Differential Diagnosis for 4 ICSI Transfer Failures

Given the context of 4 ICSI (Intracytoplasmic Sperm Injection) transfer failures with normal ERA (Endometrial Receptivity Array), normal PGTA (Preimplantation Genetic Testing for Aneuploidy), and a normal uterus, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis

  • Embryo Quality Issue: Despite normal PGTA, the issue might lie in the embryo's ability to implant due to other factors not tested by PGTA, such as mosaicism or epigenetic factors. The quality of the embryo, including its morphological and kinetic parameters, could be a significant factor.

• Other Likely Diagnoses

  • Sperm Quality or Function: Even with ICSI, sperm quality and function (e.g., DNA fragmentation) can affect implantation and pregnancy rates.
  • Endometrial Factor Not Detected by ERA: While ERA tests for receptivity, other endometrial factors such as inflammation, infection, or altered microbiome might not be detected and could hinder implantation.
  • Hormonal Imbalance: Subtle hormonal imbalances not severe enough to cause significant uterine or ERA abnormalities could still impact implantation.

• Do Not Miss Diagnoses

  • Immune Disorders: Conditions like antiphospholipid syndrome or other autoimmune disorders can lead to recurrent implantation failure and are critical to diagnose due to their potential impact on pregnancy and general health.
  • Thrombophilic Conditions: These can increase the risk of recurrent pregnancy loss and implantation failure, making them crucial to identify and manage.

• Rare Diagnoses

  • Genetic Factors in the Female Partner: Rare genetic conditions or undiagnosed chromosomal abnormalities in the female could affect implantation.
  • Uterine or Endometrial Microscopic Abnormalities: Conditions like endometrial polyps, fibroids not detected by initial ultrasound, or microscopic endometrial lesions could interfere with implantation.
  • Infectious Causes: Chronic or latent infections (e.g., mycoplasma, ureaplasma) could potentially affect the endometrium and embryo implantation.

Each of these categories and potential diagnoses should be considered and investigated further to determine the underlying cause of the repeated ICSI transfer failures, given the initial normal findings.