Treatment algorithms for high responders: What we can learn from randomized controlled trials, real-world data and models.

A high ovarian response to conventional ovarian stimulation (OS) is characterized by an increased number of follicles and/or oocytes compared with a normal response (10-15 oocytes retrieved). According to current definitions, a high response can be diagnosed before oocyte pick-up when >18-20 follicles ≥11-12 mm are observed on the day of ovulation triggering; high response can be diagnosed after oocyte pick-up when >18-20 oocytes have been retrieved. Women with a high response are also at high risk of early ovarian hyper-stimulation syndrome (OHSS)/or late OHSS after fresh embryo transfers. Women at risk of high response can be diagnosed before stimulation based on several indices, including ovarian reserve markers (anti-Müllerian hormone [AMH] and antral follicle count [AFC], with cutoff values indicative of a high response in patients with PCOS of >3.4 ng/mL for AMH and >24 for AFC). Owing to the high proportion of high responders who are at the risk of developing OHSS (up to 30%), this educational article provides a framework for the identification and management of patients who fall into this category. The risk of high response can be greatly reduced through appropriate management, such as individualized choice of the gonadotropin starting dose, dose adjustment based on hormonal and ultrasound monitoring during OS, the choice of down-regulation protocol and ovulation trigger, and the choice between fresh or elective frozen embryo transfer. Appropriate management strategies still need to be defined for women who are predicted to have a high response and those who have an unexpected high response after starting treatment.

Symposium: Update on prediction and management of OHSS. Genetics of ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is typically iatrogenic following the administration of gonadotrophins. Sporadic and familial cases of spontaneous OHSS have generated an interest in genetic mechanisms for OHSS independent of exogenous gonadotrophins. The genetic studies have addressed the genes and receptors for FSH and luteinizing/human chorionic gonadotrophin hormones. Mutations in the FSH receptor (FSHR) could be activating, leading to a predisposition to OHSS, or inactivating, resulting in sterility. Polymorphisms of FSHR have been investigated and, to date, 744 single nucleotide polymorphisms have been identified in the FSHR gene, of which only eight are located in the coding region, exons, with the rest being intronic. Ovarian response is dependent on FSHR genotype. Clinical studies on the p.N680S polymorphism of the FSHR gene have demonstrated the homozygous Ser/Ser variant to be less sensitive to endogenous or exogenous FSH in terms of oestradiol production. Polymorphism of the FSHR, Ser680Asn, in the FSHR gene is a predictor of the severity of symptoms in patients who develop OHSS. OHSS is characterized by leakage of intravascular fluids resulting in ascites and haemoconcentration. These pathological changes are mediated for the most part by vascular endothelial growth factor (VEGF). Targeting the VEGF system at different levels has been the focus of intense research for the prevention of OHSS.

Effect of glutamine on preimplantation mouse embryo development in vitro.

OBJECTIVES: The purpose of this research was to study the independent effect of the amino acid glutamine on preimplantation mouse embryo development in vitro. STUDY DESIGN: Two-cell stage mouse embryos were cultured in human tubal fluid medium in the presence and absence of 1 mmol/L of glutamine. Outcomes for morphology and cleavage rates were compared with Fisher's and Mann-Whitney's tests, respectively. RESULTS: Glutamine increased the proportion of embryos that developed to the blastocyst stage (86.4%) compared with those cultured without glutamine (59.1%) (P =.052). The percentages of embryos developing to the morula or hatching blastocyst stages were comparable in the 2 groups. Blastocyst total cell numbers were significantly higher in the glutamine group (34+/-1.7 vs 18.5+/-3.5, respectively; values are mean+/-SEM, P =.044). CONCLUSION: The amino acid glutamine independently improves preimplantation mouse embryo development in vitro. Further studies are needed to examine the applicability of these results to humans.