Description
Recurrent IVF Failure: Diagnostic and Management Approach focuses on understanding the complex causes behind repeated unsuccessful in vitro fertilization (IVF) cycles. It highlights key diagnostic evaluations, including uterine assessment, embryo quality, genetic testing, immunological factors, and endometrial receptivity. The session discusses personalized treatment strategies such as lifestyle modifications, advanced lab techniques, and tailored hormonal protocols to improve implantation success. Multidisciplinary collaboration among reproductive endocrinologists, embryologists, and counselors is emphasized for comprehensive care. This approach aims to offer renewed hope to couples facing repeated IVF setbacks through evidence-based interventions and empathetic support.
Summary Listen
- Recurrent Implantation Failure (RIF) is defined as the failure to achieve clinical pregnancy after multiple embryo transfers (3 cycles with good embryos, >5 blastocysts, or 4 good quality embryos in <40-year-old women). The European Society of Human Reproduction and Embryology (ESHRE) 2023 defines RIF as a lower-than-expected implantation probability despite transferring good quality, euploid blastocysts.
- Determining RIF involves calculating the cumulative chance of conception using factors like female age, hormone levels, endometrial status, embryo cleavage speed and euploidy, male genetic factors, and lab/clinic performance. Prediction models such as the Dylan model and the iWIF predict tool estimate success based on age, BMI, infertility cause, ethnicity, and IVF history.
- ESHRE 2023 recommends investigating lifestyle factors, endometrial thickness, and anti-phospholipid syndrome (APS) if RIF is suspected. Consider karyotyping both partners, 3D ultrasound/hysteroscopy, endometrial function testing, chronic endometritis testing, thyroid function assessment, and progesterone levels. Vitamin D testing, microbiome profiling, and uterine immune cell testing are generally not recommended.
- Lifestyle factors like smoking, alcohol, caffeine, diet, stress, and BMI should be addressed. Hysteroscopy can be considered after 3D ultrasound detects uterine anomalies. Endometrial function tests may assess endometrial receptivity, and chronic endometritis should be treated with antibiotics based on CD138 immunohistochemistry.
- Genetic factors are evaluated through karyotyping of both partners. If chromosomal abnormalities are detected, genetic counseling and preimplantation genetic testing (PGT) are recommended. Thyroid function should be assessed, and abnormal TSH levels should be treated.
- Screening for thrombophilia is recommended for RIF patients with risk factors. Antiphospholipid syndrome (APS) requires positive antibody tests (lupus anticoagulant, anticardiolipin, anti-beta2 glycoprotein) on two occasions, at least 12 weeks apart.
- Interventions for RIF include lifestyle optimization, antibiotic treatment for chronic endometritis, PGT-A, and blastocyst stage transfer. Vitamin D treatment, endometrial injury (scratching), G-CSF, intralipid infusions, IVIg, PRP infusions, HCG injections, LMWH, GnRH agonists, aromatase inhibitors, and assisted hatching are generally not recommended.
- Treatable factors include uterine defects (surgical/medical correction), embryo selection (morphology, growth dynamics, blastocyst transfer, assisted hatching, PGS), and environmental factors (endometriosis, hydrosalpinx, immune issues). Uterine defects can be corrected via hysteroscopy/laparoscopy.
- Medical treatments for thin endometrium include increasing blood flow and stromal proliferation. Medications like sildenafil, pentoxifylline, vitamin E, and PRP can be considered. Synchronizing the cycle is important. Embryo selection involves choosing morphologically best embryos, blastocysts, and using time-lapse monitoring. Assisted hatching can be considered for frozen embryos with thick zona pellucida or in women >37 years old.
- Optimal Receptivity Analysis (ORA) is a non-invasive endometrial receptivity test using microRNA biomarkers. A blood sample is taken on P+5 (progesterone plus 5 days) to determine personalized window of implantation. ORA results can be pre-receptive, receptive, or post-receptive, guiding the timing of embryo transfer. While ESHRE does not recommend ORA due to a focus on embryo-related causes of RIF, others have reported high pregnancy rates with ORA-guided personalized ET.
- Immune therapies like IVIG and steroids modulate T and B cells, NK cells, and other immune components. Low molecular weight heparin (LMWH) is not recommended routinely in RIF without thrombophilia but may be considered in cases of antiphospholipid antibody syndrome (AAPL) or previous venous thromboembolism (VTE).
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