Cc for suppression of lh surge

929
-1

Published on

An integral step in assisted reproduction is the prevention of premature LH surge. This presentation illustrate a novel way that may help in prevention of LH surge

Published in: Health & Medicine, Business
0 Comments
10 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
929
On Slideshare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
42
Comments
0
Likes
10
Embeds 0
No embeds

No notes for slide

Cc for suppression of lh surge

  1. 1. New Modality for suppression of LH surge Why & How? Hesham Al-Inany, PhD (Amsterdam)
  2. 2. Why LH suppression? • The original concept of the existence of a therapeutic window for LH during ovarian stimulation was first put forward by Hillier. • According to this, there is not only a threshold requirement for LH to guarantee an optimal cycle but also a ceiling level beyond which LH might be deleterious to ovarian stimulation.
  3. 3. The criteria for premature luteinization • Decreased cycle outcome has been reported when LH is >10 IU/L and P>1.0 ng/L • others elected to choose a cut-off value of >1.2 ng/mL for progesterone to define premature luteinization
  4. 4. The ideal IVF protocol • a high chance of embryo transfer • a low cancellation rate, • a reasonable pregnancy rate • few side-effects, • low costs • practical convenience both for the patient and the clinician
  5. 5. History • 1970 Clomifen hMG • 1980 GnRH-agonist / hMG • 1990 recFSH / hMG GnRH-antagonist / hMG or recFSH
  6. 6. Protocols for IVF GnRH Antagonist Protocols GnRH Agonist Protocols 225 IU per day (150 IU Europe) Individualized Dosing of FSH/HMG 250 mg per day antagonist Individualized Dosing of FSH/HMG GnRHa 1.0 mg per day up to 21 days 0.5 mg per day of GnRHa 225 IU per day (150 IU Europe) Day 6 of FSH/HMG Day of hCG Day 1 of FSH/HMG Day 6 of FSH/HMG Day of hCG 7 – 8 days after estimated ovulation Down regulation Day 2 or 3 of menses Day 1 FSH/HMG
  7. 7. How Science is advancing!!
  8. 8. Observation
  9. 9. Further Observation
  10. 10. Then search the medical literature
  11. 11. How Science is advancing!!
  12. 12. Idea • CC antiestrogenic effect may suppress premature LH rise while maintaining a positive influence on ovarian follicle development if continued till the day of hCG
  13. 13. How Science is advancing!!
  14. 14. Then performing a Trial
  15. 15. Current practice of O.i in IUI Clomiphene Citrate hMG or FSH ______________________________________________
  16. 16. Emerging protocol: Reversed hMG/CC Clomiphene Citrate hMG or FSH ______________________________________________
  17. 17. • Some cases are CC resistant • about 25% of IUI cycles suffer from premature LH surge cancellation. WHY
  18. 18. If true : Double Benefits • The use of hMG at start of cycle for few days will avoid CC resistant cases • use of CC till the day of hCG will prevent LH surge
  19. 19. Outcome Parameters Primary outcome parameters Clinical pregnancy rate per women randomised (i.e. fetal heart pulsations demonstrated by TVS at 6 –7 weeks’ gestation) Premature LH Secondary outcome parameters E2 levels, Number of mature follicles Endometrial thickness On day of HCG
  20. 20. Sample size calculation • if premature LH surge rate among the hMG only group is 20%. • Assuming CC is effective by reducing it by 15% • Then hMG + CC group will be 5%, • So we will need to study 75 couples in each arm in order to reach a power of 80%.
  21. 21. Drop out cases • In order to compensate for discontinuations, we recruited 115 women in each arm • If more than 10% drop out cases, this would affect the validity of the trial
  22. 22. 25 New concept has to be tested Participants RandomlyAssigned Intervention Group Control Group Follow-up Follow-up Intervention Group Control Group
  23. 23. Novel protocol 75 IU/HMG CD3 CD?7 150 mg CC hCG IUI DF ≥ 18 mm 34-36h DF ≥ 12 mm
  24. 24. Control group 75 IU/HMG CD3 hCG IUI DF ≥ 18 mm CD7 34-36h DF ≥ 12 mm CD?7
