IVF - In Vitro Fertilization

After you've undergone the embryo transfer, the hope is that the embryo will implant into the lining of the uterus and continue to develop into a viable pregnancy.

Regardless of whether you undergo a fresh or frozen embryo transfer, the process takes several days before a pregnancy test can be performed with reliable results.

This time is often referred to by both patients and clinics as the “Two Week Wait” or “TWW.”

The two week wait gets its name from the idea that in unassisted conceptions, it is typically two weeks from the time of ovulation to the time when someone would miss their period and could reliably take a pregnancy test.

In IVF, referring to the “two-week wait” is a misnomer because by the time the embryo is transferred into the uterus, it’s already 3-6 days old. This means the time until a pregnancy test can be taken is actually less than two weeks. In fact, many providers opt to test pregnancy hormone levels between 9 to 12 days following a blastocyst transfer, though this timeline can vary depending on the clinic. Despite this, “the two week wait” is still commonly used to describe this time.

Continuing Medications

After your transfer, it’s essential to continue taking medications prescribed by your physician. These medications play a crucial role in supporting a pregnancy, and it’s important not to change or stop them without instructions from your doctor.

Following the transfer, some patients may experience physical symptoms such as:

• Mild cramping
• Breast tenderness
• Nausea
• Fatigue
• Light spotting

While these symptoms can be indicative of early pregnancy, they are also common side effects of the hormonal medications prescribed during this time.

Many patients look for signs of whether or not the transfer was successful, but it’s important to note that no single symptom, combination of symptoms, or lack of symptoms can truly predict the outcome of an embryo transfer. However, if you experience severe or concerning symptoms (such as severe pain or bleeding), you should immediately contact your medical provider.

Waiting for Results

The time between the embryo transfer and learning the outcome of a pregnancy test can be emotionally challenging, with patients often reporting a mix of hope, anxiety, excitement, and fear as they wait for their test results. Self-care is critical for your mental health and well-being during this time. Follow your doctor’s instructions on what activities to avoid, but gentle exercise such as walking and yoga are generally considered safe and can be a helpful distraction as you wait for results.

Some patients choose to take a home pregnancy test prior to their official blood test. However, it’s important to approach home pregnancy test results with caution, particularly before 6-7 days after the transfer, as they may provide inaccurate results. For example, if you were given any medication containing hCG (such as a trigger shot) prior to your transfer, it may result in a false-positive home pregnancy test. Alternatively, many home tests are not sensitive enough to pick up low-levels of hCG resulting in a false-negative result.

Some patients still choose to do a home pregnancy test and repeat the test daily. In this case, a faint positive line that becomes darker across the course of several days is generally regarded as a good sign. However, the most accurate way to determine if a pregnancy is developing is the hCG blood test. We’ll cover more about pregnancy testing in the next section.

The official pregnancy test, also known as a beta hCG test or simply a "beta," is a blood test to measure the levels of human chorionic gonadotropin (hCG) hormone in a woman's bloodstream. This is a hormone associated with pregnancy.

At many clinics, a positive beta hCG is considered any number over 5 mIU/mL.

If Your Beta Is Negative

Receiving a negative result is a truly disappointing and often heartbreaking outcome for many patients. Your doctor will discuss next steps with you concerning when and how to stop your medications, as well as your options for further treatment.

It’s critical to note that a negative result following an IVF embryo transfer is not necessarily an indicator of whether IVF can work for you in the future. In fact, many patients who have an unsuccessful first embryo transfer go on to have a live birth in following transfers.

One study published in 2020 illustrated below, suggests that the cumulative live birth rate of patients who underwent three consecutive euploid embryo transfers was over 90%.

This data also indicates that the second transfer was no less likely to work than the first transfer, even if the first transfer failed. Because of this, many doctors don’t recommend changing protocols or undergoing additional testing between the first and second transfer, assuming that a thorough uterine evaluation was conducted before to the first embryo transfer.

Although it can feel frustrating to repeat the same protocol twice in a row, the cycle will always be different because the embryo itself is different.

Essentially, although an unsuccessful transfer is incredibly disappointing, it does not mean that IVF will never work for you.

It also doesn’t mean you did anything to cause the cycle to be unsuccessful. Failed embryo transfers are common and are not influenced by factors such as lifting something heavy, having a fight with a partner, drinking coffee or other similar examples. In fact, the data shows that many times, having a positive outcome is simply a matter of trying again.

Regardless, a negative beta result still represents a significant loss. Many patients need time to process the outcome and grieve the hoped-for pregnancy before considering returning to treatment.

If Your Beta is Positive

If your beta hCG result is positive, that means the embryo has continued to develop and successfully implanted into the uterine lining. Your doctor will order a second blood test and see how hCG levels change over time.

