1 / 32

Predikcija ishoda IVF postupaka u žena s niskim serumskim vrijednostima AMH

Predikcija ishoda IVF postupaka u žena s niskim serumskim vrijednostima AMH. Miro Šimun Alebić Odjel za humanu reprodukciju Klinika za ženske bolesti i porode KB Merkur. AMH. Anti-M ü llerian hormone (AMH)

darrel-levy
Download Presentation

Predikcija ishoda IVF postupaka u žena s niskim serumskim vrijednostima AMH

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Predikcija ishoda IVF postupaka u žena s niskim serumskim vrijednostima AMH Miro Šimun Alebić Odjel za humanu reprodukciju Klinika za ženske bolesti i porode KB Merkur

  2. AMH • Anti-Müllerian hormone (AMH) • dimeric glycoprotein, a memberof the transforming growth factor-beta superfamily (Jost, 1946; Cateet al., 1986) • In women, • produced by granulosa cells of pre-antral and small antral follicles (Weenen et al., 2004) • main physiological role - inhibition of the earlystages of follicular development (Themmen, 2005; Visser andThemmen, 2005).

  3. AMH • AMH – prediction of ovarianresponse • in prediction of the number of oocytesretrievedbasalAMH serum levelsare,at least, as good as antralfolliclecount (AFC) (Broer et al., 2008, La Marca et al., 2010)

  4. Pregnancychances • oocyteyield: positivelyaffects the pregnancychances (Ulug et al., 2003; Baka et al., 2006; Timeva et al., 2006) • poorrespondershave a lowerpregnancy rate comparedwithnormalresponders (Biljan et al., 2000; de SutterandDhont, 2003; Galey-Fontaine et al., 2005; Baka et al., 2006; Timeva et al.,2006; van derGaast et al., 2006; Saldeen et al., 2007; Hendriks et al., 2008; Zhen et al., 2008)

  5. POOR • poor ovarian response (POOR) is associated • mainly, • reduced number of FSH-sensitive follicles, most frequently linked tothe condition known as diminished ovarian reserve. • rarely, • suboptimal exposureto gonadotrophins(Maheshwari et al.,2007) • FSH hyposensitivity (FSH receptor subtypes less sensitive to exogenous gonadotrophins (Simoni et al.,2002).

  6. Pregnancychances in POORs POOR definitionrequires, at least, 1 IVF cycle (Ferrareti et al., 2011) identification of thoseamong poor responders who still have an acceptable prognosis counseling on whether it is worthwhile tostart or continue with IVF(Oudendijk et al., 2012)

  7. Pregnancychances in POORs BMI: >30 kg/m2 negatively influence the pregnancy chances (Orvieto et al., 2009) FSH: >12 IU/L significantly lowers the pregnancy rates (Galey-Fontaine et al., 2005)

  8. Expected POOR • expected POOR couldbediagnosed BEFORE first IVF cycleaccording to AMH, AFC… • AMH – prediction of POOR • inresponse to FSH, reported sensitivity and specificity rangedbetween 44–97% and 41–100%, respectively (La Marca et al., 2010)

  9. Pregnancychances • AMH is not suitable to be used as a single predictor of pregnancy chances following IVF (Broer et al., 2009; Weghofer et al.,2011; Ferraretti et al., 2011) • age: negatively associated with pregnancy chances (Hanoch et al., 1998; de Sutter and Dhont, 2003; Ulug et al.,2003; aley-Fontaine et al., 2005; Zhen et al., 2008)

  10. Pregnancychancesbeforefirst IVF cycle multivariate age-AMH modelsignificantlyimproved LB prediction accuracyof both univariateand age models ROC-AUCAMH-age 0.66 (95% CI 0.61–0.72) vs ROC-AUCAMH0.57, (95% CI 0.52–0.61,P<0.05) and ROC-AUCage(95% CI 0.52–0.59,P<0.05) inthe same age category, AMH is able todistinguish between pregnancyandnon-pregnancy(La Marca et al., 2011)

  11. Research inthe same AMH and age category, there are stillpatients who achievepregnancyandthosewho do not is it possible to identifythosewithacceptablepregnancyprospectsamongexpectedPOORs prior to the first IVF cycle?

