Morphological and cytogenetic observations of unfertilized human oocytes and abnormal embryos obtained after ovarian stimulation with pure follicle stimulating hormone following pituitary desensitization

1995 ◽  
Vol 10 (10) ◽  
pp. 2617-2622 ◽  
Author(s):  
Wojcik Cezary ◽  
Jean. Franiois Guerin ◽  
Marie. Claude Pinatel ◽  
Bied Veronique ◽  
Boulieu Dominique ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Follicle Stimulating Hormone ◽  
Human Oocytes ◽  
Stimulating Hormone

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 The ratio of exogenous Luteinizing hormone to Follicle stimulating hormone administered for controlled ovarian stimulation is associated with oocytes’ number and competence

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Dragos Albu ◽  
Alice Albu
Keyword(s):  
Luteinizing Hormone ◽  
Ovarian Stimulation ◽  
Follicle Stimulating Hormone ◽  
Fertilization Rate ◽  
Controlled Ovarian Stimulation ◽  
Human Menopausal Gonadotropin ◽  
Male Factor ◽  
Entire Study ◽  
Stimulating Hormone

Abstract We performed a retrospective study aiming to study the relationship between the ratio of the exogenous luteinizing hormone to follicle stimulating hormone (LH/FSH) administrated for controlled ovarian stimulation (COS) and the number and competence of the oocytes retrieved for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Eight hundred sixty-eight consecutive infertile patients (mean age 34.54 ± 4.01 years, mean anti-Müllerian hormone (AMH) 2.94 ± 2.07 ng/ml) treated with long agonist protocol and a mixed gonadotropin protocol (human menopausal gonadotropin in association with recombinant FSH (recFSH)) who performed IVF/ICSI between January 2013 and February 2016, were included. Patients with severe male factor were excluded. LH/FSH was calculated based on total doses of the two gonadotropins. We found, after adjustment for confounders, a positive relationship between LH/FSH and the retrieved oocytes’ (β = 0.229, P<0.0001) and zygotes’ number (β = 0.144, P<0.0001) in the entire study group and in subgroups according to age (<35 and ≥35 years) and ovarian reserve (AMH < 1.1 and ≥ 1.1 ng/ml). The fertilization rate was positively associated with LH/FSH in patients with LH/FSH in the lowest three quartiles (below 0.77) (β = 0.096, P=0.034). However, patients in the fourth quartile of LH/FSH had a lower fertilization rate as compared with patients in quartiles 1–3 which, after adjustment for covariates, was only marginally negatively related with LH/FSH (β = −0.108, P=0.05). In conclusion, our results suggest that the adequate LH/FSH administrated during COS can improve the oocytes’ and zygotes’ number in IVF/ICSI cycles, but also the fertilization rate when a certain proportion of LH/FSH is not exceeded.

Does serum follicle-stimulating hormone during controlled ovarian hyperstimulation predict to ovarian response and reproduction potential in IVF/ICSI clinical practice?

2020 ◽  
Author(s):  
Yujia Ma ◽  
Bo Sun ◽  
Linli Hu ◽  
Fang Wang ◽  
Ying-Pu Sun
Keyword(s):  
Clinical Practice ◽  
Ovarian Stimulation ◽  
Follicle Stimulating Hormone ◽  
Treatment Protocol ◽  
Ovarian Response ◽  
Controlled Ovarian Hyperstimulation ◽  
Fixed Dose ◽  
Ovarian Hyperstimulation ◽  
The Difference ◽  
Stimulating Hormone

Abstract Background: Although serum basal follicle stimulating hormone (FSH) is widely used to evaluate the ovarian response, the necessity of levels of serum FSH during the controlled ovarian hyperstimulation (COH) is controversy. When the ovarian response to COH is suboptimal due to the insufficient dose of FSH, which is often adjusted in subsequent treatment accordingly, we could detect serum FSH levels and considering that exogenous FSH is inadequate to optimal FSH threshold. We, therefore, aim to evaluate the association between the ovarian response and the difference value of serum FSH concentration in the first five days of ovarian stimulation. Methods: In this retrospective single-center study, patients were enrolled for first IVF/ICSI during the period from August 2015 to December 2017. The COH only included gonadotrophin-releasing hormone agonist (GnRH-a) protocols in which endogenous serum FSH values were suppressed, and stimulated with 150IU fixed-dose recombinant FSH (rFSH) during the first five days. Patients met all inclusion criteria were selected: age ≤ 40 years, body mass index (BMI) ≤ 32 kg/m2, regular menstruation cycle of 21-35 days and non-ovarian factor infertility. Groups were divided by the amount of oocytes collection as follows: (A) poor responders (n=27), (B) normal responders (n=638), (C) hyper responders (n=205). A multivariable logistic regression model was performed to evaluate the relationship between the ovarian response and difference value of serum FSH levels during the first five days of ovarian stimulation.Result(s): The difference value of serum FSH level (ΔFSH) between the sixth day and the first day during ovarian stimulation was measured as the primary outcome. Mean serum ΔFSH levels between groups B and C were 7.45 and 6.87, which had significant differences (p=0.0259). ΔFSH was stratified in quartiles as below: (a) ΔFSH≤5.16, (b) ΔFSH 5.16-7.11, (c) 7.11-9.09, (d) ΔFSH˃9.09. After adjusted by potential confounding factors, there was no relationship exists between ΔFSH levels and ovarian response.Conclusion(s): There is no relevance between the ovarian response and ΔFSH in the 150 IU fixed dose rFSH treatment protocol during COH. Serum FSH might not be used as an effective predictor for ovarian response and reproduction potential in IVF/ICSI clinical practice.

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