In this video, you’ll learn how recurrent pregnancy loss (RPL) is investigated and treated in IVF — and what can truly help reduce the risk of miscarriage.
Guest Speakers:
Dr Harry Karpouzis – Founder & Scientific Director, IVF Pelargos Fertility Group
Dr Raúl Olivares – Medical Director, Barcelona IVF
Hosted by: Dr Shabana Bora, MBBS, MRCOG, Consultant Gynaecologist, Fertility Specialist, Co-founder of ALMA fertility, UK.
Dr Raúl Olivares, Medical Director, Barcelona IVF: Recurrent miscarriage is always a difficult issue. In most cases, the main factor we can address is embryo quality. The majority of miscarriages are related to genetic abnormalities in the embryo. Therefore, our first step is to ensure that embryos are not only good-looking but also genetically normal. PGT-A becomes an essential tool, particularly in patients over 38, when the percentage of abnormal embryos increases. Transferring genetically tested embryos would be my first approach in cases of recurrent miscarriage.
Dr Raúl Olivares, Medical Director, Barcelona IVF: It is age-related. It is more difficult to explain recurrent miscarriages in a younger woman than in an older one. In younger patients, we tend to investigate after two miscarriages. In older patients, we may be slightly more tolerant before initiating investigations, but ultimately, age guides the decision.
Dr Harry Karpouzis, Founder & Scientific Director, IVF Pelargos Fertility Group: The most common cause of recurrent miscarriage is chromosomal abnormalities. Although this is related to age, it can also occur in younger women. The first step is to confirm that we are truly dealing with recurrent miscarriage. In younger women, the investigation usually starts after two losses.
If IVF is required, PGT-A is essential. Without knowing the chromosomal status of the embryo, a failed transfer or miscarriage provides no clear explanation. Other factors include uterine abnormalities such as septa, fibroids, or polyps, which often require hysteroscopy for diagnosis. Chronic infections and endometritis are increasingly recognised contributors. Blood clotting disorders, thyroid function, and immune factors must also be assessed. However, chromosomal issues should always be ruled out first before exploring rarer causes.
Dr Harry Karpouzis, Founder & Scientific Director, IVF Pelargos Fertility Group: Yes. Karyotyping both partners is essential before PGT-A. Without this information, PGT-A may be inaccurate or inappropriate. Karyotyping helps identify translocations and determines whether PGT-A or PGT-SR is required.
Dr Raúl Olivares, Medical Director, Barcelona IVF: Yes, in all IVF patients, not only those undergoing PGT-A. Sometimes karyotyping reveals the underlying cause of failure, indicating the need for genetic testing that was not initially planned. We also assess sperm genetics using FISH and DNA fragmentation testing. Male factors can contribute to recurrent miscarriage even when semen analysis appears normal.
Dr Raúl Olivares, Medical Director, Barcelona IVF: KIR AA and HLA-C interactions are complex immunological factors. Evidence suggests that issues arise mainly in egg donation cycles when transferring more than one embryo. With single embryo transfer, this interaction should not cause miscarriage.
Chronic endometritis should be investigated, as it is often asymptomatic. Microbiome testing, such as EMMA and ALICE, can identify imbalances. Treatment with antibiotics and probiotics may reduce miscarriage risk.
Dr Harry Karpouzis, Founder & Scientific Director, IVF Pelargos Fertility Group: Other causes of recurrent implantation failure must be excluded, including endometritis and uterine pathology through hysteroscopy. Evidence for ERA testing is declining, but in rare, unexplained cases, it may still be considered. Immunological treatments must be personalised and guided by specific testing. Empirical “kitchen sink” protocols are not supported by evidence.
Dr Harry Karpouzis, Founder & Scientific Director, IVF Pelargos Fertility Group: Endometriosis can contribute to implantation failure and miscarriage. Genetic testing may indicate suspicion when a laparoscopy is not performed. Downregulation can help, but the embryo transfer technique must also be optimal. Chronic endometritis and immune factors should be investigated concurrently.
Dr Raúl Olivares, Medical Director, Barcelona IVF: ERA was promising initially, but evidence now shows limited benefit. Studies suggest many cycles are required to see any advantage, which is not clinically acceptable. Natural cycles often provide a consistently open implantation window. ERA may be considered only in exceptional cases.
Dr Harry Karpouzis, Founder & Scientific Director, IVF Pelargos Fertility Group: Progesterone is a muscle relaxant and may help. Other interventions, such as activity restriction, have no supporting evidence.
Dr Raúl Olivares, Medical Director, Barcelona IVF: Uterine contractions are difficult to measure reliably, and treatments like Atosiban have not demonstrated a clear benefit.
Dr Raúl Olivares, Medical Director, Barcelona IVF: In Spain, PGT is not permitted in double donation in many cases. Using donor eggs does not guarantee euploid embryos; up to 30% may still be aneuploid. KIR typing can be informative, but problems are uncommon with single embryo transfer.
Dr Harry Karpouzis, Founder & Scientific Director, IVF Pelargos Fertility Group: Thrombophilia testing is important, especially in younger women with unexplained recurrent miscarriage. Antiphospholipid syndrome must be clearly defined using both clinical and laboratory criteria. Not all thrombophilias require treatment, and overdiagnosis must be avoided.
Dr Shabana Bora, MBBS, MRCOG, ALMA Fertility, UK: Do you ever treat it empirically?
Dr Raúl Olivares, Medical Director, Barcelona IVF: In cases of multiple miscarriages, empirical treatment with aspirin and heparin may be considered, particularly when clinical suspicion is high. Dosing must be appropriate and supervised, often with haematology input.
Dr Raúl Olivares, Medical Director, Barcelona IVF: DNA fragmentation can reduce embryo quality. Risk factors include smoking, alcohol, infections, and varicocele. Treatment may involve lifestyle changes, antioxidants, and sperm selection techniques. Interventions should be implemented for at least 2 months before IVF.
Dr Raúl Olivares, Medical Director, Barcelona IVF: Yes. At 39, a significant proportion of embryos are aneuploid. PGT-A helps ensure embryos transferred have the highest chance of resulting in an ongoing pregnancy. In recurrent miscarriage, the goal is not pregnancy alone, but a live birth.