  25. 25. Results Variable Group I (n=115) Group II (n=115) P value Age (years) 27.3 ± 4.7 28.4 ± 2.7 NS Duration of infertility (years) 3.1 ± 1.9 2.4 ± 1.6 NS Cause of infertility Mild male factor Unexplained infertility 61 (53%) 54 (47%) 58 (50.4%) 57 (49.6%) NS NS BMI 28.5 ± 1.6 28.1 ± 3.1 NS
  26. 26. Results (cont.) Variable Group I (n=110) Group II (n=107) P value Number of cancelled cycles Inadequate response Hyper response 5/110 4/5 1/5 8/107 6/8 2/8 NS NS NS Basal LH (mIU/mL) 6.4 ± 2.2 5.8 ± 2.4 NS Basal FSH (mIU/mL) 6.7 ± 2.5 7.2 ± 4.8 NS Days of stimulation 7.2 ± 1.8 8.1 ± 1.3 NS E2 at time of HCG (pg/mL) 360.3 ± 162.9 280 ± 110.0 P <.05*
  27. 27. Results (cont.) Variable HMG/CC (n=110) HMG (n=107) P value LH on day of hCG (miu/ml) for cases with no premature LH surge 7.3 ± 1.8 7.8 ± 2.2 NS Number of Follicles ≥ 16 mm 2.4 ± 0.97 1.3 ± 1.1 P < 0.05* Number of patients with premature LH surge 6 (5.45%) 17 (15.89%) P<0.001* End. Thickness (mm) 5.9 ± 0.7 4.9 ± 1.9 NS Clinical Pregnancy 11 (10%) 9 (8.41%) NS
  28. 28. How Science is advancing!!
  29. 29.  No OCP pretreatment  Check patient cycle day 2  FSH 100-225 IU  Antagonist earlier than later  LH not necessary Suggested GnRH Antagonist Protocol Cycle day 2 Transvaginal US + (if desired) hormonal profile This suggested protocol represents a “best estimate” given current data and clinical experience. Further data are required before more concrete recommendations can be made. For regular IVF patients:  5-9 antral follicles per ovary  Age <35 years  No PCOS  No history of poor responses  No endometriosis Duration of treatment based on clinical judgment in consultation with patient (usually 2 USs) Cycle day 2/3 Start FSH 150-200 IU. Continue Stimulation days 5-6 Start GnRH antagonist administered daily. Continue Monitoring according to clinic practice  US (+ blood test if required)  FSH dose adjustments may be considered 3 follicles 17 mm Day of triggering  Ensure interval between antagonist and hCG does not exceed 30 h  hCG 5000-10,000 IU Oocyte retrieval 36 h YES NO US = ultrasonogram; OCP = oral contraceptive pill. Devroey et al. Hum Reprod. 2009;24:764.
  30. 30. How Science is advancing!!
  31. 31. Antagonist shortage
  32. 32. How Science is advancing!!
  33. 33. Proof of concept study • Not a RCT • Small number • To proof the theory
  34. 34. Proof of concept study • Seven cases undergoing ICSI • Strict criteria: young age • Unexplained infertility • Mild male factor • Failed 2-3 IUI cycles • No PCOS • No endometriomas
  35. 35. • 2-3 ampoules daily • CC staring from follicle diameter 11mm • Usually for 3-4 d • hCG if follicle 17mm
  36. 36. Results • No premature lutenisation was reported till now • Number of retrieved oocytes ranged between 7-16 • MII oocytes more than 50% Waiting for pregnancy rate
  37. 37. Should we rush? • To apply it • Too early • Needs more cases • Not magic
  38. 38. There was enthusiasm for PGS • Advanced maternal age • Gianaroli 1999, Munne 1999, Kahraman 2000, Obasaji 2001, Munne 2003; Montag 2004; Platteau 2005 • Repeated IVF failure • Gianaroli 1999, Kahraman 2000, Pehlivan 2003,Munne 2003, Wilding 2004 • Recurrent miscarriage • Pellicer 1999, Rubio 2003, Rubio 2005, Munne 2005 • Severe male factor • Silber 2003, Platteau 2004
  39. 39. Preimplantation genetic screening for advanced maternal age – reduced live birth rates OR 0.59 (0.44, 0.81)
  40. 40. Triggering – GnRH agonist or hCG? Youssef et al, updated CR 2013 • 17 RCTs – 9 report OHSS – 5 report live birth rate • Risk of bias – Only 2/17 used blinding – 4/17 studies stopped prematurely for differing reasons – All studies were either funded by pharmaceutical companies or did not report their funding
  41. 41. Ovarian hyperstimulation rate is reduced with agonist trigger in high risk women only OR 0.06 (0.01, 0.34) Youssef et al, updated 2013 *4 studies no events in either arm
  42. 42. Live birth rate reduced with GnRHa triggering
  43. 43. Conclusion • It is a valid idea with scientific background evidence • Needs more cases to ensure its validity
  44. 44. For whom • for young women, • for those with unexplained infertility • mild male factor •i.e good responders
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×