Recombinant luteinizing hormone supplementation in assisted reproductive technology: a systematic review

A large body of evidence indicates that luteinizing hormone plays a crucial role during folliculogenesis and that its supplementation may be useful in specific sub- groups of women undergoing assisted reproductive technology.

Volume 109, Issue 4, Pages 644–664


Carlo Alviggi, M.D., Ph.D., Alessandro Conforti, M.D., Sandro C. Esteves, M.D., Ph.D., Claus Yding Andersen, D.M.Sc., Ernesto Bosch, M.D., Klaus Bühler, M.D., Anna Pia Ferraretti, M.D., Giuseppe De Placido, M.D., Antonio Mollo, M.D., Ph.D., Robert Fischer, M.D., Peter Humaidan, M.D., D.M.Sc. for the International Collaborative Group for the Study of r-hLH (iCOS-LH)



To assess the role of recombinant human LH (r-hLH) supplementation in ovarian stimulation for ART in specific subgroups of patients.


Systematic review.


Centers for reproductive care.


Six populations were investigated: 1) women with a hyporesponse to recombinant human FSH (r-hFSH) monotherapy; 2) women at an advanced reproductive age; 3) women cotreated with the use of a GnRH antagonist; 4) women with profoundly suppressed LH levels after the administration of GnRH agonists; 5) normoresponder women to prevent ovarian hyperstimulation syndrome; and 6) women with a “poor response” to ovarian stimulation, including those who met the European Society for Human Reproduction and Embryology Bologna criteria.


Systematic review.

Main Outcome Measure(s)

Implantation rate, number of oocytes retrieved, live birth rate, ongoing pregnancy rate, fertilization rate, and number of metaphase II oocytes.


Recombinant hLH supplementation appears to be beneficial in two subgroups of patients: 1) women with adequate prestimulation ovarian reserve parameters and an unexpected hyporesponse to r-hFSH monotherapy; and 2) women 36–39 years of age. Indeed, there is no evidence that r-hLH is beneficial in young (<35 y) normoresponders cotreated with the use of a GnRH antagonist. The use of r-hLH supplementation in women with suppressed endogenous LH levels caused by GnRH analogues and in poor responders remains controversial, whereas the use of r-hLH supplementation to prevent the development of ovarian hyperstimulation syndrome warrants further investigation.


Recombinant hLH can be proposed for hyporesponders and women 36–39 years of age.

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Go to the profile of Micah J Hill
about 4 years ago

Thank you for a great expert review of rLH in ART stimulation!

1. It seems you showed great restraint in not performing statistical meta-analysis of the data.  Could you elaborate on why you felt the data was appropriate for statistical synthesis?

2. Do you think another potential benefit of exogenous LH activity is reducing premature progesterone rise, given that it encourages 5delta steroid synthesis and CYP 17 activity, reducing progesterone build up?

Go to the profile of Carlo Alviggi
about 4 years ago

Thank you for your comment and suggestions.

1 ) This review is the result of an expert meeting held in Naples in 2016 where we initially decided to understand whether the body of evidence was sufficient for the identification of major subgroups of patients. In other word our aim was to initially identify macro-categories for further quantitative approach. Your previous work in patients over 35 was one of the most relevant starting points. Once identified main subgroups, the next step is to perform meta-analysis in each one analyzing different endpoints, maybe to much to condense in a single paper.

2) The issue of potential role of LH in preventing progesterone is still controversial. Despite some papers support your hypothesis , the emerging idea is that this phenomenon is mainly related to the impact of exceeding FSH activity in granulosa cells. The model of MERIT and MEGASET trials seems to support this interpretation. In the MERIT study, when 225 IU of recombinant FSH were compared to 225 IU of FSH/LH, the progesterone rise was more frequent in the former group. Following this observation, it was hypothesized that LH activity counteracted progesterone production. In the subsequent MEGASET trial, when the dose 150 IU was adopted in the two groups, this effects disappeared. This observations is also consistent with papers published by Filicori et al. (J Clin Endocrinol Metab. 1999 Aug;84(8):2659-63; J Clin Endocrinol Metab. 2002 Mar;87(3):1156-61) in the late Nineties. In addition, the enzymatic pathway for androgenesis in human ovary does not seem consistent with the hypothesis that LH can counteract FSH related progesterone rise. I think that literature on this issue is not conclusive and well designed trials aimed to directly investigate into this intriguing topic are required.

Go to the profile of Micah J Hill
about 4 years ago

Great answers and thank you again for the very interesting paper!