IVF and Ectopic Pregnancy: Everything You Need to Know

In vitro fertilization (IVF) offers hope to countless individuals and families struggling with infertility. However, amidst its successes, IVF also carries certain risks and complexities, one of which is ectopic pregnancy. 

In this article, we’ll explore the relationship between IVF and ectopic pregnancy, including the underlying causes and who are at increased risk. 

What is an Ectopic Pregnancy? 

An ectopic pregnancy refers to a pregnancy that develops outside the uterus.

While the fallopian tube is the most common location for ectopic pregnancies, they can also occur in other areas, such as the ovary, the interstitial part of the uterus (the area where the fallopian tube connects to the uterus), the cervix (known as cervical pregnancies), the abdominal cavity, and even within a Caesarean scar.

In some rare cases, ectopic pregnancies can coexist with a normal pregnancy in the uterus, termed a heterotopic pregnancy. These various scenarios encompass the diverse manifestations of ectopic pregnancies.

What are the Chances of Ectopic Pregnancy with IVF

The risk of ectopic pregnancy (EP) after in vitro fertilization (IVF) and embryo transfer (ET) treatment varies between fertility clinics. Studies show that chances of ectopic pregnancy range from 1.4–5.4% of IVF cycles. 

Among all patients utilizing assisted reproduction technologies, including IVF, IUI, along with other techniques, the rate of ectopic pregnancy is 2–5%.

By comparison, the rate of ectopic pregnancy for the general population with a spontaneous pregnancy is 1–2%. 

How Number of Embryos Transferred Impacts Risk of EP

Studies show that the risk of an ectopic pregnancy is influenced by the number of embryos that are transferred: 

• 1.6% with single embryo transfer
• 1.7% with two embryo transfer
• 2.2% with three embryo transfer
• 2.5% with four embryo transfer

What Causes an Ectopic Pregnancy

Patients with underlying tubal disease, damage, or trauma face an elevated risk of experiencing an ectopic pregnancy. However, it’s essential to recognize that ectopic pregnancies can occur in any pregnant woman, regardless of these predisposing factors.

Conditions that may put a woman at higher risk for ectopic pregnancy include:

• a history of prior ectopic pregnancy
• tubal surgery
• sterilization procedures
• sexually transmitted infections
• tubal infections
• pelvic adhesions
• the current use of an intrauterine device (IUD) during pregnancy, which can increase the likelihood of ectopic pregnancy if conception occurs with an IUD in place. 
• IVF and other assisted reproduction techniques

Why Does IVF Increase the Risk of Ectopic Pregnancy?

There are a number of factors that contribute to the increased risk of ectopic pregnancy for women undergoing IVF treatment.

These include: 

• Underlying tubal, hormonal, and uterine issues contribute to difficulty with becoming pregnant prior to IVF treatment. 
• Transferring more than one embryo at a time. 
• Transferring non-top quality embryos.
• Late fertility age: Women 40 and older are 2.9 times more likely to have an ectopic pregnancy than women 25-29.
• Women with decreased ovarian reserve are 2.128 times more likely to develop an EP than women with normal ovarian reserve. 

Let’s take a closer look at some of these factors. 

How the Number of Eggs Retrieved Impacts the Risk of an Ectopic Pregnancy with IVF

In autologous in vitro fertilization (IVF) cycles, where the woman’s own eggs are used, the rate of ectopic pregnancy rises as the number of eggs retrieved increases. This trend is not seen in cycles that use donor eggs (eggs from another individual used for fertilization). The analysis was conducted on a large dataset consisting of 109,140 clinical pregnancies.

A possible explanation for the elevated risk of ectopic pregnancy in cycles with a higher number of retrieved eggs is that the excessive hormonal levels that led to the production of high numbers of eggs may disrupt normal uterine contractions, potentially causing the embryo to be expelled into the fallopian tube.

