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

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Presentation on theme: "Fertiliteitsdiagnostiek anno 2011 Willem Ombelet Genk Willem Ombelet Genk Gent, 12-05-2011."— Presentation transcript:

1 Fertiliteitsdiagnostiek anno 2011 Willem Ombelet Genk Willem Ombelet Genk Gent,

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

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5 Spermatogenesis

6 Female Male Serum: infections, hormonal, thyroid, AMHSerum: infections, hormonal Semen sample FSH Prl HSG Hysteroscopy E2, Prog, LH PCT US uterus & ovaries E2, Prog 0 menses Outpatient Laparoscopy CT, MRI,... Treatment repeat semen sample US + Doppler scrotum Genetics

7 Oorzaken: vrouw  Baarmoederhalsfactor zz  Implantatiestoornis u Syndr v Asherman u Poliepen, myomen, infecties  Eileiderfactoren u Sterilisatie u post-infectie u erge endometriose  Eisprongstoornissen u PCO u hyperprolactinemie  Andere afwijkingen u Post-heelkunde

8 Meest frequente vrouwelijke factor Anovulatie   Oligomenorree (cyclus > 35 d)   Amenorree u Primair (XO - syndr v Turner) u Secundair F F normogonadotroop (hyperprolactinemie) F F hypogonadotroop F F hypergonadotroop (PCO – syndroom)

9 Hypogonadotrope amenorree u stress, vermagering, sport F Simple weight loss amenorree F Exercise-associated amenorree F Psychogene hypothalame amenorree u Lage E2, laag FSH en LH, hoog cortisol

10 Hyperprolactinemie

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

12 Ovariële reserve Website: Broekmans, FV&V in ObGyn, 2009, 2, 79-89

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14 Cavum- en tubapathologie

15 Female Male Serum: infections, hormonal, thyroidSerum: infections, hormonal Semen sample FSH Prl HSG Hysteroscopy E2, Prog, LH PCT US uterus & ovaries E2, Prog 0 menses Outpatient Laparoscopy CT, MRI,... Treatment repeat semen sample US + Doppler scrotum Genetics

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

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

19 Diagnostische Hysteroscopie

20 Laparoscopie

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22 Female Male Serum: infections, hormonal, thyroidSerum: infections, hormonal Semen sample FSH Prl HSG Hysteroscopy E2, Prog, LH PCT US uterus & ovaries E2, Prog 0 menses Outpatient Laparoscopy CT, MRI,... Treatment repeat semen sample US + Doppler scrotum Genetics

23 WHO 1987: 3555 men with male factor

24 Normaal : ≥20 mill / ml Oligozoospermie : < 20 mill / ml Asthenozoospermie : < 25 % grade a < 50 % grade a + b Teratozoospermie : < 30 % < 14 % (strict criteria) WHO 1999 : “authority-based” // not “evidence-based”

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

26 ResultsResults Area (ROC) Cut-off ROCP10 (F) Count Motility (a+b) Morphology

27 WHO men / TTP< 12 months/ P 5 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, , 2010

28 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 Evenson et al., cells /minute 5000 cells analysed/sample Denatured ss DNA: red fluorescence

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30 Aim: to investigate sperm quality in a general population Semen profile in a general population Aim: to investigate sperm quality in a general population Website: Ombelet et al., FV&V in ObGyn, 2009, 1, 18-26

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32 Azoospermia: etiology Non-obstructive u u Maturation arrest F Idiopathic, cryptorchidism, mumps, drugs … u u Sertoli cell only F Idiopathic, irridiation, drugs … u u Seminiferous tubular sclerosis F Genetic, Klinefelter, testicular torsion, … Obstructive u u Epididymal obstruction F F Post-infective, post-surgery, … u u Vas deferens obstruction F F CBAVD, post-vasectomy.. u u Ejaculatory duct obstruction F F Prostatic cysts, post-surgical, post-infective

33 Azoospermia: diagnosis Non-obstructive u Genetic testing u  FSH,  inhibine B u  testicular volume Obstructive u Genetic testing u FSH, inhibine B: nl u testicular volume: nl

34 Karyotype Count < 5 mill

35 Yq deletions 13% if nonobstructive azoospermia 3 - 7% with severe oligozoospermia “Transmitted to male offspring” AZFa, AZFb, AZFb +c, Yq deletions AZFb +c, Yq deletions All azoospermic None with sperm on diagnostic biopsy or TESE AZFc deletions 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

36 EVALUATION OF AZOOSPERMIA Kolettis PN. J Androl 23: , CF - 1/2500 births: carriers 1/25 95% - “Wolffian duct abnormalities” CF - 1/2500 births: carriers 1/25 95% - “Wolffian duct abnormalities”

37 EVALUATION OF AZOOSPERMIA Kolettis PN. J Androl 23: , 2002.

38 Grade I: Grade II: Grade III: Testicular microlithiasis tumors varicocele

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

40 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, and Bujan et al, 2000, Hum Reprod, 15,

41 Cell phones & oxidative stress Agarwal, RBMOnline, 15, 266, 2007

42 Conclusie  Accurate diagnose blijft belangrijk u Anamnese u Klinisch onderzoek u Speciale onderzoeken  Minimale onderzoeken // Maximaal rendement  Infertiliteit ≠ IVF & ICSI

43 Genk IVF team

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