IVF and Recurrent Implantation Failure (RIF): Causes, Diagnosis, and Treatment
Recurrent implantation failure can be frustrating and distressing for both patients and clinicians, and it requires a thorough evaluation and a personalized approach to management.
Recurrent Implantation Failure IVF: Causes, Diagnosis, and Treatment
Recurrent implantation failure (RIF) is a condition where embryos repeatedly fail to implant after transfer in several IVF treatment cycles. Recurrent implantation failure can be frustrating and distressing for both patients and clinicians, and it requires a thorough evaluation and a personalized approach to management.
What causes recurrent implantation failure?
Reduced endometrial receptivity:
This refers to the inability of the endometrium (the lining of the uterus) to accept and support the embryo. This can be due to anatomical abnormalities (such as polyps, fibroids, or adhesions), hormonal imbalances (such as low progesterone or thyroid dysfunction), immunological factors (such as autoantibodies or natural killer cells), or infections (such as chronic endometritis).
Embryonic defects:
This refers to the genetic or chromosomal abnormalities of the embryo that prevent its normal development and implantation. This can be due to paternal or maternal factors (such as advanced age, smoking, or exposure to toxins), or laboratory factors (such as culture conditions or manipulation techniques).
Multifactorial causes:
This refers to the combination of maternal and embryonic factors that interact and affect the implantation process. This can include epigenetic modifications, oxidative stress, metabolic disorders, or environmental influences.
According to Michalis Kyriakidis, MD, MSc, Gynecologist in Assisted Reproduction, Deputy Clinical & Scientific Director in Embryolab Fertility Clinic, "Recurrent implantation failure is an emerging problem, which fertility doctors need to deal with often. The most common cause is genetic abnormalities or morphological integrity of the embryos related to parental age. Less common causes may include uterine structural abnormalities, metabolic disorders of the mother as well as functional endometrial problems."
How is recurrent implantation failure diagnosed?
There is no consensus on the definition of RIF, as different studies and clinics use different criteria. However, a commonly used definition is the failure to achieve a clinical pregnancy after transferring at least three embryos in a minimum of three fresh or frozen cycles in women under 40 years old. The definition should also take into account the maternal age and the embryo stage (cleavage or blastocyst) at transfer.
The diagnosis of RIF requires a comprehensive evaluation of both the female and the embryo. The evaluation should include:
- A detailed medical history and physical examination of both partners
- A pelvic ultrasound and hysteroscopy to assess the uterine cavity and rule out any structural abnormalities
- A hormonal profile to check the levels of thyroid hormones, prolactin, progesterone, and vitamin D
- An immunological assessment to measure the levels of autoantibodies, natural killer cells, cytokines, and other inflammatory markers
- A microbiological assessment to detect any bacterial or viral infections in the endometrium or semen
- A genetic assessment to screen for any chromosomal abnormalities or inherited disorders in both partners
- A preimplantation genetic testing (PGT) to analyze the embryos for any aneuploidies or monogenic diseases
How is recurrent implantation failure treated?
The treatment of RIF depends on the underlying cause and should be individualized for each patient. The treatment options include:
- Correcting any anatomical abnormalities by surgery or medication
- Optimizing any hormonal imbalances by supplementation or medication
- Modifying any immunological factors by immunotherapy or medication
- Eradicating any infections by antibiotics or antivirals
- Improving any embryonic factors by PGT or assisted hatching
- Enhancing any endometrial receptivity by endometrial scratching, growth factors, or stem cells
- Adjusting any IVF protocol by changing the stimulation regimen, timing of transfer, number of embryos transferred, or type of transfer (fresh or frozen)
In addition, patients with RIF should adopt a healthy lifestyle by avoiding smoking, alcohol, caffeine, and stress, and by maintaining a normal weight, balanced diet, and regular exercise. They should also seek psychological support and counseling to cope with the emotional impact of RIF. Recurrent implantation failure is a complex problem that requires a multidisciplinary approach and a close collaboration between patients and clinicians. With proper diagnosis and treatment, patients with RIF can increase their chances of achieving a successful pregnancy and live birth.
Medical Disclaimer:
The information provided in this blog is intended for general informational purposes only and should not be considered as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your healthcare provider or qualified medical professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this blog.
