Effect of stimulation protocol on the risk of luteinized unruptured follicle (LUF) in polycystic ovarian syndrome (PCOS):does LUF affect luteal phase profile? (original) (raw)
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The Journal of Clinical Endocrinology & Metabolism, 2013
Context: The polycystic ovary syndrome (PCOS) is a common and complex disease without a clear pattern of inheritance. Anti-Müllerian hormone (AMH) has an inhibitory effect on FSH-stimulated follicle growth. Serum AMH levels are higher in women with PCOS than in normo-ovulatory women. The elevated AMH levels may reflect abnormalities in AMH signaling. Objective: The purpose of this study was to evaluate the association of the anti-Müllerian hormone receptor 2 (AMHR2) Ϫ482 AϾG polymorphism (rs2002555) with the pathophysiology of PCOS. Design: AMHR2 Ϫ482 AϾG polymorphism genotyping were performed in a large cohort of women with PCOS and in a healthy control group. Setting/Subjects: A total of 858 Caucasian Greek women with PCOS and 309 healthy control women were studied. Interventions: Genotyping and hormonal measurements were preformed. Main Outcome Measures: Hormone levels in women with PCOS were analyzed. Results: The AMHR2 polymorphism was more common in women with PCOS than in control women (P ϭ .026). Homozygous AMHR2 Ϫ482 AϾG gene polymorphisms (GG) were associated with decreased levels of LH (P ϭ .003) and lower LH to FSH ratios (P ϭ .01) in women with PCOS, as well as with lower prolactin levels (P ϭ .004). No other associations related to AMHR2 Ϫ482 AϾG polymorphisms were observed in women with PCOS or control women. Conclusion: In this study, the role of the AMHR2 Ϫ482 AϾG gene polymorphism in the pathogenesis of PCOS was suggested by the association of the variant with PCOS risk. Thus, further research is needed to elucidate a possible association of the AMHR2 Ϫ482 AϾG gene polymorphism with AMH signaling and impaired ovarian function and its clinical significance in women with PCOS.
The relevance of the individual screening for genetic variants in predicting ovarian response
Pharmacogenetics and Genomics, 2019
Objective To investigate if polymorphisms of some genes involved in folliculogenesis predict ovarian response. Methods This prospective randomized study includes 124 egg donors genotyped for six SNPs ESR1 (rs2234693), AMHR2 (rs2002555), GDF-9 (rs10491279 and rs254286), AMH (rs10407022) and LHCBR (rs229327) genes and four STRs in ESR1 rs3138774), SHBG (rs6761), CYP19A1 (rs60271534) and AR genes (CAG repeats in exon 1). All donors followed standard ovarian stimulation protocol using a daily dose of 225 UI. The genotypes obtained were compared with the ovarian stimulation outcome. Results Regarding the number of retrieved oocytes, we found statistical differences for the ESR1 SNP and STR (19.3 ± 8.9 for TT vs 15.3 ± 6.2 for CC/CT, P = 0.027; 19.1 ± 8.3 for <17repeats vs 14.7 ± 6.2 for >17repeats, P = 0.020). Moreover, women carrying TT in the ESR1 at position c.-397T>C with ESR1 (TA)n=17 retrieved the highest number of oocytes (20.4 ± 9.3) (P = 0.001). Concerning AMHR2, we observed an association with the length of stimulation (9.1 ± 1.4 d for AA vs 9.7 ± 1.3 d for AG/GG, P = 0.021) and gonadotropin received (2050 ± 319 for AA vs 2188 ± 299 for AG/GG, P = 0.017). No significant differences were observed for the other polymorphisms (P > 0.05). Conclusion The polymorphisms in ESR1 and AMHR2 genes showed a clear association with the number of retrieved oocytes and the stimulation data, respectively. Our results suggest that polymorphisms in the genes for key reproductive hormones receptors could be used to predict the ovarian response and to personalize the stimulation prior the treatment. Pharmacogenetics and Genomics 29: 216
Assessment of FSHR, AMH, and AMHRII variants in women with polycystic ovary syndrome
Endocrine, 2014
Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy present in 6-15 % of reproductive-age women . It is a heterogenous syndrome [2, 3] and according to the Rotterdam Criteria , PCOS is recognized in women who have two of three symptoms: chronic amenorrhea, clinical or biochemical hyperandrogenism and the ovarian morphology of PCO in ultrasound imaging, after other reasons have been excluded.
