Mannelijke subfertiliteit Wanneer IUI – IVF of ICSI Willem Ombelet Organon has developed recombinant FSH (Puregon, follitropin ), by transfecting Chinese hamster ovary cell lines with plasmids containing the two subunit genes encoding FSH. Puregon is marketed as Follistim in the USA and as Recagon in India. Its generic name is follitropin beta. Leuven, 04-06-2010

Mr Charles Kingsland 1st March 2004

IUI Indications Cervical factor unexplained Male factor Male factor immunological Male factor mild Male factor Moderate to severe

When to perform IUI - IVF - ICSI ? Female age Costs (couple) Duration of infertility Costs (society) Indication for fertility Treatment Complication rate Sperm quality Ethics – religion …

IUI versus IVF // ICSI: couple compliancy High couple compliancy Easy Non-invasive Minimal risks Minimal monitoring Result effective Cost effective High couple compliancy

Used: Systematic reviews Meta-analyses RCTs only Strength of evidence 1b 2a De kracht van het wetenschappelijk geleverde bewijs kan worden aangegeven met nummering van 1a tot 4, zoals ook in de onlangs gepubliceerde richtlijnen van de RCOG te Engeland. Ik zal zoveel mogelijk gebruik maken van bewijs 1a of 1b. Well designed non randomized controlled trial 2b Well designed quasi experimental 3 Descriptive/cases 4 Experts

1a

Pregnancy rates as a function of age 1b Goverde et al. Lancet (2000): 355: 13

Unexplained and moderate male factor subfertility IUI versus IVF // ICSI Unexplained and moderate male factor subfertility IVF // ICSI versus 3 x IUI Philips et al., Hum Reprod 15, 95, 2000 Stone et al., AJOG, 180, 1522, 1999 Garceau et al., Hum Reprod 17, 3090, 2002 Cost-benefit

IUI versus IVF $ 10,000 $ 43,000 IUI baby IVF baby IUI versus IVF. De kosten per levend geboren baby in de USA. IUI is evident kosten-effectief. Van Voorhis et al. Fertil Steril 1998

IUI versus IVF $ 5,000 $ 13,000 1a IUI baby IVF baby Dezelfde conclusie kan worden getrokken in Nederland al zijn wij veel goedkoper. Goverde et al. Lancet 2000

IUI versus ICSI $ 9,500 $ 16,000 IUI baby ICSI baby Bij mannelijke subfertiliteit: is ICSI beter dan IUI bij een matige mannelijke factor: neen dus. Philips et al. Hum Reprod 2000

IUI : threshold levels for sperm quality IMC Year Author Cycles (n) COH IMC 1989 Horvath 451 CC-hMG > 1 1994 Brasch 1205 - > 20 1995 Toner 395 FSH, hMG > 2 1996 Campana 1115 Nat, CC, FSH Huang 1375 CC, hMG > 5 Ombelet 1100 > 0.3 1997 Berg 3037 > 0.8 792 CC > 1 if morph > 4 1998 Van der Westlaken 1763 > 10 1999 Branigan 1160 2000 Stone 9963 Nat, CC, hMG 2001 Khalil 2473 CC,hMG,FSH Van Voorhis 3479 Nat,CC,hMG 2002 Lee 2846 Ombelet et al., RBM Online, 2003, 7, 485

1a

Sperm morphology and IUI Van Waart et al., Hum Reprod Update, 7, 495, 2001 Structured review – medline search Threshold value: 4 % (strict criteria) Odds ratio: -0.07 (-0.11 to 4.03; p < 0.001)

IUI and male factor subfertility Predictive potential of inseminating motile count (IMC) and sperm morphology W. Ombelet et al. Hum Reprod, 12,1458,1997

IUI: STIMULATION \ INSEMINATION SCHEDULE hCG Clomiphene 5000U 50 mg MENSES 34 - 38 h 14 - 18 h 5 6 7 8 9 10 11 X x+1 x+2 D1 > 18 - 20 mm U.S. OVARIES ( IUI ) IUI

< 1 106 No pregnancy MORPH < 4% Take Baby Home rate After 3 IUI’s < 1 106 MORPH < 4% No pregnancy % All patients < 1 106 < 1 106 MORPH >= 4% All patients >1 106

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

1a

PR per cycle: cycle number PR per cycle: female age

In the era of IVF, why IUI? Easier to perform Less invasive Less expensive Effective BUT major risk: ↑ multiple pregnancy rate

1a

1a

Strategies to prevent multiple pregnancies Non-IVF ( IUI ) Natural cycle / Clomiphene citrate hMG and/or rec FSH: minimal dose step-up regimen 50 IU starting dose + 25 IU increments Escape IVF Follicular punction

Indications for IVF Tubal infertility and nl / moderate semen quality IMC > 1 mill & no success after 4-6 IUI’s

Indications for ICSI Severe male subfertility : if IMC < 1.0 mill + Morphology < 4 % Immunologic male subfertility Azoospermia (MESA, TESE …)

Pros & cons