In general, fertility doctors say they like to see the first beta number at 9 days after blastocyst transfer to be between 50-100 mIU/mL; however, live births have occurred with beta results significantly lower. Regardless of the initial result, any positive beta (over 5 mIU/mL), should continue to be monitored.

The beta hCG level is expected to rise throughout the first several weeks of pregnancy and eventually plateau at approximately the tenth week of pregnancy.

In most cases, the beta will be repeated approximately 48 hours after the initial test.

Traditionally, physicians say that they hope the beta number will double during this timeframe; however, data shows that a doubling beta is not necessarily needed to predict the viability of a pregnancy. This is due to several factors which are covered below:

One factor that may impact test results comes with the lab—with lab error or differences between laboratories both potentially affecting results.

There are also circumstances that may make the numbers look like they aren't increasing the way they should, but there really is a healthy pregnancy. For example, vanishing twin syndrome— where a pregnancy starts with two embryos, but by the time you see an embryo on an ultrasound, there's only one — could lead the hCG levels to rise in unexpected ways.

It’s also important to note that the rise in hCG doesn’t always continue at a consistent rate. According to a study of over 250 women, the actual and assumed rate of “beta growth” was correlated with how high the initial beta number was. If a beta number started off lower, the 48 hour increase was higher, as seen in the table below.

If an initial hCG test was 100, the pregnancy may still be viable two days later if it grew by ~80%. Conversely, if initial results were 5,000, the pregnancy may still be viable if it only grew by ~30% two days later.

This data is helpful in showing the variability of increase in beta results, but it isn’t entirely applicable to IVF, where initial beta results are measured early and on a predictable day (unlike in this study), and should never be as high as 5,000.

While support groups can be incredibly helpful during this time, comparing your beta results to someone else's may create unnecessary stress and anxiety. Every person's body and pregnancy journey are unique, influenced by factors such as the timing of implantation, the number of embryos transferred, and individual hormone levels. It’s also important to keep in mind that the day the beta test is conducted and the laboratory used can vary by clinic, so results might not be directly comparable even if they are from the same stage of pregnancy.

Beta testing does give important information, but it’s just one part of the overall picture. To truly understand the viability of a pregnancy, ultrasound confirmation is needed, which will be covered in the following section.

After it’s been established that your beta numbers are positive, your clinic will likely schedule you for an ultrasound. Depending on the timing of the ultrasound, your provider may be able to identify various structures of the developing embryo that indicate the progression of the pregnancy.

Here are a few things they may look for or point out to you on your ultrasound:

• Location of pregnancy: your provider will confirm that the pregnancy is intrauterine (inside the uterus), rather than being outside the uterus, such as in a fallopian tube, which would be a dangerous situation and warrant immediate medical intervention. This should be clearly seen by 6 weeks gestation.

• Presence of Yolk Sac & Fetal Pole: the yolk sac provides essential nutrients to the developing embryo in the early stages of pregnancy. The fetal pole is an early embryonic structure that develops into the fetus. Your provider will also observe how many yolk sacs are present. The presence of more than one yolk sac can indicate a multiple gestation pregnancy, such as twins.

• Fetal Cardiac Activity: the early stages of heart development can typically be seen around 6-7 weeks. This is often referred to as a “heartbeat” but actually refers to the detection of electrical impulses of the developing fetal heart, rather than the coordinated contractions of a mature heart seen later in pregnancy. The presence of early fetal cardiac activity is a reassuring sign to clinicians that the pregnancy will continue to progress.

• Crown to Rump Length: this is the length of the developing embryo. In IVF, this measurement can be used to confirm that the size matches what would be expected at that specific gestational age, and monitored overtime to observe growth between scans. Normal growth of the gestational sac and crown to rump length is about 1mm/day. A crown to rump length that matches what is expected for gestational age is reassuring, while a crown to rump length that is significantly different would be a concern.

The first ultrasound can bring on a range of emotions from anxiety to excitement for a patient. It can be especially disappointing if one of these milestones is not observed during a first appointment. It’s critical to remember that each pregnancy progresses at its own rate, and in some cases, it simply may be too early to visualize fetal cardiac activity, yolk sac, etc.

One retrospective cohort study of patients who underwent a transfer of a single, euploid embryo showed that 94.8% of patients who had a yolk sac visible on ultrasound at 5 weeks gestation went on to have an ongoing pregnancy. And yet, even among patients who did not have a yolk sac visible at 5 weeks gestation, 65.9% did ultimately visualize a yolk sac on a follow up ultrasound 1-10 days later, and 54% went on to have an ongoing pregnancy. (Levin, 2023)