title: Establishing a combined stimulation protocol hFSH followed by rFSH might represent a breakthrough in the IVF practice.
abstract: BACKGROUND
  Controlled ovarian stimulation directly influences assisted reproductive technology (ART) outcomes. Indeed, several studies have shown that the total IU of gonadotropins used for ovarian stimulation inversely correlates with pregnancy rate. Nowadays, two main gonadotropins are used in ART protocols, human-derived and recombinant follicle-stimulating hormone (FSH). The difference between these two hormones is dramatic. Indeed, the human-derived FSH is an acidic isoform of the hormone while the recombinant is a less acid one. In particular, during a physiological menstrual cycle the acid isoform is produced during the follicular phase (probably it is more effective in recruiting follicles) while less acidic isoform is produced during the mid follicular phase (preovulatory). In the present study, we aim to evaluate the efficacy of a protocol that mimics the physiological shift form an acidic to a less acid FSH isoform during oocyte maturation.
  
  
  METHODS
  A total of 308 infertile couples undergoing their first Intracytoplasmic Sperm Injection (ICSI) treatment were enrolled. All patients underwent a standard down-regulation protocol with GnRH analogue hormone. Patients were randomized in two groups: group 1, patients that received 225 IU of human-derived FSH (hFSH Fostimon, IBSA, Lodi, Italy) for 6 days from the second day of the cycle and then 225 IU of recombinant FSH (rFSH Gonal-F; Serono, Rome, Italy) from the 7th day of stimulation until hCG administration, and group 2, control group, patients that received 225 IU recombinant FSH alone from the second day of the cycle until hCG administration.
  
  
  RESULTS
  The combined protocol (hFSH + rFSH) resulted in significantly less IU of FSH necessary for ovarian stimulation together with the stimulation days. Furthermore, oocyte and embryo quality was higher in the group of patients treated with the combined protocol. Noteworthy, a significantly higher implantation rate and pregnancy rate were observed in favour of group 1 compared to group 2.
  
  
  CONCLUSIONS
  We demonstrated that establishing a stimulation protocol able to mimic the physiological differences in FSH isoforms, hFSH combined with rFSH positively impact on ART outcome.
authors.affiliation: Department of Obstetrics and Gynecology, Centre for Perinatal and Reproductive Medicine, University of Perugia, Perugia, Italy. direnzo@unipg.it  
authors.forename: S
authors.initials: S
authors.lastname: Gerli
authors.forename: G C
authors.initials: GC
authors.lastname: Di Renzo