Triggering Ovulation

Recombinant Vs Urinary Gonadotrophins

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

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

Objective

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

Types of studies

Only truely randomised controlled trials in which Subfertile couples undergoing triggering ovulation were included

Types of interventions

Recombinant hCG or recombinant LH versus urinary hCG for triggering of ovulation.

Primary outcomes

ongoing pregnancy / live birth rate (per woman or per couple)

Secondary outcomes

incidence of ovarian hyperstimulation syndrome (OHSS)

clinical pregnancy rate per cycle number of oocytes retrieved miscarriage rate per woman randomised

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

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

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?

Allocation concealment

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

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

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

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)

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.

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

Ongoing pregnancy

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

Clinical Pregnancy rate

O.R 0.98 [95% C.I 0.71-1.36)

OHSS

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

Miscarriage rate

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

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.

Implications for practice

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

How To Choose

Additional factors should be considered when making the choice, including safety, cost and drug availability.

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