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Fertiliteitsdiagnostiek anno 2011

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.

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Fertiliteitsdiagnostiek anno 2011

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  1. Fertiliteitsdiagnostiek anno 2011 Willem Ombelet Genk Gent, 12-05-2011

  2. 10-15 % van de koppels met kinderwens hebben fertiliteitsproblemen • Oorzaken • 30% man • 30% vrouw • 30% man & vrouw • 10% onbekend

  3. Spermatogenesis

  4. FemaleMale Serum: infections, hormonal, thyroid, AMH Serum: infections, hormonal Semen sample E2, Prog, LH PCT US uterus & ovaries E2, Prog Hysteroscopy FSH Prl HSG 0 menses 2-3 14 28 Outpatient repeat semen sample US + Doppler scrotum Genetics Laparoscopy CT, MRI, ... Treatment

  5. Oorzaken: vrouw • Baarmoederhalsfactorzz • Implantatiestoornis • Syndr v Asherman • Poliepen, myomen, infecties • Eileiderfactoren • Sterilisatie • post-infectie • ergeendometriose • Eisprongstoornissen • PCO • hyperprolactinemie • Andereafwijkingen • Post-heelkunde

  6. Oligomenorree (cyclus > 35 d) Amenorree Primair (XO - syndr v Turner) Secundair normogonadotroop (hyperprolactinemie) hypogonadotroop hypergonadotroop (PCO – syndroom) Meest frequente vrouwelijke factorAnovulatie

  7. Hypogonadotropeamenorree • stress, vermagering, sport • Simple weight loss amenorree • Exercise-associated amenorree • Psychogenehypothalameamenorree • Lage E2, laag FSH en LH, hoogcortisol

  8. Hyperprolactinemie

  9. PCO - Syndroom Oligo- of anovulatie Cyclus > 35 dagen Hirsutisme, haaruitval Acne  testosterone Hyperandrogenisme PCO-echografisch 12 follikels < 10mm – bilat Of Ovarieel volume > 10 ml ( 0.5233 x L x B x H )

  10. Ovariële reserve Website: www.fvvo.be Broekmans, FV&V in ObGyn, 2009, 2, 79-89

  11. Broekmans, FV&V in ObGyn, 2009, 2, 79-89

  12. Cavum- en tubapathologie

  13. FemaleMale Serum: infections, hormonal, thyroid Serum: infections, hormonal Semen sample E2, Prog, LH PCT US uterus & ovaries E2, Prog Hysteroscopy FSH Prl HSG 0 menses 2-3 14 28 Outpatient repeat semen sample US + Doppler scrotum Genetics Laparoscopy CT, MRI, ... Treatment

  14. HSG: unicornuate uterus, patent tube MRI:unicornuate uterus MRI: ectopic ovary anterior to the external iliac vessels

  15. Ombelet et al., N Engl J Med, 348, 667, 2003

  16. Diagnostische Hysteroscopie

  17. Laparoscopie

  18. FemaleMale Serum: infections, hormonal, thyroid Serum: infections, hormonal Semen sample E2, Prog, LH PCT US uterus & ovaries E2, Prog Hysteroscopy FSH Prl HSG 0 menses 2-3 14 28 Outpatient repeat semen sample US + Doppler scrotum Genetics Laparoscopy CT, MRI, ... Treatment

  19. WHO 1987: 3555 men with male factor

  20. 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)

  21. Case-control study 143 fertile Men from pregnant women < 20 weeks 144 subfertile Exclusion: tubal factor & anovulation Prospective study Statistics: ROC analysis W Ombelet et al, Hum Reprod, 12, 987-993, 1997

  22. Area (ROC)Cut-off ROCP10 (F) Count 69.4 34 14.3 Motility (a+b) 60.9 45 28 Morphology 77.7 10 5 Results

  23. 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

  24. 100 Green Fluorescence 0 100 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 200 cells /minute 5000 cells analysed/sample Evenson et al., 1980 Denatured ss DNA: red fluorescence

  25. Algorithm for male subfertility treatment Tubal Factor No Tubal Factor Initial Semen Sample Washing procedure Washing procedure IMC IMC IMC IMC IMC IMC < 1 million < 1 million >= 1 million < 1 million < 1 million >= 1 million Morphology < 4% Morphology >= 4% Morphology < 4% Morphology >= 4% IUI 4 x IVF < 30% or no fertilisation IVF ICSI < 30% or no fertilisation ICSI ICSI

  26. Semen profile in a general populationAim: to investigatespermquality in a generalpopulation Website: www.fvvo.be Ombelet et al., FV&V in ObGyn, 2009, 1, 18-26

  27. Non-obstructive Maturation arrest Idiopathic, cryptorchidism, mumps, drugs … Sertolicellonly Idiopathic, irridiation, drugs … Seminiferoustubularsclerosis Genetic, Klinefelter, testicular torsion, … Obstructive Epididymal obstruction Post-infective, post-surgery, … Vas deferens obstruction CBAVD, post-vasectomy .. Ejaculatoryduct obstruction Prostaticcysts, post-surgical, post-infective Azoospermia: etiology

  28. Non-obstructive Genetictesting FSH, inhibine B testicular volume Obstructive Genetictesting FSH, inhibine B: nl testicular volume: nl Azoospermia: diagnosis

  29. Karyotype Count < 5 mill

  30. Yq deletions • 13% if nonobstructiveazoospermia • 3 - 7% with severe oligozoospermia • “Transmitted to male offspring” All azoospermic None with sperm on diagnostic biopsy or TESE AZFa, AZFb, AZFb +c,Yqdeletions 27/42 severely oligospermic 9/20 (45%) with sperm on biopsy 9/12 (75%) had sperm at TESE AZFc deletions Hopps et al, HR, 18, 1660, 2003

  31. EVALUATION OF AZOOSPERMIA CF - 1/2500 births: carriers 1/25 95% - “Wolffian duct abnormalities”

  32. EVALUATION OF AZOOSPERMIA

  33. tumors Testicularmicrolithiasis Grade I: Grade II: Grade III: varicocele

  34. Environmental factors Physical light temperature radiation electromagnetic fields Chemical medication heavy metals (Pb, Cd,...) pesticides Male Fertility Biological infections viral bacterial .... Socio-economic nutrition starvation occupation life style Behavioral psychologic stress drug addiction: coffee, smoking, alcohol extreme weight loss physical stress: competitive sports

  35. 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.

  36. Cell phones & oxidative stress Agarwal, RBMOnline, 15, 266, 2007

  37. Accurate diagnose blijft belangrijk Anamnese Klinisch onderzoek Speciale onderzoeken Minimale onderzoeken // Maximaal rendement Infertiliteit ≠ IVF & ICSI Conclusie

  38. Genk IVF team

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