An international group of fertility specialists has developed an easy-to use mathematical formula that allows a personalised approach to ovarian stimulation therapy for women seeking fertility treatment. Clinical tests demonstrated that when clinicians used the formula (or algorithm) to calculate the best starting dose for each patient, both the number of oocytes retrieved and pregnancy rates rose.
Professor François Olivennes told the 23rd annual meeting of the European Society of Human Reproduction and Embryology today (Monday 2 July) that the algorithm was based on four factors that predicted ovarian response and that were measured routinely when women were evaluated for fertility treatment: normal (or basal) levels of follicle stimulating hormone (FSH), body mass index, age and the number of small growing (antral) follicles in the ovary detected during screening.
"This FSH dose algorithm is simple and easy to use and utilises readily available patient characteristics," said Prof Olivennes, coordinator of the Centre de FIV Eylau La Muette, Paris, France. "It is the first to be tested in a prospective multi-national clinical study and it provided each patient with an individualised starting dose of FSH, which could be maintained throughout treatment and resulted in an excellent treatment outcome as testified by the number of oocytes retrieved and the high pregnancy rates.
"This approach should enable us to improve patient management, treatment outcomes and safety by reducing the chances of having to either cancel cycles because the ovaries have not been stimulated enough or of ovarian hyperstimulation syndrome (OHSS) developing because the ovaries have been over-stimulated."
Moderate or severe OHSS can occur in 3-8% of IVF cycles . Moderate OHSS can be accompanied by nausea and vomiting. Severe OHSS, which is an uncommon event, can be accompanied by ovarian enlargement and fluid imbalances, sometimes resulting in thrombosis and, very rarely, in death.
Prof Olivennes was presenting the research on behalf of a multi-national team, the CONSORT Study Group (CONsistency in r-FSH Starting dOses for individualised tReatmenT). The group treated 161 ART patients, younger than 35, in 18 centres around the world. The doctors used the algorithm to allocate the women to receive one of five different doses of a follicle stimulating hormone called "recombinant human follicle stimulating hormone, filled by mass" (r-hFSH FbM or GONAL-f FbM). 
The doses, measured in international units (IU), were 75, 112.5, 150, 187.5 and 225. The women were treated for an average of 11 days. Oocytes were retrieved from 84.4% of women, and 80.9% of the women subsequently underwent embryo transfer. Pregnancies per cycle were 31.3%, 31.1%, 35.3%, 50% and 20% per starting dose of 75IU, 112.5IU, 150IU, 187.5IU and 225IU respectively, with an average pregnancy rate of 34.2%. There were two cases of severe OHSS associated with pregnancy. One case of severe OHSS occurred in a patient allocated to the 75 IU dose group but who received a higher starting dose of FSH from the attending physician.
Prof Olivennes said: "The results of the CONSORT clinical study to validate a simple FSH starting dose calculator are very promising, with a high clinical pregnancy rate. It represents an important step forward in aiding clinicians using GONAL-f FbM to individualise the starting dose based upon four easily measured patient characteristics: basal level of FSH in early spontaneous cycle, age (less than 35 years old), body mass index and antral follicle count in early spontaneous cycle.
"However, we still have more work to do before the algorithm can be used for all patients in the clinic. Firstly, the FSH dose calculator has only been validated for GONAL-f FbM -- there are other types of FSH in use. Secondly, we have demonstrated its usefulness in women younger than 35 undergoing ART; further work is required to extend its use in other patient groups.
"The results of this clinical study will provide us with an opportunity to fine-tune the model so as to allow us to further improve its usefulness before making it more generally available. One of the next steps that we are considering is to make the CONSORT FSH dose calculator available to fertility specialists through a dedicated web site, with an appropriate follow-up procedure.
"At present, reproductive medicine specialists determine starting doses so as to induce multiple follicle development based upon some of the characteristics used to develop our model, other tests of ovarian reserve, and their previous clinical experience. We hope that this research will represent a move towards an evidence-based approach to the use of FSH."
Materials provided by European Society for Human Reproduction and Embryology. Note: Content may be edited for style and length.
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