The Effect of the Allelics of Ser680Asn Polymorphisms of Follicle-Stimulating Hormone Receptor Gene in IVF/ICSI Cycles: a Systematic Review and Meta-analysis.

A significant number of single-nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHr) can modify the response to exogenous FSH administration. A significant diversity in response to controlled ovarian stimulation (COS) in assisted reproductive technologies (ART) according to the type of allelic has been reported. We aimed to evaluate the relation between the Asn680Ser allelics and COS. A total of 4 electronic databases were searched for articles published up to August 2021. Prospective and retrospective comparative studies which reported outcomes after COS in patients who underwent genotyping for the detection of FSHr polymorphisms were considered eligible. A total of 11 studies including 4343 patients with Asn680Ser polymorphisms of the FSHr were included. Patients carrying the Asn/Asn allelic provide elevated E2 on the day of human chorionic gonadotropin (hCG) administration (1549 patients MD 262.39 pg/ml, p = 0.0007), but less transferrable embryos as compared with Ser/Ser genotype (283 patients MD - 0.11 embryos, p = 0.04). Ans/Ser versus Ser/Ser genotypes showed a higher E2 on the day of hCG administration (1799 patients, MD 207.86 pg/ml, p = 0.02). Pregnancy rates were similar in all combination of genotypes. There is currently no strong evidence suggesting that the examination of one gene in relation to genotypes can be effectively used as single tool to improve COS. However, polygenic analysis of different polymorphisms by analyzing the genetic profile of each individual could be useful. Further research is warranted to develop an algorithm that will enable simultaneous analysis of many genes, which combined with hormonal profile could promote treatment individualization.

Comparison of the Fetal Fraction of Cell-Free DNA in In-Vitro Fertilization (IVF) Versus Natural Conception Evaluation of the Fetal Fraction With IVF Parameters.

Background As the offspring of assisted reproduction techniques (ARTs) have become a substantial proportion of the population, increased attention has been placed on the safety of ART. Investigators have focused on identifying a tool that combines molecular or biological tests that can predict the outcomes of in-vitro fertilization (IVF) or intracytoplasmic sperm injection and the resulting pregnancy after ART-mediated embryo implantation. This study aimed to answer the following questions: is there a difference between natural conception and IVF pregnancies regarding fetal fraction (FF) of cell-free DNA (cfDNA) in maternal age, birth weight, gender, and gestational age? Is there a difference between FF concentration regarding the parameters of IVF as possible predictive factors affecting the outcomes of IVF? Methodology This study included 31 women with singleton pregnancies conceived via IVF who underwent cell-free fetal DNA (cffDNA) screening for trisomy 13, 18, and 21; sex determination; and FF. The control group included 55 women who experienced natural conception. For all women, anthropometric characteristics such as age, weight, height, and body mass index (BMI) were recorded. For the IVF group, early follicular phase values of follicle-stimulating hormone, luteinizing hormone, prolactin, anti-müllerian hormone, thyroid-stimulating hormone, and estradiol were recorded. Results The natural conception and IVF groups were similar regarding maternal age, BMI of the mother, gender, birth weight, and gestational age. FF was not significantly different between the natural conception and IVF groups (10 (3.8) vs. 9 (2.6); p = 0.144). The results were similar after adjusting for maternal age via regression analysis. cfDNA was not associated with maternal age, birth weight, gender, or gestational age in the entire study sample or separately for the natural conception and IVF groups. No significant correlation was found between cfDNA and IVF parameters. Conclusions The FF is an important factor for non-invasive prenatal testing (NIPT) accuracy. Several studies have found a reduction in FF in pregnancies following ART compared with natural conception, while other studies have presented no differences in the FF. All researchers agree on the importance of NIPT; however, knowledge on how the FF is affected in ART pregnancies compared with naturally conceived pregnancies is very limited. In this study, no difference in FF for the IVF group compared with natural conception women was observed. The cffDNA concentrations in maternal serum do not appear to be affected in IVF conception. We suggest that FF is an independent factor compared with IVF parameters.

Past, Present, and Future of Gonadotropin Use in Controlled Ovarian Stimulation During Assisted Reproductive Techniques.

