Papel de la ecografía en la predicción de la implantación en TRA Dr Juan A Garcia-Velasco IVI-Madrid

….1978 Future

Folículos vs Endometrio Future

Mejoría en resultados Future Implantación

En qué nos fijamos Grosor Patrón Flujo vascular volumen 3D Histeroscopia …..itis? ERA …….y si todo está bien? Key message When ovarian hyperstimulation was first introduced, the focus was on number of oocytes retrieved and clinical pregnancies.

Endometrio y TRA 1 Grosor

Grosor endometrial Gestantes (1425) No gestantes (1025) AUC 10.8 ± 2.1 estudio retrospectivo, un único centro n = 2450 primeros ciclos de FIV de 2002 a 2007 Gestantes (1425) No gestantes (1025) AUC 10.8 ± 2.1 10.4 ± 2.2 0.548 Cai et al. Hum Reprod 2011

Grosor endometrial n=2896 Sólo 0.3% de los ciclos Grosor endometrial (mm) Chen et al. Reprod Biol Endocrinol 2010

Grosor endometrial n=465 Grosor endometrial (mm) Remohí et al. Hum Reprod 1997

Grosor endometrial Check JH et al. Clin Exp Obstet Gynecol 2011

Endometrio y TRA 2 Patrón

Patrón endometrial

Patrón endometrial Check et al. Hum Reprod 1993

Endometrio y TRA 3 Flujo vascular

Flujo vascular Mercé et al. Fertil Steril 2008

Flujo vascular Abundante Insuficiente Wang et al. Reprod Biol Endocrinol 2010

Flujo vascular Bajo IR - IP Alto IR - IP Wang et al. Reprod Biol Endocrinol 2010

Flujo subendometrial 19 33 n=182 <38 años Wang et al. Reprod Biol Endocrinol 2010

Flujo vascular y grosor Wang et al. Reprod Biol Endocrinol 2010

Endometrio y TRA 4 Eco 3-D

Ecografía 3D Raga et al. Hum Reprod 1999

Ecografía 3D “Aunque la eco 3D parece muy interesante, su utilidad clínica para predecir la gestación en FIV es LIMITADA” “Se ha comprobado que el volumen endometrial es ineficaz como predictor de la gestación tras FIV en la inmensa mayoría de los estudios” Alcázar et al. Reprod Biomed Endocrinol 2006

Endometrio y TRA 5 Histeroscopia

Endometritis n=678 Sólo 2.8% tenían endometritis Ningún impacto reproductivo Fatemi et al. Fertil Steril 2012

Endometrio y TRA 6 Genes

Endometrial receptivity ERA® Receptive vs Non Receptive PILOT STUDY 1950’s Siglo XXI 238 genes relacionados con la ventana de implantación Receptive vs Non Receptive

Receptive Profile .

Muestra – receptivo RC1

Muestra –receptivo RC2

No receptivo NR1 .

No receptivo NR2 .

Endometrial Receptivity Array (ERA) - Resultados INTERPRETACION DE RESULTADOS Receptivo (R): El perfil de expresión génica se corresponde a un endometrio receptivo normal Se recomienda hacer la transferencia en la ventana de implantación No Receptivo (NR): El perfil de expresión génica no se corresponde con una endometrio receptivo normal Se recomienda personalizar la ventana de implantación

ERA Clinical Outcome in Non Receptive patients Example of Case 6272 Case 6272 P+5 Case 6272 P+7 Post-Recep Pre-Receptive Receptive Proliferative

Endometrio y TRA Y si todo está bien, ¿qué hacemos?

Sildenafilo y endometrio Estudio de cohortes One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Sher and Fish. Fertil Steril 2002

Sildenafilo y endometrio One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Khazaei et al. Int J Fertil Steril 2011

Estradiol vaginal One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Fanchin et al. Fertil Steril 2001

Estradiol prolongado 4% 38% n=1550 36 mujeres <8mm 23 ET 13 FET 14-82 días One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Chen et al. J Assist Reprod Gen 2006

Aspirina 22 estudios AAS vs no tratamiento ninguna diferencia One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Cochrane 2010

Estimulación mecánica Evidencia directa Posible impacto beneficioso de una biopsia endometrial en el ciclo previo Datos limitados: retrospectivos y observacionales Aún muchas respuestas sin contestar Barash 2003 Raziel 2007 Zhou 2008 N 45 63 60 Fallos previos 4 7 n.d. Edad 33.8 33.1 31.6 TG/TE 66 vs 30 30 vs 12 48 vs 27 One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Almog et al. Fertil Steril 2010; Barash et al: Fertil Steril 2003

Estimulación mecánica Evidencia Indirecta n = 421 FIV fallida - 2 ó más no Hx HX b1. sin hallazgos b2. operatoria 21.6% 32.5% * 30.4% * One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Expresión diferencial de genes relacionados con la implantación tras la bx endometrial Demirol et al. RBM Online 2004; Mooney et al Fertil Steril 2003; Rama et al. Arch Gyn Obstet 2006

G-CSF 4 casos con endometrio inadecuado ¿Facilita el desarrollo de la endometriosis? Perfusión intracavitaria de 300mg de G-CSF Expansión endometrial en 48h Las 4 embarazadas ….pendiente aún de RCT’s One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. Gleicher N et al. Fertil Steril 2011

Movilizar stem cells 33 años Infertilidad primaria 8 años Legrado en el pasado Hipomenorrea 3 IAH 1 FIV 8mg E2 y 75mg AAS endometrio 3.2mm FSH 19.7 IU DO + surrogación One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. aspiración de médula ósea 45 ml cresta iliaca céls angiogénicas endom 24h dps 0.7ml con 39 mill Nagori et al. J Hum Reprod Sci 2011

Impacto de la estimulación

Vitrification (eggs) Cryotop efficiency -196ºC 25ºC Ice (Freezing) No Ice (Vitrification) Freeze Sol. Vitri Cobo A et al. Fertil Steril 2008

Conclusiones Aún hoy, la ecografía bidimensional sigue siendo el método más sencillo y eficaz para evaluar un endometrio Las nuevas tecnologías no superan en capacidad predictiva a la ecografía bidimensional Ante un endometrio inadecuado, la mejor opción es congelar -ovocitos o embriones- y transferir cuando tengamos un endometrio adecuado One injection of corifollitropin alfa replaces 7 daily injections of rFSH during COS. The number of injections is reduced by about 70% compared with the long agonist protocol (from 35 to 10). In combination with the GnRH antagonist, this COS protocol can considerably reduce the treatment burden on patients. Additional daily rFSH after day 7 is to be determined by physician assessment. So what exactly is corifollitropin alfa? Let’s take a look at its molecular makeup on the next slide to see how it can perform as a sustained follicle stimulant. No existe ningún protocolo que haya demostrado una superioridad frente a otro: es importante que el paciente conozca que son protocolos que se encuentran en un entorno experimental

¡Gracias! juan.garcia.velasco@ivi.es