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LH hormone in assited reproduction
This document discusses the use of recombinant luteinizing hormone (rLH) in assisted reproduction. It begins by asking if an appropriate patient population has been defined that could benefit from rLH supplementation. It then discusses LH and FSH action on follicles, the LH therapeutic window concept, and how central nervous system influence can cause hypothalamic-pituitary-hypogonadism. The document presents studies showing improved follicular development and outcomes like pregnancy rates with the addition of rLH for poor responders and women over 35 undergoing fertility treatments. It also discusses dose-finding studies that identified a safe and effective dose of 75IU/day rLH. In conclusion, the risks of rLH supplementation are addressed as
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LH hormone in assited reproduction
- 1. Lh in assistedReproductionDr G A RAMA RAJU.KRISHNAIVF VISAKHAPATNAM.
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- 4. Is there aneed for recombinant luteinizing hormone?Has the appropriate patient population been defined?Has a safe and effective dose been identified?75 IU/dayIs the composite primary endpoint of follicular development an appropriate endpoint to assess efficacy in this patient population?4
- 5. Luveris® (lutropin alfafor injection)
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- 7. LH and FSHAction on the FollicleE2ATheca externa cellsFSH receptors on granulosa cellsTheca interna cellsLH receptorson theca cellsGranulosacellsFSHFollicularantrumZona pellucidaOocyteCumulusOophoruscellsLHCapillary networkBasement membrane7
- 8. The LH TherapeuticWindow ConceptSuppression of granulosa cell proliferation
- 9. Follicular atresia (nondominantfollicles)
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- 11. Oocyte development compromisedLHceilingNormal follicular growth and developmentNormal androgen and estrogen biosynthesisNormal oocyte maturationLH thresholdFollicular growth impaired
- 12. Inadequate androgen (andestrogen) synthesis
- 13. No full oocytematurationBalasch J, Fábreques F. Curr Opin Obstet Gynecol 2002, 14:265-2748
- 14. CNS InfluenceGnRHLH FSHSteroidalandNonsteroidalFeedback9HH Can Be Caused by Hypothalamic Disorders, Pituitary Disease or BothHypothalamusPituitaryOvary
- 15. HH Treated withr-hFSH Alone90r-hFSH15FollicleFollicle Size(mm)and FSH(IU/L)Estradiol(pg/ml)10Serum FSH5Estradiol10050005101520DaysEndometrialThickness(mm)Shoham Z et al. Fertil Steril 1993; 59:73810
- 16. HH Treated withr-hFSH and r-hLHFollicle2040035015300Follicle Size(mm)and FSH(IU/L)25010200Serum FSH1505100Estradiol500005101520DaysEndometrialThickness(mm)90r-hFSHr-hLHEstradiol(pg/ml)Serono data Study 625311
- 17. 12Follicular Development inHHGive back what’s missing
- 18. Beneficial effect ofLH supplementation in ART> 5< .5
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- 20. Beneficial effect ofLH supplementation in ART
- 21. Women > 35years:16
- 22. Poor responders: 10-15% ofIVF patients have an inadequate response to FSH stimulation by day 8De Placido et al, 2001, 2004 Women showing a hypo-responsive response in IVF down regulated cycles had asignificant increase in pregnancy and implantation rates with the addition ofrecombinant LH (40.7% vs. 22%) Ferraretti et al, 2004 Prospective randomised controlled trial rLH supplementation is more effective than increasing the dose of rFSH inpatients with an initial inadequate ovarian response to r FSH aloneDe Placido et al, 2005Multicenter, prospective, randomised controlled trial
- 23. Beneficial effect ofLH supplementation in ART
- 24. How did an optimal dose found. Dose Finding Studies LHControlled ovarian stimulation and HH19
- 25. Percentage of Patientswith Follicular DevelopmentTrend Test*p = 0.0041/92/87/117/10p = 0.467p = 0.020p = 0.012p-values vs 0 IU LH* Statistically significant and robust 20
- 26. 21RisksKnown complications ofgonadotropins in infertility treatmentOvarian Hyperstimulation Syndrome (OHSS)Multiple birthsOther minimal/transient treatment-related adverse events (minor)Risks mitigated with proper diagnosis, dosing and observation
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Editor's Notes
- #2 The most common protocol in assisted reproduction is daily injection of gonadotrophin .these are generally combined with gonadotrophin agonist or antagonist to avoid premature lh surge Shoohan in 2002 demonsrttrated follicles increasingly become sensitive and ultimatleydpendent on lhSome scientistb advocated adding lh as adback and other felt unnessaryA cochrane review was published in 2009 Mochart
- #3 The most common protocol in assisted reproduction is daily injection of gonadotrophin .these are generally combined with gonadotrophin agonist or antagonist to avoid premature lh surge Shoohan in 2002 demonsrttrated follicles increasingly become sensitive and ultimatleydpendent on lhSome scientistb advocated adding lh as adback and other felt unnessaryA cochrane review was published in 2009 Mochart
- #4 Bad controlled imposrtant harmful and helpful in some Primary aim of thw talk to give clarity with scientific work Invidualised the protocol
- #8 PhysiologySecretion of gonadotrophin FSH LH play a distint complementary role to ensure growth and ovulation The only cell containgfsh receptors is the granulosa cellLh receptors are found in granulosa theca cell and uterus Androgen diffuse into the granulosa cell where aromatase enzyme agumented by fshconvertes to estrogenThis action occurs at 10-12 mmFollicular steroidogenesisStimulation of androgen synthesis by theca cellsFollicular maturationCan support terminal stages of follicular maturationOvulationResumption of meiosisOvulationLuteinizationMaintenance of luteal function
- #13 Follicular development can iniated by any of the following 1 GNRH2 U HMGHuman fsh and fshThe concept is giving back what is needed
- #14 Not every woman needs lh supplementation and as most of the women will respond with extremly low levels of lh .Infact only 1 % receptor occupation will be suffice Day 6 lh level 0.5 miu/mlThese pt had more oocyte ,6.3 to 7.3 ,higher fertilization rate 92% versus 69%pregnancy rate and implanatation rate and on going pregnancy rate 22% and 5 %
- #15 Only when lh is given in a dose of 1325 units then it crosses celing window
- #16 Not every woman needs lh supplementation and as most of the women will respond with extremly low levels of lh .Infact only 1 % receptor occupation will be suffice Day 6 lh level 0.5 miu/mlThese pt had more oocyte ,6.3 to 7.3 ,higher fertilization rate 92% versus 69%pregnancy rate and implanatation rate and on going pregnancy rate 22% and 5 %
- #19 Not every woman needs lh supplementation and as most of the women will respond with extremly low levels of lh .Infact only 1 % receptor occupation will be suffice Day 6 lh level 0.5 miu/mlThese pt had more oocyte ,6.3 to 7.3 ,higher fertilization rate 92% versus 69%pregnancy rate and implanatation rate and on going pregnancy rate 22% and 5 %