To add or not to add LH: comments on a recent commentary

doi:10.1016/S1472-6483(10)60998-4

Reproductive BioMedicine Online

Volume 12, Issue 3, 2006, Pages 284-285

https://doi.org/10.1016/S1472-6483(10)60998-4 Get rights and content

Abstract

From a period of time when LH activity supplementation in stimulation protocols for assisted reproductive technology was questioned, recent scientific evidence seems to prove a role of LH activity in optimizing the clinical results of certain subgroups. Until now, apart from the hypogonadotrophic hypogonadal patient, two subgroups of patients have attracted attention: patients over 35 years of age, and normogonadotrophic patients with an initial low response to recombinant FSH (rFSH). However, in a recent paper, another subgroup of patients has been identified: normogonadotrophic patients with high endogenous LH levels (>1.99 IU/l) on day 8 of stimulation after a long GnRH agonist down-regulation. By adding recombinant LH (rLH) from day 8 to the stimulation protocol, this subgroup of patients achieved good implantation rates, similar to those of patients with lower LH levels. Interestingly, the dynamics of the endogenous LH levels during down-regulation in this group of patients differed from those of patients with lower LH levels. The immunoreactivity of the LH molecule does not necessarily reflect the bioactivity, which might explain the beneficial effect of LH activity supplementation in patients with high endogenous LH levels after down-regulation. Future studies should be focused on subgroups to further explore the effect of LH activity supplementation in assisted reproduction techniques.

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Cited by (12)

Outcomes after early or midfollicular phase LH supplementation in previous inadequate responders
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Citation Excerpt :
Besides the specificity and sensitivity of the immunoassay used may affect the value of serum LH concentration (Costagliola et al., 1994). Moreover, it was demonstrated that measuring serum LH throughout the follicular phase does not predict ovarian response and assisted reproductive treatment outcome (Balasch et al., 2001; Humaidan, 2006; Peñarrubia et al., 2003). A daily dose of 75 IU recombinant LH was usually found effective in promoting optimal follicular development (De Placido et al., 2001, 2004, 2005; Lisi et al., 2001).
Second cycle outcomes of 75 patients who had previous inadequate ovarian response with recombinant FSH (rFSH)-only ovarian stimulation during gonadotrophin-releasing hormone analogue (GnRHa) down-regulated cycles were evaluated retrospectively. In these second cycles, both rFSH and human menopausal gonadotrophin (HMG) in GnRHa long down-regulation were given to all patients, HMG initiated either on day 1 (group A, n = 37) or day 5–6 of the ovarian stimulation (group B, n = 38). Total HMG dose was higher (1198 ± 514 IU versus 726 ± 469 IU; P < 0.001), cumulative rFSH consumption was lower (1823 ± 804 IU versus 2863 ± 1393 IU; P = 0.001) and duration of stimulation was shorter (8.94 ± 1.15 days versus 10.37 ± 1.80 days; P < 0.001) in group A than in group B. No significant differences were found regarding fertilization, implantation or pregnancy rates and embryo quality between the groups. Further analysis by supplementary HMG dose (75 IU versus 150 IU) revealed that total gonadotrophin and HMG consumption was lower in 75 IU-supplemented subgroups. Notably, pregnancy rate was higher in patients where 75 IU HMG was supplemented on day 5–6 of ovarian stimulation, which deserves further evaluation.
To add or not to add LH: Comments on recent commentaries
2006, Reproductive BioMedicine Online
Human reproductive evolution, involving a complex interaction of the hypothalamic–pituitary–ovarian axis, the release of pulsatile and threshold concentrations of gonadotrophins and positive and negative feedback systems, has ensured the release of a single viable egg and functioning corpora lutea in the natural menstrual cycle. The use of follicular stimulation regimens to obtain multiple eggs has resulted in a compromise – in terms of the risk of ovarian hyperstimulation, cost, multiple pregnancies, wastage of or the need for cryopreservation of surplus embryos. Even some women with apparently normal menstrual cycles might become ‘poor responders’ when administered with follicular stimulants, and we still do not know if the incidence of oocyte aneuploidy is artificially raised after stimulation. After the advent of recombinant FSH and LH, the precise roles of these hormones individually needs to be elucidated to understand the physiological requirements for successful ovarian stimulation in each woman undergoing IVF, to maximize her chance and minimise attendant risks. One of the key debates is the role of LH, which in the natural cycle is significant, but may be redundant during ovarian stimulation for IVF. Current outcome indicators are crude when attempting to understand the physiology, and more basic research and randomized, focused clinical trials are needed.
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The role of LH in the natural menstrual cycle is not disputed. However, there are a variety of opinions regarding the potential role of exogenous LH in ovulation induction and whether it is actually needed. Recent years have seen renewed interest in this issue for several reasons. First, ovulation-inducing drugs are increasingly being administered to normally ovulating women. Second, recombinant human FSH products completely devoid of LH activity are now available. Third, gonadotrophin-releasing hormone (GnRH) analogues (agonists and antagonists) prevent the untimely LH surge but also suppress endogenous LH activity during the follicular phase. This review analyses whether or not all patients need LH for follicular growth stimulation and new opportunities for improved treatment as a result of the availability of recombinant human LH both in patients with ovulatory disorders (World Health Organization (WHO) groups I and II anovulatory patients) and those undergoing multiple follicular development for assisted reproduction.
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Recombinant human follicle-stimulating hormone produces more oocytes with a lower total dose per cycle in assisted reproductive technologies compared with highly purified human menopausal gonadotrophin: A meta-analysis
2010, Reproductive Biology and Endocrinology

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CommentaryTo add or not to add LH: comments on a recent commentary

Abstract

Molecular and Cellular Endocrinology

Reproductive BioMedicine Online

Reproductive BioMedicine Online

Reproductive BioMedicine Online

Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH. A multicentre, prospective, randomised controlled trial

Human Reproduction

Commentary
To add or not to add LH: comments on a recent commentary