The addition of clomiphene citrate to ovarian stimulation protocols for poor responders.

Poor ovarian response (POR) is one of the most challenging problems in assisted reproduction. Several strategies have been used to improve pregnancy rates. The use of Clomiphene Citrate (CC) has been shown to improve ovarian stimulation outcomes and decrease gonadotropin requirements in women of advanced reproductive age. However, the combination of CC and gonadotropins to improve pregnancy rates after in IVF in poor responders is still unexplored due to the small number of trials with few participants. This is a prospective cohort trial involving 12 patients diagnosed with poor ovarian response who underwent ovarian stimulation during the period between June 2015 and September of 2017. All patients were treated with the maximum dose of gonadotropins (hMG, 300 IU/day, hMG group) according to a short gonadotropin/GnRH antagonist protocol. In a subsequent cycle those patients underwent the same stimulation protocol with the addition of 100 mg of CC from day 3 to day 7 (CC-hMG group). Supplementation with 100 mg of CC resulted in a statistically significant increase in estradiol levels, number of follicles and number of oocytes retrieved, as well as an increase in the number of total embryos available for transfer. Furthermore, a significant reduction was observed in cancellation rates in the CC-hMG group. Two clinical pregnancies, which resulted in two live births and 3 biochemical pregnancies were achieved in the CC/hMG group. Furthermore, by employing open-source, biological data we identified a common gene (Estrogen Receptor 1, ESR1) between genetic targets of clomiphene treatment and POR which could explain the benefits of clomiphene in this group of patients. In conclusion, the addition of CC 100 mg to the stimulation regimen in women diagnosed with POR and previous failed IVF cycles could improve stimulation results, but this study could not demonstrate any benefit in terms of clinical pregnancies and live births. The effectiveness of this treatment requires further investigation.

Improving ICSI: A review from the spermatozoon perspective.

Intracytoplasmic sperm injection (ICSI) is the most frequently applied method for fertilization making the process of identifying the perfect spermatozoon fundamental. Herein we offer a critical and thorough presentation on the techniques reported regarding (i) handling and preparing semen samples, (ii) identifying and 'fishing' spermatozoa, and (iii) improving key factors, such as motility for a successful ICSI practice. These approaches are suggested to make the process easier and more effective especially in atypical and challenging circumstances. Furthermore, we present an epigrammatic opinion-where appropriate-based upon our collective experience. Techniques such as intracytoplasmic morphologically selected sperm injection, hyaluronic binding, polarized light microscopy, and annexin V agent identification for comparing sperm cells and their chromatin integrity are analyzed. Moreover, for the demanding cases of total sperm immotility the use of the hypoosmotic swelling test, methylxanthines, as well as the option of laser assisted immotile sperm selection are discussed. Finally, we refer to the employment of myoinositol as a way to bioreactively improve ICSI outcome for oligoasthenoteratozoospermic men. The diversity and the constant development of novel promising techniques to improve ICSI from the spermatozoon perspective, is certainly worth pursuing. The majority of the techniques discussed are still a long way from being established in routine practices of the standard IVF laboratory. In most cases an experienced embryologist could yield the same results. Although some of the techniques show great benefits, there is a need for large scale multicenter randomized control studies to be conducted in order to specify their importance before suggesting horizontal application. Taking into consideration the a priori invasive nature of ICSI, when clinical application becomes a possibility we need to proceed with caution and ensure that in the pursuit for innovation we are not sacrificing safety and the balance of the physiological and biological pathways of the spermatozoon's dynamic. ABBREVIATIONS: ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; PGD: reimplantation genetic diagnosis; IVM: in vitro maturation; HCV/HIV: hepatitis C virus/human immunodeficiency virus; IMSI: intracytoplasmic morphologically selected sperm injection; DGC: density gradient centrifugations; S-U: swim-up; ART: assisted reproduction technology; IUI: intrauterine insemination; PVP: polyvinylpyrrolidone; HA: hyaluronic acid; MSOME: motile sperm organelle morphology examination; ZP: zona pellucida; MACS: magnetic activation cell sorting; HOST: hypo-osmotic swelling test; TESE: testicular sperm extraction; MMP: mitochondrial membrane potential; OAT: oligoasthenoteratozoospermic.

Making ICSI Safer and More Effective: A Review of the Human Oocyte and ICSI Practice.

Intracytoplasmic sperm injection (ICSI) has become an indispensable procedure of every assisted reproduction unit. This has created as much controversy as it has awe. As this is a multistep invasive technique, every part of the procedure has become subject to investigation. We contribute this review aspiring to offer the embryologist insight into all available approaches of securing an effective ICSI practice. Herein we present all the different approaches with respect to handling of the human oocyte, taking into consideration the important steps of the technique such as the oocyte positioning, timing of performing ICSI, the option of viewing the meiotic spindle and further individual action such as artificial oocyte activation, rescue ICSI and in vitro maturation. We enrich this by including our view based on our collective experience and current practice. Published studies have led to various options for performing ICSI, resulting in in vitro fertilization units around the world adopting different approaches. The steps that ICSI technique entails discussed from the oocyte perspective are still a long way from being organized into one secure and optimal protocol. Our stressing of the need to secure an efficient ICSI protocol could be the trigger for further well-designed larger scale studies with all the latest technological advantages. We aim to approach this subject in categories and assess them separately. However, ICSI is a multifaceted procedure involving several consecutive steps and when evaluating one we cannot exclude the end effect of the previous, or the overall effect of the different practitioners involved form beginning to end.