Fresh versus frozen-thawed blastocyst transfer in high responders

Objective: This study aimed to investigate and compare the pregnancy and live birth rates in IVF cycles of frozen-thawed embryo transfers and fresh embryo transfers in a group of women with a high risk of Ovarian hyperstimulation syndrome (OHSS). Material and methods: The study group consisted of 254 women with a high level of response to controlled ovarian hyperstimulation. The patients who received fresh cycle embryo transfers with calcium infusions are referred to as the Fresh Ca+ group, and those without the calcium therapy are called the Fresh Ca- group; and we used correspondingly similar terminology for the Frozen group. Results: We observed no statistically significant differences between the cycles of fresh and frozen-thawed embryo transfers in patients with a high risk of OHSS in terms of implantation, clinical pregnancy, and live birth rates. Furthermore, these implantation, clinical pregnancy and live birth rates were not different in the cycles with or without calcium treatment. There was no statistical difference in the OHSS rates between the fresh and frozen-thawed cycles; although, the OHSS rates were less in the two calcium infusion groups (Fresh Ca+ and Frozen-thawed Ca+) than in the without-calcium group. There was no OHSS development in the subjects of the Frozen-thawed Ca+ group. Conclusion: Our study results suggest that fresh and frozen-thawed embryo transfers have similar IVF results in patients with a high risk of OHSS. Calcium infusion is beneficial in preventing OHSS without altering pregnancy rates. Both IVF protocols with calcium infusion can safely be applied in high-responder patients without lowering success rates

Drug discovery for male subfertility using high-throughput screening:a new approach to an unsolved problem

STUDY QUESTIONCan pharma drug discovery approaches be utilized to transform investigation into novel therapeutics for male infertility?SUMMARY ANSWERHigh-throughput screening (HTS) is a viable approach to much-needed drug discovery for male factor infertility.WHAT IS KNOWN ALREADYThere is both huge demand and a genuine clinical need for new treatment options for infertile men. However, the time, effort and resources required for drug discovery are currently exorbitant, due to the unique challenges of the cellular, physical and functional properties of human spermatozoa and a lack of appropriate assay platform.STUDY DESIGN, SIZE, DURATIONSpermatozoa were obtained from healthy volunteer research donors and subfertile patients undergoing IVF/ICSI at a hospital-assisted reproductive techniques clinic between January 2012 and November 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSA HTS assay was developed and validated using intracellular calcium ([Ca2+]i) as a surrogate for motility in human spermatozoa. Calcium fluorescence was detected using a Flexstation microplate reader (384-well platform) and compared with responses evoked by progesterone, a compound known to modify a number of biologically relevant behaviours in human spermatozoa. Hit compounds identified following single point drug screen (10 μM) of an ion channel-focussed library assembled by the University of Dundee Drug Discovery Unit were rescreened to ensure potency using standard 10 point half-logarithm concentration curves, and tested for purity and integrity using liquid chromatography and mass spectrometry. Hit compounds were grouped by structure activity relationships and five representative compounds then further investigated for direct effects on spermatozoa, using computer-assisted sperm assessment, sperm penetration assay and whole-cell patch clamping.MAIN RESULTS AND THE ROLE OF CHANCEOf the 3242 ion channel library ligands screened, 384 compounds (11.8%) elicited a statistically significant increase in calcium fluorescence, with greater than 3× median absolute deviation above the baseline. Seventy-four compounds eliciting ≥50% increase in fluorescence in the primary screen were rescreened and evaluated further, resulting in 48 hit compounds that produced a concentration-dependent increase in [Ca2+]i. Sperm penetration studies confirmed in vitro exposure to two hit compounds (A and B) resulted in significant improvement in functional motility in spermatozoa from healthy volunteer donors (A: 1 cm penetration index 2.54, 2 cm penetration index 2.49; P &lt; 0.005 and B: 1 cm penetration index 2.1, 2 cm penetration index 2.6; P &lt; 0.005), but crucially, also in patient samples from those undergoing fertility treatment (A: 1 cm penetration index 2.4; P = 0.009, 2 cm penetration index 3.6; P = 0.02 and B: 1 cm penetration index 2.2; P = 0.0004, 2 cm penetration index 3.6; P = 0.002). This was primarily as a result of direct or indirect CatSper channel action, supported by evidence from electrophysiology studies of individual sperm.LIMITATIONS, REASONS FOR CAUTIONIncrease and fluxes in [Ca2+]i are fundamental to the regulation of sperm motility and function, including acrosome reaction. The use of calcium signalling as a surrogate for sperm motility is acknowledged as a potential limitation in this study.WIDER IMPLICATIONS OF THE FINDINGSWe conclude that HTS can robustly, efficiently, identify novel compounds that increase [Ca2+]i in human spermatozoa and functionally modify motility, and propose its use as a cornerstone to build and transform much-needed drug discovery for male infertility.</p

