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IUI with gonadotrophins

Discussion on stimulating ovulation in women for fertility treatment, comparing IUI with gonadotrophins, and strategies to prevent multiple pregnancies. Recommendations on ovulation enhancement and monitoring during the process.

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IUI with gonadotrophins

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  1. IUI with gonadotrophins P Devroey Centre for Reproductive Medicine Dutch - speaking Brussels Free University Laarbeeklaan 101 1090 Brussels Belgium

  2. Debate is an intellectual game between friends • Stimulation of ovulatory women • Is IUI not an intellectual blunder ?

  3. Intellectual blunder ? Of miskleun ? • Ovulation induction in anovulatory women • Ovarian (superovulation) in IVF • Ovarian stimulation in ovulatory women (ovarian enhancement)

  4. Primary endpoint • Singleton life birth • (Significant) reduction of multiple pregnancies • At present ~ 35 children / 100 are members of a multiple pregnancy ~

  5. Ovulation enhancement in ovulatory women (IUI)

  6. Aanbevelingen voor ovulatie inductie • Monitoring van clomifeen stimulatie • Echografische monitoring met hormonale screening op dag 10 is nuttig • Zuiver echografische screening zonder hormonale screening kan een alternatief zijn • Monitoring tijdens stimulatie met gonadotrophines • Is essentieel om multiple zwangerschappen te voorkomen • Hormonale bepalingen dag 5 van de cyclus • Hormonale follow-up om de 2/3 dagen of frequenter • Echografische follow-up Werkgroep Reproductieve Geneeskunde VVOG

  7. Ovulation enhancement in ovulatory women (IUI) (continued)

  8. % multiple pregnancies age Dickey FS 2001

  9. Strategies to prevent (high order) multiple pregnancies (IUI) • Selective follicular aspiration of supernumerary follicles • Might be useful in experienced hands • Needs further investigation in large RCT • Applicability in non - IVF centers needs further investigation Cohlen 2004

  10. Strategies to prevent (high order) multiple pregnancies (IUI) • Conversion to IVF • Suddenly surprise • Non - informed couples • Treatment more expensive • Treatment more invasive • Conversion to IVF / ET should be discouraged Cohlen 2004

  11. IUI versus IVF - cost effectiveness • Goverde • Karande • IUI is more cost effective but no costs for multiple pregnancies !!

  12. Clomiphene citrate versus gonadotrophins Small RCT ! Balasch HR 1994 FSH is superior Matorras HR 2002 FSH is superior Echocard FS 2000 FSH is not superior Hughes HR 1997 CC seems less effective Cohlen Data Base Syst Rev 2002 CC seems less effective

  13. Clomiphene citrate versus gonadotrophins “ However large RCTs with sufficient power to detect clinical relevant differences in cost effectiveness between CC and gonadotrophins in IUI cycles are still lacking” Cohlen 2004

  14. Current best evidence for advanced treatment of unexplained subfertility • There is a call for a large international factorial study • No treatment • CC IUI • FSH IUI • IVF Collins HR 2003

  15. Current best evidence for advanced treatment of unexplained subfertility (continued) • While such a study might cost millions of dollars, if it is not done many more millions could be wasted on treatments that are not as effective as they now seem Collins HR 2003

  16. Published data IUI and gonadotrophines • Male factor infertility (1998 - 2000) • Pregnancy rate 14 % • Multiple 12.3 % • Unexplained infertility (1998 - 2000) • Pregnancy rate 22 % • Multiple 20 % D’Hooghe TG 2002

  17. Published data IUI and gonadotrophines • Male factor infertility (1994 - 2000) • Pregnancy rate 12.7 % • Multiple 15.6 % • Normospermic group (1994 - 2000) • Pregnancy rate 21.3 % • Multiple 15.6 % Spiessens FS 2003

  18. “ Ovarian stimulation for IUI was performed either with clomiphene citrate (CC 50 or 100 mg / d) from day 3 to day 7 of the menstrual cycle (n : 271) or with hMG (75 or 150 IU / d) from day 2 of the cycle (n : 601) “ Spiessens D’Hooghe page 1186 FS 2003

  19. “ When women had two or more mature follicles (> 14 mm) at the time of hCG injection, selective follicle aspiration was offered and usually one or two follicles were kept intact after this procedure“ Spiessens D’Hooghe page 1186 FS 2003

  20. IUI donor Clasen (Werkgroep)

  21. Multiple pregnancies - cost Twins AZ - VUB 6 926 - 51 348 Euro USA 51 715 US dollar Singleton 9 000 US dollar Infertility therapy - associated multiple pregnancies : an ongoing epidemic RBM OnLine 2003

  22. Comparison between clomiphene citrate and gonadotrophins • Subject of several small RCTs • Regret fully, the conclusions are contradictory Cohlen

  23. Conclusions IUI is an effective option (10 % pregnancy rate) If 1 000 000 sperm cells after sperm preparation But lowe dose step-up protocols (50 U) not withstanding close monitoring Still strict cancellation criteria to prevent multiple pregnancies Probably in experienced hands selective aspiration may be an effective alternative

  24. Coda IUI associated with gonadotrophins treatment • Invasive • Follicular aspiration • Cancellation • IVF • Enhance ovulation • Results in 30 % of children, member of a multiple pregnancy

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