Transcript Obstructive
Fertiliteitsdiagnostiek anno 2011 Willem Ombelet Genk Gent, 12-05-2011 10-15 % van de koppels met kinderwens hebben fertiliteitsproblemen Oorzaken 30% man 30% vrouw 30% man & vrouw 10% onbekend Spermatogenesis Female Male Serum: infections, hormonal, thyroid, AMH FSH HSG Prl Hysteroscopy 0 2-3 Serum: infections, hormonal Semen sample E2, Prog, LH US uterus & ovaries PCT E2, Prog 14 28 menses Outpatient Laparoscopy CT, MRI, ... Treatment repeat semen sample US + Doppler scrotum Genetics Oorzaken: vrouw Baarmoederhalsfactor zz Implantatiestoornis Eileiderfactoren Sterilisatie post-infectie erge endometriose Eisprongstoornissen Syndr v Asherman Poliepen, myomen, infecties PCO hyperprolactinemie Andere afwijkingen Post-heelkunde Meest frequente vrouwelijke factor Anovulatie Oligomenorree (cyclus > 35 d) Amenorree Primair (XO - syndr v Turner) Secundair normogonadotroop (hyperprolactinemie) hypogonadotroop hypergonadotroop (PCO – syndroom) Hypogonadotrope amenorree stress, vermagering, sport Simple weight loss amenorree Exercise-associated amenorree Psychogene hypothalame amenorree Lage E2, laag FSH en LH, hoog cortisol Hyperprolactinemie PCO - Syndroom Oligo- of anovulatie Cyclus > 35 dagen Hirsutisme, haaruitval Hyperandrogenisme Acne testosterone PCO-echografisch 12 follikels < 10mm – bilat Of Ovarieel volume > 10 ml ( 0.5233 x L x B x H ) Ovariële reserve 100 100 104 75 50 103 25 102 0 10 20 30 40 50 60 Ir r e gul ar i ty 25 M en opa use Irregular cycles 105 50 rilit y Menopause Ons et End of fertility Ste Declining fertility lity Optimal fertility 106 75 Sub fert i Number of follicles 107 Cumulative % Proportion of poor quality oocytes Proportion of poor quality oocytes (%) Number of follicles 0 21 31 41 46 Age (years) Female Age (yrs) Website: www.fvvo.be Broekmans, FV&V in ObGyn, 2009, 2, 79-89 51 61 Accuracy Non Pregnancy prediction 1 0.9 0.8 Sensitivity 0.7 0.6 0.5 0.4 sROC curve AFC sROC curve AM H sROC curve FSH AFC studies AM H studies FSH studies 0.3 0.2 0.1 Accuracy Poor Response prediction 0 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1 1 - Specificity 0.9 0.8 Broekmans, FV&V in ObGyn, 2009, 2, 79-89 Sensitivity 0.7 0.6 0.5 0.4 sROC curve AFC 0.3 sROC curve AM H AFC studies 0.2 AM H studies 0.1 0 0 0.1 0.2 0.3 0.4 0.5 0.6 1 - Specificity 0.7 0.8 0.9 1 Cavum- en tubapathologie Female Male Serum: infections, hormonal, thyroid FSH HSG Prl Hysteroscopy 0 2-3 Serum: infections, hormonal Semen sample E2, Prog, LH US uterus & ovaries PCT E2, Prog 14 28 menses Outpatient Laparoscopy CT, MRI, ... Treatment repeat semen sample US + Doppler scrotum Genetics HSG: unicornuate uterus, patent tube MRI: unicornuate uterus MRI: ectopic ovary anterior to the external iliac vessels Ombelet et al., N Engl J Med, 348, 667, 2003 Diagnostische Hysteroscopie Laparoscopie Female Male Serum: infections, hormonal, thyroid FSH HSG Prl Hysteroscopy 0 2-3 Serum: infections, hormonal Semen sample E2, Prog, LH US uterus & ovaries PCT E2, Prog 14 28 menses Outpatient Laparoscopy CT, MRI, ... Treatment repeat semen sample US + Doppler scrotum Genetics WHO 1987: 3555 men with male factor WHO 1999 : “authority-based” // not “evidence-based” Normaal : ≥20 mill / ml Oligozoospermie : < 20 mill / ml Asthenozoospermie : < 25 % grade a < 50 % grade a + b Teratozoospermie : < 30 % < 14 % (strict criteria) Case-control study 143 fertile Men from pregnant women < 20 weeks 144 subfertile Prospective study Exclusion: tubal factor & anovulation Statistics: ROC analysis W Ombelet et al, Hum Reprod, 12, 987-993, 1997 Results Area (ROC) Cut-off ROC P10 (F) Count 69.4 34 14.3 Motility (a+b) 60.9 45 28 Morphology 77.7 10 5 WHO 2010 4500 men / TTP< 12 months/ P5 Volume < 1.5 ml Sperm concentration < 15 million spermatozoa/ml Total Sperm number < 39 million spermatozoa Motility (grade A+B) < 32 % progressive motile Morphology < 4 % normal Vitality < 58 % Cooper et al., HRU, 16, 231-245, 2010 TUNEL assay. TUNEL-positive nuclei (with double-strand nuclear DNA fragmentation) of spermatozoa as represented by the intense (A) and dull (B) Texas red fluorescence in the nuclear region. The healthy nuclei (without DNA