Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

Sindiani, Amer; Batiha, Osamah; Al‐zoubi, Esra’a; Khadrawi, Sara; Alsoukhni, Ghadeer; Alkofahi, Ayesha; Alahmad, Nour Alhoda; Shaaban, Sherin; Alshdaifat, Eman; Abu‐Halima, Masood

doi:10.5653/cerm.2020.03706

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…The previous study showed that some young normogonadotrophic patients were to be unexpected hypo-response in standard GnRHa long protocol. [ 12 ] At present, ovarian hypo-response in assisted reproduction technology remains to be elucidated, increasing evidence suggests that the presence of genetic mutations or single nucleotide polymorphisms of gonadotropins and their receptors could influence ovarian sensitivity to gonadotropin stimulation, which may need more starting dose of FSH and total consumption of FSH during COS. [ 13 ] But, the selection of starting dose FSH in long-term GnRH-agonist protocol depended on age, weight, anti-Müllerian hormone, and antral follicle number, which also should decrease ovarian hyperstimulation syndrome risk. [ 14 ] In this study, starting doses did not differ significantly between the +LE group (225 [150–225]/day) and the +Gn group (200 [150–225]/day).…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of letrozole in pituitary downregulated normogonadotrophic young women with an initial poor response

Sun

Bian

et al. 2023

Medicine

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It has been reported that 10 to 15% of young normogonadotrophic women show suboptimal response to standard long protocols. Letrozole (LE), an aromatase inhibitor, was shown to improve ovarian sensitivity to follicle stimulating hormone (FSH) and follicular response to gonadotrophin treatment in poor ovarian response patients. We reasoned that it might be possible to utilize LE in young normogonadotrophic patients with unexpected hypo-response in standard gonadotropin-releasing hormone agonist long protocol. A total of 652 patients defined as normogonadotrophic patients with unexpected hypo-response were divided into 2 groups, the +LE group and the +Gn group. +LE group: A fixed daily dose of 2.5 mg of LE was added on day 8 of stimulation. +Gn group: A fixed daily dose of 75 U of human menopausal gonadotrophin was added on day 8 of stimulation. The primary outcome measures were the number of oocytes obtained, fertilization rate, days of stimulation, and total FSH dosage. The secondary outcome measures were the implantation rate and ongoing pregnancy rate. There were no significant differences in the clinical and hormonal characteristics between the 2 groups. A shorter duration of stimulation and a lower dosage of recombinant FSH consumption on the day of human chorionic gonadotropin administration were all observed in the +LE group. Patients who received LE therapy showed a higher number of oocytes obtained and significantly higher fertilization rates. The implantation rate and ongoing pregnancy rate were comparable in both groups. LE significantly improves the number of oocytes obtained in patients with suboptimal response to standard gonadotropin-releasing hormone agonist long protocol.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of letrozole in pituitary downregulated normogonadotrophic young women with an initial poor response

Sun

Bian

et al. 2023

Medicine

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“…Genetic variation makes a noteworthy contribution to ovarian response. Single nucleotide polymorphisms have been identified in genes with key roles in oogenesis, folliculogenesis, and female reproduction, such as in estrogen receptor 2 ( ESR2 ), follicle-stimulating hormone receptor ( FSHR ), FSH β-chain ( FSHB ), luteinizing hormone β-chain ( LHB ), LH/choriogonadotropin receptor ( LHCGR ), growth differentiation factor-9 ( GDF9 ), anti-Müllerian hormone ( AMH ), and AMH type II receptor ( AMHR2 ) genes [ 31 – 34 ]. However, the usefulness of sequence variants in clinical practice is limited due to inconclusive results from population-based studies [ 31 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Personalized prediction of the secondary oocytes number after ovarian stimulation: A machine learning model based on clinical and genetic data

