LH activity for Gonadotrphin in controlled ovarian hyperstimulation : LH or just FSH?

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LH like activity is claimed to be of importance for COH in IVF/ ICSI cycles. is this real. Does addition of LH make GN more superior? this talk may answer this

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  • Show fill and trill, regression analysis
  • LH activity for Gonadotrphin in controlled ovarian hyperstimulation : LH or just FSH?

    1. 1. Does the addition of LH-Does the addition of LH- activity to FSH makeactivity to FSH make gonadotrophins moregonadotrophins more superior:superior: a systematic review and meta-analysis Hesham G. Al-Inany, M.D., Ph.D.
    2. 2. Background
    3. 3. Classification of gonadotrophins • Source of gonadotrophins: – Urinary vs. Recombinant gonadotrophins (Gn) • Chemical composition: – FSH only vs. FSH + LH-containing Gn • Isoforms: – Fixed isoforms (recFSH, recLH) vs. multiple isoforms (HP-FSH, HP-hMG, hCG) FSH: 8 main isoforms LH: 12 main isoforms hCG: 30 main isoforms
    4. 4. Previous systematic reviews • Primarily focused on sources of Gn • Urinary hMG vs. Recombinant FSH – Higher pregnancy and live-birth rates with hMG – No difference in OHSS rates Al-Inany et al., 2008; Coomarasamy et al., 2008Al-Inany et al., 2008; Coomarasamy et al., 2008 • Urinary HP-FSH vs. Recombinant FSH – Similar pregnancy and live-birth rates – No difference in OHSS rates Al-Inany et al., 2011; Moustafa et al., 2009Al-Inany et al., 2011; Moustafa et al., 2009
    5. 5. Objective To systematically locatesystematically locate, reviewreview and analyzeanalyze the best available evidence for the use of gonadotrophins according to their chemical compositionchemical composition rather than their sourcesource
    6. 6. Methods
    7. 7. • Computerized search: – MEDLINE (1978 to present) – EMBASE (1980 to present) – Cochrane Central Register of Controlled Trials (CENTRAL) – Trial registries of controlled trials (e.g. www.controlled-trials.com) • Hand search: – Reference lists of all known primary studies – Review articles – Citation lists of relevant publications – Abstracts of major scientific meetings Search strategy
    8. 8. Inclusion Criteria: PICOTS • Population: Randomized women undergoing IVF/ ICSI • Intervention/ Control: - Arm 1: FSH only (recFSH) - Arm 2: FSH + LH-activity (recFSH + recLH or hMG) • Timing: - FSH + LH concomitantly - FSH then FSH + LH
    9. 9. Inclusion Criteria: PICOTS • Outcomes: - Primary outcomes: - Live-birth rate - OHSS rate - Secondary outcomes: - Ongoing pregnancy rate - Clinical pregnancy rate - Cycle characteristics
    10. 10. Exclusion criteria • Non-randomized trials • Trials using LH priming - LH only then FSH only • Trials using HP-FSH instead of recFSH - not pure FSH - contains some LH
    11. 11. • For the meta-analysis, the number of participants experiencing the event was recorded • Data was extracted to allow for an intention- to-treat analysis • Defined as including in the denominator all randomized cycles Meta-analysis - Dichotomous
    12. 12. • Meta-analysis was performed: – Mantel-Haenszel method, utilizing a random- effects model – Odds ratio (OR) and 95% confidence intervals (CI) evaluated Meta-analysis - Dichotomous
    13. 13. • Meta-analysis was performed: – Inverse variance method, utilizing a random- effects model – Mean difference (MD) and 95% confidence intervals (CI) evaluated – Standardized Mean Difference (SMD) used when multiple scales provided (E2) Meta-analysis - Continuous
    14. 14. Results
    15. 15. 31 RCTs 10 RCTs recFSH vs. recFSH + recLH 21 RCTs recFSH vs. hMG/ HP-hMG Follow-up 9 OHSS9 LBR
    16. 16. Primary outcomes
    17. 17. Live-birth rates recFSH (304/ 1120; 27.14%) vs. FSH/LH (324/ 1110; 29.19%) (P = 0.29; O.R = 0.90, 95% CI = 0.75 to 1.09)
    18. 18. OHSS rates recFSH (34/ 1888; 1.80%) vs. FSH/LH(29/ 1843; 1.57%) (P = 0.79; O.R = 1.08, 95% CI = 0.63 to 1.83)
    19. 19. Secondary outcomes
    20. 20. Ongoingpregnancyrate recFSH (544/ 2385; 22.81%) vs. FSH/LH (589/ 2363; 24.93%) (P = 0.31; O.R = 0.93, 95% CI = 0.81 to 1.07)
    21. 21. Clinicalpregnancyrates
    22. 22. Cycle characteristics
    23. 23. No. of oocytes retrieved recFSH vs. FSH/LH (P = 0.002; M.D = 1.25, 95% CI = 0.48 to 2.02)
    24. 24. Other cycle characteristics • Treatment duration • Amount of FSH • Estradiol on day of hCG • Progesterone on day of hCG • Rate of poor responders NSNS
    25. 25. Interpretation
    26. 26. Interpretation • LH activity during ovulation induction is not paramount • Live-birth and OHSS rates were not significantly different with LH- containing protocols • CPR significantly favored additional LH-activity while number of oocytes were higher with FSH-only protocols
    27. 27. Questioning LH-activity • Subgroup analysis of CPR showed a significant difference in favor of hMG but not recFSH + recLH • Therefore LH-activity per se may not be the underlying source driving this significant difference • Multiple isoforms found in hMG/ HP- hMG or larger sample size for CPR may be a factor (Type II error)
    28. 28. Possible explanations • Multiple gondotrophin isoforms in hMG/ HP-hMG may provide better coverage than a single isoform • Glycosylated isoforms of FSH, LH and hCG have been shown to be important for the biological activities of these hormones that allow for pleiotropic signals to be transduced effectively at the receptor-level Arey et al., 2011Arey et al., 2011
    29. 29. Future research • HP-hMG vs. HP-FSH ‾ Distinguish importance between LH-activity or multiple isoforms • recFSH + recLH in subgroups: ‾ Poor responders ‾ Advanced maternal age
    30. 30. Thank You…

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