fragmentation) are stained blue with DAPI (C) used as counterstain. Angelopoulou et al., Reprod Biol Endocrinol, 5, 36, 2007 Sperm Chromatin Structure Assay – SCSA Green Fluorescence 100 200 cells /minute 5000 cells analysed/sample Evenson et al., 1980 0 100 Denatured ss DNA: red fluorescence Algorithm for male subfertility treatment Tubal Factor No Tubal Factor Initial Semen Sample Washing procedure IMC IMC < 1 million < 1 million Morphology < 4% Morphology >= 4% Washing procedure IMC >= 1 million IMC IMC < 1 million < 1 million Morphology < 4% Morphology >= 4% IMC >= 1 million IUI 4 x IVF < 30% or no fertilisation ICSI IVF < 30% or no fertilisation ICSI ICSI Semen profile in a general population Aim: to investigate sperm quality in a general population Website: www.fvvo.be Ombelet et al., FV&V in ObGyn, 2009, 1, 18-26 Azoospermia: etiology Non-obstructive Maturation Idiopathic, cryptorchidism, mumps, drugs … Sertoli arrest cell only Idiopathic, irridiation, drugs … Obstructive Epididymal Post-infective, post-surgery, … Vas deferens obstruction CBAVD, post-vasectomy .. Ejaculatory Seminiferous tubular sclerosis Genetic, Klinefelter, testicular torsion, … obstruction duct obstruction Prostatic cysts, post-surgical, post-infective Azoospermia: diagnosis Non-obstructive Genetic FSH, testing inhibine B testicular volume Obstructive Genetic FSH, testing inhibine B: nl testicular volume: nl Karyotype Count < 5 mill Yq deletions 13% if nonobstructive azoospermia 3 - 7% with severe oligozoospermia “Transmitted to male offspring” AZFa, AZFb, AZFb +c, Yq deletions AZFc deletions All azoospermic None with sperm on diagnostic biopsy or TESE 27/42 severely oligospermic 9/20 (45%) with sperm on biopsy 9/12 (75%) had sperm at TESE Hopps et al, HR, 18, 1660, 2003 EVALUATION OF AZOOSPERMIA Azoospermia Vasectomy Endocrine evaluation CBAVD < 15 years > 15 years CF testing Hypogonadotropic hypogonadism Semen volume < 1 cc Vas reversal Sperm retrieval/ ICSI Sperm retrieval/ ICSI Gonadotropins TRUS CF - 1/2500 births: carriers 1/25 95% - “Wolffian duct abnormalities” Semen volume > 1 cc FSH < 2x normal Dilated SV’s Genetic evaluation Testis biopsy/ sperm retrieval Testis biopsy/ sperm retrieval Normal spermatogenesis Vasogram/ SV gram Ejaculatory duct obstruction ICSI No sperm Decreased sperm production TID adoption TESE/ICSI FSH > 2x normal Normal spermatogenesis Vasogram Sperm retrieval/ ICSI Epididymal exploration/VE +/- sperm retrieval TURED balloon dilation Kolettis PN. J Androl 23:293-305, 2002. EVALUATION OF AZOOSPERMIA Azoospermia Vasectomy Endocrine evaluation CBAVD < 15 years > 15 years CF testing Hypogonadotropic hypogonadism Semen volume < 1 cc Vas reversal Sperm retrieval/ ICSI Sperm retrieval/ ICSI Gonadotropins TRUS Semen volume > 1 cc FSH < 2x normal Dilated SV’s Genetic evaluation Testis biopsy/ sperm retrieval Testis biopsy/ sperm retrieval Normal spermatogenesis Vasogram/ SV gram Ejaculatory duct obstruction ICSI No sperm Decreased sperm production TID adoption TESE/ICSI FSH > 2x normal Normal spermatogenesis Vasogram Sperm retrieval/ ICSI Epididymal exploration/VE +/- sperm retrieval TURED balloon dilation Kolettis PN. J Androl 23:293-305, 2002. Testicular microlithiasis tumors Grade I: varicocele Grade II: Grade III: Environmental factors Physical Chemical light medication heavy metals (Pb, Cd,...) pesticides Biological Male Fertility infections viral bacterial .... temperature radiation electromagnetic fields Socio-economic nutrition starvation occupation Behavioral life style psychologic stress drug addiction: coffee, smoking, alcohol extreme weight loss physical stress: competitive sports Occupational heat exposure and male fertility Cumulative conception rate according to the male partners exposure to heat. Exposed = exposed to heat or seated in a vehicle for more than 3 hours per day. Thonneau et al, Lancet, 1996, 347, 204-5 and Bujan et al, 2000, Hum Reprod, 15, 1355 - 7. Cell phones & oxidative stress Agarwal, RBMOnline, 15, 266, 2007 Conclusie Accurate diagnose blijft belangrijk Anamnese Klinisch onderzoek Speciale onderzoeken Minimale onderzoeken // Maximaal rendement Infertiliteit ≠ IVF & ICSI Genk IVF team