Background: Polycystic ovaries and irregular menstruation/anovulation are important diagnostic criteria along with hyperandrogenism as per the Androgen Excess Society–2006 criteria for polycystic ovarian syndrome (PCOS). In the etiopathogenesis of PCOS, one of the candidate genes causing ovarian failure is the luteinizing hormone (LH) chorionic gonadotropin hormone receptor (LHCGR). Our aim was to study the association of LHCGR polymorphism (rs2293275) with PCOS in our study population. Materials and Methods: Genetic case– control study from multiple gynecological centers from Hyderabad, a cosmopolitan city in South India. The study involved 204 women with PCOS and 204 healthy, sex-, and age-matched controls. Anthropometric and biochemical profiles were taken in a well-designed pro forma. Isolation of deoxyribonucleic acid (DNA) and genotype analysis were done for the entire study population using the polymerase chain reaction–restriction fragment length polymorphism method followed by 12% polyacrylamide gel electrophoresis. Results: In this study, we have demonstrated an association between LHCGR (rs2293275) polymorphism and PCOS. The frequency of the G allele was 0.60 in PCOS and 0.49 in controls (odds ratio [OR] 1.531, confidence interval [CI] 1.16–2.01, and p-value = 0.0026), which indicates that the G allele is associated with PCOS in our population. The GG genotype conferred a significant risk of developing PCOS (OR 3.36, CI 1.96–5.75, and p-value < 0.0001). We found a significant association of the GG allele with body–mass index, waist to hip ratio, insulin resistance, LH, and LH/follicle-stimulating hormone (FSH) ratio in PCOS when compared with controls. The AA allele showed high basal FSH levels. Conclusions: This study suggests that LHCGR (rs2293275) polymorphism is associated with PCOS and could be used as a relevant molecular marker to identify women with the risk of developing PCOS in our population and may provide an understanding about the etiology of PCOS.
Significance of LHCGR polymorphisms in polycystic ovary syndrome: an association study
Scientific Reports, 2023
This study was conducted to analyze the association of Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) gene rs4953616 and rs7371084 polymorphisms with the risk of polycystic ovary syndrome (PCOS) in Punjab, India. A total of 823 women (443 PCOS cases and 380 healthy controls) were enrolled in the present study. The polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP) was used for genotyping. Anthropometric parameters, lipid and hormonal profiles, were compared between the two groups. Demographic features were compared using Mann Whitney U test while the Chi-square test and odds ratios (ORs) were used to assess the genetic association and risk towards PCOS, respectively. A one-way analysis of variance (ANOVA) test was employed to analyze the correlation of genotypes with baseline parameters in PCOS cases. A statistically significant difference was revealed in the genotypic and allelic frequencies of rs4953616 polymorphism between PCOS cases and controls (p = 0.01 and p = 0.004, respectively). The mutant genotype (TT), mutant allele (T), and recessive model of rs4953616 polymorphism conferred 1.77, 1.3, and 1.5 times risk towards PCOS, respectively. No significant distribution for genotypes and alleles was found for rs7371084 in both groups (p = 0.25 and p = 0.26, respectively). In addition to dyslipidemia, PCOS women also had significantly higher body mass index (BMI) and waist-to-hip ratio (WHR), testosterone (T), and luteinizing hormone (LH). Upon haplotype analysis, the TT haplotype was found to be significantly associated with the increased risk of PCOS. Our results demonstrated a significant role of LHCGR rs4953616 polymorphism in the development of PCOS. PCOS is the most prevalent endocrine-metabolic condition in women of fertile age with a global prevalence of 5% to 20% 1,2. The variation in the prevalence of PCOS could be due to the heterogeneity in ethnicity and age distribution in the population from which data has been collected 3. During the 2003 Rotterdam Consensus Workshop, PCOS was defined as a multi-system matrix of anomalies including obesity, hyperinsulinemia, menstrual irregularities, hyperandrogenism, small cysts in one or both ovaries, and elevated concentrations of LH 4. In addition, PCOS has also been linked to impaired glucose tolerance, increased risk of type 2 diabetes, endometrial cancer, cardiovascular diseases, dyslipidemia, and depression which further worsen the quality of life 5,6. Several hypotheses have been proposed over time to pinpoint the precise underlying processes that lead to the development of PCOS. However, due to its heterogeneous nature and uncertain etiology, by the time a diagnosis is made, PCOS manifests as a self-perpetuating cycle of multiple system dysfunction 7. Family studies and genome-wide association studies (GWAS) have supported the contribution of genetic factors to the pathophysiology of PCOS 8,9. The phenotype of PCOS, diagnostic criteria employed, and racial background, all influence the narrowing down of the PCOS susceptibility loci 10. However, a few genetic loci that were found to be associated with PCOS development include LHCGR , FSHR, THADA, and DENND1A and the interaction among these loci and multiple proteins under the influence of environmental factors affects PCOS progression 11. The LHCGR is directly involved in the orchestrated series of events that regulate normal sexual maturation and fertility in males and females 12. LHCGR acts as a high-affinity receptor for LH and upon binding leads to steroidogenesis, follicular development, and formation of corpus luteum 13. The LHCGR belongs to the G-protein coupled receptor family, and in women, is primarily expressed in ovarian theca cells and differentiated granulosa cells 14,15. In contrast to theca cells which constitutively express LHCGR, granulosa cells express LHCGR only at the later stages of follicular development after they become fully differentiated. Induction of LHCGR allows the preovulatory follicle to respond to the mid-cycle surge of LH with ovulation 13 .
