Honey! She saved our embryo back! Who is she?

A negative pregnancy test is expensive, but starting over is even more expensive! Is it right to ignore the embryos after transfer and wait for "14 days" before taking a pregnancy test?

What can we do while waiting for a pregnancy test? I don't believe in the resurrection from the dead, but "resurrection from the brink" is definitely possible. 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. Why is it that IVF has been developed for over 40 years without "Implanted-Blastocyst Rescue" and "reproductive ICU"?

Which IVF clients are suitable for "Implanted-Blastocyst Rescue"?  In 2008, Stork Fertility Center was the first in Taiwan to introduce the third generation IVF. The technology platform at that time was aCGH, which could not accurately detect mosaic embryos (high miscarriage rate), and it was troublesome and time-consuming to send the embryo specimen to the U.S. Until 2015, we introduced next-generation sequencing platform PGT-A and set up our own laboratory, and in 2016, we also introduced ERA. This is the birth of "IVF 3+". However, the highest rate of IVF 3+ pregnancy is only about 80%, and 10-15% of them are biochemical pregnancies, what is happening to this group?

That's right! IVF3+ with biochemical pregnancy is the most suitable for "Implanted-Blastocyst Rescue". In early 2021, "Brave Mommy" 趙小僑 had a successful pregnancy with "IVF 3+", but unfortunately intrauterine fetal death at 16 weeks of pregnancy, and we were determined not to let this happen again. In early 2022, we started to try to save the dying embryos at the stage of implantation, and we have had some success so far. Here we share three recent successful cases and one unexpected case to explore the secret of biochemical pregnancy with you.

First case（822*2）

Scenario 1: Each reproductive center

If she did not take a pregnancy test early on day 7, she would have been "biochemically pregnant" on day 14 and the reason was unknown. After leaving the clinic in tears, how can the mystery of "biochemical pregnancy" be solved? Biochemical pregnancy is the second line on the pregnancy test that appears to be absent. The blood test usually shows a pregnancy indicator slightly higher than 0.1mIU/mL, which is commonly referred to as "shallow implantation". The "experts" are called those who know what is written in the book and those who don't know what is not written in the book, and the "reproductive experts" will then say: stop the medication and try again next time!

Scenario 2: Stork Fertility Center at 2021

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.

 Real Situation 1: Stork Fertility Center at 2022

What if we were more curious and asked our clients to return to the clinic every two days to track their pregnancy indicators, 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 there time to save the blastocyst when the client is in a panic? The client was unable to return to the clinic on the same day and was expected to return the next morning for a biologic injection, 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

At that moment, the client decided to save the blastocyst 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: ICU at fertility center

After the day 20 pregnancy test, the partners who are working hard start to expect the fetal heartbeat. 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.

5. In this case, all three embryo transfers were done in the south and we performed an emergency intervention on the seventh day after the third transfer.

Second case（588*0）

Forty-nine years old, she has had six IVF treatments, one with blighted ovum for unknown reasons, and came to the clinic for the purpose of borrowing eggs. The first implantation was still blighted ovum, and one day the blastocyst was expelled in the middle of the night with heavy bleeding, too late for chromosomal analysis. This time is the second transfer, and the early pregnancy test on the 6th day was 17.19. The next day the test was 18.69. The slow rise means that the blastocyst is not living well in the uterus and needs company. The problem is that all immune parameters are normal, except for the D-dimer value of 0.58 which is slightly higher on the day of transfer and the anticoagulant has been given every day, and the D-dimer has dropped to less than 0.55. So, where to start emergency treatment?

Real Situation 1: ICU at fertility center

All the visible test values are normal, only the D-dimer is not low enough. Is it because of the failure of the implantation due to the irregular blood flow in the uterus? Is it reversible to switch to heparin and give a higher dose? It is said that heparin is painful and bruises easily, how can the client do it three times a day? Afraid! Afraid! Afraid!

Real Situation 2: Implanted-Blastocyst Rescue

From day 14 pregnancy value is 1041. Look back, on day 7 immediately adjusting the anticoagulant is right, if the moment did not do anything, the day 14 pregnancy value is very likely to be less than 0.1, and wondering why it failed. At this point, the experts will say it is a "probability". Only a fetal heartbeat is considered a successful rescue.

Real Situation 5: Resurrection from the brink

 What did we learn?

1. The "reference value" of the thrombus indicator may not be applicable to every case because of the "diversity" of organisms and not every client can apply the formula. As the first case of TNFα, which is only "slightly higher" than the reference value, it is lethal to the blastocyst.

2. When all the "high-level immune indicators" are normal, unexplained failure or miscarriage, improving the uterine "microcirculation" can improve the pregnancy rate.

3. Bleeding after an anticoagulant is not always an overdose, but sometimes the opposite, as the first transfer in this case.

    

Case Three (702*9)

She is 30 years old, trying to be pregnant for 4 years and still can’t find any reason. Worst of all, she tried the best product “3+ IVF” in our fertility center; however, we failed and referred to the immunologist. Not only spending money on IVIG and Humira but also Clexane twice a day still only got chemical pregnancy.  It is really strange that we gave Immune Level 3 medication but also in vain. To this end, the “specialist” will say IVIG doesn’t work.

