One of the fundamental steps for the definition of the role of FSH and LH in reproduction was the formulation of the “two cells - two gonadotrophin theory” which states the following: FSH stimulates follicular development; both LH and FSH are required for oestradiol (E2) synthesis; LH triggers androgen precursors transfer from the thecal layer to the granulosa cells, where, under the FSH-stimulated effect of aromatase, they are converted to oestrogen. The ”window of recruitment” model was proposed combining observations on time of occurrence of follicle selection and on trends of gonadotrophins during unstimulated cycles. Accordingly, during the intercycle the rise of FSH reaches a threshold level allowing the projection of the largest, healthiest follicle through for ovulation.
Zeev Shoham addressed the concept of threshold and ceiling for LH concentration during the follicular phase. He opened his lecture with a comprehensive review of studies for and against the two cells-two gonadotrophin theory. Several authors, and the speaker himself, evaluated the difference of E2 production in gonadotrophin-deficient women treated with human menopausal gonadotrophin (hMG) or with urine-derived human FSH and the available data overall confirmed the two cell–two gonadotrophin theory. He showed results of studies performed when recombinant human FSH (r-hFSH) became available that provided further support to that theory, showing that both FSH and LH are required for oestrogen biosynthesis but also revealing that only very small amounts of LH activity are sufficient to increase E2 secretion to measurable plasma levels. Zeev Shoham presented the results of a multicentre study which randomized patients with World Health Organization (WHO) type-I anovulation to receive four doses (0, 25, 75, or 225 IU/day) of recombinant human LH (r-hLH) in addition to a fixed dose of r-hFSH (150 IU/day). The results of this trial suggested that 75 IU r-hLH is sufficient for promoting optimal follicular development. His lecture also included an exhaustive review of studies focused on LH ceiling. The conclusions based on the available data were that LH in the stimulation protocol is obligatory in patients with HH (hypogonadotrophic hypogonadism). In subjects that develop multiple follicles, such as those with PCOS, supplementation with high doses of r-hLH appears to increase the proportion of patients developing a single dominant follicle, but the feeling expressed by the speaker was that FSH is sufficient for the majority of normogonadotrophic patients undergoing GnRH down-regulation.
Michael Ludwig showed the results of a survey that addressed the use of LH supplementation from research to the everyday practice. Physicians in France, Germany, Italy and Spain were asked about their current gonadotrophin treatment decisions and future treatment options related to new gonadotrophin formulations availability. A complete analysis of the survey results was presented showing that approximately one-quarter of the existing cycles included the addition of LH activity, either as r-hLH or u-hMG, and that most physicians use an FSH:LH ratio of 2:1. Another interesting result of the survey was that a fixed combination of r-hFSH and r-hLH was considered as a valid alternative to r-hLH or hMG in the management of patients were LH supplementation is required.
In his talk Peter Humaidan defined the subgroup of patients undergoing ovarian stimulation where LH supplementation should be recommended. He confirmed that it is mandatory in HH patients and explained the controversies on other possible indications of LH supplementation due to variability in the protocols of the performed trials that make them non-comparable. The speaker then presented the outcomes of the most recent of these studies. In some trials LH supplementation did not provide benefits to the studied population, for example in profoundly suppressed patients, but showed advantages in subgroups, such as women aged 35 or more or with endogenous LH levels ≥1.99 IU/l on day 8 after GnRH agonist down-regulation. Other subgroups studied as possible target for LH supplementation have been normogonadotrophic women with an initially inadequate response to r-hFSH. Peter Humaidan also explained the possible link among different subpopulations that benefit from LH supplementation. A progressive decrease in LH bioactivity, in contrast with unchanged immunoreactivity, and of ovarian paracrine activity that usually enhances LH activity can be related to ovarian ageing. Polymorphic variants of the hormone can explain initial low response and high levels of LH detected in some subjects.
Lars Westergaard confirmed the relevance of threshold and ceiling in LH supplementation in women with WHO I anovulation and added that evidences suggest that 75 IU is the right dose in the majority of subjects where LH supplementation is effective. He had a comprehensive overview of data available on normogonadotrophic women where a GnRH antagonist causes a steep drop in serum LH levels and concluded that results of trials are conflicting and confusing and overall seem to not affect reproductive outcome in most normogonadotrophic women. Lars Westergaard closed his lecture speculating on the apparent discrepancy between HH and normogonadotrophic women and suggested that lack of activity of the hormone could be as relevant as lower levels of LH secretion.
Jean Noël Hugues presented an exhaustive review of most recent meta-analysis on the effect of r-hLH supplementation in GnRH analogue cycles. He pointed out the variability of results and related it to the heterogeneity of designs of the considered trials concluding that data in favour of LS supplementation are lower spontaneous miscarriages and higher E2 levels observed in cycles with GnRH antagonists. More suggestive were the results of a prospective, randomized, multicenter study evaluating LH supplementation following agonist down-regulation with individualization of r-hFSH and r-hLH according to the age. LH supplementation induced a significant and dose-dependent increase in serum LH levels on the day of hCG administration versus FSH alone and no significant differences between the two groups were detected with respect to ovarian parameters. The large sample size of this study allowed a sub-analysis to evaluate which patients are more likely to benefit from the addition of LH. This analysis confirmed that patients with low serum LH levels benefit from LH supplementation but failed to find significant differences in pregnancy rates after LH supplementation according to age. Jean Noël Hugues also addressed the topic of optimal timing of LH-like activity supplementation with a comprehensive review of available data.
