Comparison of IVF and IVM outcomes in the same patient treated with a modified IVM protocol along with an oocytes-maturing system containing melatonin: A pilot study.

AIM: To compare embryonic developmental competence and clinical outcomes of oocytes matured in vivo (IVF oocytes) and those matured in vitro (IVM oocytes) from the same IVM/IVF cycles, and to analyze the clinical efficiency of a melatonin-supplemented in vitro maturation system combined with a modified IVM/IVF protocol. MAIN METHODS: We randomly recruited 22 patients undergoing IVM/IVF treatment protocol in our medical centre. The fertilization, cleavage and blastocyst formation rates, as well as clinical pregnancy, implantation and live birth/ongoing pregnancy rates were analysed and compared between IVF and IVM oocytes. We evaluated mitochondrial function indicators by fluorescence staining and confocal microscopy, including mitochondrial membrane potential, reactive oxygen species and calcium (Ca2+) levels in 15 IVF and 15 IVM oocytes. KEY FINDINGS: There were no significant differences in fertilization or blastocyst formation rates between the IVF and IVM groups, whereas the cleavage rate was significantly higher in the IVF versus IVM group (100% vs 93.4 ± 10.9%, p = 0.03). There were no significant differences in the clinical pregnancy, implantation or live birth/ongoing pregnancy rates between the two groups. The cumulative clinical pregnancy and ongoing pregnancy/live birth rate per pick-up oocyte in the IVM/IVF treatment cycles were 68.2% (15/22) and 54.5% (12/22), respectively. The reactive oxygen species and Ca2+ levels were significantly increased, and mitochondrial membrane potential was significantly decreased, in IVM compared with IVF oocytes. SIGNIFICANCE: The modified IVM/IVF protocol can be effectively applied to the treatment of some indicated patients and achieve ideal clinical outcomes, even though the developmental potential of IVM oocytes may not be as high as IVF oocytes.

Combination therapy with ropivacaine-loaded liposomes and nutrient deprivation for simultaneous cancer therapy and cancer pain relief.

Autophagy allows cancer cells to respond changes in nutrient status by degrading and recycling non-essential intracellular contents. Inhibition of autophagy combined with nutrient deprivation is an effective strategy to treat cancer. Pain is a primary determinant of poor quality of life in advanced cancer patients, but there is currently no satisfactory treatment. In addition, effective treatment of cancer does not efficiently relieve cancer pain, but may increase pain in many cases. Hence, few studies focus on simultaneous cancer therapy and pain relief, and made this situation even worse. Method: Ropivacaine was loaded into tumor-active targeted liposomes. The cytotoxicity of ropivacaine-based combination therapy in B16 and HeLa cells were tested. Moreover, a mice model of cancer pain which was induced by inoculation of melanoma near the sciatic nerve was constructed to assess the cancer suppression and pain relief effects of ropivacaine-based combination therapy. Results: Ropivacaine and ropivacaine-loaded liposomes (Rop-DPRL) were novelly found to damage autophagic degradation. Replicated administration of Rop-DPRL and calorie restriction (CR) could efficiently repress the development of tumor. In addition, administration of Rop-DPRL could relieve cancer pain with its own analgestic ability in a short duration, while repeated administration of Rop-DPRL and CR resulted in continuous alleviation of cancer pain through reduction of VEGF-A levels in advanced cancer mice. Further, dual inhibition of phosphorylation of STAT3 at Tyr705 and Ser727 by Rop-DPRL and CR contribute to the reduction of VEGF-A. Conclusion: Combination therapy with Rop-DPRL and nutrient deprivation simultaneously suppresses cancer growth and relieves cancer pain.

Gene expression profiling of human blastocysts from in vivo and 'rescue IVM' with or without melatonin treatment.

To evaluate the effect of melatonin supplementation in maturation medium for human 'rescue IVM' and investigate differences in transcriptomic profile of blastocysts developed from oocytes matured in vitro with/without melatonin treatment and in vivo, a total of 314 GV oocytes and 320 MI oocytes were collected from 200 patients younger than 35 years old undergoing ICSI cycle. The oocytes were randomly distributed in the control group (no melatonin) and four other groups of varying melatonin concentrations (10­11, 10­9, 10­7, 10­5 mol/l). Gene profiling was performed on blastocysts developed from in vivo maturation oocytes (in vivo group), and in vitro maturation (IVM) oocytes with an optimal concentration of melatonin treatment (IVM­anti group) or without melatonin (IVM group). The ratio of high quality blastocysts was significantly higher in the groups treated with 10­5 mol/l melatonin compared with others groups. The large­scale analysis of the transcriptome revealed significant differences in mRNA expression levels. In each group, nine blastocysts were selected for gene expression profiling. The differentially expressed genes were involved in cysteine and methionine metabolism, regulation of apoptotic process, mineral absorption, steroid hormone biosynthesis, Wnt signaling, p53 signaling pathway and other functions. The findings indicated that the IVM procedure may potentially affect DNA methylation and the canonical Wnt signaling pathway. Exogenous melatonin positively influenced quality of blastocysts, which may be mediated via upregulation of p53 signaling and correcting DNA methylation changes caused by 'rescue IVM'. However, this study reflected what was generally referred to as 'rescue IVM' and was not a true reflection of clinical IVM techniques. Therefore, melatonin required further investigation as a promising supplement for use in IVM.

Dehydroepiandrosterone plus climen supplementation shows better effects than dehydroepiandrosterone alone on infertility patients with diminished ovarian reserve of low-FSH level undergoing in-vitro fertilization cycles: a randomized controlled trial.

BACKGROUND: This study aimed to assess the effect of dehydroepiandrosterone (DHEA) plus climen (estradiol valerate and cyproterone acetate drug combination) on infertility patients with diminished ovarian reserve (DOR) and to determine if the combination of DHEA plus climen is superior to DHEA alone in improving ovarian response. METHODS: A total of 124 women were randomized into the DHEA group (n = 64) and the DHEA plus climen group (n = 60) for 12 weeks before being subjected to in-vitro fertilization (IVF) cycles. To investigate if there is a FSH-related difference on the effect of the addition of climen, the DHEA group and the DHEA plus climen group were further divided into four subgroups according to a basal FSH level cut-off of 10 mIU/ml. We performed a comparison of Day 3 blood samples before and after treatment and IVF outcome parameters, including AMH, FSH, E2, AFC, oocytes retrieved, MII oocyte numbers, embryo numbers and accumulated embryo scores. RESULTS: After 12 weeks of pretreatment, the DHEA plus climen group demonstrated a significantly higher level of AMH (P = 0.001) and a significantly lower level of FSH (P = 0.001) compared with the DHEA group. When the two groups were divided into four subgroups based on the FSH cut-off of 10 mIU/mL, a significant increase of AMH (P = 0.034) was found in the high-FSH DHEA plus climen group, whereas there was no significant difference in the high-FSH DHEA group (P = 0.322). A significantly higher accumulated score of embryos was observed in the low-FSH DHEA plus climen group compared with the low-FSH DHEA group (P = 0.034). CONCLUSIONS: These observations suggest that patients with DOR of a low-FSH level might benefit more from DHEA plus climen supplementation than from DHEA supplementation alone.