Role of Letrozole in Management of Female Infertility; Review Article

Background: Letrozole is a highly steroidal and selective oral aromatase inhibitor (AI). Serval studies shows that Co-treatment with letrozole significantly reduced gonadotropin consumption and the incidence of Ovarian Hyperstimulation Syndrome in normal/high responders, with pregnancy outcomes comparable to or better than the other groups. In this article we will be looking at role of letrozole in treatment of infertility Methodology: A simple systematic review was carried out, searching databases PubMed, Google Scholar, and EBSCO. The authors extracted qualitative data, and then the author's names, year, study type, methodology, and the result were reported. Results and Conclusion: Letrozole has effectiveness which is near the usage of the Human Menopausal Gonadotrophin in the numbers of pregnancies per cycle but have much less cost which indicates cost effectiveness of the drug. Furthermore, studies show that administration of the drug is effective in inducing pregnancy, with higher dose more than 5mg and 7.5mg more effective.

Two human menopausal gonadotrophin (hMG) preparations display different early signaling in vitro

Commercial hMG drugs are marketed for the treatment of infertility and consist of highly purified hormones acting on receptors expressed in target gonadal cells. Menopur® and Meriofert® are combined preparation of FSH and hCG and are compared in vitro herein. To this purpose, the molecular composition of the two drugs was analyzed by immunoassay. The formation of FSH receptor and LH/hCG receptor (FSHR; LHCGR) heteromer, intracellular Ca2+ and cAMP activation, β-arrestin 2 recruitment and the synthesis of progesterone and estradiol were evaluated in transfected HEK293 and human primary granulosa lutein cells treated by drugs administered within the pg-mg/ml concentration range. Molecular characterization revealed that Meriofert® has a higher FSH:hCG ratio than Menopur® which, in turn, displays the presence of LH molecules. While both drugs induced similar FSHR-LHCGR heteromeric formations and intracellular Ca2+ increase, Meriofert® had a higher potency than Menopur® in inducing a cAMP increase. Moreover, Meriofert® revealed a higher potency than Menopur® in recruiting β-arrestin 2, likely due to different FSH content modulating the tridimensional structure of FSHR-LHCGR-β-arrestin 2 complexes, as evidenced by a decrease in bioluminescence resonance energy transfer signal. This drug-specific activation of intracellular signaling pathways is consistent with the molecular composition of these preparations and impacts downstream progesterone and estradiol production, with Menopur® more potent than Meriofert® in inducing the synthesis of both the steroids. These findings are suggestive of distinct in-vivo activities of these preparations, but require cautious interpretation and further validation from clinical studies.

Coculture of porcine cumulus–oocyte complexes with porcine luteal cells during IVM: effect on oocyte maturation and embryo development

Coculture with somatic cells is an alternative to improve suboptimal invitro culture conditions. In pigs, IVF is related to poor male pronuclear formation and high rates of polyspermy. The aim of this study was to assess the effect of a coculture system with porcine luteal cells (PLCs) on the IVM of porcine cumulus–oocyte complexes (COCs). Abattoir-derived ovaries were used to obtain PLCs and COCs. COCs were matured invitro in TCM-199 with or without the addition of human menopausal gonadotrophin (hMG; C+hMG and C-hMG respectively), in coculture with PLCs from passage 1 (PLC-1) and in PLC-1 conditioned medium (CM). In the coculture system, nuclear maturation rates were significantly higher than in the C-hMG and CM groups, but similar to rates in the C+hMG group. In cumulus cells, PLC-1 coculture decreased viability, early apoptosis and necrosis, and increased late apoptosis compared with C+hMG. PLC-1 coculture also decreased reactive oxygen species levels in cumulus cells. After IVF, monospermic penetration and IVF efficiency increased in the PLC-1 group compared with the C+hMG group. After invitro culture, higher blastocysts rates were observed in the PLC-1 group. This is the first report of a coculture system of COCs with PLCs. Our model could be an alternative for the conventional maturation medium plus gonadotrophins because of its lower rates of polyspermic penetration and higher blastocysts rates, key issues in porcine invitro embryo production.

Bioactivity of human Menopausal Gonadotrophin (hMG) and Deglycosylated hMG (hMGdG) from Urine of Post-Menopausal Women On invitro Bovine Embryonic cleavage

The aim of this study was to produce hMG from the uterus of post-menopausal women and to evaluate the influence of glycan removal from hMG glycoprotein molecule underwent deglycosylation (hMGdG) on the onset of in vitro bovine embryonic cleavage. The study identified hMG from the uterus of post-menopausal women by confirmation of the glycoprotein characteristic, examined the biochemical characteristics of deglycosylated hMG using N-glycanase and determined the influence of deglycosylated hMG on the onset of in vitro bovine embryonic cleavage. Urine samples were collected from 30 post-menopausal women. The results of SDS-PAGE demonstrated that the protein bands ranged between 19.4 and 107 kDa. Western blot revealed immune-reactivity of the 30 kDa band, which was a glycoprotein. The concentration of glycoprotein was 99860.00 ug/ml (PAS), the protein was 66939.29 µg/ml (Biuret) and carbohydrate 32920.71 µg/mL (PAS). The glycoprotein, protein and carbohydrate ratio within the hMG molecule was 3:2:1. Chemical characteristic of hMG following enzymatic deglycosylation using N-glycanase reduced the molecular weight to 26 kDa. The deglycocylated hMG reduced the onset of in vitro cleavage of bovine embryo from 24 to 20 hours (p < 0.01). Keywords: hMG, hMGdG, embryo cleavage, glycoprotein, deglycocylation, in vitro