Exploring the benefit of different methods to perform assisted hatching in the ART laboratory: A narrative review.

In the last decades, to enhance success rates in assisted reproductive technology (ART) cycles, scientists have continually tried to optimize embryo culture and selection to increase clinical outcomes. In this scenario, the application of laser technology has increased considerably worldwide and is currently applied across ART in several ways: for assisted hatching (AH) or thinning of the zona pellucida (ZP), embryo biopsy, to immobilize and select the sperm during intracytoplasmic sperm injection, as well as to induce artificial blastocyst shrinkage before cryopreservation. Laser-AH has been suggested as a procedure to improve embryo implantation: the concept is that drilling holes through or thinning of the ZP could improve the hatching process and implantation. The artificial disruption of the ZP can be performed by different approaches: mechanically, chemically and with the laser, which is one of the most favourable and easy methods to remove part of the ZP and to augment the possibilities of implantation in patients defined as having a poor prognosis of success, or when the ZP is too thick. However, in the current literature, there is not sufficient evidence about the potential risk or impairment that laser utilization might induce on embryo development; therefore, the main aim of the current review is to provide an overview of the existing knowledge on the ZP and the mechanisms of manipulating it to improve the effectiveness of ART. Also, it emphasizes the positive aspect of laser application as a powerful tool that might increase the chance of pregnancy for infertile couples undergoing ART cycles.

FOLFIRINOX or nab-paclitaxel plus gemcitabine in metastatic pancreatic adenocarcinoma: an observational study.

Aim: Comparison of first-line FOLFIRINOX (FFN) and nab-paclitaxel plus gemcitabine (NabGem) in patients with metastatic pancreatic ductal adenocarcinoma. Patients & methods: The authors analyzed data from 160 patients with metastatic pancreatic adenocarcinoma receiving first-line FFN (n = 43) or NabGem (n = 117). Results: FFN and NabGem were similar in median progression-free survival (24.43 vs 26.28 weeks; hazard ratio [HR]: 0.88) and medial overall survival (47.43 vs 42.86 weeks; HR: 0.90). Of the 43 patients receiving FFN, 26 (60.4%) were treated with second-line NabGem; 14/117 (12.0%) patients receiving NabGem received second-line FFN (p < 0.0001). In the FFN → NabGem and NabGem → FFN groups, median overall survival was 51.2 and 71.6 weeks (HR: 0.69; p = 0.15). In patients receiving NabGem, second-line FFN, compared with FOLFOX/CAPOX or FOLFIRI, improved median progression-free survival 2 (25.6 vs 12.1 weeks; HR: 0.47; p = 0.0067) and median overall survival 2 (39.0 vs 19.14 weeks; HR: 0.49; p = 0.032). Conclusion: First-line FFN and NabGem promote similar clinical outcomes. Second-line FFN should be considered after NabGem.

Use of FOLFIRINOX or Nab-Paclitaxel Plus Gemcitabine for the Treatment of Locally Advanced Pancreatic Adenocarcinoma: A Single Institution Observational Study.

Patients with locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) do not present distant metastases but are not eligible for surgery upfront. Chemotherapy regimens, such as FOLFIRINOX (FFN) or nab-paclitaxel plus gemcitabine (GemNab) in combination with loco-regional treatments are generally used in this setting. However, the best treatment choice is unknown. We retrospectively analyzed the information of 225 patients with stage II-III PDAC treated at our institution between October 2011 and December 2020. A total of 94 patients with LA PDAC who are non-eligible for surgery upfront received neoadjuvant FFN or GemNab. Of the 67 patients receiving FFN, 28 (41.8%) underwent surgery after neoadjuvant therapy. Of the 27 patients treated with GemNab, 6 (22.2%) became eligible for resection. The median overall survival (OS) was 85.1 weeks and 54.3 weeks in the FFN and GemNab groups, respectively (HR = 0.54, p = 0.0109). The median OS was 189.7 weeks and 76.4 weeks in the resected and unresected cohorts, respectively (HR = 0.25, p < 0.0001). Neutropenia (37.3%), anemia (6.0%), and diarrhea (6.0%) in the FFN group and neutropenia (22.2%) and thrombocytopenia (18.5%) in the GemNab groups were the most frequent grade 3-4 side effects. Higher rates of thrombocytosis (p < 0.0001) and peripheral edema (p < 0.0001) were observed in the GemNab group. Our results suggest that the use of FFN is associated with more favorable clinical outcomes than GemNab for patients with LA PDAC. Future randomized and controlled clinical trials are needed to further elucidate the role of these regimens and loco-regional treatments in this setting.

Sperm chromosome abnormalities in patients with normal karyotype and in translocation carriers: clinical relevance for assisted reproductive technology.

RESEARCH QUESTION: What is the proportion of chromosomally abnormal spermatozoa in men with a history of reproductive failure, including patients with normal karyotype and carriers of translocations? Should this analysis be included in a clinical setting to define the best treatment options for infertile couples? DESIGN: Aneuploidy for chromosomes XY, 13, 15, 16, 17, 18, 21, 22 was tested by fluorescent in-situ hybridization (FISH) in 1665 samples from couples with normal karyotype having had at least three previous IVF failures, miscarriages, or both (group-A). A FISH test was also carried out in 76 samples from carriers of translocations (group B) to detect the proportion of spermatozoa with unbalanced rearrangement. RESULTS: In group A, the lowest incidence of aneuploid sperm cells was found in men with normozoospermia (1.3%, range 0.09-6.31%) compared with men with moderate oligoasthenoteratozoospermia (2.1%, range 0.41-16.6%, P < 0.001), severe oligoasthenoteratozoospermia (4.7%, range 0.53-30.77, P < 0.001), microepididymal sperm aspiration (3.1%, range 1.19-24.24, P < 0.001) and testicular sperm extraction samples (5.8%, range 1.54-33.3, P < 0.001). In group B, the proportion of spermatozoa with unbalanced rearrangement was significantly higher in reciprocal (63%, range 10.0-87.6%) than in Robertsonian translocations (16%, range 4.3-51.0%, P < 0.001). CONCLUSIONS: Patients with poor prognosis of term pregnancy tend to generate high proportions of chromosomally abnormal spermatozoa, especially in severe male factor cases. Corresponding frequencies occur at wide ranges; therefore, the FISH test is needed to assess the proportion of spermatozoa with altered chromosome condition. A flowchart, which included the FISH test, was designed to assist clinicians guide couples with poor prognosis of pregnancy, on the most indicated treatment options.