIU/mL, your healthcare provider should expect to see a doubling every second day (a 99% chance of a 49% increase in 48 hours). As β-hCG level rises, the rate slows, with at least a 40% increase for 1,500 to 3,000 mIU/mL and 33% for levels over 3,000 mIU/mL. Slow-rising, plateauing, or decreasing β-hCG indicates early pregnancy loss or ectopic pregnancy.⁸

Transvaginal ultrasound

Transvaginal ultrasound is the optimal technique for the diagnosis of a suspected ectopic pregnancy. It is most reliable in detecting the location of embryo implantation and determining further details, including identification of the foetal pole and detecting a foetal heartbeat. In cases where the patient may have significant pathologies such as fibroid(s), ovarian cyst(s) or an enlarged uterus; a transabdominal ultrasound would be recommended. MRI scanning may also be a diagnostic tool of choice if ectopic pregnancy at caesarean scar is suspected.

Treatment

Once an ectopic pregnancy is suspected, treatment options include:

Expectant management: 

Women who are stable and without pain can have expectant management. This is also called ‘watchful wait’; your healthcare professional will assess the risk of internal bleeding via transvaginal ultrasound and monitor for decreasing β-hGC levels twice per week until they fall below a threshold of 5 mIU/mL.

Medical management: 

Methotrexate is the most successful medication available to treat cases where the patient’s symptoms fit a specific set of criteria.¹⁰ For medical management with methotrexate, they must have:

• A confirmed, unruptured, ectopic pregnancy 
• Increasing levels of β-hCG above, or plateaued at, 1500 mIU/mL
• Absence of significant pain 
• An ectopic mass smaller  than 3.5 cm;  

Surgical management

Laparoscopic surgical management is considered for patients who have:

• A confirmed, unruptured, ectopic pregnancy
• Serum β-hCG levels between 1500 mIU/mL and 5000 mIU/mL 
• Absence of significant pain 
• An ectopic mass smaller than 3.5cm 
• No detectable foetal heartbeat
• Absence of an intrauterine pregnancy, confirmed by an ultrasound scan 
• Full capability of returning for follow-up 

Laparoscopy and other surgical procedures

Laparoscopic procedures called salpingectomy and salpingostomy are the treatment choices for ectopic pregnancy.

Salpingostomy is the removal of ectopic pregnancy only, and salpingectomy is the removal of ectopic pregnancy along with the affected fallopian tube. Both surgical procedures are carried out laparoscopically (via a camera and a telescope), can take up to 60 minutes, and are minimally invasive in relation to post-surgery pain and scarring. In the majority of cases, if the patient’s other fallopian tube is present and normal, a salpingectomy is considered the optimal treatment. In the event of rupture and internal bleeding (an emergency situation), a laparotomy (where the abdomen is opened up) is the surgical intervention required 

Follow up

Monitoring: Patients, except those who underwent salpingectomy (additional removal of fallopian tube), must follow up with their healthcare professional so that β-hCG levels can be monitored closely. Serial blood tests will conclude if β-hCG levels have decreased to an acceptable or pre-pregnancy level.

Anti-D immunoglobulin (Anti-D): Your healthcare provider will establish your Rhesus (Rh) status via a blood test. If you are Rh-negative,  Anti-D injections are administered following surgical removal of an ectopic pregnancy.

Complications and health risks

Methotrexate can endanger the viability of a healthy, intrauterine pregnancy in women who present early in pregnancy, and ectopic pregnancy has been misdiagnosed. 

If the β-hCG level does not drop by 15% between days 4 and 7 of the single-dose methotrexate regimen, the patient is deemed to be experiencing treatment failure, necessitating a second dose regimen.¹¹

If the ectopic pregnancy is located at the cervical ostium and the patient presents with vaginal bleeding and pelvic pain,  it is possible these symptoms could be mistaken for an ongoing abortion.. 

In patients with a cervical ectopic pregnancy, a dilation and curettage is performed, and this procedure presents a risk of bleeding and possible hemodynamic instability.

Treatment failure can result from improper management of ectopic pregnancy at any stage. If the patient develops hemodynamic instability, it is a serious and life-threatening condition, regardless of early surgical intervention.¹  

Future fertility

After an ectopic pregnancy, patients often inquire about their chances of having a normal pregnancy in the future. If there were no previous fertility issues or fallopian tube disease, fertility should remain unaffected. However, if other risk factors are present (history of infertility, tubal disease, IVF procedures), or surgery was required in a previous ectopic pregnancy, there may be a higher risk of infertility and further incidence of ectopic pregnancy. 

Reassuringly, there is still a 6 in 10 chance of a future normal pregnancy, even with one fallopian tube removed. 

It's normal to feel anxious or sad after treatment, and discussing concerns with a doctor is advised. 

Summary

Losing a pregnancy can be a devastating experience for a patient and their family. Ectopic pregnancy is a life-threatening situation with a risk of complications from tissue rupture and massive bleeding. 

Risk factors include previous ectopic pregnancy, scar from caesarean surgery, tubal diseases, use of intrauterine hormonal contraceptives (at the time of conception) and a history of pelvic infection. 

Missed periods, vaginal bleeding, lower abdominal pain (often on one side) and dizziness are symptoms of ectopic pregnancy. Shoulder tip pain or loss of consciousness are symptoms that indicate an emergency situation. 

Treatment could be expectant or active management, depending on the patient’s stability and other criteria. Early detection and intervention is necessary for reducing mortality and morbidity with ectopic pregnancy.