A variety of protocols have evaluated the use of several forms of gonadotropins in controlled ovarian stimulation (COS). We aim to review the evolving trends on the use of gonadotropins human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) over time and their combinations in COS for patients who undergo assisted reproductive techniques (ART) protocols. A meticulous search of three electronic databases was performed for articles published in the field up to September 2020. The administration of hCG seems a promising alternative to conventional modalities for COS related to the enhancement of LH activity. The use of gonadotropins was associated with significantly elevated pregnancy rates that ranged from 20.8% to 46.2%. However, the currently available outcomes with regards to oocytes retrieved, number of embryos are still conflicting. A potential beneficial effect was observed by the majority of the studies in terms of the number of embryos and implantation rates, which is, however, highly affected by the type of protocol used (gonadotropin-releasing hormone [GnRH] agonist or antagonist). Further studies are warranted to elucidate the exact pathways of action of gonadotropins in controlled ovarian stimulation to attain the optimal effect.

Polymorphism Gln27Glu of ß2 Adrenergic Receptors in Patients with Ischaemic Cardiomyopathy.

BACKGROUND: Polymorphisms of the Adrenergic Receptors (ARs) might affect the development and progression of Heart Failure (HF) and the response to treatment with ß-blockade therapy. OBJECTIVE: To examine the role of the Gln27Glu polymorphism of ß2-AR in HF development and to assess the hypothesis that Gln27Glu is associated with coronary artery disease in patients with ischaemic HF. METHODS: In this case control study we enrolled 155 consecutive patients with symptomatic HF of ischaemic aetiology with impaired Left Ventricular Ejection Fraction (LVEF) ≤35%. The control group consisted of 133 patients with no obstructive coronary artery disease and or evidence of HF. RESULTS: Concerning HF and control subjects there was no significant differences in the prevalence of Gln27Gln homozygotes (46 vs. 44%, p=0.82). In HF patients concerning the differences in patient characteristics between allele categories (Gln27Gln vs. Gln27Glu/Glu27Glu) there was no difference in risk factors, LVEF, treatment, the clinical status and NYHA categorization of patients, and in the prevalence of multi-vessel coronary artery disease. Interestingly, participants homozygous for Gln had significant higher prevalence of previous myocardial infarction (Gln27Gln vs. Gln27Glu/Glu27Glu: 77 vs. 23%, p=0.02). CONCLUSION: The present study shows that the Gln27Gln genotype of ß2-AR is the most predominant while the Glu27Glu is the least prevalent in our HF population. There was no difference in the prevalence of polymorphism Gln27Glu between HF patients and control subjects. However, the presence of Glu allele was associated with lower myocardial infarction rate.

"hCG priming" effect in controlled ovarian stimulation through a long protocol.

BACKGROUND: Recently, it has been demonstrated that, in patients down-regulated by GnRH analogues (GnRHa), a short-term pre-treatment with recombinant LH (rLH), prior to recombinant FSH (rFSH) administration, increases the number of small antral follicle prior to FSH stimulation and the yield of normally fertilized embryos. However, no data exist in the literature regarding the potential beneficial effect of "hCG priming" in controlled ovarian hyperstimulation (COH) through a long GnRH-a protocol, which binds the same receptor (LH/hCGR), though it is a much more potent compared to LH. The primary aims of this study were to assess the effect of short-term pre-rFSH administration of hCG in women entering an ICSI treatment cycle on follicular development, quality of oocytes and early embryo development. The secondary endpoints were to record the effects on endometrial quality and pregnancy rate. METHODS: Patients with a history of at least one previous unsuccessful ICSI cycle were randomly assigned into two groups to receive treatment with either a long protocol with rFSH (control group) or a long protocol with rFSH and pre-treatment with hCG (hCG group). In particular, in the latter group, a fixed 7 days course of 200 IU/day hCG was administered as soon as pituitary desensitization was confirmed. RESULTS: The mean number of oocytes retrieved was not significantly different between the two treatment groups, although the percentage of mature oocytes tended to be higher but not significantly different in hCG-treated patients. The percentage of patients with more than one grade 3 embryos was higher in the pre-treatment group, which also showed a higher pregnancy rate. CONCLUSION: All the above clinical observations, in conjunction with previous data, suggest a point towards a beneficial "hCG priming" effect in controlled ovarian hyperstimulation through a long GnRH-a down-regulation protocol, particularly in patients with previous ART failures.