IVF3.0+: The Devil Is In The Details.

Even under the precision implantation, it still failed. Miss Liao could accept this result better than I, and asked me, what else can we do? When can I do implantation again?
Author: Dr. Jia-Lin Hsieh, MD

Donor's Eggs or My Own Eggs?

39-year-old Miss Liao, who has lived in the United States for a long time, has undergone two times IVF treatments in the United States, but because of the low AMH, the number of eggs retrieved is few, and no blastocyst formed in the end, so she thought of "egg donation". We have frequently discussed through emails, but She still can’t decide to use the donor's eggs or her own.

High Rate of Chromosomal Abnormalities in Aged Eggs. Choose the Normal Embryo Precisely by PGS.

Because Ms. Liao's home is in Hsinchu, She decided to take a vacation coming back to Taiwan to go through the egg donation procedures. On the day of the consultation, Ms. Liao took out all the detailed reports in the United States. In the conversation, it was obvious that she had not given up the idea of ​​using her eggs. Although her husband was aside quietly holding his wife's hand, seemed to tell that he would support all her decisions. In the end, we decided to try the last IVF treatment with her eggs. If it still fails, she will change to the egg donation program. Considering the poor ovarian function, we decided to use a mild stimulation program to help the follicles grow up smoothly. At the same time, due to the high rate of chromosome abnormalities in older eggs, it is recommended to perform PGS/PGT-A (pre-implantation chromosome screening) to avoid the implantation of abnormal blastocysts.

The next day, they completed the registration and notarization procedures for egg donation and froze the sperms for future fertilization. We designed a personalized treatment, the dosage of ovulation drugs is adjusted according to the customer’s age and the basic follicles of the current cycle. 4 eggs were successfully retrieved and there was still a small follicle less than 1 cm left. Each egg is very precious for Ms. Liao, so she decided to perform a second egg retrieval one week after the operation, and finally, the egg was retrieved smoothly. Combining two fertilizations, we finally got 1 5BB, 1 6BB, and 2 5BC blastocysts. The good result of creating four good blastocysts with five eggs had made us quite amazing. The PGS report of the 2 BB-grade blastocysts was released. Fortunately, the PGS reports are normal and implantable. According to the experience in Stork fertility center, the average probability of a blastocyst of a 39-year-old woman is 33%. Half of the treatment was completed. Although the blastocyst was prepared, we were still worried about the success of implantation. In the past, the timing for implantation was all based on the doctor's experience and luck.

ERA Finds the Best Timing of Embryo Implantation, Which is Called “Precise Implantation”

Since 2016, Stork Fertility Center introduced endometrial receptivity analysis (ERA), which is based on the concept of "simulated implantation". Through biopsy small amount of endometrium, which is infiltrated 120 hours progesterone, analysis of 248 gene performance, accurately finds the best implantation time. To ensure the successful pregnancy rate and not to waste blastocysts, Ms. Liao accepted the suggestion to do an ERA examination before implantation, although she had to make another trip to Taiwan. The report came out about 2 weeks later. Ms. Liao’s ERA analysis result was 132 hours, which means that it needs to be infiltrated 12 hours more than 120 hours before implantation. We transfer a 5BB blastocyst with normal PGS data according to the ERA result. On the day of the pregnancy test, Ms. Liao and I were confident that there would be at least an 80% success rate this time. However, the b-HCG value was only 0.47, which failed even under the precision implantation. Ms. Liao could accept this result better than I, and asked me, what else can we do? When can I do implantation again?

Review the Problem After Failing and Find Out Where the dDevil is.

Review what went wrong? From autoimmunity to thrombotic factors, from hysterosalpingogram to hysteroscopy, all were rechecked one by one. The reason was found in the dose of progesterone infiltration before implantation. The purpose of the ERA test is to find the "optimal implantation time". Therefore, the frequency and dosage of natural progesterone in the ERA cycle and implantation cycle must be the same. When Ms. Liao was undergoing ERA, the way of taking progesterone was two tablets after three meals. However, the dosage was increased to three tabs after three meals in her first transfer cycle since we were eager to make things perfect. Although the starting time of the progesterone is the same, the different concentrations of lutein in the blood may affect the endometrial implantation window. Perhaps this is where the devil is.

After reviewing this key point, Ms. Liao decided to try the last time to transfer all her blastocysts. At the beginning of the implantation cycle, Ms. Liao was reminded again of the importance of medication frequency and dosage. The thrombotic factors were also confirmed within the normal range on the day of implantation. After 15 days, the pregnancy test strip showed two deep lines, and the β-HCG was 4758, the pregnancy rate was no longer just 80%, we achieved 100%.

Ms. Liao was unconfident about retrieving her eggs in the beginning, she finally got the maternal health booklet in the end and seriously did the prenatal checkups. We all looked forward to welcoming a new family member this Christmas.

When patients ask about the pregnancy rate and success rate, I always tell the truth:

“There is no 100% absolute in medicine. The pregnancy rate is a statistical representation.”

With precision medicine, to eliminate the controllable variables that affect pregnancy as much as possible, then the uncontrollable variables will become fewer. With ERA, we can avoid misjudging the implantation time and waste embryos; With PGS, we can avoid transferring embryos with abnormal chromosomes. Last but not least is to stick it out. Bless those who are still on the road to having a baby. 

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