Correlation of differential ascites volume with primary cytoreductive surgery outcome, lymph node involvement, and disease recurrence in advanced ovarian cancer.

OBJECTIVE: High-grade serous ovarian cancer accounts for a disproportionate number of deaths from gynecologic malignancies. It typically presents at an advanced stage and with a high volume of ascites a common presenting feature. The aims of this study is to evaluate the association between ascites volume at the time of primary surgery for advanced stage ovarian cancer with surgical outcomes and patterns of recurrence. METHODS: A retrospective review of stage III/IV high-grade serous ovarian cancer patients who underwent primary surgery at two centers between March 2003 to June 2016. Patients were categorized as low-volume ascites (≤ 200 mL) vs high-volume (≥ 1 L). Patients with an unknown volume of ascites or neoadjuvant chemotherapy were excluded. Patients' characteristics were compared for the two groups. Probability of recurrence over time and the HR from a proportional hazards model for sub-distribution were calculated. RESULTS: A total of 210 patients were included, 90 (42.9%) patients in the low-volume and 120 (57.1%) patients in the high-volume group. Patients in the low-volume group were older with a median age of 60.2 years vs 56.8 years in the high-volume group and had lower serum CA-125 levels (mean 223 vs 971.5 U/mL). The low-volume group had better surgical outcome with suboptimal debulking (> 1 cm residual disease) in only 17.8 % vs 39.2 % in the high-volume group and had longer median time to recurrence (2.8 years in low-volume vs 1.6 years high-volume group). At the time of recurrence, the low-volume group had a less disseminated pattern of recurrence, lower rates of ascites (20 % in the low-volume group vs 37.2 % in the high-volume group), and a trend toward lower serum CA125 levels (mean 352.8 vs 596.9 U/mL). CONCLUSIONS: Advanced stage serous ovarian cancer patients who present with low-volume ascites have lower serum CA125 levels, more optimal cytoreduction rates, and longer disease-free interval. The low-volume group had less ascites, less disseminated disease, and a trend toward lower serum CA125 levels at the time of recurrence.

Cysts of the canal of Nuck: A rare sonographic diagnosis.

The canal of Nuck is a remnant of a peritoneal evagination associated with the round ligament in women. Rarely, the canal of Nuck can remain patent allowing for development of cysts. These cysts are difficult to diagnose due to their rare incidence and because they are often mistaken for other causes of inguinal pain in women. This case series of three women presenting with groin or labial masses highlights the role of sonography as the primary imaging modality in the diagnosis of canal of Nuck cysts. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:175-178, 2017.

Transfers of lower quality embryos based on morphological appearance result in appreciable live birth rates: a Canadian center's experience.

OBJECTIVE: To determine the reproductive outcomes resulting from transfer of lower-grade blastocysts to support the practice of cryopreserving and transferring lower-grade embryos. DESIGN: Retrospective chart review. SETTING: Single infertility center. PATIENTS: Women who have undergone a fresh (n = 570) or frozen (n = 885) transfer of a single blastocyst embryo between December 2013 and December 2018. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was live birth rate. The secondary outcomes included implantation rate, ongoing pregnancy rate, associations with inner cell mass (ICM) and trophectoderm epithelium (TE) grades determined by morphological assessment, and antenatal/perinatal complications. RESULTS: Reproductive outcomes directly correlated with embryo quality. Transfers of AA embryos resulted in a 41.4% live birth rate compared to 31.1% for BB embryos and 13.3% for CC embryos. The TE grade was significantly associated with the live birth rate. Embryos with a TE grade of "B" had an odds ratio of 0.677 and embryos with a TE grade of "C" had an odds ratio of 0.394 compared to embryos with a TE grade of "A" for live birth. CONCLUSION: Embryos with a TE "C" grade should be considered for transfer and cryopreservation, as they are shown to result in appreciable live birth rates. Such treatment should involve a thorough discussion with patients, however, as these live birth rates are significantly lower than those associated with higher-grade embryos.

Automated microinjection of recombinant BCL-X into mouse zygotes enhances embryo development.

Progression of fertilized mammalian oocytes through cleavage, blastocyst formation and implantation depends on successful implementation of the developmental program, which becomes established during oogenesis. The identification of ooplasmic factors, which are responsible for successful embryo development, is thus crucial in designing possible molecular therapies for infertility intervention. However, systematic evaluation of molecular targets has been hampered by the lack of techniques for efficient delivery of molecules into embryos. We have developed an automated robotic microinjection system for delivering cell impermeable compounds into preimplantation embryos with a high post-injection survival rate. In this paper, we report the performance of the system on microinjection of mouse embryos. Furthermore, using this system we provide the first evidence that recombinant BCL-XL (recBCL-XL) protein is effective in preventing early embryo arrest imposed by suboptimal culture environment. We demonstrate that microinjection of recBCL-XL protein into early-stage embryos repairs mitochondrial bioenergetics, prevents reactive oxygen species (ROS) accumulation, and enhances preimplantation embryo development. This approach may lead to a possible treatment option for patients with repeated in vitro fertilization (IVF) failure due to poor embryo quality.

Developmental consequences of alternative Bcl-x splicing during preimplantation embryo development.

Elevated cell death in human preimplantation embryos is one of the cellular events compromising pregnancy rates after assisted reproductive technology treatments. We therefore explored the molecular pathways regulating cell death at the blastocyst stage in human embryos cultured in vitro. Owing to limited availability of human embryos, these pathways were further characterized in mouse blastocysts. Gene expression studies revealed a positive correlation between the cell death index and the expression of Bcl-x transcript. Cell death activation in human blastocysts was accompanied by changes in Bcl-x splicing, favoring production of Bcl-xS, an activator of cell death. Expression of Bcl-xS was detected in a subset of human blastocysts that show particular clustering in dying and/or dead cells. Altering the Bcl-xL/Bcl-xS ratio in mouse embryos, in antisense experiments, confirmed that upregulation of Bcl-xS, with concomitant downregulation of Bcl-xL, compromised developmental potential and committed a subset of cells to undergoing cell death. This was accompanied by increased accumulation of reactive oxygen species levels without any impact on mtDNA content. In addition, altered Bcl-x splicing in favor of Bcl-xS was stimulated by culture in HTF medium or by addition of excessive glucose, leading to compromised embryo development. Thus, we conclude that inappropriate culture conditions affect Bcl-x isoform expression, contributing to compromised preimplantation embryo development.