Combined study on the single nucleotide polymorphisms in the follicle-stimulating hormone receptor (Ser680Asn) and anti-Müllerian hormone receptor type II (−482A>G) as genetic markers in assisted reproduction

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Ioannis G. Papanikolaou ◽  
Polina Giannelou ◽  
Elli Anagnostou ◽  
Despoina Mavrogianni ◽  
Petros Drakakis ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Gene Polymorphisms ◽  
Follicle Stimulating Hormone ◽  
Average Concentration ◽  
In Vitro Fertilisation ◽  
Control Group ◽  
Type Ii ◽  
Infertile Women ◽  
Stimulating Hormone

Abstract Background Infertile women may have underlying genetic abnormalities. There is, at present, a significant number of studies on the relation between the follicle stimulating hormone receptor (FSHR) or anti-Müllerian hormone type II receptor (AMHRII) polymorphisms and response to in-vitro fertilisation (IVF) treatment. However, it is not yet clear which genotype or combination of genotypes is favourable towards a better ovarian stimulation and pregnancy outcome. Materials and methods In this study we assessed the distribution of the genotypes of FSHR Ser680Asn and of AMHRII −482A>G gene polymorphisms in a group of 126 infertile women and a control group of 100 fertile women by using real-time polymerase chain reaction (RT-PCR). Results Statistical analysis showed that the frequency of the genotypes is similar in both control and IVF/ intracytoplasmic sperm injection (ICSI) groups. Further investigation of the frequency of the nine possible combinations of these polymorphisms in the groups revealed no correlation between infertility and combination of the polymorphisms. Women with one polymorphism have on average 5.5 units higher levels of AMH compared to women carrying no polymorphism. In women with no polymorphisms, for each unit of FSH increase, the average concentration of blood AMH is expected to be 72% lower. Conclusion The distribution of the FSHR Ser680Asn and of the AMHRII −482A>G gene polymorphisms, in the Greek population is similar in fertile and infertile women. The study showed that FSH and AMH correlated levels in certain cases could be used to estimate a patient’s ovarian reserve.

P–715 Nomogram for anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH) in healthy infertile women according to the cause of subfertility

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Breed
Keyword(s):  
Ovarian Reserve ◽  
Follicle Stimulating Hormone ◽  
Ovarian Response ◽  
In Vitro Fertilisation ◽  
Control Group ◽  
Male Factor ◽  
Age Related ◽  
Registration Number ◽  
Stimulating Hormone

Abstract Study question Does the cause of subfertility affect any age-related changes observed in anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH)? Summary answer There was no significant effect of the cause of subfertility on AMH and FSH, however women with unexplained subfertility were significantly older than controls. What is known already Ovarian reserve and consequently female fecundity irreversibly diminish with age. Subfertility is an increasingly prevalent clinical presentation with a multitude of underlying pathologies. Ovarian reserve testing, including biomarkers, plays a crucial role in the management of subfertility, particularly in predicting ovarian response during in-vitro fertilisation (IVF) treatment. For some couples, no cause can be identified and their subfertility remains unexplained thus making prognosis and treatment challenging. It has been proposed that these couples may have an ovarian reserve at the extreme lower end of normal. Study design, size, duration: This clinical audit retrospectively investigated 864 subfertile healthy women who had undergone investigation at the Royal Derby Hospital fertility clinic. Data were collected in Excel including age, serum AMH, serum FSH if available, and subfertility diagnosis. The data were collected from a pre-existing database produced by a group of researchers pre–2016 at the Royal Derby Hospital. The researchers had access to pathology lab reports and computerised hospital records containing clinical details. Participants/materials, setting, methods: Subfertility diagnoses were categorised by cause: male factor and tubal factor were combined and served as a control group, oligo-anovulatory factor, endometriosis factor, and unexplained subfertility. If multiple factors were present, oligo-anovulation was taken as the presiding factor. One-way ANOVA using Minitab was used for statistical analysis to assess the effect of cause of subfertility on age, on AMH, and on FSH. For AMH and FSH, age was incorporated as a covariate. Main results and the role of chance AMH significantly decreased with age (p < 0.001) and FSH significantly increased with age (p < 0.05). The age-related change in AMH was more pronounced than in FSH. The cause of subfertility had a statistically significant effect on age. The nature of this was that the unexplained group was significantly older than the control group and the oligo-anovulatory group (p < 0.001). Compared to the control group, AMH was lower in the unexplained and endometriosis groups and higher in the oligo-anovulatory group. However, after adjusting for age, the effect of cause of subfertility on AMH was not significant (R2(adj)=24.91%, p > 0.05). Compared to the control group, FSH was lower in the unexplained, oligo-anovulatory, and endometriosis groups. However, after adjusting for age, the effect of cause of subfertility on FSH was not significant (R2(adj)=2.05%), p > 0.05). Limitations, reasons for caution The previous group of researchers may have exhibited selection bias and clinical interpretation during data collection. The study population was unevenly distributed across the different causes of subfertility. Only the effect of age was accounted for despite many factors being known to affect female fertility. Wider implications of the findings: Respective nomograms for AMH and FSH according to cause of subfertility provide a reference point for clinicians, especially to predict ovarian response during IVF treatment. Although AMH was not significantly lower in the unexplained group compared to the control group, the women were significantly older implying a lower ovarian reserve. Trial registration number Not applicable

