"Resurrection from the dead" is a fantasy, but is it possible to "resurrection from the brink"? It is the normal way to save a person's life to be sent to the emergency room, to be treated in the intensive care unit after a successful emergency, and then to be admitted to the general ward until the vital signs stabilize. In vitro fertilization (IVF) has been developed for more than 40 years. After the embryos are transferred into the uterus, they are "left alone", and the weak embryos face an "immune attack" from the mother in an "unfamiliar environment". How can we know if the embryos are doing well in the critical 14 days? How to reach out for help if they are attacked?

After the birth of the world's first IVF baby in 1978, ovulation needles evolved from urine products in the 1960s to genetically engineered long-acting ovulation needles (Elonva) in the 2010s, which can provide 6-7 days of effect with one injection, benefiting clients who are afraid of injections. Controlled Ovarian Hyperstimulation (COH) protocols have progressed from long, short, 4-less treatments to "no ultrasound", which means you can predict the day of egg retrieval without ultrasound, which is extremely convenient! The laboratory also evolved from 2-3 days of culture in the 1990s to blastocyst culture (5-7 days), from fresh implantation to frozen implantation, and from superficial visual observation to "precise selection" and "precise transfer" of embryos for preimplantation genetic testing for aneuploidy (PGT-A) and preimplantation genetic testing for monogenetic disorders (PGT-M), except that the pregnancy test date remained at "14 days''.

To be honest, it was a long 14 days, with the torment of anticipation and fear of failure, and the last moment was cruel. For decades, fertility experts used to say that the result of IVF is either 0 or 100. The process is like extreme gambling, with no chance of reversal. Even with the most accurate IVF 3.0 Plus, 20 out of every 100 patients somehow "get a negative pregnancy test" or "biochemical pregnancy" because there is no way to make a difference through hard work.

Shallow implantation is the second line on the pregnancy test that appears to be absent. A serum pregnancy indicator slightly higher than 0.1, is commonly referred to as "biochemical pregnancy".

Weird! The implantation of "good embryos" at the "right time" should have been successful, but why did it fail? The "right time" is to find the most suitable "window of implantation (WOI)" through Endometrial Receptivity Analysis (ERA), and the good embryo refers to "no chromosomal abnormalities" (e.g. Down's syndrome) detected by PGT-A, both of which are trusted "precision medicine" and there is obviously another killer if the result is failed.

To find the murderer! We need to design the "murder coordinates" first, so that we can clearly identify the murder timeline

The first and second weeks after transfer and before and after the fetal heartbeat are the most commonly encountered murder. The first two are called shallow implantation and the last one is blighted ovum (the embryo sac is visible on ultrasound but no fetal heartbeat).

Therefore, these three time points should be placed on "special tests" also known as "advanced immunological indicators" for evidence collection, which we call "dynamic triple detection" to randomly detect the presence of the murderer.

With these two detection tools, even if the results are not as expected, we can collect "valuable" parameters and "pre-protect" them before the next implantation to avoid repeating the same mistake, but will everything really be fine next time? What if we encounter turbulence again?

We redefine the "pregnancy test date", advancing the time by one week. Use the concept of the intensive care unit (ICU), design the "fertility ICU", and use "big data" to find out the murderers at different times. The five common killers are white blood cell (WBC), tumor necrosis factor-α (TNF-α), blood clots, natural killer (NK) cells, and B cells. Protecting the embryo from attack in different ways against different killers is the essence of "Implanted-Blastocyst Rescue" (IBR).

To make it easy to understand, let's give an example. She (822X2) is less than 35 years old and this is her third "precise transfer" (ERA108). If she did not take the pregnancy test early on day 7, she should be biochemically pregnant on day 14 and the reason is unknown. The current practices of reproductive centers around the world are as follows.

Scenario 1: Traditional practice

Unlike the previous two pregnancies where the reason for failure was unknown, this time she took her pregnancy test one week earlier and was happy with the result on the 7th day. She took another pregnancy test a week later and the result was "very sad" because she did "nothing" during the waiting period and blindly thought that the result of the second pregnancy test would be as expected.

Scenario 2: Innovation 1

A more innovative approach is as follows: not only take the pregnancy test a week earlier, but also use the concept of "fertility ICU" to track the pregnancy indicators every two days. On the 9th day, we found that they were climbing weakly, and on the 11th day, we took another test and found that the value had dropped. Is it too late to save?

Real Situation 1: Innovation 2

Give him a hand! At this moment, IVIG is the best medicine, with her weight, it is estimated that 15 vials are needed to be effective, eight vials were administered on the morning of the 22nd day, and the next day, before the other seven vials were administered, the fetal heart rate had risen to 159 beats per minute, which is considered a successful rescue again. The client was unable to return to the clinic on the same day and was expected to return the next morning for rescue, but before the emergency, the pregnancy indicator was tested again and found to be even lower, so do we still need an emergency for this situation?

Real Situation 2: Implanted-Blastocyst Rescue

Having failed twice, she decided to take the plunge and immediately administered a biological agent (monoclonal antibodies) and an anticoagulant. The next day, the pregnancy indicators were tracked and began to slowly rise, which meant that the embryo was not dead and was gradually returning to life. However, the real challenge is whether the fetal heartbeat will appear in another three weeks. Only a fetal heartbeat is considered a successful rescue.

Real Situation 3: Fertility ICU

After the 14th day of the pregnancy test, we will observe by ultrasound every week. The blastocyst appeared after one week as expected, the yolk sac and embryo bud appeared in the second week, and the fetal heartbeat appeared in the third week. But the heart rate is a little slower, usually 160-180 beats per minute in this period, below 135 may be dying, how to accompany at the critical moment?

Real Situation 4: Rescue again

Give him a hand! At this moment, IVIG is the best medicine, with her weight, it is estimated that 15 vials are needed to be effective, eight vials were administered on the morning of the 22nd day, and the next day, before the other seven vials were administered, the fetal heart rate had risen to 159 beats per minute, which is considered a successful rescue again.

Real Situation 5: Resurrection from the brink

What did we learn?

1. The reason for not getting pregnant with IVF 3+ is usually due to an immune attack or a blood clot.
2. The administration of biologics and anticoagulants prior to embryo transfer can create a friendly environment for implantation, which is a benefit for pregnancy.

3. If the embryo is not given medication before the transfer, the pregnancy test is early on day 7 and the pregnancy indicator is monitored every 1-2 days, if the rising rate slows down, there is a chance for the emergency treatment to resurrect within "24-48 hours", and the murderers in this period are mostly blood clots or tumor necrosis factor.

4. If the fetal heartbeat is too slow three weeks after the formal pregnancy test, immunoglobulin is effective, but you should pay attention to whether there is a sudden drop in estrogen and lutein, and it is best to keep supplementing with large amounts of estrogen and lutein for one to two weeks.

Conclusion

For decades, fertility experts used to say that the result of IVF is either 0 or 100. After we invented the "Implanted-Blastocyst Rescue", with PGS and ERA, we can reverse the fate of being scored 0. When we redefine the pregnancy test date, the distance between 0 and 100 is shortened to unimaginable!