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GDF9 polymorphisms: influence on ovarian response in women undergoing controlled ovarian hyperstimulation.

ABSTRACT: OBJECTIVE:The study looked into the possible influence of GDF9 polymorphisms on ovarian response in women with a normal ovarian reserve undergoing controlled ovarian hyperstimulation for in vitro fertilization (IVF). METHODS:This cross-sectional study included 67 women with normal ovarian reserve aged 30-39 years submitted to controlled ovarian hyperstimulation for IVF. We sequenced four polymorphisms in the GDF9 gene (C398G, C447T, G546A, and G646A) and analyzed their influence on follicular and oocyte outcomes. RESULTS:The mutant allele C398G decreased the total number of follicles >17mm (6.49 vs. 4.33, p=0.001), total number of follicles (10.11 vs. 7.33, p=0.032), number of MII oocytes retrieved, and serum progesterone levels on trigger day. The C447T polymorphism was associated with a greater number of follicles between 12 and 14 mm on the day of r-hCG, while the G546A polymorphism was associated with lower serum progesterone levels on trigger day. CONCLUSIONS:GDF9 gene polymorphisms C398G and C447T adversely affected ovarian response in women undergoing controlled ovarian hyperstimulation. These findings show that in addition to playing a role in the early stages of folliculogenesis, GDF9 polymorphisms have an important impact on the final stage of oocyte development.

SUBMITTER: Bilibio JP

PROVIDER: S-EPMC7558902 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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GDF9 polymorphisms: influence on ovarian response in women undergoing controlled ovarian hyperstimulation.

Bilibio João Paolo JP Meireles Arivaldo José Conceição AJC Conto Emily De E Lorenzzoni Panila Longhi PL Nascimento Fábio Costa do FCD Cunha-Filho João Sabino da JSD

JBRA assisted reproduction 20201006 4

<h4>Objective</h4>The study looked into the possible influence of GDF9 polymorphisms on ovarian response in women with a normal ovarian reserve undergoing controlled ovarian hyperstimulation for in vitro fertilization (IVF).<h4>Methods</h4>This cross-sectional study included 67 women with normal ovarian reserve aged 30-39 years submitted to controlled ovarian hyperstimulation for IVF. We sequenced four polymorphisms in the GDF9 gene (C398G, C447T, G546A, and G646A) and analyzed their influence o ...[more]

PMID: 32510893

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Project description:IntroductionAge, polycystic ovary syndrome (PCOS), low body mass index (BMI), high antral follicle count (AFC), increased anti-Muller hormone (AMH) levels, and elevated serum estradiol (E2) concentrations are risk factors for ovarian hyperstimulation syndrome (OHSS). However, data on the relationship between risk factors and OHSS severity in patients with PCOS are rare.ObjectiveThis retrospective study examined the risk factors for OHSS and their effect on OHSS severity in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).MethodThe records of 2,699 women were reviewed and included in this study. These women were diagnosed with PCOS during their first IVF/ICSI cycle between January 2010 and December 2017. We analyzed the association between each of the interrogated risk factors (including female age, BMI, AFC, basal serum E2, and the number of oocytes retrieved) and OHSS. The effects of each risk factor on OHSS severity were further explored. Logistic regression was performed as part of the above analysis.ResultsOf the 2,699 women with PCOS who underwent assisted reproductive technology (ART), 75.2% had a normal response to controlled ovarian hyperstimulation (COH), while 24.8% developed OHSS. All OHSS patients were younger and had lower BMIs and basal serum follicle-stimulating hormone (FSH) and E2 levels but higher AFCs than those in the normal group. AFC demonstrated a strong correlation with OHSS, with a cutoff value of 24 in patients with PCOS. A total of 19.5% of the patients had mild OHSS, while 80.5% had moderate OHSS. Compared with those in the moderate OHSS group, those in the mild OHSS group were older and had higher basal serum FSH levels and lower serum E2 and T levels. However, BMI and AFC were not different between the mild and moderate OHSS groups. Basal serum E2 showed a strong correlation with OHSS severity, with a cutoff value of 37.94 pg/ml.ConclusionsAFC is a strong marker of OHSS, and basal serum E2 is the best predictor of OHSS severity in women with PCOS undergoing IVF treatment.

Project description:BackgroundFertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality.MethodsIn this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups.ResultsFF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4-438) vs 64.4 (43.8-152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5-466.7) vs 354 (179-511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa.ConclusionsLet-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients.Trial registrationClinicaltrials.gov - NCT02661932 , registered 25 January 2016, retrospectively registered.

Project description:INTRODUCTION: Obtaining an adequate number of high-quality oocytes is a major challenge in controlled ovarian hyperstimulation (COH). To date, a range of hormonal and clinical parameters have been used to optimize COH but none have significant predictive value. This variability could be due to the genetic predispositions of single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the ovarian response to rFSH stimulation for patients undergoing intracytoplasmic sperm injection program (ICSI). RESULTS: Univariate analysis revealed that only FSHR, ESR2 and p53 SNPs influenced the number of mature oocytes. The association was statistically significant for FSHR (p=0.0047) and ESR2 (0.0017) in the overall study population and for FSHR (p=0.0009) and p53 (p=0.0048) in subgroup that was more homogeneous in terms of clinical variables. After Bonferroni correction and a multivariate analysis, only the differences for FSHR and ESR2 polymorphisms were still statistically significant. In a multilocus analysis, only the FSHR and AMH SNP combination significantly influenced oocyte numbers in both population (p<0.01). DISCUSSION: We confirmed the impact of FSHR and ESR2 polymorphisms on the IVF outcome. Furthermore, we showed for the first time that a p53 polymorphism (which is already known to impact embryo implantation) could influence the ovarian response. However, given that this result lost its statistical significance after multivariate analysis, more data are needed to draw firm conclusions. Only the FSHR and AMH polymorphism combination appears to influence mature oocyte numbers but this finding also needs to be confirmed. MATERIALS AND METHODS: A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(-397T>C), BMP15(-9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(-725C>G), VEGF(+405G>C), TNF?(-308A>G), AMHR(-482 A>G), PAI-1 (4 G/5 G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the overall study population (n=427) and a subgroup with homogeneous characteristics (n=112).

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GDF9 polymorphisms: influence on ovarian response in women undergoing controlled ovarian hyperstimulation.

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GDF9 polymorphisms: influence on ovarian response in women undergoing controlled ovarian hyperstimulation.

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