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Fertilitet , infertilitet og assisteret reproduktion i et overordnet perspektiv

Fertilitet , infertilitet og assisteret reproduktion i et overordnet perspektiv. Anders Nyboe Andersen Professor dr med, Fertilitetsklinikken , Rigshospitalet U- kursus i Infertilitet , Odense 2014. Infertilitet Ikke et nyt problem – men nye behandlinger.

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Fertilitet , infertilitet og assisteret reproduktion i et overordnet perspektiv

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  1. Fertilitet, infertilitetogassisteretreproduktioni et overordnetperspektiv Anders Nyboe Andersen Professor dr med, Fertilitetsklinikken, Rigshospitalet U-kursusiInfertilitet, Odense 2014

  2. InfertilitetIkke et nyt problem – men nyebehandlinger In “marriages which had lasted five years or more, and in which the husbands were under 75 years of age, ... one marriage in 6·5 was unproductive". J Y Simpson Survey of 495 British Peers, cited in Gibbons (1911)

  3. Den humane forplantning • De frivilligt frugtbare fødslerne • De frivilligt ufrugtbare svangerskabsforebyggelse • De ufrivilligt frugtbare provokerede aborter • De ufrivilligt ufrugtbareinfertilitet

  4. Sex og reproduktion • 1960’erne Sex uden reproduktion • 1990’erne Reproduktion uden sex

  5. Da jeg blev født i 1948….. de store efterkrigsårgangeop

  6. Antalbørnfødti Denmark P-piller Fri abort Små fødselsårgange giver små fødselsårgange

  7. Reproductive health ”Reproductive health is a state of complete physical, mental and social well-being and not merely the abscence of disease or infirmity, in all matters relating to the reproductive system and to its function and processes. Reproductive health therefore implies that people are able to have a satisfying and safe sex life and that they have the capability to reproduce and the freedom to decide if, when and how often to do so”. United Nations, 1995, p. 40

  8. European Parliament Report G. ”Infertility is one of the causes of demographicdecline and it shouldberecognised as a public-healthconcern and as a social problem affectingboth men and women” 26. ”Notes thatinfertility is a medicalconditionrecognised by WHO thatcan have severeeffectssuch as depression; points out thatinfertilitymaybeon the increase …; callson the Member States to ensure the right of couples to guarantee universal access to infertilitytreatment and medicallyassistedprocreation by taking steps with a view to reducing the financial and otherobstacles” European Parliament. Reporton the demographic future of Europe. (2007/2156(INI)), 30th January 2008

  9. ART and fertility treatments From scepticism to acceptance to promotion • European Parliament report on the demographic future of Europe (2008): • “... calls on the Member States to ensure the right of couples to guarantee universal access to infertility treatment and medically assisted procreation by taking steps with a view to reducing the financial and other obstacles.” OECD: The Role of Policies, 2005; Report 2007/2156(INI) 2008.

  10. I. Definitioner • Infertilitet og subfertilitet defineres som > 12 mdrs. forsøg på at opnå graviditet. • Primær og sekundær infertilitet.

  11. Pregnancies in fertile and subfertile couples Bongaards JA. A method for estimation of fecundability. Demography 1975; 12, 645-60.

  12. Definitioner af infertilitet Primær Kvinden har aldrig opnået graviditet trods mindst 12 måneders ubeskyttet sexuelt samliv Sekundær Kvinden har tidligere været gravid med har efterfølgende ikke opnået graviditet trods mindst 12 måneders ubeskyttet sexuelt samliv WHO, 1993 Sterilitet anvendes ved definitivt ophævet graviditetsmulighed (hysterektomi, bilateralt salpingectomi, azoospermi)

  13. Befolkningsundersøgelser Prævalenser blandt deltagere, der har forsøgt at få mindst et barn Livstidsprævalensen af infertilitet > 1 år 17-26% Livstidsprævalensen af infertilitet > 2 år 12-14% Primær ufrivillig barnløshed (infekunditet) 3-8% Sek. ufrivillig barnløshed (infekunditet) 4-6% Andel infertile, der har søgt læge 50-80%

  14. Definitioner • Fertilitet eller fekunditet betyder frugtbarhed og anvendes både om evnen til at opnå graviditet og om evnen til at opnå fødsel af levende barn. • Fertilitet eller fekunditet kvantiteres som den månedlige chance for graviditet/fødsel efter ubeskyttet samliv ( fx 0.25 eller 25%). • Time to pregnancy (TTP) er et følsomt mål for fertiliteten/fekunditeten og angives som antallet måneders ubeskyttet samliv før graviditet opstår

  15. Fecundity according to age Live births per cycle Couples: 544 Children: 3,846 Post-partum Amenorrhea: 10 months Children/woman: 10,8 Larsen U et al. Social Biology 2000; 47: 34-50

  16. Donor IUI. Pregnancies/100 cycles 6,139 IUI-D cycles 1,001 treated women All during 18 years Li/02 Botchan A et al. Hum Reprod 2001; 16: 2298-2304

  17. Age related chances of pregnancy over time. Natural conception Adapted from H. Leridon (2004) and D. Habbema

  18. Pregnancy and live-birth rates after ART in relation to age. USA 2005

  19. Fertiliteten falder med alderen – det ovarielle ur Broekmans et al, Trends in Endocrinologi & Metabolism, 2007

  20. Oligo-follikulære, lille, follikel depleterede ovarium Multifollikulære, store ”unge” ovarium AFC = 34 AMH = 51 nmol/l AFC = 2 AMH < 3 nmol/l

  21. Total Fertility rate Total fertilitets rate er antallet af levende-fødte børn per kvinde, efter afslutning af hendes reproduktive periode (typisk udgangen af 49 år). Total fertility rate er sammensat af biologiske, medicinske og samfundsmæssige forhold.