scholarly journals Discovery and Preclinical Development of Orally Active Small Molecules that Exhibit Highly Selective Follicle Stimulating Hormone Receptor Agonism

2021 ◽  
Vol 11 ◽  
Author(s):  
Selva Nataraja ◽  
Henry Yu ◽  
Joie Guner ◽  
Stephen Palmer
Keyword(s):  
Ovarian Stimulation ◽  
Hormone Receptor ◽  
Ovulation Induction ◽  
Low Dose ◽  
Intrauterine Insemination ◽  
Follicle Stimulating Hormone ◽  
Controlled Ovarian Stimulation ◽  
Orally Active ◽  
Stimulating Hormone

An orally active follicle stimulating hormone receptor allosteric agonist would provide a preferred treatment for over 16 million infertile women of reproductive age in low complexity methods (ovulation induction-intrauterine insemination) or in high complexity methods (controlled ovarian stimulation-in vitro fertilization). We present two oral follicle stimulating hormone receptor allosteric agonist compounds that have the desired pharmacology, drug metabolism, pharmacokinetics, and safety profile for clinical use. These molecules provide a single agent suitable for ovulation induction-intrauterine insemination or controlled ovarian stimulation-in vitro fertilization that is more convenient for patients and achieves similar preclinical efficacy as rec-hFSH. TOP5668, TOP5300 were evaluated in vitro in Chinese hamster ovary cells transfected with individual glycoprotein receptors measuring cAMP (FSHR, LH/CGR, thyroid stimulating hormone receptor). TOP5668 was found to have solely follicle stimulating hormone receptor allosteric agonist activity while TOP5300 was found to have mixed follicle stimulating hormone receptor allosteric agonist and LHR-AA activity. Both compounds stimulated concentration-dependent increases in estradiol production from cultured rat granulosa cells in the presence or absence of low dose rec-hFSH, while only TOP5300 stimulated testosterone production from rat primary Leydig cells. In pooled human granulosa cells obtained from patients undergoing controlled ovarian stimulation-in vitro fertilization, TOP5300 stimulated 7-fold greater maximal estradiol response than rec-hFSH and TOP5668 was 10-fold more potent than TOP5300. Both TOP5300 and TOP5668 stimulated follicular development in immature rat to the same efficacy as recombinant follicle stimulating hormone. In mice treated with TOP5300, in the presence of low dose of follicle stimulating hormone, there were no differences in oocyte number, fertilization rate, and hatched blastocyst rate in mice with TOP5300 and low dose follicle stimulating hormone vs. reference proteins pregnant mare serum gonadotropin or high dose rec-hFSH. ADME/PK and safety profiles were favorable. In addition, there was no appreciable activity on thyroid hormones by TOP5300 in 14-days toxicological study in rat or dog. The selected lead compound, TOP5300 stimulated a more robust increase in estradiol production from granulosa-lutein cells from women with polycystic ovarian syndrome patient compared to rec-hFSH. Conclusions: Two novel oral FSHR allosteric agonist, TOP5668 and TOP5300, were found to mimic the biological activity of rec hFSH in preclinical studies. Both compounds led to folliculogenesis and superovulation in rat and mice. Specifically, TOP5300 led to a similar number of ovulated oocytes that fertilized and developed into hatched blastocysts in mice when compared to rec-hFSH. The safety profile demonstrated lack of toxicity.

scholarly journals Association of estrogen, progesterone and follicle stimulating hormone receptor polymorphisms with in vitro fertilization outcomes

2018 ◽  
Vol 64 (4) ◽  
pp. 260-265 ◽  
Author(s):  
Vijaya Ganesh ◽  
Vettriselvi Venkatesan ◽  
Teena Koshy ◽  
Sanjeeva Nellapalli Reddy ◽  
Suruli Muthumuthiah ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Hormone Receptor ◽  
Follicle Stimulating Hormone ◽  
Vitro Fertilization ◽  
Stimulating Hormone
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