Abstract
IntroductionSeveral studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age candidates for assisted reproduction.Material and methodsUsing a preregistered protocol we systematically searched Medline/PubMed, Scopus and the ISI Web of Science databases to identify randomized controlled trials in which r-hFSH monotherapy protocols were compared with r-hFSH/r-hLH co-treatment in women ≥35 years undergoing fresh IVF cycles. We calculated the pooled odds ratio (OR) for dichotomous data and the weight mean difference (WMD) for continuous data with an associated 95% confidence interval (CI). The meta-analyses were conducted using the random-effect model. P values < 0.05 were considered statistically significant. Subgroup analyses of all primary and secondary outcomes were performed only in women aged 35–40 years.ResultsTwelve studies were identified. In women aged between 35 and 40 years, r-hFSH/r-hLH co-treatment was associated with higher clinical pregnancy rates (OR 1.45, CI 95% 1.05–2.00, I2 = 0%, P = 0.03) and implantation rates (OR 1.49, CI 95% 1.10–2.01, I2 = 13%, P = 0.01) versus r-hFSH monotherapy. Fewer oocytes were retrieved in r-hFSH/r-hLH-treated patients than in r-hFSH-treated patients both in women aged ≥35 years (WMD -0.82 CI 95% -1.40 to − 0.24, I2 = 88%, P = 0.005) and in those aged between 35 and 40 years (WMD -1.03, CI − 1.89 to − 0.17, I2 = 0%, P = 0.02). The number of metaphase II oocytes, miscarriage rates and live birth rates did not differ between the two groups of women overall or in subgroup analysis.ConclusionAlthough more oocytes were retrieved in patients who underwent r-hFSH monotherapy, this meta-analysis suggests that r-hFSH/r-hLH co-treatment improves clinical pregnancy and implantation rates in women between 35 and 40 years of age undergoing ovarian stimulation for assisted reproduction technology. However, more RCTs using narrower age ranges in advanced age women are warranted to corroborate these findings.
Highlights
Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production
Conclusion: more oocytes were retrieved in patients who underwent recombinant human follicle stimulating hormone (r-hFSH) monotherapy, this metaanalysis suggests that r-hFSH/recombinant-human LH (r-hLH) co-treatment improves clinical pregnancy and implantation rates in women between 35 and 40 years of age undergoing ovarian stimulation for assisted reproduction technology
Group A1 N = 21 r-hFSH +r-hLH r-hLH started at stimulation day 8 r-hLH dosage r-hFSH r-hLH ratio 2:1
Summary
Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. A retrospective analysis of 1296 embryos screened by next-generation sequencing indicated that the probability of blastocyst euploidy progressively decreases with every year of female age [3]. This effect is mainly due to the higher incidence of chromosomal abnormalities in oocytes of advanced-age women [5]. Reproductive endocrine function progressively declines with advancing age [6] In detail, this process seems to affect the luteinizing hormone (LH) system and androgen production [7–9]. Ishihara et al reported that the global proportion of women aged ≥40 years seeking ART treatment increased from 15.5 to 19.8% between 2006 and 2007 [12]. The focus now is to find measures to counteract the natural age-related decline in fertility [12, 14]
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