Towards a personalized approach to aromatase inhibitor therapy: a digital microfluidic platform for rapid analysis of estradiol in core-needle-biopsies.

Despite advances in breast cancer prevention and treatment, variability in patient-response has revealed the need for a more "personalized" approach to medicine, in which treatments are tailored to each patient's biology. Motivated by this idea, we introduce a technique that allows for quantification of small-molecule analytes directly from core needle biopsy (CNB) tissue samples on a miniaturized platform. The new technique, powered by digital microfluidics, integrates tissue-liquid extraction and magnetic bead-based competitive immunoassay for quantification of estradiol in milligram-sized CNB samples. Each measurement (from start to finish) requires ∼40 minutes, a duration consistent with a visit to a doctor's office. The performance of the new technique was validated by the gold-standard analysis method (high performance liquid chromatography coupled to tandem mass spectrometry), and was applied to evaluate human patient samples before and after a course of treatment with aromatase inhibitor therapy. We propose that the new technique has great potential for eventual use for fast, automated, and quantitative analysis of biomarkers in tissue samples, towards a personalized medicine approach.

Elective single embryo transfer: Is frozen better than fresh?

OBJECTIVE: Single embryo transfer (SET) has been recommended to avoid multiple births following assisted reproductive technology (ART) procedures. Many studies have shown that frozen embryo transfer may yield better pregnancy rates than fresh embryo transfer. This study looked into pregnancy rates following fresh versus frozen single embryo transfer procedures in age-matched patients. METHODS: This retrospective case control study was carried out at a private clinic [NewLife Fertility Clinic, ON, Canada]. Patient groups included infertile women treated with IVF/ICSI and elective single embryo transfer (eSET) given either fresh or frozen embryos. Cycle outcomes were compared between patient groups matched by age. The primary endpoints were positive testing for ß-hCG and viable ongoing pregnancy. The secondary endpoints were live birth and miscarriage rates. RESULTS: A total of 583 eSET cycles (212 fresh transfer cycles and 371 frozen transfer cycles) were performed. Significantly higher pregnancy and live birth rates were observed among patients aged ≤ 39 years given frozen embryos. CONCLUSION: Frozen single embryo transfer was associated with higher pregnancy and live birth rates when compared to fresh single embryo transfer.

A microfluidic technique for quantification of steroids in core needle biopsies.

Core needle biopsy (CNB) sampling is known to be inexpensive and minimally invasive relative to traditional tissue resectioning. But CNBs are often not used in analytical settings because of the tiny amount of sample and analyte. To address this challenge, we introduce an analytical method capable of multiplexed steroid quantification in CNB samples-those studied here ranged in mass from 2 to 8 mg. The new method uses digital microfluidics to extract steroids from CNB tissue samples (including a solid-phase extraction cleanup step) followed by analysis by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The method has limits of detection of 3.6, 1.6, 5.8, and 8.5 fmol for estradiol, androstendione, testoterone, and progesterone, respectively. We propose that future generations of this method may be useful for regular quantification of steroids in core needle biopsy samples of breast tissue to inform dosage and timing of antihormone or hormone replacement therapies as part of a personalized medicine approach to treating a variety of hormone-sensitive disorders.

Non-synchronized endometrium and its correction in non-ovulatory cryopreserved embryo transfer cycles.

The aim of this case series study was to investigate the effect of adjusting the length of progesterone exposure on clinical pregnancy rates in cryopreserved embryo transfer cycles of patients with out-of-phase classic endometrial dating. Eighty infertile women with previous implantation failure and good-quality embryos underwent endometrial biopsy before cryopreserved embryo transfer and were included in this study. The main outcome measures were clinical pregnancy rate and histologic endometrial dating. After adjusting the length of progesterone exposure according to endometrial dating, a significantly higher implantation rate was observed in blastocyst transfers (P = 0.02) and the clinical pregnancy rate for all cycles was 36.4%, similar to that in patients with in-phase endometrium (22.5%). In conclusion, the use of classic histologic endometrial dating to estimate the timing of the window of implantation and to adjust progesterone exposure accordingly may increase the implantation rate in frozen embryo transfer cycles.

Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF.

BACKGROUND: To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. METHODS: A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. RESULTS: A significant increase in number of mature and fertilized eggs was observed in women over 40 years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. CONCLUSION: Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40 years and could be of potential benefit for IVF cycles in older infertile women.