**7. Conclusion**

64 Enhancing Success of Assisted Reproduction

comparable outcomes (108).

1.64).

**5.1. Summary points** 

**6. Special patient groups**

p=0.09) (24).

1. hCG can be used to provide LH action

2. 50-200 IU per day is an appropriate hCG dose

3. hCG supplementation decreases FSH requirement and ART cycle cost

4. hCG supplementation when the lead follicle is 12-14mm improves clinical pregnancy

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,

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

stimulation results in a decreased requirement for rFSH, leading to a cost savings with

A recent meta-analysis summarized the evidence on the use of hCG in ovarian stimulation (111). The analysis included 11 RCT and 1,068 ART cycles. While the conclusions were limited due to heterogeneity with the source studies, significant conclusions were reached. It was demonstrated that the total dose of FSH was decreased by over 800 IU in patients who were supplemented with hCG. The use of hCG resulted in a small decrease in the number of MII oocytes retrieved (WMD -0.30, 95%CI -0.44 to -.66) (111). This data is consistent with the effect of LH on follicular growth discussed earlier in the chapter and a reduction of 0.3 oocytes per patient may be of small clinical impact. In analysis of 3 of trials reporting on early follicular phase hCG administration, there was no demonstrable benefit in clinical pregnancy. However, analysis of five of the trials reporting on late follicular phase hCG demonstrated a significant benefit in clinical pregnancy (RR 1.32, 95%CI 1.06-

> The action of LH is vital to both natural and assisted human reproduction. Normogonadotropic patients often have adequate endogenous LH levels, even after GnRH analogue pituitary downregulation, to have successful assisted reproduction with FSH stimulation alone. However, the addition of LH activity to ovarian stimulation has been demonstrated to improve the odds of achieving a live birth. We find the 3-4% improvement in live birth with the use of LH activity to be clinically relevant. The inclusion of LH in the stimulation of poor responders and women thirty-five and older has been shown to improve ART outcomes. Since there are currently no proven methods to determine which patients will benefit most from the addition of LH, we recommend clinicians consider some form of LH activity in the ovarian stimulation of all patients.
