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Treatment of poor responders: Review of Systematic reviews 2016

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Treatment of poor responders:
Review of Systematic reviews

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Treatment of poor responders: Review of Systematic reviews 2016

  1. 1. Treatment of poor responders: Review of Systematic reviews 2016 Aboubakr Elnashar Benha University Hospital, Egypt
  3. 3. 1. INTRODUCTION qDIAGNOSIS (ESHRE: Bologna criteria 2011) § At least 2 of 3: § Age (≥40 y) or any other risk factor for POR § Previous POR (≤3 oocytes with a conventional stimulation protocol) § Abnormal ORT (i.e. AFC <5–7 follicles or AMH <0.5–1.1 ng/ml). § 2 episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in absence of advanced maternal age or abnormal ORT. ABOUBAKR ELNASHAR
  4. 4. qPREDICTION OF TREATMENT OUTCOME 1. Female age 2. Number of oocytes retrieved (Oudendijk et al, 2012) ABOUBAKR ELNASHAR
  6. 6. qINTERVENTIONS: 33 (Most popular intervention first). (Papathanasiou et al, 2016) 1. Antagonist 2. Microdose flare 3. Long protocol 4. LH added 5. Letrozole + FSH+antagonist 6. DHEA 7. Short protocol 8. Transdermal testosterone 9. Growth hormone 10.HCG added at stimulation ABOUBAKR ELNASHAR
  7. 7. 11. Increase of FSH dose 12. CC+ FSH/HMG + -antagonist 13. Luteal FSH start 14. Estrogen for luteal support 15. Follicular flushing 16. Long-stop protocol 17. FSH/HMG only (no agonist or antagonist) 18. FSH dose 300 IU 19. Late FSH start 20. Metformin 21. Ultrashorta-antagonist 22. Modified flare 23. Low-dose aspirin 24. Natural cycle 25. Mini-long protocol 26. Step-down of FSH dose 27. Luteal phase antagonist 28. Gamete intrauterine transfer 29. Day of embryo transfer 30. Early (Day 1) FSH start 31. FSH dose 450 IU 32. FSH dose 600 IU 33. Clomiphene citrate onlyABOUBAKR ELNASHAR
  8. 8. qWhat are the most popular interventions? What are the recent Trends in last 5 years? (Papathanasiou et al, 2016) ABOUBAKR ELNASHAR
  10. 10. qWhat is a systematic review? § A review of a clearly formulated question that uses systematic and explicit methods to 1. identify, select and critically appraise relevant research 2. collect and analyse data from the studies that are included in the review (Cochrane Reviewers’ Handbook 4.1.5) ABOUBAKR ELNASHAR
  11. 11. Systematic review Meta-analysis Literature review qWhat is Meta-Analysis? The use of statistical techniques in a systematic review to integrate the results of included studies. ABOUBAKR ELNASHAR
  12. 12. 2. OBJECTIVE Review SR in treatment of poor responders ABOUBAKR ELNASHAR
  13. 13. 3. METHODS §Pub med: From 2003 till April 2016 §Key words •Treatment of poor responders •ICSI •Systematic review •Meta analysis §Outcome CPR ABOUBAKR ELNASHAR
  14. 14. 4. RESULTS §31SR: oRandomized controlled trials oCase control studies oSelf controlled studies §Classified into: I. COS: 1. Gnt type 2. Gnt dose 3. Protocol II. Adjuvants III. Lab ABOUBAKR ELNASHAR
  15. 15. I. Controlled ovarian stimulation 1. Gnt type qRec FSH §Not improve outcome. (Tarlatzis et al, 2003) §Insufficient evidence to recommend one type of Gnt over another. (Nardo et al, 2013) ABOUBAKR ELNASHAR
  16. 16. 2. Gnt dose qIncrease dose Little or no benefit. (Tarlatzis et al, 2003) qPatients who failed to conceive with 450 IU/d will not benefit from increasing dose to 600 IU (Haas et al.,2015) ABOUBAKR ELNASHAR
  17. 17. 3. Protocol 1. Natural cycle Vs long agonist protocols No difference (Tarlatzis et al, 2003) ABOUBAKR ELNASHAR
  18. 18. 2. Short Vs long agonist No difference (Sunkara et al, 2007) 3. Flare up GnRHa Vs long agonist protocol Better results (Tarlatzis et al, 2003) 4. Flare up GnRHa Vs Antagonist/Let protocol Better (Song et al, 2014) ABOUBAKR ELNASHAR
