Reply: Comment on ‘Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35 years or older undergoing IVF/ICSI: a randomized controlled multicentre study’

Sir,

We highly appreciate the interest and comments made by the group of Bosch et al. regarding our recent publication on recombinant LH supplementation to a standard GnRH antagonist IVF/ICSI protocol in women of 35 years or older (König et al., 2013). We agree that there are a few methodological differences between our study and the study of Bosch et al. (2011) which might explain discrepancies in reported results. These differences generate some interesting questions on the mechanism of a possible beneficial effect of LH administration in a specific group of older women seeking IVF/ICSI treatment receiving a specific treatment protocol. Although we agree with some of the comments that are made, a number of raised questions are hypothetical and open to debate.

Our study showed no beneficial effect of recombinant (r)LH supplementation from stimulation Day 6 on ongoing pregnancies in women of advanced age receiving a short (no oral contraceptive pill pretreatment) GnRH antagonist protocol. However, Bosch et al. found a beneficial effect of LH on implantation rates, which could be explained by lowering basal LH levels after oral contraceptive pill pretreatment. The clinical implication of this could be questioned, since the use of oral contraceptive pills prior to a GnRH antagonist protocol is controversial and much debated (Smulders et al., 2010). There is evidence that suggests that oral contraceptive pill pretreatment adversely affects the IVF outcome in GnRH antagonist cycles (Nardo et al., 2013).

In contrast to our findings of no effect of rLH on progesterone levels, Bosch et al. found lower progesterone levels on the day of hCG. This could be explained by a possible effect of LH administration on stimulation Day 1 by the action of LH on the theca layer in the early follicular phase. However, in the late follicular phase FSH also stimulates the granulosa cell to produce progesterone. Since Bosch et al. reduced the amount of rFSH in patients randomized to rLH administration, this effect of FSH on the granulosa cell cannot be ruled out. Furthermore, the relation of progesterone levels on pregnancy rates is still a matter of debate (Venetis et al., 2013).

LH supplementation from stimulation Day 6 onwards does not seem to be beneficial. However, we agree that there might be a potential beneficial effect of LH supplementation from stimulation Day 1 in an antagonist cycle especially with pretreatment of oral contraceptives in this specific group of older women. Further studies are indeed necessary to address this issue.