Sequential-contingent strategy for fallopian tube evaluation using hysterosalpingo foam sonography: a cost analysis.

Background: Tubal pathology is the etiological factor in 20% of couples with female infertility. Historically, diagnostic evaluation of the fallopian tubes has been performed by means of hysterosalpingography (HSG). Hysterosonosalpingography with EXEM® foam is a recent technique with supposedly comparable effectiveness to HSG, but with better tolerability for patients. Methods: Tubal patency was assessed in patients who were candidates for intrauterine insemination (IUI) between January 2020 and July 2021. (I) Hysterosonosalpingography with EXEM® foam. (II) If the patient had both tubes patent, IUI was proposed. In case of inconclusive or pathological results, HSG was performed. (III) If the HSG concludes tubal patency, IUI is proposed. On the other hand, if it results in tubal obstruction, in vitro fertilization (IVF) is proposed. Results: Assessment of tubal patency by HSG showed concordance with previous Hysterosonosalpingography with EXEM® foam results in 45.5% (n=15) of cases of unilateral obstruction and 66.7% (n=6) of cases of bilateral obstruction. When we compare the total cost of HSG (€54,899.46) with the sum of patients who only required Hysterosonosalpingography with EXEM® foam together with those who underwent both tests (€45,575.96), it shows that the latter represents a cost benefit strategy (cost difference €9,323.50). Conclusions: Our results suggest a benefit of €9,323.50 when performing the contingent sequential strategy, in case of pathological or inconclusive results, compared to performing a systematic HSG in all patients. Patients with an obstructive hysterosalpingogram with EXEM® and a patent hysterosalpingogram will be the subgroup that will benefit the most, as IUI can be proposed instead of IVF. In addition, there is a benefit in terms of optimizing the medical procedure, hospital visits and speeding up the time to start assisted reproductive technology (ART).

PGT-HLA programmes for the cure of a sick sibling: clinical strategies for this challenging search.

The ultimate goal of a preimplantation genetic testing and human leukocyte antigen (PGT-HLA) matching programme is the birth of a healthy, HLA-compatible child for the treatment or cure of a sick sibling. Several authors have published successful cases of the births of children HLA-matched to siblings affected by different conditions and diseases. However, there are many reports of failed attempts. Couples seeking an HLA-matched sibling for their affected child look for positive outcomes in the shortest possible time. Nevertheless, there is no published consensus or guidelines with recommendations for these cases. Here, the authors aimed to analyse different approaches for these programmes, highlighting the most promising strategies for the families and fertility units. Furthermore, the authors mention a successful case of a PGT-HLA matching programme after a previous failed attempt following the strategies proposed. Which is the most cost-effective and time-efficient approach in a PGT-HLA matching programme?

Effect of Sperm Selection by Magnetic-Activated Cell Sorting in D-IUI: A Randomized Control Trial.

Clinical outcome in assisted reproduction techniques (ARTs) is mainly influenced by the quality of gametes used. It is known that a high percentage of sperm DNA fragmentation (DNAf) decreases the success of ART clinical results. Therefore, techniques such as magnetic-activated cell sorting (MACS) help to improve results in cases of patients with a high percentage of DNAf. Cryopreservation of sperm in donor intrauterine insemination (D-IUI) treatments increases sperm DNAf, so patients using these sperm samples can benefit from using this technique. This prospective randomized national multicenter study analyzed clinical outcomes of 181 D-IUI treatments. MACS was performed after density gradient centrifugation (DGC) in 90 thawed semen donor samples (MACSG), whereas only DGC was performed in 91 thawed semen donor samples (CG). To our knowledge, this is the first study analyzing the effect of MACS on D-IUI cycles. Our results show no significant differences in gestation, live birth, or miscarriage rates between the two groups. We believe that further studies with a larger sample size are needed to evaluate the application of MACS in combination with standard IUI donor sperm preparations in fertility clinics.

Diagnostic Accuracy Study Comparing Hysterosalpingo-Foam Sonography and Hysterosalpingography for Fallopian Tube Patency Assessment.

INTRODUCTION: Simplified ultrasound-based infertility protocols that appear to provide enough information to plan effective management have been described. Thus, the objective of this study is to compare the diagnostic accuracy of the hysterosalpingo-foam sonography (HyFoSy) in tubal patency testing with the traditional hysterosalpngography (HSG) for establishing a new diagnostic strategy in infertility. MATERIAL AND METHODS: Prospective observational diagnostic accuracy was performed in a private fertility clinic in which 106 women undergoing a preconceptionally visit were recruited. All of them had low risk for tubal disease, had performed an HSG and were negative for Chlamydia trachomatis antibody. Main outcome measures were tubal patency and pain grade. RESULTS: Evaluation of tubal patency by HyFoSy showed a total concordance with the results of the previous HSG in 72.6% (n = 77), and a total discordance for 4.7% (n = 6), with the inter-test agreement Kappa equal to 0.57, which means moderate concordance. Among the patients, 59.1% did not report pain during the procedure, while the remaining 48.1% indicated pain in different degrees; patients usually report less pain and only 6.6% described more pain with HyFoSy than with HSG (OR 6.57 (CI 95% 3.11-13.89)). Clinical outcomes after performing HyFoSy were not affected. CONCLUSIONS: HyFoSy is in concordance with HSG regarding tubal patency results and it is a less painful technique than HSG. HyFoSy is more economical and can be performed in an exam room only equipped with an ultrasound scanner. Based on these results, HyFoSy could be the first-choice diagnostic option to assess tubal patency in patients with low risk of tubal disease.