Journal of Assisted Reproduction and Genetics, 2016
Purpose Genetic variation may influence women's response to ovarian stimulation therapy. The purpose of this study was to investigate any effects of genetic variants in the anti-Müllerian hormone (AMH) and AMH type II receptor genes on ovarian response/treatment outcomes and on current markers of ovarian reserve in individuals undergoing in vitro fertilisation (IVF) treatment. Methods In this prospective observational study, we genotyped the AMH c.146G>T, p.(Ile49Ser) and AMHR2-482A>G variants in 603 unrelated women undergoing their first cycle of controlled ovarian stimulation for IVF and ICSI (intracytoplasmic sperm injection) using gonadotrophins at a tertiary referral centre for reproductive medicine. Pelvic ultrasound and blood hormone levels were taken on days 2-3 of the cycle. Genotypes were determined using TaqMan allelic discrimination assay. Regression analysis was performed to assess the relationship between the genotypes and the ovarian reserve markers (FSH, AMH, antral follicle count) and the early outcomes of response (number of oocytes retrieved and gonadotropin dose) as well as the treatment outcome (live birth). Results There were no significant associations between the variants AMH c.146G>T and AMHR2-482A>G with ovarian response in terms of number of oocytes retrieved (p = 0.08 and p = 0.64, respectively), live births (p = 0.28 and p = 0.52) and/ or markers of ovarian reserve. Conclusions Genotyping of the AMH c.146G>T and AMHR2-482A>G polymorphisms does not provide additional useful information as a predictor of ovarian reserve or ovarian response and treatment outcomes.
Journal of Assisted Reproduction and Genetics
The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in selected genes, responsible for hormonal regulation of folliculogenesis, are associated with response to controlled ovarian hyperstimulation (COH) and clinical characteristics of women enrolled in in vitro fertilization (IVF) programs. Methods In a cross-sectional study, 60 (IVF) patients underwent COH by using gonadotropin-releasing hormone (GnRH) antagonist and recombinant follicle-stimulating hormone (rFSH) protocol. Patients were classified into three groups: poorresponders (according to Bologna criteria), normo-responders (≤ 15 oocytes), and hyper-responders (> 15 oocytes). Genotyping of SNPs AMH rs10407022, AMHR rs3741664, FSHR rs1394205 and rs6166, and ESR1 rs2234693 was performed using high-resolution melting analysis (HRMA). Basal FSH (bFSH), estradiol (E2), and anti-Müllerian hormone (AMH) were measured by enzyme-linked immunosorbent assay (ELISA). Results Patients with GG genotype of FSHR rs1394205 had significantly lower AMH level (P = 0.016) and required higher rFSH dose per oocyte compared to women with AA or AG genotype (P = 0.036). We also found higher frequency of GG genotype of FSHR rs1394205 in poor-(76.5%) than in hyper-responders (37.5%, P = 0.002). Patients with AA genotype of FSHR rs6166 had higher level of measured bFSH compared to those with AG or GG genotypes (P = 0.043). Women with GG genotype of AMHR rs3741664 required higher rFSH dose in comparison with patients carrying genotypes AA or AG (P = 0.028). Conclusions The GG genotype at position rs1394205 is associated with poor ovarian response to COH. Patients with this genotype may require higher doses of rFSH for ovulation induction.
Journal of Assisted Reproduction and Genetics, 2015
Purpose Previous studies identified follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/ choriogonadotropin receptor (LHCGR) genes as polycystic ovary syndrome (PCOS) susceptibility loci, which was dependent on the racial/ethnic background of studied population. We investigated the association of genetic variants in FSHR and LHCGR with PCOS in Bahraini Arab women. Methods A retrospective case-control study, involving 203 women with PCOS, and 211 age-and ethnically-matched control women. FSHR and LHCGR genotyping was done by allelic exclusion method (real-time PCR).
International Journal of Reproductive Medicine, 2021
Background Several studies have investigated on the polymorphism Ser680Asn of FSHR and its use as a predictive indicator of response to an IVF/ICSI protocol. Furthermore, measurement of AMH in serum and follicular fluid is a useful prognostic indicator for the outcome of an assisted reproduction attempt. The purpose of this study is to examine the FSH receptor Ser680Asn polymorphism in combination with AMH levels in both serum and follicular fluid, on the day of oocyte collection. Materials and Methods A total of 32 women who underwent IVF/ICSI were included. Women were grouped into 2 groups: those who received rFSH (n = 11) and those who received hMG (n = 21). Serum AMH was measured on day 3 of the cycle, and AMH in the follicular fluid on the day of oocyte retrieval; the same day peripheral blood was collected for the genotyping of Ser680Asn. Results No statistical significant difference was found between serum AMH and follicular fluid AMH regarding the FSH receptor genotype for t...