Want to Meet You So Bad! After repeated miscarriages (2)

Her immune attacks were categorized as 'severe.' Only with the use of last-resort medications did the situation resolve. Such cases, among the hundreds of 'auto-immune mommies' treated at Stork Fertility Center each year, are relatively rare, with a level of complexity comparable to that of celebrity Xiaoqiao Zhao.
Consultation
2024-05-17
Author: Dr. Hsing-Hua Lai, MD
Translator: Phillip

Every incident has its cause! Searching for the murderer at the 'crime scene coordinates'.

How many miscarriages can you endure? Would experiencing four in two years drive you insane?

Over two years, she(555*3) experienced miscarriage four times, including two surgical miscarriages. Sending the miscarriage tissues for chromosomal analysis resulted in normal, which is perplexing. Despite undergoing four precise IVF implantations, why does every implantation lead to miscarriage?

Every incident has its cause! Without curiosity, the mastermind would still be at large, and she cannot become a mother this year. Unlike 'repeated implantation failures,' 'recurrent miscarriages' present a different challenge. Despite normal chromosomal results, why the pregnancy termination remains a mystery.

Want to find the murderer? First, let's design the 'crime scene coordinates' to pinpoint when the fetus was harmed. Come on! It'll be clearer and easier to understand if we have a lesson before the storytelling.

The crime scene coordinates for the embryo

In the first and second weeks after embryo transfer, as well as before and after the appearance of fetal heartbeat, the most common incidents occur. The first two are referred to as shallow implantation, and the last one is blighted ovum (the blastocyst is visible on ultrasound but no fetal heartbeat). Therefore, in these three critical time points, it is necessary to insert 'specialized tests' or 'advanced immune examinations' for evidence collection. We call it "Dynamic Triple Detection", always ready to dynamically detect whether the murderer is present.

The common murderers include five: blood clots, white blood cells, tumor necrosis factor, natural killer cells, and B cells. Different murderers require different treatment approaches. Typically, immunologists will administer medications step by step, known as 'first-line' if ineffective, switch to 'second-line,' and so on. For individuals with severe immune attacks, it means undergoing a maximum of four trial-and-error attempts. My goodness! Where do so many good embryos come from? It is speculated that biologics beyond the 'second-line' are affordable to few.

Dynamic Triple Detection" to rescue Auto-Immune mommies

In her first transfer, it was a shallow implantation; in the second, it resulted in a blighted ovum. Chromosomal analysis of the miscarriage tissue was normal. In the third attempt, it was still a shallow implantation. For the first three attempts, only 'first-line' immunotherapy was used, depleting all good embryos. In the fourth attempt, she switched to using donor eggs, transferred two embryos, and upgraded to 'third-line' immunotherapy. All four attempts involved precise transfer and included Endometrial Receptivity Analysis (ERA). Despite these efforts, the result was still a blighted ovum. Speechless! Furious!

In the fourth attempt, expensive immunoglobulins and Humira were used, with each course costing at least two hundred thousand. Although the result did not meet expectations, there was some progress. In the "second detection" after transfer, it was found that B cells surged to 26, white blood cells increased to 15900, and tumor necrosis factor soared to 43.8. These data proved valuable for the fifth attempt.

In early 2021, Stork Fertility Center pioneered the "Dynamic Triple Detection," helping identify the murderer in the fourth attempt and providing empirical evidence for the fifth attempt. In the two and a half months before transfer, two rounds of "MabThera" were administered, effectively suppressing B cells and white blood cells. Combined with medication from the fourth attempt, we successfully brought back a baby. This baby went through an "immunity feast" to be born, truly a "priceless baby"! She is also one of the early beneficiaries of the "Dynamic Triple Detection."

In early 2020, we shared "Want to Meet You So Bad! After Repeated Implantation Failure(I)" where all three Ms. Ye have become mothers. They belong to the category of moderate immune rejection, requiring "third-line" immunotherapy. However, for her, the immune attack was classified as "severe," and it could only be resolved at the highest tier of medication. Such cases, among the hundreds of "auto-immune mommies" treated at Stork Fertility Center each year, are relatively rare, with a level of complexity comparable to that of celebrity Xiaoqiao Zhao.

 

*This article only reflects the treatment status at the time of writing, and the actual situation should be discussed with the doctor.

Comment

Dr. Hsing-Hua Lai, MD
Dr. Hsing-Hua Lai, MD
  1. The crime scene coordinates of the four implantation attempts for her are as follows:

    Embryo transfer

    First transfer

    Second transfer

    Third transfer

    Fourth transfer

    Time of the incident

    First week

    Fifth week

    First week

    Sixth week

    Number of embryos

    x

    two

    x

    one

    Size of the embryos

    x

    x

    x

    x

    Embryo bud

    x

    None

    x

    Yes

  2. In her fourth transfer, what valuable information was collected through the "Dynamic Triple Detection"?

    Suspect

    Blood clots

    White blood cells

    Tumor necrosis factor

    Natural killer cells

    B cells

    Murderer

    x

    v

    v

    x

    v

  3. Why didn't she use any medication in her second transfer, and the fourth transfer, despite using expensive biological agents, the result was the same?Typically, immune attacks strengthen with the "number of miscarriages." If immunoglobulins and Humira were not used to protect in the fourth transfer, my observation usually concludes with a "shallow implantation." Even with medication escalated to the "third line" in the fourth attempt, it still resulted in a blighted ovum. The main reason is that dealing with B cells requires medication from the "fourth" or "fifth line" for a significant therapeutic effect.

    fourth transfer

    Seventh day after transfer

    Tenth day after transfer

    Fourteenth day after transfer

    Twenty-third day after transfer

    Conclusion

    β-HCG

    52

    266

    1879

    4677

    Blighted ovum

    Remarks

    At a normal pace

    At a normal pace

    At a normal pace

    Developmental delay

    Blighted ovum

  4. On the seventh day after the fifth transfer, almost all five major murderers were nearly neutralized, as follows:

    From the data in the table on natural killer cell, it can be inferred that there is still a chance for a successful live birth even without immunoglobulin.

    Murderer

    Blood clots

    White blood cells

    Tumor necrosis factor

    Natural killer cells

    B cells

    Values

    Normal

    11100

    27.1

    12.6

    0

  5. If developmental delays are observed after the transfer, is there still time to reverse the fate of being attacked to death?

    In Q2 2022, we invented “Implanted-Blastocyst Rescue (IBR),” and to date, we have successfully saved more than a dozen babies. Please refer to “Implanted-Blastocyst Rescue”.