L. Jalalian

Follicle-stimulating hormone administered at the time of human chorionic gonadotropin trigger improves oocyte developmental competence in in vitro fertilization cycles: a randomized, double-blind, placebo-controlled trial

OBJECTIVE To determine whether an additional follicle-stimulating hormone (FSH) bolus administered at the time of the human chorionic gonadotropin (hCG) trigger can improve the developmental competence of the oocyte. DESIGN Randomized, double-blind, placebo-controlled, clinical trial. SETTING Academic medical center. PATIENT(S) Women undergoing a long agonist suppression in vitro fertilization (IVF) protocol for treatment of infertility. INTERVENTION(S) FSH bolus at time of hCG trigger versus placebo. MAIN OUTCOME MEASURE(S) Primary outcome; fertilization; secondary outcomes: oocyte recovery, implantation rate, and clinical and ongoing pregnancy/live birth rates. RESULT(S) A total of 188 women (mean age: 36.2 years; range: 25 to 40 years) were randomized. Fertilization (2PN/#oocyte) was statistically significantly improved in the treatment arm (63% vs. 55%) as was the likelihood of oocyte recovery (70% vs. 57%). There was no statistically significant difference in clinical pregnancy rate (56.8% vs. 46.2%) or ongoing/live birth rate (51.6% vs. 43.0%). CONCLUSION(S) Improvements in IVF success rates have largely been due to optimization of embryo culture and stimulation protocols; less attention has been directed toward methods to improve induction of final oocyte maturation. This was the first randomized, double-blind, placebo-controlled trial to modify the ovulation trigger to improve oocyte competence, as demonstrated by the statistically significant improvement in fertilization.

The Difficult MESA: Findings From Tubuli Recti Sperm Aspiration

AbstractPurpose: To investigate sperm quality aspirated from the tubuli recti compared to that obtained from microsurgical epididymal sperm aspiration (MESA). Methods: Sixteen patients with congenital bilateral absence of the vas deferens (CBAVD) underwent MESA. Six MESA procedures were difficult, and therefore sperm were retrieved from the tubuli recti ductules. Intraoperative sperm parameters, recovery after freeze–thaw, and ICSI outcomes were analyzed and compared between tubuli recti and MESA sperm. Results: Mean initial sperm concentration was similar in both groups (18 vs. 16 million sperm/mL). Initial sperm motility was significantly higher in the tubuli recti group (35%) than the MESA group (25%). However, post thaw motility was higher with MESA compared to tubuli recti sperm (8.7 vs. 1.5%). ICSI fertilization rates after sperm freeze–thaw were 66% for tubuli recti sperm and 71% for MESA sperm. Conclusions: Tubuli recti sperm may provide an attractive alternative to testis sperm extraction. Poor sperm recovery after freeze–thaw should be expected.

Microfluidic sorting selects sperm for clinical use with reduced DNA damage compared to density gradient centrifugation with swim-up in split semen samples

STUDY QUESTION Does microfluidic sorting improve the selection of sperm with lower DNA fragmentation over standard density-gradient centrifugation? SUMMARY ANSWER Microfluidic sorting of unprocessed semen allows for the selection of clinically usable, highly motile sperm with nearly undetectable levels of DNA fragmentation. WHAT IS KNOWN ALREADY Microfluidic devices have been explored to sort motile and morphologically normal sperm from a raw sample without centrifugation; however, it is uncertain whether DNA damage is reduced in this process. STUDY DESIGN, SIZE, DURATION This is a blinded, controlled laboratory study of differences in standard semen analysis parameters and the DNA fragmentation index (DFI) in split samples from infertile men (n = 70) that were discarded after routine semen analysis at an academic medical center. PARTICIPANTS/MATERIALS, SETTING, METHODS Sperm concentration, progressive motility and forward progression were assessed by microscopic examination. For each sample, the unprocessed semen was tested for DNA fragmentation and split for processing by density-gradient centrifugation with swim-up or sorting by a microfluidic chip. DNA fragmentation was assessed in unprocessed and processed samples by sperm chromatin dispersion assay. The DFI was calculated, from up to 300 cells per slide, as the number of cells with fragmented DNA divided by the number of cells counted per slide. MAIN RESULTS AND THE ROLE OF CHANCE The median DFI in unprocessed samples was 21% (interquartile range (IQR): 14-30). In paired analyses of all samples, those processed by the microfluidic chip demonstrated significantly decreased DFI compared to those processed by density-gradient centrifugation (P = 0.0029) and unprocessed samples (P < 0.0001). The median DFI for chip specimens was 0% (IQR: 0-2.4) while those processed by density-gradient centrifugation had a median DFI of 6% (IQR: 2-11). Unprocessed samples in the highest DFI quartile (DFI range: 31-40%) had a median DFI of 15% (IQR: 11-19%) after density-gradient centrifugation and DFI of 0% (IQR: 0-1.9%) after processing with the microfluidic chip (P = 0.02). LIMITATIONS, REASONS FOR CAUTION While a high DFI has been associated with poor outcomes with IVF/ICSI, there are limited data illustrating improvements in clinical outcomes with a reduction in DFI. As this study utilized discarded, non-clinical samples, clinical outcomes data are not available. WIDER IMPLICATIONS OF THE FINDINGS While microfluidic sorting of unprocessed semen allowed for the selection of clinically usable, highly motile sperm with nearly undetectable levels of DNA fragmentation, standard processing by density-gradient centrifugation with swim-up did not increase DNA fragmentation in an infertile population. The proposed microfluidic technology offers a flow-free approach to sort sperm, requiring no peripheral equipment or filtration step, while minimizing hands-on time. STUDY FUNDING/COMPETING INTEREST(S) No external funding to declare. Utkan Demirci, PhD is the Co-founder and Scientific Advisor for DxNow Inc., LevitasBio Inc. and Koek Biotech. Mitchell Rosen, MD is a member of the Clinical Advisory Board for DxNow Inc.