The safety and effectiveness of stepwise and low-dose administration of follicle stimulating hormone in WHO group II anovulatory infertile women: Evidence from a large multicenter study in Spain

1996 ◽  
Vol 13 (7) ◽  
pp. 551-556 ◽  
Author(s):  
Juan Balasch ◽  
Rosa Tur ◽  
José A. Peinado
Keyword(s):  
Multicenter Study ◽  
Low Dose ◽  
Follicle Stimulating Hormone ◽  
Dose Administration ◽  
Infertile Women ◽  
Large Multicenter Study ◽  
Group Ii ◽  
Stimulating Hormone

scholarly journals Pilot study of the optimal protocol of low dose step-up follicle stimulating hormone therapy for infertile women

2018 ◽  
Vol 17 (3) ◽  
pp. 315-324 ◽  
Author(s):  
Toshiya Matsuzaki ◽  
Takeshi Iwasa ◽  
Rie Yanagihara ◽  
Mizuki Komasaka ◽  
Kiyohito Yano ◽  
...  
Keyword(s):  
Pilot Study ◽  
Hormone Therapy ◽  
Low Dose ◽  
Follicle Stimulating Hormone ◽  
Infertile Women ◽  
Optimal Protocol ◽  
Dose Step ◽  
Stimulating Hormone

scholarly journals Ovarian Stimulation in Obese and Non-Obese Polycystic Ovary Syndrome Using a Low-Dose Step-Up Regimen with Two Different Starting Doses of Recombinant Follicle-Stimulating Hormone

2008 ◽  
Vol 36 (6) ◽  
pp. 1197-1204 ◽  
Author(s):  
R Yildizhan ◽  
E Adali ◽  
A Kolusari ◽  
M Kurdoglu ◽  
B Yildizhan ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Low Dose ◽  
Polycystic Ovary ◽  
Follicle Stimulating Hormone ◽  
Obese Group ◽  
Ovary Syndrome ◽  
Infertile Women ◽  
Starting Dose ◽  
Dose Step ◽  
Stimulating Hormone

Sixty-seven infertile women with polycystic ovary syndrome (PCOS) were divided into two groups, obese and non-obese, according to their body mass index. Waist-to-hip ratio, insulin resistance, total testosterone and dehydroepiandrosterone sulphate levels were significantly elevated in obese, compared with non-obese, patients. Both groups were treated with a low-dose step-up protocol of recombinant follicle-stimulating hormone (rFSH) with a starting dose of 50 IU/day and, every third day, a 25-IU increase in the dose until the appropriate dose was achieved for each individual, up to a maximum of 175 IU/day. In the obese group only, repeat therapy commenced in the second ovulatory cycle in women who had not become pregnant, however a starting dose of 75 IU/day was then used, with incremental and maximum dose as before. The results of the starting dose of 75 IU/day rFSH were compared with the results of a 50 IU/day rFSH starting dose in the obese group. A starting dose of 50 IU/day rFSH in a low-dose step-up regimen was found to be effective, safe and well-tolerated for inducing follicular development in non-obese infertile women with PCOS. However, for obese PCOS patients, a starting dose of 75 IU/day rFSH is recommended.

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.

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