Sam68 mediates leptin signaling and action in human granulosa cells: possible role in leptin resistance in PCOS.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, obesity, and insulin resistance, that leads to subfertility. Sam68 is an RNA-binding protein with signaling functions that is ubiquitously expressed, including gonads. Sam68 is recruited to leptin signaling, mediating different leptin actions. OBJECTIVE: We aimed to investigate the role of Sam68 in leptin signaling, mediating the effect on aromatase expression in granulosa cells and the posible implication of Sam68 in the leptin resistance in PCOS. MATERIALS AND METHODS: Granulosa cells were from healthy donors (n = 25) and women with PCOS (n = 25), within the age range of 20 to 40 years, from Valencian Infertility Institute (IVI), Seville, Spain. Sam68 expression was inhibited by siRNA method and overexpressed by expression vector. Expression level was analysed by qPCR and immunoblot. Statistical significance was assessed by ANOVA followed by different post-hoc tests. A P value of <0.05 was considered statistically significant. RESULTS: We have found that leptin stimulation increases phosphorylation and expression level of Sam68 and aromatase in granulosa cells from normal donors. Downregulation of Sam68 expression resulted in a lower activation of MAPK and PI3K pathways in response to leptin, whereas overexpression of Sam68 increased leptin stimulation of signaling, enhancing aromatase expression. Granulosa cells from women with PCOS presented lower expression of Sam68 and were resistant to the leptin effect on aromatase expression. CONCLUSIONS: These results suggest the participation of Sam68 in leptin receptor signaling, mediating the leptin effect on aromatase expression in granulosa cells, and point to a new target in leptin resistance in PCOS.

Effect of Group Embryo Culture under Low-Oxygen Tension in Benchtop Incubators on Human Embryo Culture: Prospective, Randomized, Controlled Trial.

To evaluate the efficacy of group embryo culture under low-oxygen tension in benchtop incubators on human embryo development in vitro. The study was designed as a prospective, patient blind, randomized, controlled trial of a complex intervention. One hundred forty-eight women undergoing IVF were recruited in our fertility practice and randomized into two groups: intervention group (study culture strategy) or control group (control culture strategy). Intervention group embryos were cultured grouped under low-oxygen tension in benchtop incubators while control group embryos were cultured individually under atmospheric oxygen tension in large-box incubators. Using the study culture strategy, there were a significantly higher implantation rate (65.1% vs 49.2%; RR, 1.42; 95% CI, 1.17-1.73) and live birth delivery rate per embryo transfer (52.7% vs 39.5%; RR, 1.33; 95% CI, 1.02-1.75) with the first fresh embryo transfer. Cumulative implantation rate (56.7% vs 43.6%; RR, 1.30; 95% CI, 1.05-1.62) and cumulative live birth rate per embryo transfer (47.4% vs 36.2%; RR, 1.31; 95% CI, 1.01-1.69) were also statistically significantly increased in the study culture strategy. Human embryos exposed to our study culture condition strategy had statistically significant increased cumulative implantation rate and cumulative live birth rate per embryo transferred. Our findings suggest that this strategy specially favours poor quality embryos. Clinical Trial Registration Number: NCT01904006.

Tachykinins and Kisspeptins in the Regulation of Human Male Fertility.

Infertility is a global disease affecting one out of six couples of reproductive age in the world, with a male factor involved in half the cases. There is still much to know about the regulation of human male fertility and thus we decided to focus on two peptide families that seem to play a key role in this function: tachykinins and kisspeptins. With this aim, we conducted an exhaustive review in order to describe the role of tachykinins and kisspeptins in human fertility and their possible implications in infertility etiopathogenesis. Many advances have been made to elucidate the roles of these two families in infertility, and multiple animal species have been studied, including humans. All of this knowledge could lead to new advances in male infertility diagnosis and treatment, but further research is needed to clarify all the implications of tachykinins and kisspeptins in fertility.

Effect of dietary supplementation with a highly pure and concentrated docosahexaenoic acid (DHA) supplement on human sperm function.

The aim of this study was to evaluate the possible beneficial effects of diet supplementation with a highly concentrated and purified docosahexaenoic acid (DHA) formula on human sperm function. We performed a prospective, randomized, double blind, placebo-controlled intervention study. One-hundred eighty human semen samples from sixty infertile patients recruited in a private assisted reproduction center were included. All samples were examined according to World Health Organization guidelines. We analyzed macroscopic and microscopic sperm parameters, oxidative stress, apoptosis, lipid peroxidation, mitochondrial membrane potential and DNA fragmentation before and after supplementation with different DHA daily doses (0.5, 1 and 2 g) or placebo for 1 and 3 months. No differences were found in traditional sperm parameters except for progressive sperm motility, with a significant increase after DHA ingestion after the first month with 1 or 2 g doses and after 3 months with 0.5 g of DHA. This effect was more evident in asthenozoospermic patients. No differences were found in any molecular semen parameter except oxidative stress, in which a slight benefit was observed after DHA treatment. In conclusion, this study support previous indications that highlight the importance of DHA supplementation as a means of improving sperm quality in asthenozoospermic men.