A rapid and low-cost method to fabricate well of the well (WOW) dishes with arbitrary 3D microwell shapes for improved embryo culture.

Despite its high cost, the success rate for in vitro fertilization (IVF) remains < 33% in humans, driving the need for new techniques to improve embryo culture outcomes. The well-of-the-well (WOW) culture system is a platform for in-vitro mammalian embryo culture that has been shown to enhance the developmental competence of embryos and clinical pregnancy rates in humans. However, discovery and testing of the best design for optimal embryo culture quality is hindered by the lack of a method to flexibly produce WOW dishes of various designs. Here, we present a low-cost and simple method to fabricate WOW dishes with microwells of arbitrary shapes and dimensions. We use a low-cost 3D printing service to fabricate a poly(dimethylsiloxane) (PDMS)-based WOW insert that can be paired with a standard in vitro fertilization (IVF) dish to create WOW dishes with new microwell shapes, including pyramidal and hemispherical designs. We validate the fabrication quality of the WOW inserts and demonstrate the utility of the assembled WOW dishes for observation and grading of mouse embryo quality. Moreover, our results indicate that WOW dishes with hemispherical microwells result in better culture outcomes than traditional flat-bottomed IVF dishes and those with other microwell shapes, including the semi-elliptical microwells used in commercial WOW dishes. The proposed fabrication strategy thus provides a way to rapidly fabricate and test new WOW dishes that may bolster IVF success rates.

Effect of delayed versus immediate embryo transfer catheter removal on pregnancy outcomes during fresh cycles.

A retrospective study was performed to determine whether the timing of embryo transfer catheter removal effects pregnancy rates in fresh, day 3 IVF cycles. Two hundred eighteen patients were evaluated, and no difference was noted between delayed versus immediate catheter removal techniques.

Luteal support with intravaginal progesterone increases clinical pregnancy rates in women with polycystic ovary syndrome using letrozole for ovulation induction.

OBJECTIVE: To determine the effect of intravaginal micronized P on pregnancy rates in clomiphene citrate and letrozole ovulation induction cycles in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective chart review. SETTING: University-based assisted reproductive technology program. PATIENTS: Women with PCOS who underwent ovulation induction with either clomiphene citrate (n = 90) or letrozole (n = 31) from January 2002 to December 2008. INTERVENTION(S): Clomiphene citrate (50-250 mg x 5 days) or letrozole (5 mg x 5 days) were used for ovulation induction. After either intercourse or IUI, patients received intravaginal micronized P (200 mg twice daily) according to prescribing physician preference. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): In clomiphene cycles, clinical pregnancies were documented in 15.3% of cycles (19 of 124) in the P group, compared with 12.1% (11 of 91) of the non-P group. In letrozole cycles, clinical pregnancies were documented in 21.1% of cycles (8 of 38) in the P group, compared with none (0 of 13) in the non-P group. CONCLUSION(S): Women with PCOS who used letrozole for ovulation induction had higher clinical pregnancy rates when using intravaginal P support. Luteal supplementation with P should be strongly considered in women with PCOS, especially in those using letrozole for ovulation induction.

Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult.

Prostate cancer cells are dependent on androgen for growth and survival; as such, inhibition of androgen receptor (AR) activity is the first line of intervention for disseminated disease. Recently, specific cytotoxic agents have been shown to extend survival times in patients with advanced disease. Given the established ability of androgen to modify cell survival in prostate cancer cells, it is imperative to determine the effect of the hormonal environment on cytotoxic response. Here, we show that the response of prostate cancer cells to taxane-induced cell death is significantly enhanced by androgen stimulation in AR-positive, androgen-dependent prostate cancer cells. Similar results were observed on androgen-independent AR activation. By contrast, AR-positive yet androgen-independent or AR-negative cells were refractory to androgen influence on taxane function. The ability of androgen to potentiate taxane activity was dependent on its mitogenic capacity and was separable from overall AR activity, as coadministration of AR antagonists, G(1) cyclin-dependent kinase inhibitors, or high-dose (growth inhibitory) androgen nullified the proapoptotic function of androgen. Observed induction of cell death was attributed to caspase-dependent apoptosis and correlated with p53 activation. Combined, these data indicate that the cytotoxic effects of taxanes are substantially influenced by the hormonal environment and/or status of AR activity in prostate cancer cells and provide the foundation for refinement and optimization of cytotoxic intervention in prostate cancer.