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Shahar Kol, Maccabi Health Care Services Rambam Health Care Campus Technion, Israel Institute of Technology.

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Presentation on theme: "Shahar Kol, Maccabi Health Care Services Rambam Health Care Campus Technion, Israel Institute of Technology."— Presentation transcript:

1 Shahar Kol, Maccabi Health Care Services Rambam Health Care Campus Technion, Israel Institute of Technology

2 Faculty Disclosure No, nothing to disclose X Yes, please specify: Company Name Honoraria / Expenses Consulting/ Advisory Board Funded Research Royalties / Patent Stock Options Equity Position Ownership / Employee Other (please specify) Merck Serono Israelx Off-Label Product Use Will you be presenting or referencing off-label or investigational use of a therapeutic product? XNo Yes, please specify:

3 LH is vital during the follicular phase. GnRH analogs are used to prevent premature LH rise, and untimely ovulation. GnRH analogs attenuate endogenous LH secretion.

4 GnRH agonist-based stimulation: Global LH supplementation is of no benefit. Advantage in LH-suppressed patients. Lisi et al Marrs et al LH level [U/L] Days

5 GnRH antagonist-based stimulation: Global LH supplementation is of no benefit Konig et al LH level [U/L] Days

6 GnRH antagonist-based stimulation: Drop in LH concentration during antagonist treatment is associated with low pregnancy rate, with no relevance to the actual concentrations. Huirne et al. 2005

7

8 Ganirelix dose finding study Bad reproductive outcome with 1mg and 2 mg doses

9 Response to GnRH antagonist: “Bell shape” “hypo-responders”“hyper-responders”

10 OPTIMALH: Antagonist – Luveris study Who needs exogenous LH during ovarian stimulation after administration of a GnRH antagonist?

11 Objectives What is the proportion of patients that sharply decrease their LH levels following the first GnRH antagonist 0.25 mg administration?  Do these patients benefit from added LH?

12 Definition of GnRH antagonist hyper-responder: <50% pre-antagonist LH level recovery 24 hours later mg 0.5 mg 1.0, 2.0 mg

13  Ovarian stimulation from day of cycle.  First Cetrotide dose 4 – 5 days later, following baseline blood test.  24 hours later: another blood test to determine LH recovery.  If recovery is <50% = hyper-responder, add Luveris 150 IU daily until trigger day.  Rest is routine IVF treatment.  Cost: 1 additional blood test.

14  12 patients out of 46 were defined as “hyper- responders” with a mean LH recovery of 34%.  34 patients – “normal responders” with a mean LH recovery of 75%.

15 High responders (n=12) Normal responders (n=34) P Age (years) 32 (2.5)30 (4)0.17 BMI (kg/m 2 ) 20.6 (1.9)21.9 (3.2)0.23 Infertility duration(months) 44 (30)32 (19)0.11 Basal E 2 (pmol/l) 169 (46)180 (49)0.51 Basal P (nmol/l) 2.7 (0.9)2.8 (0.9)0.61 Basal LH (IU/l) 7.0 (2.6)5.5 (2.7)0.09

16 High responders (n=12) Normal responders (n=34) P E 2 before antagonist2138 (1500)1749 (736)0.24 P before antagonist2.0 (1.3)2.6 (1.2)0.18 LH before antagonist4.9 (5.3)2.2 (0.9)0.005 E 2 24 hours later2452 (1755)2384 (1021)0.88 P 24 hours later2.1 (1.2)2.7 (0.9)0.11 LH 24 hours later1.34 (0.9)1.66 (0.78)0.25 E 2 increment per oocyte first 24h 28 (32)68 (49)0.01 E 2 trigger day6571 (3678)5454 (2436)0.25 E 2 increment per oocyte total 481 (377)266 (220)0.02 Total FSH dose (units)1703 (452)1597 (467)0.5 Endometrial width (mm)9.7 (1.7)9.4( 2.1)0.66

17 High responders (n=12) Normal responders (n=34) P oocytes 9.7 )4.7)11.6 (7.5)0.4 Fertilization rate (%) 68 (32)62 (29)0.54 No. embryos obtained 6.7 (4.3)5.2 (3.5)0.25 No. embryos transferred 1.58 (0.79)2.1 (0.79)0.06 No. embryos frozen 5.1 (3.8)3.3 (3.6)0.16 Clinical pregnancy 6 (50%)10 (29%)0.204

18 It is widely accepted that to secure the best clinical results of assisted reproductive technology, an individualized approach is required. Implication to the LH question: Give to the patient that needs it!  Follicular phase LH physiology: LH levels are more or less constant, allowing for a sufficient supply of androgens, and for a continuous rise in E 2 levels.  We hypothesized that a sharp drop in LH causes a sudden decrease in precursor availability.  The result is insufficient E 2 production by the growing follicles.

19  In 'long' agonist-based, pituitary down-regulation ovarian stimulation, LH levels are low, but with minimal fluctuations.  in antagonist-based cycles, a sudden antagonist- mediated LH drop leads to depleted E 2 biosynthesis.  the LH-starved system quickly recovers with exogenous LH, resulting in accelerated E 2 production.

20  About 25% of patients treated with the antagonist protocol hyper-respond, and may benefit from LH supplementation.  High basal LH is associated with hyper response.  This simple approach can shift “individualized treatment” from slogan to practice.


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