A pharmacogenetic-driven approach for controlled ovarian hyperstimulation by FSH treatment.

AIM: The aim of this study was to develop a pharmacogenetic- (PGx) driven approach for a controlled ovarian hyperstimulation (COH) treatment protocol used for in vitro fertilization procedures. The enrolled patients were genotyped for a single nucleotide polymorphism (SNP) N680S, within the FSHR. METHODS: Seventy-eight women, who had previously received at least two COH cycles without positive fertilization with FSH and AMH values <10 mUI/mL and >0.3 ng/mL respectively were enrolled. They were genotyped for N680S and then categorized in high (HR), intermediate (IR), and poor responders (PR). Each subgroup received a tailored FSH treatment of 100, 225, and 400 UI/mL, respectively. The response was evaluated considering differences with previous COH cycle in terms of number of follicles (FR), oocytes (OR), and embryos produced (EMB). RESULTS: With regards to the endpoint considered comparing the non-PGx with the PGx approach, for what regards the FR a statistically significant increase of their numbers was observed with the PGx-tailored approach (HR P<0.0001; IR P=0.00892; PR P=0.0032). Similar statistical significant results were also achieved for OR but only for HR (P<0.0001) and IR (P=0.00169). Last but not least for the EMB (HR P<0.001; IR P=0.00670 and PR P<0.0001) all the different genotype considered achieved a statistical significance. CONCLUSION: This study, although with a limited number of enrolled patients, showed that a FSH treatment with a PGx-driven approach might have the potential to improve COH clinical outcome.

The 312N variant of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) confers up to 2·7-fold increased risk of polycystic ovary syndrome in a Sardinian population.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a frequent condition, affecting about 15% of women of reproductive age. Because of its familial occurrence, a multifactorial model of susceptibility, including both genetic and environmental factors, has been proposed. However, the identification of genetic factors has been elusive. DESIGN: Case-control study aimed at evaluating possible associations between functionally relevant variants of the luteinizing hormone/choriogonadotrophin receptor gene (LHCGR) and PCOS phenotype. PATIENTS: A total of 198 PCOS and 187 non-PCOS women, aged 14-35 years, of Sardinian origin, were referred to the outpatient clinic of the Department of Obstetrics and Gynaecology of the University of Cagliari (Sardinia). PCOS diagnosis was based on the Rotterdam criteria. MEASUREMENTS: We determined the genotype of ins18LQ, S291N and S312N variants at the LHCGR locus. Genotype was related to the presence or absence of PCOS and to several clinical and biochemical characteristics. RESULTS: The presence of at least one 312N allele was strongly associated with PCOS risk (OR, 2·04; 95% CI, 1·32-3·14; χ(2) , 10·47; P = 0·001). 312N homozygosity was associated with a further risk increase (OR, 2·73; 95% CI, 1·25-5·95; χ(2) , 6·65; P = 0·01). The number of ins18LQ alleles was associated with LH serum levels in controls (χ(2) , 8·04, P = 0·017). CONCLUSIONS: For the first time, we have identified a genetic variant that is strongly associated with PCOS in an isolated population. These results, if confirmed in other cohorts, may provide the opportunity to test the S312N genotype at the LHCGR locus in fertile women to assess the risk of PCOS. The avoidance of triggering factors like weight increase may improve the reproductive outcome of potentially at-risk subjects.

Could antispasmodic drug reduce pain during hysterosalpingo-contrast sonography (HyCoSy) in infertile patients? A randomized double-blind clinical trial.

OBJECTIVE: To assess the effectiveness of an antispasmodic drug, hyoscine-N-butylbromide, in reducing pain during hysterosalpingo-contrast sonography (HyCoSy). METHODS: Eight hundred and sixteen patients undergoing HyCoSy were randomized to receive 10 mg hyoscine-N-butylbromide (n = 408) or placebo (n = 408) per os, 30 min before the procedure, in a double-blind randomized controlled trial. Immediately after the procedure, the patient was asked to describe any pain experienced in comparison with pain usually suffered during the menstrual cycle, and the operator assigned a pain score between 0 and 4 as follows: 0 (no reaction or discomfort), 1 (slight pain, less than menstrual pain), 2 (moderate pain, exceeding menstrual cramps but no vasovagal reaction), 3 (vasovagal reaction or pain requiring observation in a hospital) and 4 (vasovagal reaction or pain requiring resuscitation). The primary aim was to estimate the difference in pain score, considered as a categorical value, between the active arm of the trial and the control group. The secondary aim was to evaluate if pain is related to tubal patency. RESULTS: There was no difference in pain score between the hyoscine-N-butylbromide group and the placebo group (P = 0.807). There was a negative correlation between pain and tubal patency, regardless of treatment group (P < 0.0001). CONCLUSIONS: Administration of 10 mg antispasmodic drug hyoscine-N-butylbromide does not reduce pain in patients undergoing HyCoSy.