During this webinar, Dr Ksenia Khazhylenko
, Obstetrician-gynecologist, Fertility Specialist & Geneticist at IVMED – Fertility Center talked about 2 of her past patients who experienced recurrent miscarriages and were able to finally achieve their final goal – a healthy baby.
Repeated miscarriages – real-life cases
Dr Khazhylenko started by presenting the first case about a young patient who was 28 years old and her husband of much older age at 54. They had 5 previous biochemical pregnancies (she had a positive pregnancy test, but her hCG of max, 300 UI/mL). When she came to the clinic, she was exhausted and disappointed and wanted to find a reason for her miscarriages and wanted to check all options.
- 28-year-old with a husband of 54 years old, 5 previous biochemical miscarriages, antiphospholipid syndrome, a smoker, thrombosis in her near family
Firstly, we checked her test results, and she had a normal karyotype, normal BMI, normal uterine anatomy, and she had a normal ovarian reserve, her husband, despite his age, had normal semen parameters. She also had a normal thyroid function and endometrium with no signs of endometritis, however, she also had a higher risk of traumatic events because she had a high level of antiphospholipid antibodies and was also a smoker, she smoked 10 cigarettes a day for a very long time. Additionally, she was homozygous on PAI-I, plus her mother died quite early from thrombosis at 46 years old, and it’s always important to check a family history. She had a very high risk of thrombotic events during pregnancy, and she had recurring pregnancy losses, the antiphospholipid syndrome is a big problem during the pregnancy. It’s significant to mention that thrombotic events can happen a bit later in the second and third trimesters. There is some publication about antiphospholipid antibodies in patients who underwent IVF programs where they suggest that patient sometimes such patients can have even increased possibility to become pregnant in IVF program, but unfortunately, this can result in a miscarriage during the second and third trimester.
Therefore, we’ve explained that the reason for her early miscarriage was an antiphospholipid syndrome, although the most common cause of early pregnancy losses is chromosomal pathology. We advised to either continue with a natural conception and antithrombotic therapy or go ahead with IVF and PGT-A with antithrombotic therapy using low molecular weight heparin and aspirin. The patient decided to proceed with IVF, so we started with ovarian stimulation.
We obtained 20 eggs which was a good result for her age, and almost all eggs were fertilized, we got 8 blastocysts, and it was again a good result, but PGT-A testing revealed that only 1 embryo was euploid, the rest were abnormal. Therefore, the first conclusion was that all previous pregnancy losses could be because of chromosomal issues. We did an embryo transfer with 1 euploid embryo in a natural cycle, and we started low molecular weight heparin (LMWH) and aspirin from the embryo transfer, and 12 days later, she got a positive pregnancy test.
After 2 weeks, she had her first ultrasound, and it turned out to be a twin pregnancy despite transferring a single embryo. Approximately 2% of single embryo transfers can end in a twin pregnancy because of embryo splitting in the very early stage after implantation. However, the majority of these twins are monozygotic, so they come from 1 embryo, and usually, in this type of twins, when we do the first ultrasound, we can see just one amniotic sac, however, in this case, we saw 2 amniotic sacs with 2 different embryos.
What can be the reason for such a situation? It’s possible that it was not the splitting of the embryo, but that it was a natural conception before the embryo transfer. We always recommend using contraception before transfer in a natural cycle, but unfortunately, not all patients go forward with our recommendations. Therefore, dichorionic twins, in this case, meant that it was due to a natural conception plus a pregnancy from the transfer, but it was good news because this was a program with genetic testing, and we knew that 1 embryo was healthy, however, we didn’t know anything about the second embryo.
The antithrombotic therapy was very complicated during the pregnancy because the patient bled from early pregnancy, it wasn’t just spotting, it was severe bleeding sometimes, we decided to stop aspirin, and it was cancelled in a typical week of pregnancy, and later we have cancelled LMWH at 12 weeks. The pregnancy progressed normally till 30 weeks of pregnancy, but then intrauterine growth restriction started from one fetus, and after 1 month, the condition of one of the fetuses became worse. Therefore, we decided to induce delivery, the delivery was done by caesarean section, and 2 baby girls were delivered, the discordance between these twins was almost 50%, but fortunately, despite this both girls were healthy, and now they are 6 years old, and they are identical. This was a very uncommon situation with monochronic twins with 2 different amniotic sacs, it was really rare.
The conclusion from this case is that Repeated Pregnancy Loss (RPL) can be caused by different conditions, and despite some very obvious conclusions, we need to continue our examination even if we think we know all the possible reasons.
Early losses mostly happen due to chromosomal pathology, so we need to provide full examination at all costs. The next conclusion is that antiphospholipid syndrome means a higher risk of pregnancy, and without treatment, a patient often has not just pregnancy losses but also complications with neonatal risks, so the treatment is very important.
If we suspect chromosomal pathology is the reason for recurrent miscarriages, we should at least discuss the IVF program with PGT-A, which can be very helpful in this situation. We should also strongly recommend contraception before transfer in the natural cycle and we should keep in mind that sometimes single embryo transfer can result in twins.