Recombinant versus urinary human chorionic gonadotrophin for ovulation induction in assisted conception

For the last few decades urinary human chorionic gonadotrophin has been used to induce final follicular maturation and for triggering ovulation in assisted conception. Recombinant technology has allowed the production of two drugs that can be used for the same purpose: to mimic the endogenous luteinizing hormone (LH) surge. This would allow commercial production to be adjusted according to market requirements. In addition all urinary contaminants would also be removed. Hence, this would allow the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, the effectiveness of the recombinant drugs should be known, compared to the currently used urinary human chorionic gonadotrophins.

To assess the safety and efficacy of subcutaneous rhCG and high dose rLH compared with intramuscular uhCG for inducing final oocyte maturation and triggering ovulation.

We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (27 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, issue 4, 2003), MEDLINE (1966 to Feb 2004) and EMBASE (1980 to Feb 2004). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data.

Two reviewers independently scanned titles and abstracts, and selected those that appeared relevant for collection of the full paper. Only truly randomised controlled trials comparing rhCG or high dose r-LH with urinary hCG for triggering ovulation in assisted conception for treatment of infertility in normogonadotrophic women were included.

Assessment of inclusion/exclusion, quality assessment and data extraction were performed independently by at least two reviewers. Discrepancies were discussed in the presence of a third reviewer and a consensus reached. Quality assessment included method of randomisation, allocation concealment, blinding of participants and assessors, reporting of a power calculation, intention to treat analysis, and handling of dropouts. Data extraction included characteristics of participants, the intervention and control procedures, and outcomes.

Seven RCTs were identified, four comparing rhCG and uhCG and three comparing rhLH and uhCG. There was no statistically significant difference between rhCG vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.98, 95% CI 0.69 to 1.39), pregnancy rate, miscarriage or incidence of OHSS. There was no statistically significant difference between rhLH vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.94, 95% CI 0.50 to 1.76), pregnancy rate, miscarriage or incidence of OHSS. The manufacturer of rhLH has decided not to further develop this product. rhCG was associated with a reduction in the incidence of local site reactions and other minor adverse effects (OR 0.47, 95% CI 0.32 to 0.70).

There is no evidence of difference in clinical outcomes between urinary and recombinant gonadotrophins for induction of final follicular maturation. Additional factors should be considered when choosing gonadotrophin type, including safety, cost and drug availability.