Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles

Mohamed A Youssef, Ahmed M Abou‐Setta, Wai Sun Lam

For the last few decades urinary human chorionic gonadotrophin (uhCG) has been used to trigger final oocyte maturation in cycles of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Recombinant technology has allowed the production of two drugs, recombinant human chorionic gonadotrophin (rhCG) and recombinant luteinising hormone (rLH), that can be used for the same purpose, to mimic the endogenous luteinising hormone (LH) surge. This allows commercial manufacturers to adjust production according to market requirements and to remove all urinary contaminants, facilitating the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, it is necessary to compare the effectiveness of the recombinant drugs to the currently used urinary human chorionic gonadotrophin (uhCG). To assess the effects of subcutaneous rhCG and high dose rLH versus uhCG for inducing final oocyte maturation in subfertile women undergoing IVF and ICSI cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (April 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE (1946 to April 2015), EMBASE (1980 to April 2015) and PsycINFO (1806 to April 2015) as well as trial registers at ClinicalTrials.gov on 13 May 2015 and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal on 14 May 2015. Two review authors independently scanned titles and abstracts and selected those that appeared relevant for collection of the full paper. We included randomised controlled trials comparing rhCG and rLH with urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles for treatment of infertility in normogonadotropic women. Two authors independently performed assessment for inclusion or exclusion, quality assessment and data extraction. We discussed any discrepancies in the presence of a third author to reach a consensus. The primary review outcomes were ongoing pregnancy/live birth and incidence of ovarian hyperstimulation syndrome (OHSS). Clinical pregnancy, miscarriage rate, number of oocytes retrieved and adverse events were secondary outcomes. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) and assessed statistical heterogeneity using the I(2) statistic. We evaluated the overall quality of the evidence for the main comparisons using GRADE methods. We included 18 RCTs involving 2952 participants; 15 compared rhCG with uhCG, and 3 compared rhLH with uhCG. The evidence for different comparisons ranged from very low to high quality: limitations were poor reporting of study methods and imprecision. Pharmaceutical companies funded 9 of the 18 studies, and 5 studies did not clearly report funding source. Ongoing pregnancy/live birthThere was no conclusive evidence of a difference between rhCG and uhCG (OR 1.15, 95% CI 0.89 to 1.49; 7 RCTs, N = 1136, I(2) = 0%, moderate quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.51 to 1.78, 2 RCTs, N = 289, I(2) = 0%, very low quality evidence) for ongoing pregnancy/live birth rates. OHSSThere was no evidence of a difference between rhCG and uhCG in the incidence of OHSS: moderate to severe OHSS (OR 1.76, 95% CI 0.37 to 8.45; 3 RCTs, N = 417, I(2) = 0%, low quality evidence), moderate OHSS (OR 0.78, 95% CI 0.27 to 2.27; 1 RCT, N = 243, I(2) = 0%, low quality evidence), mild to moderate OHSS (OR 1.00, 95% CI 0.42 to 2.38; 2 RCTs, N = 320, I(2) = 0%, low quality evidence) or undefined OHSS (OR 1.18, 95% CI 0.50 to 2.78; 3 RCTs, N = 495, I(2) = 0%, low quality evidence). Likewise, there was no evidence of a difference between rhLH and uhCG in OHSS rates for moderate OHSS (OR 0.82, 95% CI 0.39 to 1.69, 2 RCTs, N = 280, I(2) = 5%, very low quality evidence). Other adverse eventsThere was no evidence of a difference in miscarriage rates between rhCG and uhCG (OR 0.72, 95% CI 0.41 to 1.25; 8 RCTs, N = 1196, I(2) = 0%, low quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.38 to 2.40; 2 RCTs, N = 289, I(2) = 0%, very low quality evidence). For other adverse effects (most commonly injection-site reactions) rhCG was associated with a lower number of adverse events than uhCG (OR 0.52, 95% CI 0.35 to 0.76; 5 RCTS, N = 561; I(2) = 67%, moderate quality evidence). However, when we used a random-effects model due to substantial statistical heterogeneity, there was no evidence of a difference between the groups (OR 0.56, 95% CI 0.27 to 1.13). Only one study comparing rLH and uhCG reported other adverse events, and it was impossible to draw conclusions. We conclude that there is no evidence of a difference between rhCG or rhLH and uhCG for live birth or ongoing pregnancy rates or rates of OHSS.