Prevalence of candidate single nucleotide polymorphisms on p53, IL-11, IL-10, VEGF and APOE in patients with repeated implantation failure (RIF) and pregnancy loss (RPL).

Recurrent pregnancy loss (RPL; defined as the loss of three or more consecutive pregnancies) and recurrent implantation failure (RIF; when implantation is not achieved after at least three cycles of IVF) are two of the major challenges that reproductive medicine faces. Some polymorphisms have been identified as possible causes of an increased risk of these diseases. This paper studies the prevalence of the polymorphisms in p53, VEGF, IL-10, IL-11 and APOE in RIF and RPL patients that determines the risk for these pathologies. A total of 255 patients were selected (89 RPL patients, 77 RIF patients and 89 controls) and genotyped for p53-R72P; IL-11-1082-AG; VEGF-1154-AG; IL-10; APOE-R112C; APOE-R158C. Statistically significant differences were found in the prevalence of the E4 isoform (R122-R158) of the APOE gene in RPL patients (p < 0.05), and in RIF patients, the R72P polymorphism of the p53 gene and the 1154-AG of the VEGF gene showed different distribution (p < 0.05). Regarding the p53 and IL-11 studied polymorphisms, PP of p53 gene and GG of IL-11 are more prevalent in RPL patients without reaching statistical significance. In conclusion, our results suggest patients carrying variants in p53 and VEGF would be at risk of RIF, and those carrying variants in APOE gene would suffer RPL.

Androgen receptor CAG repeat length is associated with ovarian reserve but not with ovarian response.

The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat sequence within exon 1. In-vitro studies have shown a relationship between CAG repeats in the AR gene and its transactivation potential. This variation in length may play a role in anovulatory infertility. The objective of this study was to investigate whether CAG polymorphism of the AR gene has a predictive value for ovarian reserve, response and cycle outcome in an egg donor programme. CAG length of the AR gene was determined in 147 oocyte donors. All donors underwent ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol (n = 355). No differences were reported in days of stimulation, gonadotrophin doses, and number of oocytes retrieved. Clinical outcomes were not affected by the CAG repeat length of the AR gene; the primary end-point, antral follicle count, was significantly affected (P < 0.05). In conclusion, in a population of fertile egg donors AR gene CAG polymorphism does not affect ovarian response to gonadotrophins. Antral follicle count was associated with the CAG polymorphism genotype. This suggests that genetic factors may increase susceptibility to poor ovarian reserve, and that AR gene genotype could play a role in the natural ovarian ageing process.

Negative effect of P72 polymorphism on p53 gene in IVF outcome in patients with repeated implantation failure and pregnancy loss.

PURPOSE: Investigate whether R72P on p53 gene polymorphism has a higher prevalence among women with a history of recurrent implantation failure (RIF) and pregnancy loss (RPL) and its influence in their IVF cycle outcome. MATERIAL AND METHODS: p53 polymorphism R72P has been studied in 181 women. The control group included 83 oocyte donors. In the study group 98 women were included: 44 with RIF and 54 with RPL. From the study group, 76 patients underwent IVF-cycles (55 RPL and 21 RIF). RESULTS: The frequency of PP genotypes on p53 among RIF was 11.4% compared with 18.5% for RPL and 6% in controls (p < 0.01). There were no significant differences with respect to patient characteristics. Significant differences were reported in pregnancy rate (69.4% for RR/RP and 33.3% for PP; p < 0.05), embryo implantation rate (33.3% for RR/RP and 7.3% for PP; p < 0.05) and ongoing pregnancy rate (53.1% for RR/RP and 14.3% for PP; p < 0.05) among RIF and RPL. CONCLUSIONS: This investigation reveals that in RIF and RPL patients R72P on p53 gene is more prevalent than fertile population. Moreover, patients carrying a PP genotype on p53 codon 72 will have less chance to achieve an ongoing pregnancy. This information together with some additional markers will allow development of diagnostic tests for detects risk for RIF and RPL before infertility treatment is initiated.

Effect of follicle-stimulating hormone receptor N680S polymorphism on the efficacy of follicle-stimulating hormone stimulation on donor ovarian response.

OBJECTIVE: The aim of this study was to investigate whether N680S FSHR polymorphism has a predictive value for the ovarian response to stimulation with gonadotropins and cycle outcome in our egg donor program. METHODS: The oocyte donor candidates were selected according to the Instituto Bernabeu egg donation program requirements and ASRM and ESHRE guidelines for oocyte donation. The FSHR polymorphism N680S was studied in 145 oocyte donors. All donors underwent controlled ovarian hyperstimulation (COH) (n=355) using urinary follicle-stimulating hormone in a GnRH antagonist protocol and receiving a GnRH agonist triggering. The main outcome measures were oocyte yield, days of stimulation, gonadotropin doses, biochemical pregnancy, ongoing pregnancy, and miscarriage rates. RESULTS: Significant differences were reported in the antral follicle count (16.5 ± 5.0 for NN, 14.5 ± 4.7 for NS, and 14.1 ± 3.8 for SS), number of eggs retrieved (21.5 ± 9.2 for NN, 18.5 ± 8.2 for NS, and 19.8 ± 8.9 for SS), and gonadotropin doses (2098.5 ± 639.4 IU for NN, 2023 ± 490.1 IU for NS, and 2149.5 ± 552.3 IU for SS) between the genotypes. The clinical outcome was not affected by the N680S polymorphism of the FSHR gene in the egg donors. CONCLUSION: In a population of fertile egg donors, the FSHR gene polymorphism at position 680 is associated with different ovarian responses to COH. The genotype of the FSHR gene is an important factor for determining the prognosis of the COH cycles in normo-ovulatory fertile women.