Real Situation 1: The experience of Getting Pregnant

We did the observation during the third transfer and found that Humira didn't work in this case and there was no other abnormal immune-marker. Fortunately, there were still 11 BC level embryos for the fourth transfer. We will change Humira to other manufacturers and no expensive IVIG is okay.

Real Situation 2: ICU Fertility Center

The fourth transfer we put two BC level embryos which were not suggested to be biopsy. BC level embryos were stigmatized by the internet world. The specialists only see the appearance and try to find a reason for the failure. We can see Dd(Thrombosis index) was okay(<0.55), however, B-HCG was only 8.8 5 days after transfer, which means the baby was dying. We changed Arixtra to Clexane twice a day, two days later, day 7 B-HCG raised to 39.28. We changed Clexane to three times a day on day 9, after that the B-HCG level climbed faster and more stable. Three weeks later we heard the strong heartbeat as expected.

Real Situation 3: Resurrection

 What did we learn?

1. Fake news is all over the world, appearance is not everything. Sometimes, famous doctors will also follow without thinking. When failure they don’t want to face the immune or thrombosis problems. Blaming the BC level embryos is easier. We can not always trust what was written in the book. This case is the same as artist Ms.Yen(47-years-old who gave birth to twins), they both succeeded by the BC level embryos. The real “murders” are thrombosis and TNFa.
2. Sometimes immunologists will misjudgement, for example, the third transfer.
3. Dd (Thrombosis index) is not low enough may be the reason for failure.
4. Every drug has a minority that doesn’t work well. We can’t tell before we try it. We learned that we should change the drug from the chemical pregnancy of the third transfer.
5. Work hard so you can find the secret that is invisible. Take customers as teachers so that you can find a way to test whether it  works and save the embryo to make a better world. If you take books as teachers you will panic when you face the situation that books didn’t write, the only thing you can do is follow the crowd.

Case Four（718*8）

She is 32 years old, trying to be pregnant for 5 years but fails. The first transfer was a precise implantation (ERA143). We transferred one non-biopsy embryo with only anticoagulant injection, however the result turned out to fail. After failure, this case started to take quinine for three months. The second transfer we put two non-biopsy embryos. Due to the young age and the past medical record of this case we check B-HCG level 7 days after transfer. We frequently test the B-HCG level just as ICU do to patients(We are like ICU Fertility Center). The climbing rate was okay during the first two weeks. Day 16-18 after transfer, the climbing of B-HCG level became slow. Day 19 after transfer, the baby was dying. Who was the murder?

Real Situation 1: ICU Fertility Center

Reports of high-class immune indexes need 1-2 weeks to get done. If we can’t rescue the baby immediately it will end in failure. Until day 18 we got the report of day 14. The report shows the murder was NK, however, it was a bit too late. To deal with NK, we need to give IVIG(Intravenous immune globulin) which costs a lot. The embryos she transferred this time were level AC and BC which were disliked by most people. Though the big data showed there will be one euploid among two embryos at her ages, it was worth giving it a try.  Save it or not decided by the customer herself, because it costs a lot of money.

Real Situation 2: Implanted Blastocyst Rescue

I couldn’t tell whether I could save the baby or not. So, I suggested IVIG 8 bottles and checked the B-HCG level frequently. If the B-HCG level climbs up again add another IVIG 8 bottles. After the first IVIG 8 bottles, B-HCG level stabilized. After two days(Day 21 after transfer), B-HCG climbed higher. After another two days(Day 23 after transfer), B-HCG climbed slowly again. We added IVIG 8 bottles immediately, after that B-HCG climbed again, three days later we added additional IVIG 8 bottles. 

Real Situation 3: Rescue Again

Twenty-two days after embryo transfer we use ultrasound to check the growth of blastocyst. Sac and heartbeat appeared as expected 35 days after embryo transfer, however the rate was a bit slow. We kept observation until 42 days after embryo transfer. The heartbeat rate and growth rate finally returned to normal level as the table shown below.

Real Situation 4: Resurrection

Extreme joy is usually followed by sorrow. She did her regular pregnancy checks until 11 weeks. However, one day in the 12th week she threw up dozens of times and got a fever after eating shaved ice. Two days after  that, the doctor found the baby’s heartbeat stopped. After the abortion surgery, the report showed that cervix was infected by Staphylococcus aureus and the chromosome was a normal boy, 46XY. We couldn't tell whether the abortion was related to food poisoning or not. But, the infection was for sure. What a pity.

What did we learn?

1. Don’t feel released before you hear a strong and stable heartbeat. Even if you pass the first and second week after embryo transfer, the murder can show up in the third week, the week that heartbeat should be heard.
2. IVIG should be used 2-3 days before embryo transfer. Rescue should use high dose IVIG, continue giving two days has the highest effect.
3. There are many different conditions during the first three months of pregnancy, you may pay attention to daily life.

Conclusion

For over ten decades, reproductive specialists often say “making a baby either 0 or 100”. After IBR, 3+ IVF can reverse 0. We redefine the 14 days after transfer and shorten the distance between 0 and 100.

Rescue or not have nothing to do with profession, but an attitude toward “life”. Save and rescue the treasure embryo in the uterus and bring it to life. Create the touching moment that mom meets with the healthy baby.