Sequential (hFSH + recFSH) vs homogenous (hFSH or recFSH alone) stimulation: clinical and biochemical (cumulus cell gene expression) aspects

Abstract

FSH is a key hormone in the regulation of follicular development. Together with the EGF network, these molecules mediate oocyte maturation and competence in preparation for the action of LH. FSH isoforms regulate distinct biological pathways and have specific effects on granulosa cell function and maturation of the ovarian follicle. Their dynamic interactions occur during the follicular cycle; shortliving forms are predominant in the pre-ovulatory phase, whereas long-acting molecules characterize the lutealfollicular transition. Recombinant FSH (rFSH) molecules have a reduced number of isoforms and are less acidic, with a shorter half-life. We have investigated sequential stimulation, comparing hFSH + rFSH, vs. rFSH alone and hFSH alone for the entire stimulation phase. Sequential stimulation leads to an E2 per MII oocyte ratio that is much lower than is seen during treatment with the two drugs individually. Although there is a positive tendency in favor of the sequential treatment, there was no significant difference in pregnancy rates, even taking frozen embryos into consideration. The cumulus cell transcriptome varies considerably between the treatments, although with no clear significance. When comparing pregnant vs. non-pregnant patients, in general a decrease in mRNA expression can be observed in the pregnant patients, especially in expression of folic acid receptor 1 and ovostatin 2. This indicates that material has been transferred from CC to the oocyte. However, a common observation in the literature is that variations in the transcriptome of the cumulus cells are highly dependent upon the patient genotype; the potential for applying this strategy as a basis for selecting embryos is, at the very least, questionable.

Follicle stimulating hormone receptor in mesenchymal stem cells integrates effects of glycoprotein reproductive hormones

“…The assay and a result using this highly pure pituitary FSH are shown in previous work . The physiological FSH has a longer half‐life, includes more isoforms, and is physiologically glycosylated . Since response to isoforms might vary, and the physiological hormone works best with the novel low‐level receptor, we used the Fitzgerald highly pure FSH (specific activity >5000 IU/mg) in subsequent work.…”

Biosimilar FSH preparations- are they identical twins or just siblings?

“…When examining the different commercial FSH preparations, the isoforms present in uFSH are more acidic than those in rFSH [ 18 ]. Interestingly, based on the natural distribution of FSH isoforms during the follicular phase of the menstrual cycle, Gurgan et al [ 19 ] have demonstrated favorable outcomes and improved efficacy, while using a sequential administration of uFSH followed by rFSH compared with either FSH preparation alone. Moreover, when prospectively evaluating the efficacy of a protocol that mimics the physiological shift form an acidic to a less acid FSH isoform during oocyte maturation, Gerli and Di Renzo [ 20 ] could demonstrate that the combined protocol (hFSH + rFSH) resulted in significantly less IU of FSH necessary for ovarian stimulation together with shorter stimulation days and with higher number of oocyte yield, embryo quality, implantation and pregnancy rates.…”

Genome-wide association study using haplotype alleles for the evaluation of reproductive traits in Nelore cattle

“…Gurgan et al [ 72 ], aiming to identify markers capable of predicting the quality of human oocytes detected the presence of the RCHY1 gene as a possible hormone regulator involved in follicular development, further emphasizing that this gene is close (383 kb) to the conception rate and daughter pregnancy rate QTL.…”