Trying IVF3.0 plus after two miscarriages by artificial insemination.
Ms. Y first came to the clinic for a premarital checkup, but also because she had irregular periods and wanted further advice on pregnancy. The initial assessment was that both partners were in good condition except for the woman's ovulation problem, and Ms. Y was very young herself; of course, the first treatment was ovulation pills plus natural intercourse.
After four months of trying and failing to get pregnant, we began to change our plan to intrauterine insemination (IUI), and this is where all the confusion began! During her first IUI cycle, Ms. Y started bleeding about 10 days after the insemination. She didn't return until the bleeding became more and more obvious when the cycle resulted from a pregnancy test failure. After reviewing the medication history, I thought that the amount of luteinizing hormone was sufficient, but I discussed adding a luteinizing injection to strengthen the endometrial support in the next cycle according to her condition and asked her to come back to the clinic immediately if she had the same condition next time.
During the second IUI cycle, Ms. Y also started bleeding about 10 days after the insemination. She followed the doctor's instructions very carefully and returned to the clinic. This time we took a blood test for pregnancy and found that the embryo had actually implanted, but 12 days after insemination, the HCG (human chorionic hormone) was 4.03 mIU/mL, which was not ideal. After telling Ms. Y that the prognosis was not good, I tracked her HCG again 4 days later, but it unexpectedly rose to 32 mIU/mL. At this point, I had mixed feelings - on one hand, I was happy to see that the embryo was continuing to develop, but on the other hand, I was worried that it might be an ectopic pregnancy. However, the subsequent rise in HCG was so rapid that the gestational sac could be seen in the uterine cavity, ruling out the possibility of an ectopic pregnancy. However, the joy did not last long, and within a few days, Ms. Y suffered heavy bleeding, ending the pregnancy with an early miscarriage.
Successful pregnancy after confirming the correct window of implantation
After the second IUI failure, I began to guess whether the bleeding in the first IUI cycle was implantation bleeding, as the HCG on day 12 was 4 mIU/mL, which meant that the embryo had only implanted for 1-2 days, which was 5 days different from the normal schedule. Therefore, I suggested Ms. Y follow the IVF 3.0 plus, thinking that Ms. Y must be a case of the shifted window of implantation, with a later forming embryo, which might have a higher chance of chromosomal abnormality.
After ovarian stimulation, although Ms. Y obtained 13 eggs, the development of the embryos was not very ideal, and in the end, only 2 blastocysts of 5BB grade were obtained. Preimplantation Genetic Testing for Aneuploidy (PGT-A) were made, and it was found that one of them was an abnormal embryo and the other one was a low-rate mosaic. On the other hand, it was confirmed that the autoimmune, tubal, and hysteroscopic factors that may cause miscarriage were normal.
However, to my surprise, Miss Y's final ERA result was 108 hours and not the backward shift in the window that I thought it would be, and I blushed at the thought of my rather confident guess. After discussing the risks of transferring a mosaic embryo, we decided to transfer the low-rate mosaic embryo with the ERA results, 16 days after transfer, Ms. Y was confirmed pregnant with an HCG of 2846 mIU/mL.
Despite the initial good news, Ms. Y's pregnancy was a difficult process, beginning with a rise in antiphospholipid antibodies after the transfer, followed by repeated bleeding, rising blood clot values, and uterine contractions. According to the recommendations of the American College of Obstetricians and Gynecologists, the transfer of mosaic embryos should be done by amniocentesis as a secondary chromosome confirmation. However, the uncertainty of Ms. Y's pregnancy was a cause for concern about the risks of amniocentesis; therefore, after discussion, we decided to use non-invasive chromosomal testing as a preliminary screening method, and the results of the test revealed no abnormalities.
Due to blood clots and uterine contractions, Ms. Y continued to use heparin until 30 weeks of pregnancy and luteinizing injections until 34 weeks, and finally had a healthy, medium-weight baby at 39 weeks of pregnancy. One of the unforgettable things about the follow-up process was that every time Ms. Y came back to the clinic, although she looked nervous, she still gave us a smile, which eased the nervousness of the follow-ups.
Transfer in the wrong window of implantation will still progress but may face miscarriage.
After entering the clinic, the patients are often the ones who teach us the most. As the saying goes, seeing is better than hearing. No matter how much one reads in a textbook, it is never as impressive as seeing for oneself. Therefore, I am always grateful to the patients who trust us.
There is much more to explore in Ms. Y's story, including the transfer of mosaic embryo, blood clots, immune, early uterine contractions ... etc. However, the most impressive thing is that I personally saw that the embryo fell out of the WOI and was still able to implant and develop into a visible gestational sac. After Ms. Y, I encountered several cases with the same ERA result as Ms. Y, but the embryos were finally miscarried after they got out of the window and implanted. Now, if a patient asks me whether to consider ERA if the embryo is implanted, I think I can confidently give an answer.