Zieliński¹,

Pukszta²,

Mickiewicz³

et al. 2023

PLoS Comput Biol

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Controlled ovarian stimulation is tailored to the patient based on clinical parameters but estimating the number of retrieved metaphase II (MII) oocytes is a challenge. Here, we have developed a model that takes advantage of the patient’s genetic and clinical characteristics simultaneously for predicting the stimulation outcome. Sequence variants in reproduction-related genes identified by next-generation sequencing were matched to groups of various MII oocyte counts using ranking, correspondence analysis, and self-organizing map methods. The gradient boosting machine technique was used to train models on a clinical dataset of 8,574 or a clinical-genetic dataset of 516 ovarian stimulations. The clinical-genetic model predicted the number of MII oocytes better than that based on clinical data. Anti-Müllerian hormone level and antral follicle count were the two most important predictors while a genetic feature consisting of sequence variants in the GDF9, LHCGR, FSHB, ESR1, and ESR2 genes was the third. The combined contribution of genetic features important for the prediction was over one-third of that revealed for anti-Müllerian hormone. Predictions of our clinical-genetic model accurately matched individuals’ actual outcomes preventing over- or underestimation. The genetic data upgrades the personalized prediction of ovarian stimulation outcomes, thus improving the in vitro fertilization procedure.

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“…The FSHR SNPs, including A2039G (rs6166), are the most common studied genetic variants related to ovarian response in ART treatment [ 16 , 17 , 18 , 19 , 20 , 21 ]. A recent meta-analysis indicated that FRHR rs6166 is associated with premature ovarian insufficiency (POI) in an Asian population [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…The AMH 146 T > G is at the coding region of AMH and causes amnio acid substitution. FSHR Asn680Ser (rs6166) is the most common reported SNP that related to ovarian responses in ART cycles [ 16 , 17 , 18 , 19 , 20 , 21 ]. GnRH (rs6185) and GnRHR (rs3756159) are chosen to discriminate the different activities of GnRHa and GnRHanta in ART treatment.…”

Section: Methodsmentioning

confidence: 99%

“…The single nucleotide polymorphism (SNP) in the hormones and hormone receptors related to follicular growth and development might cause such inadequate ovarian response [ 14 ]. For example, SNPs of AMH [ 14 , 15 ], follicular stimulating hormone (FSH) [ 16 , 17 ], and FSH receptor ( FSHR ) [ 16 , 17 , 18 , 19 , 20 , 21 ] have been surveyed to explain the ovarian response subsequent to controlled ovarian stimulation in ART cycles [ 14 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Association between GnRH Receptor Polymorphisms and Luteinizing Hormone Levels for Low Ovarian Reserve Infertile Women

Weng

Tzeng

Lee

et al. 2021

IJERPH

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The choice of ovarian stimulation protocols in assisted reproduction technology (ART) cycles for low ovarian reserve patients is challenging. Our previous report indicated that the gonadotrophin-releasing (GnRH) agonist (GnRHa) protocol is better than the GnRH antagonist (GnRHant) protocol for young age poor responders. Here, we recruited 269 patients with anti-Müllerian hormone (AMH) < 1.2 ng/mL undergoing their first ART cycles for this nested case-control study. We investigated the genetic variants of the relevant genes, including follicular stimulating hormone receptor (FSHR; rs6166), AMH (rs10407022), GnRH (rs6185), and GnRH receptor (GnRHR; rs3756159) in patients <35 years (n = 86) and patients ≥35 years of age (n = 183). Only the genotype of GnRHR (rs3756159) is distributed differently in young (CC 39.5%, CT/TT 60.5%) versus advanced (CC 24.0%, CT/TT 76.0%) age groups (recessive model, p = 0.0091). Furthermore, the baseline luteinizing hormone (LH) levels (3.60 (2.45 to 5.40) vs. 4.40 (2.91 to 6.48)) are different between CC and CT/TT genotype of GnRHR (rs3756159). In conclusion, the genetic variants of GnRHR (rs3756159) could modulate the release of LH in the pituitary gland and might then affect the outcome of ovarian stimulation by GnRHant or GnRHa protocols for patients with low AMH levels.

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Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

Cited by 11 publications

References 39 publications

Effectiveness of letrozole in pituitary downregulated normogonadotrophic young women with an initial poor response

Effectiveness of letrozole in pituitary downregulated normogonadotrophic young women with an initial poor response

Personalized prediction of the secondary oocytes number after ovarian stimulation: A machine learning model based on clinical and genetic data

Association between GnRH Receptor Polymorphisms and Luteinizing Hormone Levels for Low Ovarian Reserve Infertile Women

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