Ernesto Bosch started the last lecture discussing criteria that define poor and low responders where LH supplementation can be effective. He introduced the concepts of quantitative and qualitative response to gonadotrophins in order to explain that, for example, in older women the response can be normal in quantitative terms, but poor qualitatively. Furthermore the speaker mentioned that reproductive outcomes decline when patients have their own eggs, whereas outcome in patients with donor eggs remains relatively constant with increasing age, confirming that poor outcome relates to the oocyte rather than uterine factors. He then proceeded to discuss the relationship between chronological and reproductive age, pointing out that the latter is influenced by a wide inter-individual variability, and introduced the definition of oopause. In addition to clinical signs, hormonal patterns in ageing ovaries are modified and Ernesto Bosch dedicated the following part of his lecture to this aspect and to the dynamics of the ageing ovary that, under stimulation, are different compared with the younger ovary. He lastly showed studies that evaluated the efficacy of LH supplementation in older women. The meeting ended with a panel discussion on the controversies on the role of LH in ovarian stimulation.
Click here to view the Presentations
Click here to view the Final Program and Abstracts
As Professor Giancarlo Comi welcomed delegates to the meeting he explained, “This is an exciting time for us so deeply involved in this very difficult disease”. Professor Bates then informed the delegates of the interesting scientific programme: “you will get information on the analysis of data about early treatment, you will be helped to evaluate the information available about long-term data, you will be helped to examine the role of and the potential for surrogate markers, both of disease and therapy, and you will understand more fully and perhaps amend the concept of adherence to therapy”.
Click here to view the Symposium Review
Click here to view the Presentations
Click here to view the Final Program and Abstracts
The following are brief reports from our congresses that have taken place from April to July 2007.
This pre-congress course during the 6th annual meeting of the Mediterranean Society for Reproductive Medicine (MSRM) was regarded as positive by the attendees and there was an overall recognition the importance of “Recent advances in Art”. Particularly appreciated were the talks on the role of LH, lutheal phase support and PCS and Art.
Click here for the Final Program and Abstracts
Click here for the Presentations
Click here for the Final Program and Abstracts
Click here for the Final Program and Abstracts
 |
New online course in Reproductive Health & Endocrinology:
Culture Media and In-Vitro Embryo Development is now available on the Serono Symposia International Foundation website. |
Click here for the Final Program and Abstracts
Click here for the Final Program and Abstracts
Click here for a Symposium Review of last year's edition
 |
New online course in Neurology:
MS Preceptorship: Updating Knowledge on Multiple Sclerosis is now available on the Serono Symposia International Foundation website. |
A closer look at the area of fertility preservation in those with malignant disease is the aim of this congress. The program is designed to benefit clinicians, scientists and paramedical staff involved in the treatment of reproductive and oncological disorders.
An indepth analysis of the diverse surgical techniques used to treat sterility will be addressed here. Also under discussion will be the ongoing debate regarding whether there is an effective need to undergo surgery for purely reproductive purposes as an alternative, or in association, to the current pharmacological therapies to treat infertility. The conference will offer a live session on endoscopic surgery, and also renowned national and international experts will confront their respective experiences on gynecological problematics which still have not reached a consensus on the best therapeutic approach in order to explore the universe of reproductive medicine where many questions still remain to be clarified.
The objective of this course is to provide participants with the most updated knowledge on IVF procedures and with skills useful in IVF practice. At the end of the workshop, among the various learning objectives, the attendees will have acquired information on the current ethical, regulatory and legal issues on IVF in Europe, the ability to diagnose infertility in males and females, the background needed to choose the right IVF procedure and the best way to interact with patients.
The aim of this congress is provide a forum where researchers and/or clinicians who address the problematics involved in the treatment of multiple sclerosis, Parkinson’s and Alzheimers, may gather to review their respective experiences and acquire new knowledge that can assist identifying common aspects, as well as pathologic differences, to assist reaching optimal and innovative therapeutic approaches.
MS Nurse is an annual workshop created to encourage the dissemination of scientific knowledge among nurses from all over the world in the field of Multiple Sclerosis. Presentations will provide the latest information in MS in the following areas: Advanced Disease Management, Problem Symptoms and Psychosocial & Cognitive Aspects. In addition to didactic presentations, group workshops will allow nurses to discuss these topics in relation to their own practice.
This is an educational programme created to encourage the dissemination of scientific knowledge in the field of MS. It will stress the benefits of new diagnostic tools for defining the natural history of MS and disease activity monitoring. Current diagnostic criteria for MS will also be reviewed in the light of new medical evidence. A review of recent clinical trials and treatment optimisation guidelines will also be presented.
