Kadri Haller

IgG, IgA and IgM Antibodies against FSH: Serological Markers of Pathogenic Autoimmunity or of Normal Immunoregulation?

Autoimmune mechanisms are often involved in causing infertility. Among the possible targets of autoantibodies, the follicle‐stimulating hormone (FSH) which regulates the follicular maturation in human ovary is a promising candidate. We aimed to study whether anti‐FSH‐antibodies might be involved in different clinical types of infertility.

Protein tyrosine phosphatase non-receptor type 22 gene variants at position 1858 are associated with type 1 and type 2 diabetes in Estonian population

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is considered an important regulator of T-cell activation. Polymorphisms within the PTPN22 gene have been suggested to confer susceptibility to autoimmune endocrine disorders. To evaluate the impact of a functional variation in the PTPN22 gene in type 1 (T1D) and type 2 diabetes (T2D), the PTPN22 C1858T single nucleotide polymorphism (SNP) was studied in the population of Estonian origin, including 170 T1D patients, 244 T2D patients and 230 controls. Using two methods for PTPN22 C1858T detection in parallel, we found that not only T1D but also T2D is associated with the PTPN22 1858T allele. The role of PTPN22 gene in the pathogenesis of T2D is yet unclear and needs further investigation.

Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome: a preliminary report

Progress has been made towards ascertaining the genetic predictors of ovarian stimulation in IVF. Aromatase cytochrome P450, encoded by the CYP19A1 gene, catalyses a key step in ovarian oestrogen biosynthesis. Hence, the aromatase gene is an attractive candidate for genetic studies. This study aimed to examine the genetic influences of CYP19A1 TCT trinucleotide insertion/deletion (Ins/Del) and (TTTA)(n) microsatellite intronic polymorphisms on ovarian stimulation outcome and aetiology of female infertility. IVF patients (n = 152) underwent ovarian stimulation according to recombinant FSH and gonadotrophin releasing hormone antagonist protocol. Del/Del homozygous patients with shorter TTTA repeats exhibited decreased ovarian FSH sensitivity in ovarian stimulation, which may reflect variations in aromatase gene expression during early antral follicle development. Accordingly, this study demonstrates correlations between Del allele and shorter (TTTA)(n) repeat sizes with smaller ovaries (r = -0.70, P = 0.047) and fewer antral follicles (r = 0.21, P = 0.018) on days 3-5 of spontaneous menstrual cycle, respectively. Furthermore, Del variation linked with low-repeat-number (TTTA)(n) alleles are involved in enhanced genetic susceptibility to unexplained infertility (adjusted OR = 4.33, P = 0.039) and endometriosis (r = -0.88, P = 0.026), which corroborates evidence on the overlapping patient profiles of ovarian dysfunction in both types of female infertility.

ANTI-FSH ANTIBODIES ASSOCIATE WITH POOR OUTCOME OF OVARIAN STIMULATION IN IVF

FSH is required for spontaneous folliculogenesis and is widely used in ovarian stimulation in IVF. Previously, increased concentrations of antibodies against FSH (anti-FSH) have been demonstrated in infertile women. This study aimed to: (i) assess the possible association of anti-FSH with an adverse outcome of IVF with regard to clinical parameters characterizing the ovarian reserve; and (ii) compare serum and follicular fluid (FF) anti-FSH concentrations in relation to follicle size and endocrine markers. IVF patients (n = 182) subjected to gonadotrophin-releasing hormone-antagonist protocol were assessed for anti-FSH using enzyme-linked immunosorbent assay. Increased concentrations of serum anti-FSH immunoglobulin (Ig)G and IgA were associated with impaired ovarian stimulation outcome, with cut-off values <1.0 arbitrary units predicting poor ovarian response (<or=3 oocytes) (adjusted odds ratio for IgG = 6.95, P = 0.005 and IgA = 3.60, P = 0.039). FF anti-FSH IgG and IgA were positively associated with serum anti-FSH concentrations and FSH concentration in FF. Additionally, FF anti-FSH IgG increased with follicle growth (linear regression coefficient = 0.02, P = 0.022). Collectively, these data suggest that serum anti-FSH antibodies are associated with poor ovarian response to FSH stimulation in IVF, with anti-FSH IgA and IgG potentially exerting a local FSH antagonizing effect in maturing follicles.

Putative Predictors of Antibodies Against Follicle‐Stimulating Hormone in Female Infertility: A Study Based on In Vitro Fertilization Patients

We have previously demonstrated the presence of naturally occurring antibodies against follicle‐stimulating hormone (FSH) in patients with endometriosis and polycystic ovary syndrome (PCOS). Here, we investigated the parameters associated with anti‐FSH antibodies in in vitro fertilization (IVF) patients.

Controlled ovarian hyperstimulation changes the prevalence of serum autoantibodies in in vitro fertilization patients

Problem  Autoimmune mechanisms are involved in etiology of female infertility, the medical problem frequently treated by in vitro fertilization (IVF). Controlled ovarian hyperstimulation (COH) with supraphysiological levels of sex hormones is achieved by IVF.

VNTR I/I genotype of insulin gene is associated with the increase of follicle number independent from polycystic ovary syndrome.

Background. Polycystic ovary syndrome (PCOS) is accompanied by selective insulin resistance and enhanced ovarian steroidogenic effects of insulin. We analysed the minisatellite variations of the insulin gene (INS VNTR) with regard to the clinical features of PCOS. Methods. Retrospective, adjusted association study. Infertile patients with PCOS (n = 30) and tubal factor (n = 75) were screened for anthropometrical, clinical and ovarian morphology parameters, as well as hormonal values. INS VNTR was genotyped by its surrogate marker at −23 HphI locus. Results. INS VNTR genotype distribution was similar in PCOS and tubal infertility group. The mean ovarian follicle number was higher in VNTR I/I individuals compared to VNTR I/III and III/III individuals (adjusted OR = 1.28, p = 0.03), independent from the cause of infertility, the age, the follicle stimulating hormone level on day 3–5 of menstrual cycle, BMI and the previous surgical ovarian tissue removal. In addition, higher level of the luteinising hormone in VNTR I/I individuals was associated with the increase in follicle number. Conclusions. We suggest that INS VNTR genotypes are not associated with PCOS in general, but could have a certain influence on the phenotypic spectrum of the syndrome.