Future fertility of patients with zero oocytes yield in their first IVF cycle attempt.

PURPOSE: We aim to estimate the future fertility of patient undergoing their first IVF cycle attempt with no oocyte retrieved, and to identify factors that might predict those who will conceive in subsequent IVF cycle attempt. METHODS: A cohort retrospective study of all consecutive women attending our IVF unit, for their first IVF cycle attempt, between January 2013 to December 2019, who reached the ovum pick-up (OPU) stage with zero oocyte retrieved. Patients' characteristics and infertility-treatment-related variables in the first IVF cycle attempt were compared between those who conceived in a subsequent cycle and those who did not. Moreover, infertility-treatment-related variables during successful cycles resulting in pregnancy were compared to those without. RESULTS: 59 met the study inclusion criteria, yielding zero oocytes. During the follow-up period, 12 (20.3%) women conceived (one conceived twice), and 8 (14%) gave birth to a live infant. Cumulative live-birth rate per OPU and per patients were 4% and 14%, respectively. Clinical pregnancies were achieved after 3.61+1.4 cycle attempts (range: 1-6), with no live-births following the fifth IVF cycle attempt. No in-between group differences were observed in ovarian stimulation variables of their first IVF cycle attempt. Moreover, in those cycles resulting in pregnancy, patients achieved a significantly higher number of fertilized oocytes (2.15+1.5 vs 0.94+1.5, respectively; p<0.01) and a higher mean top-quality embryos (TQE) (1.76+0.9 vs 0.73+1.2, respectively; p<0.003). CONCLUSION: Women yielding zero oocytes at their first IVF cycle attempt, may achieve 14% cumulative live-birth rate after 5 IVF cycle attempts. Moreover, those who conceived in subsequent IVF cycle attempts were those achieving 2 or more fertilized oocytes/TQE.

Computational and biochemical design of a nanopore cleavable by a cancer-secreted enzyme.

Many proteinaceous macromolecules selectively transport substrates across lipid bilayers and effectively serve as gated nanopores. Here, we engineered cleavage-site motifs for human matrix metalloprotease 7 (MMP-7) into the extracellular and pore-constricting loops of OprD, a bacterial substrate-specific transmembrane channel. Concurrent removal of two extracellular loops allowed MMP-7 to access and hydrolyze a cleavage-site motif engineered within the pore's major constricting loop, in both membrane-incorporated and detergent-solubilized OprDs. Import of antibiotics by the engineered OprDs into living bacteria pointed to their proper folding and integration in biological membranes. Purified engineered OprDs were also found to be properly folded in detergent. Hence, this study demonstrates the design of nanopores with a constriction cleavable by tumor-secreted enzymes (like MMP-7) for their potential incorporation in lipid-based nanoparticles to accelerate drug release at the tumor site.