Human Reproduction Update Advance Access originally published online on March 31, 2006
Human Reproduction Update 2006 12(3):326-327; doi:10.1093/humupd/dml006
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Letter to the Editor |
Reply: Are endogenous LH levels during ovarian stimulation for IVF using GnRH analogues associated with the probability of ongoing pregnancy? A systematic review
1 Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki 2 McMaster University, Hamilton, and Dalhousie University, Halifax, Canada 3 Centre for Reproductive Medicine, Dutch-Speaking Brussels Free University, Laarbeeklaan 101, 1090 Brussels, Belgium
4 To whom correspondence should be addressed at: E.M.Kolibianakis Unit for Human Reproduction, Papageorgiou General Hospital, Nea Efkarpia Peripheral Road, Thessaloniki 54603, Greece. E-mail: Stratis.Kolibianakis{at}otenet.gr
We would like to thank Dr Humaidan for his interest in the systematic review published by Kolibianakis et al. (2006)
in Human Reproduction Update.
The review objective was to examine the association between endogenous LH levels and the probability of ongoing pregnancy beyond 12 weeks in patients undergoing IVF using GnRH analogues. It did not examine the value of LH supplementation in patients with low endogenous LH levels. For that purpose, a different research question needs to be asked.
Therefore, Dr Humaidan’s interpretation that ‘according to present scientific evidence, LH activity supplementation in patients with low endogenous LH levels after down-regulation does not seem to be justified’ is not supported by the results presented in the review by Kolibianakis et al. (2006). As clearly stated in the article, the review served to show that ‘an adverse effect of low endogenous LH levels on the probability of ongoing pregnancy beyond 12 weeks is not a sensible rationale for LH supplementation during ovarian stimulation for IVF’. Whether LH supplementation is associated or not with a better probability of pregnancy remains to be tested in properly designed randomized controlled trials (RCTs).
We would also like to thank Dr Humaidan for the summary of the recently published study by their group (Humaidan et al., 2004). This study was not included in the systematic review by Kolibianakis et al. (2006) because it did not examine the review question. The RCT by Humaidan et al. (2004) tested the concept of LH supplementation of recombinant FSH stimulation in normogonadotropic patients down-regulated with GnRH agonists. Although underpowered to show a clinically important difference in pregnancy rate, the best estimate from that RCT was that no beneficial effect of LH supplementation is to be expected in the population analysed.
We noted with interest the subgroup analysis that Humaidan et al. performed after the primary hypothesis of their RCT (LH supplementation affects beneficially the probability of pregnancy) was rejected. The authors used arbitrary thresholds for LH and female age to define subgroups of patients to evaluate the effect of LH supplementation on the probability of pregnancy.
Although the observations are interesting, they arise from subgroup analysis and can only serve as hypothesis generating ideas and not as proof of an effect of LH supplementation on the probability of pregnancy. It cannot be excluded that a population of women defined using arbitrary LH or female age thresholds might have increased probability of pregnancy by having LH added to recombinant FSH stimulation. This cannot be convincingly shown, however, by a subgroup analysis among women randomized for a different purpose. The only valid way to estimate whether LH supplementation increases the probability of pregnancy in a specific population is to perform an RCT in that population. The interesting observations of Dr Humaidan suggest that this may be worth pursuing.
Dr Humaidan’s letter discusses also whether the discrepancy between immunoreactive and bioactive LH concentrations affects the observed association between immunoreactive LH and the probability of pregnancy. It is necessary that a clear approach needs to be undertaken by researchers regarding this issue. Either we accept that it is appropriate to measure LH immunoreactivity and draw conclusions regarding its association with IVF outcome (ignoring the bioactive LH) or we should abandon measurement of LH immunoreactivity because it may not reflect LH bioactivity. Using selectively the argument of unknown LH bioactivity in the presence of known LH immunoreactivity levels to justify an unexpected result of a subgroup analysis is at least confusing.
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 TOP References |
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Humaidan P, Bungum M, Bungum L and Yding Andersen C (2004) Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study. Reprod Biomed Online 8,635–643.[Web of Science][Medline]
Kolibianakis EM, Collins J, Tarlatzis B, Papanikolaou E and Devroey P (2006) Are endogenous LH levels during ovarian stimulation for IVF using GnRH analogues associated with the probability of ongoing pregnancy? A systematic review. Hum Reprod Update 12,3–12.
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