Is there a difference between recombinant and urinary hCG? this talk may help in answering this

1. Triggering Ovulation
Recombinant Vs Urinary
Gonadotrophins

2. Introduction
♦ LH surge is very important in the final
follicular maturation and triggering
ovulation.
♦ In addition, the LH surge promotes
luteinization forming an active corpus
luteum.
♦ These effects of LH are essential for
conception to occur

3. For triggering
♦ urinary hCG has been used for several years
to mimic the endogenous LH surge.
♦ Recently recombinant hCG and LH have
been introduced . The high purity of this
product facilitates subcutaneous injection
and hence self-administration

4. Objective
♦ To investigate the efficacy and safety of
(rhCG) or recombinant LH preparation vs
(uhCG) for inducing final follicular
maturation and triggering ovulation

5. Types of studies
♦ Only truely randomised controlled trials in
which Subfertile couples undergoing
triggering ovulation were included

6. Types of interventions
♦ Recombinant hCG or recombinant LH
versus urinary hCG for triggering of
ovulation.

7. Primary outcomes
♦ongoing pregnancy / live birth rate (per
woman or per couple)

8. Secondary outcomes
♦ incidence of ovarian hyperstimulation
syndrome (OHSS)
♦ clinical pregnancy rate per cycle
♦ number of oocytes retrieved
♦ miscarriage rate per woman randomised

9. Search strategy for identification
of studies
♦ The Cochrane MDSG Group specialised
register
♦ MEDLINE
♦ EMBASE database
♦ Hand searching of abstracts of major
international meetings.
♦ Contacting pharmaceutical industries

10. To assess internal Validity
♦ Was the assigned treatment adequately concealed
prior to allocation?
♦ Was an "intention to treat" analysis applied?
♦ Were the outcome assessors blind to assignment
status?
♦ Were the treatment and control group comparable
at entry?
♦ Were the subjects & treatment providers blind to
assignment status following allocation?
♦ Were the withdrawals <10% of the study
population

11. To assess external Validity
♦ Were the inclusion and exclusion criteria
for entry clearly defined?
♦ Were the outcome measures used clearly
defined?
♦ Were the accuracy and precision of the
outcome measures adequate?
♦ Was the timing of the outcome measures
appropriate?

12. Allocation concealment
♦ The quality of allocation concealment was
graded as either adequate (A), unclear (B),
or inadequate (C).

13. Analysis
♦The results were combined for meta-
analysis with RevMan software (using the
Mantel-Haenszel method).
♦Results were pooled using a fixed-effects
model only after confirming that
heterogeneity was not present

14. Results
♦ Fourteen trials were identified and only seven
studies were included
♦ Chang et al., 2001,
♦ Driscoll et al, 2000,
♦ The European rHCG Study Group, 2000
♦ The International rHCG Study Group, 2001
♦ The European rLH Study Group, 2001,
♦ Manau et al, 2002
♦ Serono Study 21447

15. Description of studies
♦ All trials had parallel design with true
randomisation using computer generated
randomization list
♦ Randomization was done at time of recruitment of
participants
♦ All trials were multicenter except Manau , 2002
♦ All trials were in IVF/ICSI cycles except IRHCG
Group, 2001 (O.I)
♦ The methodological quality of the trials was high
♦ All were Double blinded except (Manau & Chang)

16. R-LH studies
♦ pregnancy rate was found to be
significantly lower when the recombinant
LH is used for triggering ovulation,
♦ hence, Serono company has decided not to
pursue further development and registration
of recombinant LH high dose for triggering
ovulation.

17. ♦ Accordingly, The European rLH Study
Group, 2001, Manau et al and Serono
Study 21447 were excluded from the
analysis but kept in the review

18. Ongoing pregnancy
O.R 0.98 [95% C.I 0.69-1.39]

19. Clinical Pregnancy rate
O.R 0.98 [95% C.I 0.71-1.36)

20. OHSS
O.R 1.83 [95% C.I 0.75-4.51)

21. Miscarriage rate
O.R 1.1 [95% C.I 0.52-2.31)

22. Tolerability
♦ The three, randomized, placebo-controlled,
double-blind and double-dummy studies,
Driscoll et al, 2000; ERHCG Group, 2000;
IRHCG Group, 2001 consistently found a
2- to 3-fold reduction in the incidence of
local site reactions.
♦ Chang et al, 2001-an open RCT reported no
difference between both drugs.

23. Implications for practice
♦ There is no difference in clinical outcomes
between urinary and recombinant hCG for
induction of final follicular maturation and
triggering ovulation.

24. How To Choose
♦ Additional factors should be considered
when making the choice, including safety,
cost and drug availability.

25. THANK YOU