**6. Special patient groups**

The use of rLH has been evaluated specifically in patients of advanced reproductive age, defined as 35 years of age and older in most studies. Eight RCT trials have compared rLH with rFSH versus rFSH stimulation only in this patient population (24, 29, 41, 88, 91, 93, 94). None of the trials reported a significant difference in oocytes retrieved with rLH. One trial reported a significant decrease in MII oocytes retrieved (5.5 versus 6.9) per patient with the use of rLH (29). The majority of the trials were small and no differences in outcomes were demonstrated with the use of rLH. The largest trial published by Bosch *et al.* enrolled 720 total patients (24). In patients 35 years old and younger, there was no benefit to rLH administration. However, in the advanced reproductive age group, there was a significantly increased fertilization rate (68% versus 61%) and implantation rate (26.7% versus 18.6%) with the use of rLH (24). There was a trend towards increased clinical pregnancy in the patients of advanced reproductive age who were supplemented with rLH (33.5 versus 25.3, p=0.09) (24).

A meta-analysis by Hill *et al*. evaluated seven of these trials (45). In that analysis, there was a significant increase in implantation (OR 1.36, 95%CI 1.05-1.78) and in clinical pregnancy (OR 1.37, 95%CI 1.03-1.83) with the use of rLH (45). While the smaller trials have been underpowered to detect important clinical outcomes such as implantation and clinical pregnancy, both the largest trial and the meta-analysis suggest a clinical benefit to including rLH in the ovarian stimulation of patients with advanced reproductive age.

It has also been suggested that poor responders will benefit from the addition of LH. A common approach to increase LH in poor responders involves the use of the microdose flare protocol. This protocol avoids the profound suppression of endogenous LH and FSH in the early follicular phase normally achieved with long luteal downregulation protocols. Scott and Novat's initial investigation of the microdose flare found it to have higher peak estradiol, more mature follicles and more mature oocytes than a traditional agonist protocol (112). While this protocol represents a well-established approach to increasing endogenous LH and FSH, randomized controlled trials have been small and inconclusive on whether this protocol increases live birth rates (113-116). One RCT did not show any benefit to adding either rLH or low-dose rHCG to a microdose flare protocol for poor responders (117). A Cochrane review has suggested that poor responders may benefit from the addition of rLH (98). In this meta-analysis there was a marked increase in live birth with the use of rLH (OR 1.85, 95%CI 1.10-3.11) (98).