  12. Research • Objective: • to investigate • whetherany of theendocrine and/or clinical characteristic (s) obtainableprior to the first (GnRH antagonist )IVFcyclecouldimprovethe accuracy of IVF outcome prediction based on the female age alone in expectedpoorresponders (bylow AMH levels) • to identifyparameter(s) able to discriminatepatientswithfavorableandunfavorableprognosiswithin the same age and AMH category

  13. Uvod • groundwork(N=1088): • the optimalcut-off for the numberof oocytesretrieved(NOR) to discriminatebetweenpregnancyand non- pregnancy - AUC 0,61; 95% CI 0,58-0,64;P<0,001 <3 oocytes: +LR for non-pregnancyof2.82; 95%CI 2.0 - 4.0

  14. Research • groundwork • to set the AMH cut-off for POOR (<3 oocytes): AUC= 0,71; 95% CI 0,68-0,74; P<0,001; <6.5 pmol/L +LR 3.18; 95%CI 2.6 - 3.9

  15. Istraživanje • M&M: Inclusion criteria: serum AMH concentration <6.5 pmol/L null gravidity normal uterus and uterine cavity no history of pelvicdisease or surgery no history of the use of medicationsthat could interfere with basal hormone status, spermcount of, at least, 1 × 106 /mL first IVF/ICSI cycle, AMH and other laboratory tests values obtained withinthree months preceding controlled ovarian stimulation, a fixed doseof 300 I.U. hMG from the day 3; GnRH antagonist protocol N=129

  16. Research • main outcome: • AUC-ROC of model combining age and other potential predictive factors for the clinical pregnancy. • studydesign: • retrospectivestudy

  17. Research

  18. Research • LRA: • univariateshowedsignificantpredictivepower for both, age and DHEAS • multivariateexcluded age from the predictive model leavingonly DHEAS as predictive for pregnancy (DHEAS 1,59; 95%CI 1.58-2.2) • the negative correlationbetween age and DHEAS couldnotentirelyexplain the associationbetween DHEAS andpregnancyprospects • the usefullness of continousmultivarate model wasfailed to be demonstrated

  19. Research • however, discriminativecapacityof DHEAS wasnotdemonstrated to behigherthan age • AUC-ROCDHEAS0.726 (95%CI 0.641–0.801) • AUC-ROCage0.662 (95%CI 0.573–0.743) 𝑃 = 0.522 • since age is aneasy-to-obtainparameter, the use of DHEAS, as a singlepredictor, insteadof age couldnotbeadvised

  20. Research • therefore, according to cut-offsderivedby ROC curveanalysis: • age - 37.5 y (OR=6.7; 95% CI 1.5–31.2) • DHEAS - 5.7 𝜇mol/L (OR 7.9;95% CI 2.5–25.4)

  21. Research theusefullnessofcombined age and DHEAS categoric model for pregnancypredictionwasassesedbycomparisonwithdiscriminativecapacityofunivariate age model AUC-ROCage-DHEAS 0.796 (95%CI 0.716–0.862) AUC-ROCage0.662 (95%CI 0.573–0.743) 𝑃 = 0.013 combininginformation on DHEAS and age couldimprovetheability to predictpregnancycomparedtotheinformationof age alone

  22. Research

  23. P<0.05 NS Research

  24. Research Discussion: DHEAS is a sulfated metabolite of DHEAandacts as a intraovarianhormone precursor for active androgens andestrogens (Casson et al., 2000) DHEAS to DHEA conversiontake place in GC- sulphatase (Bonser et al., 2000)

  25. Research Discussion: decline linearly with age (Labrie et al., 1997) may have beneficial effect onage-related conditions (van Muhlen et al., 2007) thebeneficial effectof DHEA supplementationin some patientswithdiminishedovarianreserve (GleicherandBarad, 2011).

  26. Research Discussion: potentialy, sufficientquantitiesof DHEAS anditsmetabolitesintheoocytemicroenviroment are needed to ensureadequatesteroidogenesisandsufficientoocytequality

  27. Research Discussion: hipotheticaly, DHEAS deficiency in younger patients reduce their pregnancy chances tothe level inherent to the higher age categories

  28. Research Discussion: notall poor responders are similar in terms of loss of oocyte quality the link betweenremaining quantity of antral follicles and the quality of the oocytes heldwithin these follicles is missing (Oudendijk et al., 2012)

  29. Research DHEA(S)? Discussion:

  30. Research Conclusion: addinginformation on DHEAS to female age couldimprovethe predictionofclinicalpregnancy prior to the first IVF cycles improvedcounselingaccuracyregardingthe probabilities for successful IVF treatmentin women with low AMH who were younger than 37.5 years hypotheticaly, observedassociationbetween DHEAS andpregnancychancescouldbeexplainedbytheassociation of DHEAS andoocytequality

  31. Research

  32. Reprodukcijski tim KB Merkur

More Related