  22. ---------------------------- Total fertility rate ------------------------------

  23. Childness women due to infertility (UK data) • A cohort of 40-55 årige ( n=6584) • Involuntarilyneverpregnant and thusneverdelivered 2.4% • Involuntarilyneverdelivered, althoughachievedpregnancy 1.9% SUM: 4.5% unresolvedinfertility Oakley et al. Lifetimeoprevalence of infertility and infertilitytreatment in the UK. Hum Reprod. 2008; 23, 447-50.

  24. II. Ændringen i fertilitetsmønstret

  25. Fertility desires in Europe Federal Institute for Population Research; DIALOG (http://www.bosch-stiftung.de/content/language1/downloads/PPAS_en.pdf). The Demographic Future of Europe – Facts, Figures, Policies. Results of the Population Policy Acceptance Study (PPAS) Slide from Mark Connolly

  26. Fertility desires in different countries • In some countries the desired number of children would be 3-4. • In other countries the desired number would include delivery of a boy.

  27. Kvindens alder vedførstefødselDenmark 1965-2012 Danmarks Statistik Online: www.dst.dk

  28. Age 1 child in Spain • Mean age at first pregnancy (INE 2011) 32.1 years From Data Juan-C Velasque (Spanish Institute of statistics www.ine.es)

  29. Number of children – by age of the firstchild

  30. Antalbørnog alder vedførste barn Birth cohort 2012 Birth cohort 1983 Infertile couples 2012

  31. Why is female age and delayedchildbearing so important? • Lowerfecundity (lesspregnancies - more miscarriages) with age. • Accumulatedrisks of • reproductivediseases • endometriosis • diseaseswithreproductiveconsequences. • sexuallytransmitteddiseases, fibroids, gastrointestinalsurgery • sum of lifestyle factors • obesity, smoking

  32. III. Causes of infertility

  33. Causes of infertility (n=4972) Female age Diagnosis < 35 > 35 Ovulatory dysfunction 24% 11% Endometriosis 5% 3% Tubal factor 18% 25% Unexplained 21% 27% Male factor 35% 33% Maheshwari, Hamilton and Bhattacharya. Hum Reprod, 208; 23,538-42

  34. Worldwide patterns of infertility: is Africa different? WHO task force on diagnosis and treatmnent of infertility. Lancet, 1985, sept. 14. 596-8 Analysis of prospective, standardised data from 42 countries. Secondary infertility (16 – 40%) Africa 52% Total tubal occlusion (11–20%) Africa 49%

  35. Is infertility increasing? life-time prevalence 4466 women, 2007. Scotland. 400 (9%) did not wantchildren 4066 wishedchildren 3283 (81%) conceivedwithin 12 month 783 (19%) experiencedinfertility (prim, sec, both) 550 (70%) soughtmedicaladvice 320 (58%) conceived 230 (29%) remainedinvolutarilychildless Comparedwith a similarsurvey in the same geographical area 20 yearsago, the prevalence of infertilitywaslower Bhattacharya et al. Hum Reprod, 24, 12, 3096-3107. Templeton et al. BMJ, 1990,301, 148-152

  36. Treatment of infertilityAssisted Reproductive Technology ART

  37. The ideal demands for a “successful” Health Technology (ART) Appropriate Acceptable Available Accessible Affordable

  38. Development of recorded ART cycles in Europe Data from ESHRE’s EIM consortium

  39. Development of recorded ART cycles in the United States Data from CDC

  40. Expansion of ART Cycles in Japan 41 FER: Frozen & Thawed Embryo Replacement JSOG data

  41. ART and IUI in Denmark, 2012The contribution to annualbirths – an estimate

  42. In women > 35 years 10 - 18% of all Danishdeliveries in 2011 were due to ART Danish National ART Registry

  43. IVF,ICSI, FER and ED in Denmark1994 - 2010 TreatmentsPregnancies, % Embryos 2010 15.830 23.0 2009 14.884 24.0 2008 13.316 23.7 2007 11.055 25.4 2006 9.936 26.1 2005 9.541 23.81 2004 9.598 26.7 2003 9.292 26.9 2002 9.650 25.2 2001 8.805 24.5 2000 8.282 24.5 2 1999 7.624 24.9 1998 7.281 24.0 1997 6.768 23.3 1996 4.763 24.5 1995 4.285 23.0 3 1994 3.480 20.6 4

  44. ART cycles / million in Europe, 2006(Countries with complete recording) France, UK, Germany ↓ ↓ ↓ ESHRE EIM, Data from 2006, Amsterdam July 2009.

  45. ART cycles / million in selected countries around the world,2002 Canada? ICMART World Report, 2002. Hum Reprod, 2009, 24, 2310

  46. Is ART accessible in Montana or Wyoming ? Montana Wyoming

  47. ART cycles / million in different states United States ART cycles in Massachusetts ↓ In Wyoming ↓ Wright et al. Surveillance Summaries, 2006, 55, SS-4

  48. Use of ART The conclusion: ART is increasingly used around the world – but the technology may not be equaly available for all those who need it – the infertile couples?

  49. Denmark: 21 Fertility Clinics 9 public, 12 private Cycles per million inhabitants 1.206 3.221 3.750 1.568 Public Private 851

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