[Immunization Case] 31-year-old Immune Infertility Case, Finally Succeeded In the 4th IVF Implantation

Immune infertility has always been hurt for infertile mothers. These mothers have not been able to find the reason and do not know what happened. There have been a lot of discussions in IVF immune infertility, but there is no clear final decision and treatment direction.
Author: Dr. Ryh-Sheng Li, MD

Immune infertility has always been hurt for infertile mothers. These mothers have not been able to find the reason and do not know what happened. 

“There have been a lot of discussions in IVF immune infertility, but there is no clear final decision and treatment direction.”

Today, we will share with you a case. This rough immune-infertility mother experienced two failed IVF implantations. After being diagnosed with immune efficiency, she went through primary immunotherapy also failed, and then successfully implanted after secondary immunotherapy.

How do we diagnose? How do we choose primary and secondary treatments? And what might we have learned? How can we do better in the future? We are going to share with you.

Pregnancy history

The pregnancy history and past conceiving history of IVF women are very important.

This young (31-year-old woman) has nothing special in the past conceiving history. For special reasons, She needed to undergo IVF treatment.

After a series of complete examinations, without any special abnormalities, we started egg retrieval and embryo culture treatment.

The Stage of Egg Retrieval and Embryo Culture

During the egg retrieval cycle, since the mother's AMH is 3.8 (normal range), we arranged a long-acting stimulation treatment. The first week she got a long-acting injection, the second shot was short-acting stimulation, and followed with a short-acting trigger, finally, we got a total of 21 eggs, 14 of which were mature (M2 oocyte), without symptoms of early ovarian hyperstimulation.

We choose ICSI as the fertilization method. A total of 14 eggs were fertilized by ICSI, and 12 eggs were successfully fertilized (86%, in line with international high standards), and finally 9 good blastocysts were formed (with a blastocyst-cultured rate of 75%).

Because they were young, the couple did not choose PGS. After eggs were retrieved and fertilized, we freeze the blastocysts to avoid late ovarian hyperstimulation.

Follow-up preparations for implantation.

The First Implantation

Blastocyst grade 4AB, traditional progesterone infiltration 120 hours, pregnancy index b-hCG 1.06.

In the first implantation, we transferred a good blastocyst 4AB, which was transferred after 120 hours of progesterone infiltration (without ERA), combined with low-dose aspirin.

The pregnancy index b-hCG on the 16th day after implantation showed only 1.06, which was low. The embryo seemed to have bedding, but then it did not develop.

The result of this implantation is not good, there might be many reasons. To improve the chance and understand more details, after discussion, she decided to do ERA to confirm whether the implantation window was shifted.

ERA 120 hours

The ERA examination revealed that the implantation window was 120 hours long, and there was no deviation.

In this way, we think and discuss in reverse, the time of the first implantation should be right. Young women, the first IVF with the good quality of the blastocyst and transfer at the right time. It should be a success. How can the pregnancy index bHCG only 1.06 which feels like nothing? Is there an immune abnormality?

So we arranged an examination for "antiphospholipid syndrome", and the results were all normal (including Anti-cardiolipin IgG/IgM, Anti-glycoprotein IgG/IgM, Lupus anticoagulant, Protein C/Protein S); other hormones, including TSH and Prolactin, are also normal.

Therefore, the first implantation is abnormal, and the follow-up inspections are all normal.

(In fact, before the first implantation, we have started to treat ATA antibody positive with quinine.)

Second implantation

Two good blastocysts 4BB/4BC, ERA 120 hours, normal immunity, b-HCG 0.68.

For the second implantation, given the first experience, the immunity was normal and the ERA time was right. However, whether the embryo bedding or not should be the problem of the embryo itself. So, this time we implanted one more, a total of two blastocysts (because at 31 years old, at least one of the two blastocysts is normal), to ensure that we will get pregnant.

The pre-implantation examinations were all normal, and the b-HCG result was 0.68, which was even lower than the first implantation result.

This is even more confusing, transfer more blastocysts, no change in medication, and lower pregnancy index. This is the second implantation failure, which meets the criteria for repeated implantation failure (RIF), and twice abortion, which also meets recurrent pregnancy loss (RPL).

After this implantation, We also checked whether there were immune abnormalities, and the result was still normal.

After this implantation, we recommend resting for six months. Also, we will consult an immunologist to see if there is anything we don’t know. (It's mid-2019)

immunological suggestion :

Adding heparin injections according to previous pregnancy history.

Even though auto-immune blood panel results are normal, medical history is very significant. Which includes past conceiving history, pregnancy, miscarriage histories, and RIF experiences. Heparin injections are suggested by immunology for the next implantation.

Third Implantation

Transfer 2 blastocysts: 4BB/4BC, ERA 120-hour, daily heparin injection, b-HCG 0.613

For the third implantation, we transfer 2 blastocysts to make sure at least one of them is euploid. Transfer blastocyst at the optimal time referring to the ERA test result, 120-hour. Adding heparin injections based on the conceiving history. Unfortunately, the result was not what we expected, beta-HCG data was 0.613.

We did blood tests for antibodies during this treatment. Found that some of the data turned positive surprisingly. Anticardiolipin IgM was normal at the last two transfer treatments, both before and after the implantation. But this time turned positive(13.8/ ref.<12.5). 

The result shocked us. But it was the writings on the wall. As repeated implantation irritated the immune system of the maternal body. That's why the result came positive at the third transfer treatment. 

The failure brought us some new perspectives : 

  1. Conceiving history is more important than blood test results. Test results might come out normal/abnormal. But unusual  

  2. abnormal ATA means "maybe" there are other abnormalities even though the blood test results are normal. 

  3. If miscarriage occurred after transferring transfer the embryo with ERA test, with the normal embryo. It usually had to do with the auto-immune system.

After this implantation, ACM turns positive, but the data is not sky high, we refer the patient to immunology for further discussion. immunologists suggested IVIG((Intravenous immunoglobulin) according to the medical history of the patient.

Forth Implantation

Transfer 2 blastocysts aAB/4BC, ERA 120-hour, heparin injections, IVIG, B-HCG data 5497.

For the fourth implantation, we choose 2# good blastocysts. Using the ERA 120-hour result. And except for heparin, we added IVIG as well. 

We did a blood test 7 days after the transfer surgery for a sneak peek, as IVIG cost a lot, and had to prepare days before the injection. The B-HCG data was 196.6, which was very good news! On day 15 after the transfer, our B-HCG data is 5497! Finally! 

The data was well, so we continued with the IVIG injection, trying to keep the maternal immune system in a calm status, not to attack the embryo, and not to affect its development. In the meantime, Plaquenil, Bokey, and heparin were used continuously. Now the baby is over AP16 weeks, growing stronger and stronger every day. 

Conceiving history is more important than the blood test results

"Conceiving history is more important than the blood test results, do every step well, do the next step better! "

Going through her medical history, the pregnancy test came positive, but the data was a bit low. We suspected the embryos didn't develop after the implant. So if we focused on her history instead of the blood test data, maybe we could have put heparin in use earlier at the second transfer treatment, we might get a better outcome. 

Of course, it might be the same as well. Since the final success is due to the IVIG. Using IVIG is because RIF 3 times and the auto-immune data turned positive. Infertility with auto-immune problems is very difficult to handle. You might get frustrated and feeling down. My suggestion is to take it slow, step by step, find the reason behind it. I am sure that you can have a happy ending just like the case I shared.

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