In IVF treatments, failed pregnancy still occurs even with top quality embryos, normal chromosome tests, or optimal embryo transfer timing. There must be some underlying problems interfering with the embedding of the embryos. But what exactly are the problems? The immune status of the maternal body is the answer.

In normal pregnancy, embryos embed the endometrium by causing inflammatory-like responses. After embedding, the embryo will begin to divide into the fetus and the placenta, and then it will absorb nutrients from the maternal body through maternal-fetal circulation.  At this point, the maternal immune system should be adjusted into accepting the embryo as if it is part of the maternal body for further embryo development. During pregnancy, if the maternal body sees the embryo as an outsider, it will activate the immune system and attack the embryo, which leads to failed embedding or miscarriage, also known as auto-immune infertility.

When to check for auto-immune infertility?

If the patient experienced more than 2 times of spontaneous miscarriages, more than 2 times of failed IVF treatments, or after transferring more than 4 good-quality embryos, it’s time to check for auto-immune infertility.

What is the 3-time dynamic test?

We set 3 checkpoints (blood tests) to evaluate maternal immune status for it being dynamic. The first checkpoint is before the IVF treatment. The second checkpoint is set during the first transfer treatment. The third checkpoint would be during the second transfer treatment if the first time did not succeed. If the first checkpoint shows abnormality, continued medication is suggested and no further embryo transfer arrangement until the data shows controllable immune status. After the transfer surgery, follow-up blood tests and medication adjustment are suggested all the way to successful childbirth.

Why do the 3-time dynamic test?

It costs more than NT$100K for one single IVF treatment. If we do auto-immune checkups after more than 2 failures like we mentioned earlier, the cost might be too high. The time and money spent, and the impact on mental health might knock people down. Hence, for those with miscarriage or repeated implantation failure history, or with extremely low AMH level (low ovarian reserve), or for those who simply want a baby in the shortest period of time, can adopt “advanced deployment” (the 3-time dynamic test) to evaluate and regulate the immune system in order to improve pregnancy rate and lower miscarriage rate.

What’s the outcome?

We collect the data starting from Sep., 2020, from both of our centers, and the outcome is shown below. 1st negative means we can roughly rule out infertility caused by auto-immunity, therefore the pregnancy rate is up to 70%. If the first result is positive and treatment is arranged immediately (1st positive), we can reach around 60% pregnancy rate. If 1st positive is followed by 2nd checkup (1st positive+2nd checkup), which means that we keep adjusting immune medication during transfer treatment, the pregnancy rate is also around 60%. The close pregnancy rate makes the 2nd checkup seem unnecessary. But don’t jump to conclusions yet, let’s stick around and dig deeper.

Interestingly, if 1st negative is followed by 2nd checkup(1st negative+2nd checkup), we can reach up to 84% pregnancy rate. Meanwhile, the pregnancy rate is only around 64% if 2nd checkup is not conducted after 1st negative(1st negative-2nd checkup). Although we can roughly rule out immunity problems after 1st negative, activation of the immune system attacking the embryo might still happen as the maternal immune status is dynamic. Without 2nd checkup, we can’t save the embryo in time, and it might be the reason for the relatively lower pregnancy rate.

Moreover, for those who did 2nd checkup after 1st negative, and with applied medication (1st negative + 2nd checkup + medication), we can reach up to 100% pregnancy rate, though currently there’s only 3 cases. For 2nd checkup after 1st negative, without medication (implying both negative results) (1st negative + 2nd checkup - medication), the pregnancy rate is 81% (16 cases). Further data collection is needed to prove the effectiveness of the 3-time dynamic test.

Since only a few patients do 3rd checkup, the data is excluded from this research. The statistics show that the underlying maternal immune status may cause auto-immune infertility, and with the 3-time dynamic test, there’s a chance for us to look further into it, solve it and improve pregnancy rate. Although the guideline tells us only to check for immune problem after miscarriages or IVF failures, why not do it earlier? Why don’t we give “advanced deployment” a try in order to make your dream come true earlier?

Reference:

1. Moustafa S, Young SL. Diagnostic and therapeutic options in recurrent implantation failure. F1000Res. 2020;9:F1000 Faculty Rev-208. Published 2020 Mar 25. doi:10.12688/f1000research.22403.1

http://www.tsrm.org.tw/news/content.asp?id=49  ,2018