  19. 19. 5. GnRHa 'stop' Vs long protocol No difference (Tarlatzis et al, 2003) ABOUBAKR ELNASHAR
  20. 20. 6. Antagonist Vs long agonist Better Griesinger et al, 2006 Franco et al, 2006 No difference Tarlatzis et al, 2003 Sunkara et al, 2007 Pu et al, 2011 Xiao et al, 2013 Nardo et al, 2013 ABOUBAKR ELNASHAR
  21. 21. 6. Antagonist Vs flare up protocols. Better (Franco et al, 2006) ABOUBAKR ELNASHAR
  22. 22. II. Adjuvants 1. GH No significant improvement. §Tarlatzis et al, 2003 §Yu et al, 2015 Significant improvement §Cochrane Database Syst Rev. 2003 §Kyrou et al, 2009 §Kolibianakis et al, 2009 ABOUBAKR ELNASHAR
  23. 23. qDose: 4-12 IU of GH SC on the day of stimulation qEffects: § stimulates steroidogenesis, follicular development and responsiveness to FSH (Jia et al. 1986). § acts synergistically with FSH (Adashi & Rohan 1993) § may improve the number of oocytes qDisadvantages: § expensive and routine use can not be justified (Cochrane SR, Kotarba et al. 2002) ABOUBAKR ELNASHAR
  24. 24. 2. DHEA supplementation Not beneficial §Bosdou et al, 2012 §Narkwichean et al, 2013 Beneficial §Fouany , Sharara, 2013 §Li et al, 2015 §Cochrane Database SR, Nagels et al, 2015 §Zhang et al, 2016 ABOUBAKR ELNASHAR
  25. 25. q Mild androgen q Dose: 75 mg – 100mg/d for at least 12 w q Effects: (Zhang et al, 2016) Increase in AMH levels Decrease in baseline FSH Improves oocyte numbers embryo quality spontaneous PR IVF PR q Advantages: Available over the counter Minimal side effects Inexpensive ABOUBAKR ELNASHAR
  26. 26. 3. Transdermal testoeterone Beneficial §GonzálezComadran et al, 2012 §Bosdou et al, 2012 §Luo et al, 2014 §Cochrane Database SR, Nagels et al, 2015 Insufficient evidence §Sunkara et al, 2011 ABOUBAKR ELNASHAR
  27. 27. 4. rLH Beneficial §Cochrane Database Syst Rev. 2007 §Nardo et al, 2013 Not beneficial §Bosdou et al, 2012 §Fan et al, 2013 ABOUBAKR ELNASHAR
  28. 28. 5. Luteal phase E2 Beneficial §Chang et al, 2013 §Reynolds et al, 2013 ABOUBAKR ELNASHAR
  29. 29. Estrogen Primed Antagonist Protocol § Pretreatment cycle is a natural cycle (no BCP). § About a week after ovulation ú GnRHan is started {prevent premature recruitment of follicles} ú Estrogen {provides the young follicles an optimal condition to grow in the future}. § Stimulation medications are started on day 3 of the next menses. ABOUBAKR ELNASHAR
  30. 30. 6. OCP pretreatment §Tarlatzis et al, 2003 §±help ovarian response. qNardo et al, 2013 §GnRHan cycles: •Adversely affects IVF outcome §GnRHa cycles. •No effect ABOUBAKR ELNASHAR
  31. 31. 7. Corticosteroids §Reduces the incidence of poor ovarian response (Tarlatzis et al, 2003) §British Fertility Society, 2014 There is limited evidence ABOUBAKR ELNASHAR
  32. 32. qDexamethasone § 1mg/d orally till retrieval § directly influence granulosa cells via isoform or by increasing GH & IGF-1 § improve the endometrial microenvironment. (Miell et al. 1993, Polak 1993, Smith et al. 2000, Keay et al. 2001) ABOUBAKR ELNASHAR
  33. 33. 8. Nitric oxide donors §The limited data are encouraging. (Tarlatzis et al, 2003) ABOUBAKR ELNASHAR
  34. 34. III. Lab 1. Assisted hatching No benefit (Tarlatzis et al, 2003) 2. Embryo transfer on day 2 Vs day 3 improve CPR (Kyrou et al, 2009) 3. Follicular flushing §does not increase the number of oocytes retrieved §lower IR and CPR. (Mok-lin et al, 2013) ABOUBAKR ELNASHAR
  35. 35. 5. CONCLUSIONS qAccording to available SR: The following interventions are associated with increase CPR in poor responders: §Flare up GnRHa protocol §Estrogen Primed Antagonist Protocol §DHEA supplementation §Transdermal testoeterone §Embryo transfer on day 2 ABOUBAKR ELNASHAR
  36. 36. ABOUBAKR ELNASHAR You can get this lecture from: 1.My scientific page on Face book: Aboubakr Elnashar Lectures. 44884091351/ 2.Slide share web site