Quality of Embryo and Chance of Ectopic Pregnancy

A 2022 study looking at data from 15,006 clinical pregnancies found that the transfer of non-top-quality embryos is associated with a higher rate of ectopic pregnancy.  This is particularly important to keep in mind in treatments with only non-top embryos available, even in the absence of tubal factor infertility. 

Conversely, there is approximately a 28% reduction in the relative odds of ectopic pregnancy following a top-quality embryo transfer compared to a transfer of a non-top quality embryo.

Fresh vs Frozen Transfer

A 2022 study from Finland found that out of 15,006 clinical pregnancies, ectopic pregnancy was observed in 2.3% of cycles and that there was no significant difference in the rate of ectopic pregnancy after fresh embryo (2.4%) vs. frozen embryo transfer (2.2%).

Another 2022 study looking at data from over 16,000 patients found a slightly lower, but not significant rate of ectopic pregnancy with frozen embryo transfers compared to fresh embryo transfers.

Ectopic Pregnancy with IVF for Patients with PCOS

Studies have found that women with PCOS are at an increased risk of ectopic pregnancy after fresh embryo transfer cycles (7.0%), but not after frozen embryo transfers (2.4%).

How Having an Ectopic Pregnancy Effects Overall IVF Success

A large study of women who underwent 51,268 fresh cycles of IVF-ICSI found that having a previous tubal ectopic pregnancy does not affect subsequent live birth outcomes with IVF. Nor does it contribute to any perinatal outcomes, including stillbirth, low birth weight, preterm birth, admission to neonatal ICU, and first-minute birth asphyxia.

According to statistics from the UK, approximately 65% of women achieve a healthy pregnancy within 18 months following an ectopic pregnancy. Some research indicates that this percentage increases to around 85% over a two-year period.

How is an Ectopic Pregnancy Diagnosed?

Ectopic pregnancy is primarily diagnosed through blood tests to measure hCG levels and ultrasound examinations, which are the most effective methods for early detection. 

A key indicator is the rate of hCG increase, which ideally should be at least 53% over a 48-hour period. Once hCG levels reach this threshold, it’s expected that the pregnancy should be visible within the uterus. 

If hCG levels are not rising appropriately or exceed the threshold without evidence of pregnancy in the uterus, patients are considered at high risk for ectopic pregnancy and require closer monitoring.

How is an EP Treated? 

Typically, when an ectopic pregnancy is not ruptured, methotrexate is commonly used for treatment. There are two main protocols for methotrexate treatment, with the single methotrexate protocol being the preferred approach. This involves administering a single dose of methotrexate once an ectopic pregnancy is suspected and there are no contraindications to its use.

However, if the ectopic pregnancy is ruptured or there’s an urgent medical concern, such as the risk of bleeding and hemodynamic instability, surgery becomes necessary.

Symptoms of an Ectopic Pregnancy with IVF

Symptoms of Ectopic Pregnancy include :

• Pain: Experienced in the lower abdomen, lower back, or pelvis.
• Bleeding: May include vaginal bleeding or spotting, with characteristics such as watery consistency and dark brown color, differing from a regular menstrual period.
• Other Symptoms: Nausea, vomiting, fatigue, frequent urination, breast tenderness, or amenorrhea (missed period).
• Additional Symptoms if Rupture Occurs: Sudden and severe pain in the lower abdomen, shoulder pain, extreme dizziness or fainting, intense pressure in the rectum, low blood pressure, or very pale skin.

If you’re having an ectopic pregnancy from IVF and/or if you’re concerned about your chances, reach out to your fertility specialist immediately. 

IVF and Ectopic Pregnancy: The Bottom Line

Though women undergoing IVF are at increased risk of ectopic pregnancy, this increase is likely due in large part to underlying tubal, endometrial, and hormonal issues leading to difficulty getting pregnant and the need for IVF. 

That said, there are a few factors that can reduce the risk of ectopic pregnancy, including: 

• Transferring only one egg
• Transferring only a high-quality embryo when available

If you’re navigating an ectopic pregnancy post-IVF or have concerns about your fertility journey, don’t hesitate to seek guidance from your fertility specialist promptly.