Systematic and standardized hysteroscopic endometrial injury for treatment of recurrent implantation failure

International audienceResearch question: To investigate the effect of hysteroscopic endometrial injury for treatment of recurrent implantation failure (RIF). Design: This prospective and randomized controlled trial included 239 patients who had failed to achieve a clinical pregnancy after the transfer of at least four good-quality embryos in a minimum of three fresh or frozen-thawed embryo transfer cycles and were under the age of 40 years, who were randomized into two groups. The injury group (n = 124) received endometrial injury during their hysteroscopic procedure, whereas the control group (n = 115) did not. Patients who had endometrial pathologies were excluded from the study. Results: There were no statistically significant differences in duration of gonadotrophin use (8.23 versus 8.30 days), total dose of gonadotrophins (2330 versus 2338 IU), number of oocytes (7.03 versus 8.21), number of mature oocytes (5.27 versus 6.02), number of fertilized oocytes (4.19 versus 4.55), number of good-quality embryos (2.07 versus 2.43), number of embryos transferred (1.97 versus 1.93) or endometrial thickness (9.04 versus 9.35 mm) between the injury group and control group, respectively. Clinical pregnancy rates (25.8% versus 15.6%, P = 0.047), live birth rates (21.8% versus 12.2%, P = 0.049) and implantation rates (14.2% versus 8.8%, P = 0.036) were significantly different, favouring the injury group. Conclusion: This study suggests that endometrial injury is beneficial in RIF patients to increase the odds of implantation, clinical pregnancy and live birth

Maternal nutrition and reproductive functions of female and male offspring

This study aimed to investigate the effects of maternal unhealthy nutrition on the reproductive functions of female and male adult offspring. This was an animal study carried out with 24 virgin female Wistar rats (dams) and their male and female offspring. Rats were divided standard diet (SD) or cafeteria diet (CD) groups, after 10 weeks of feeding, all rats were paired with a Wistar stud male, and each group was again divided into CD and SD groups during the pregnancy and lactation periods. After birth, six female and six male pups in each group, were subjected to study. Following 3 weeks of lactation, the pups were fed with SD for 8 weeks and killed when they were considered adult at 11th week for analysis. Primordial and antral follicle counts, serum anti-Mullerian hormone (AMH) and phosphatase and tensin homolog (PTEN) in the oocyte cytoplasm were examined to evaluate ovarian function, and E-cadherin and integrin-beta 1 levels were examined in endometrial tissues for the evaluation of endometrial receptivity in female offspring. Sperm analysis was performed in male offspring. In groups in which the dams were fed CD, primordial follicular pool, PTEN, and endometrial receptivity were reduced. In contrast, AMH and the number of antral follicles were not changed. In male offspring, the testicles were smaller, testosterone production decreased, AMH increased and the number and function of sperm were not changed. Sperm analysis results were not changed. All negative effects on reproductive functions were more apparent in groups fed with the CD during the pregestational period