Table 2.

Statements approved by the Scientific Board.

Statement
Follicular development and stimulation with gonadotropins
1.	Exogenous r-hFSH alone is probably sufficient for follicular development in normogonadotropic patients aged <35 years.
2.	There is a strong association between the number of oocytes and the LBR following fresh IVF cycles and a positive linear association with cumulative live birth rates (in fresh and frozen).
3.	Most studies on ART examine LBR per cycle. However, this data tries to predict the probability of successful pregnancies in successive fresh IVF cycles. For patients, data on the cumulative probability of pregnancy/live birth are highly informative yet there is scarce data on cumulative live birth rate.
4.	Glycosylation is an important quality attribute and is critical for the efficacy of therapeutic hFSH. The sialylation and complexity of hFSH oligosaccharides affect endocrine activity, gene expression and regulate granulosa cell function. The higher the sialic acid content in the FSH molecule, the lower the clearance rate which leads to higher in vivo half-life. The different clinically available hFSH preparations have identical polypeptide chains but a somewhat different glycosylation pattern, that may affect their activity.
5.	While the proportion of acidic FSH isoforms is higher during the early to mid-follicular phase compared to the preovulatory phase, the basic FSH isoforms are secreted before ovulation. hFSH preparations consist of a wide range of isoforms including the most acidic produced during menopause or the early follicular phase, when estradiol level is low. When examining the different commercially available hFSH preparations, the FSH isoforms present in u-hFSH are more acidic than those in r-hFSH.
6.	When compared to treatment with r-hFSH alone, r-hFSH:r-hLH treatment might improve the ongoing pregnancy rate in some groups of low prognosis patients.
7.	When compared to treatment with hMG, the effects observed across studies show a tendency towards an improved embryo number and pregnancy rate while using r-hFSH:r-hLH treatment. Nevertheless, further studies are needed before drawing a firm conclusion on the comparison between hMG and r-hFSH:r-hLH preparations.
8.	In patients with severe FSH and LH deficiency undergoing ovulation induction, there is moderate evidence suggesting a significantly higher pregnancy rate with a lower time-to-pregnancy was achieved with r-hFSH:r-hLH treatment compared to hMG. And, r-hFSH:r-hLH treatment is superior compared to hMG in cost efficacy improving pregnancy rate with significant less units of r-hLH.
9.	LH and hCG are characterised by specific molecular and biochemical features; they interact with distinct binding sites on the same receptor, and the dissociation rates from these sites are lower for hCG compared with LH. r-hLH has a shorter terminal half-life (around 10 hours) compared to hCG (terminal half-life 28 to 31 hours). Downstream effects of gonadotropins’ signalling consist of LH-related proliferative and anti-apoptotic signals, vs. high steroidogenic potential and pro-apoptotic activity of hCG in vitro.
Pituitary suppression
10.	The live birth rate using the long GnRH-agonist and multiple-dose GnRH-antagonist are comparable in terms of efficacy, but the incidence of any grade of OHSS and cycle cancellation due to it is significantly lower after pituitary suppression with a GnRH antagonist compared to pituitary downregulation with a GnRH agonist.
11.	After the administration of GnRH analogues, a functional state of hypogonadotropic hypogonadism with LH deficiency could be achieved, potentially affecting folliculogenesis, steroidogenesis and oocyte competence, impinging on clinical outcomes. The concept of serum LH dynamic changes following GnRH analogue employment as an indicator for LH threshold should be pursued, instead of a single serum LH evaluation.
Final oocyte maturation triggering
12.	The use of recombinant hCG and urinary hCG demonstrated the same efficacy for triggering final oocyte maturation during controlled ovarian stimulation protocols and represents the gold standard in fresh cycles.
13.	In the modified natural cycle of frozen embryo transfer in patients with regular ovulatory cycles, the hCG trigger demonstrates controversial efficacy compared to monitoring the LH peak or other therapeutic approaches such as hormone replacement therapy to optimise natural ovulation in endometrial preparation.
14.	Compared with hCG trigger, due to an additional FSH surge and the different effects of LH and hCG on the downstream signalling, the combined administration of hCG and GnRH agonist (dual/double trigger) for final oocyte maturation was found in a recent meta-analysis to be associated with a significantly higher pregnancy rate. Dual/Double trigger could represent a valid option but additional evidences have to be provided to recommend this approach as first-line treatment.
15.	A GnRH agonist trigger, in a GnRH antagonist protocol, is recommended for final oocyte maturation in women at risk of OHSS.
Luteal-phase support
16.	Vaginal progesterone therapy represents the gold standard approach for luteal phase support after IVF/ICSI. The route of progesterone administration does not influence outcomes.
17.	Addition of GnRH agonist injections to progesterone in luteal phase support appears to improve outcome.
17 (revote).	Addition of GnRH agonist injections to progesterone in luteal phase support appears to improve outcome. Nowadays mid-luteal GnRH-agonists are frequently introduced in addition to progesterone for luteal support.
18.	Addition of LH activity to progesterone in luteal phase support improves pregnancy outcomes in GnRH agonist trigger fresh embryo transfer cycles.