Successful sperm retrieval and live birth after ICSI in a man with laboratory-reported partial AZFb and complete AZFc microdeletion: a case report

Recuperación exitosa de espermatozoides y nacimiento vivo tras ICSI en un varón con microdeleción parcial de AZFb y completa de AZFc informada por el laboratorio: reporte de un caso

Background: Y-chromosomal azoospermia factor b (AZFb) and AZFbc deletions are associated with near-complete absence of spermatogenesis in their classical forms, and microdissection testicular sperm extraction (micro-TESE) is typically discouraged; non-classical partial patterns may carry a different prognosis. A live birth, however, is not necessarily a healthy one. Case: A 36-year-old man with 16 years of primary azoospermia presented with a deletion profile characterised by preservation of proximal AZFb markers (sY105, sY121), loss of the distal AZFb marker sY153, and complete absence of all tested AZFc markers (sY1191, sY1291, sY254, sY255), with a 46,XY karyotype. This sequence-tagged site (STS) profile, generated by standard multiplex polymerase chain reaction (PCR), was laboratory-reported as partial AZFb with complete AZFc deletion. Right-sided micro-TESE demonstrated a mixed-atrophy phenotype with focal residual spermatogenesis (mean Johnsen score 2); a small number of motile spermatozoa were retrieved and cryopreserved. After counselling, the couple declined preimplantation genetic testing (PGT). Intracytoplasmic sperm injection (ICSI) of thawed motile spermatozoa fertilised three of seven oocytes, and a frozen-thawed embryo transfer resulted in a male live birth. The infant carried the same AZF deletion and showed multiple dysmorphic features with high-risk aneuploidy screening (trisomy 21); a confirmatory karyotype was pending. Conclusions: Laboratory-reported partial AZFb with complete AZFc deletions may correspond to atypical AZFbc configurations compatible with residual spermatogenesis and successful ICSI. However, a live birth is not synonymous with a healthy child: comprehensive genetic counselling, PGT and prenatal diagnosis are essential, given the obligate transmission of the deletion to male offspring and the increased aneuploidy risk associated with these deletions.

Resumen

Antecedentes: Las deleciones de las regiones del factor azoospérmico b (AZFb) y AZFbc del cromosoma Y se asocian con ausencia casi completa de espermatogénesis en sus formas clásicas, y la extracción de espermatozoides testiculares por microdisección (micro-TESE) generalmente está desaconsejada. Sin embargo, los patrones de deleción parcial no clásicos pueden presentar un pronóstico sustancialmente diferente. Caso clínico: Un hombre de 36 años con 16 años de azoospermia primaria presentó un perfil de deleción caracterizado por preservación de los marcadores AZFb proximales (sY105, sY121), pérdida del marcador AZFb distal sY153 y ausencia completa de todos los marcadores AZFc analizados (sY1191, sY1291, sY254, sY255), con cariotipo 46,XY. Este perfil de sitios de secuencia etiquetada (STS), obtenido mediante reacción en cadena de la polimerasa (PCR) múltiple estándar, fue informado por el laboratorio como deleción parcial de AZFb con deleción completa de AZFc. La micro-TESE del lado derecho demostró un fenotipo de atrofia mixta con espermatogénesis residual focal (puntuación media de Johnsen: 2); se recuperaron y criopreservaron un pequeño número de espermatozoides móviles. Tras el asesoramiento, la pareja rechazó el diagnóstico genético preimplantacional (DGP). La inyección intracitoplasmática de espermatozoides (ICSI) con espermatozoides móviles descongelados fecundó tres de siete ovocitos y una transferencia de embriones descongelados resultó en el nacimiento de un varón. El recién nacido portaba la misma deleción AZF y presentaba múltiples rasgos dismórficos con cribado de aneuploidía de alto riesgo (trisomía 21); el cariotipo confirmatorio estaba pendiente. Conclusiones: Las deleciones de AZFb parcial con AZFc completo informadas por el laboratorio pueden corresponder a configuraciones AZFbc atípicas compatibles con espermatogénesis residual e ICSI exitoso. Sin embargo, un nacimiento vivo no es sinónimo de un hijo sano: el asesoramiento genético integral, el DGP y el diagnóstico prenatal son esenciales, dada la transmisión obligada de la deleción a la descendencia masculina y el mayor riesgo de aneuploidía en estas parejas.

AZF microdeletion; Azoospermia; ICSI; Live birth; Micro-TESE; Preimplantation genetic testing; Aneuploidy; Y chromosome

Palabras Clave
Deleción AZFbc; Azoospermia; ICSI; Nacimiento vivo; Micro-TESE; Diagnóstico genético preimplantacional; Aneuploidía; Cromosoma Y

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