calcimycin and Infertility

Phthalic acid esters (PAEs) are recognized endocrine disruptors. Detection of PAEs in semen from idiopathic infertile males suggests possible direct mechanisms of sperm toxicity. In this study we aimed to correlate sperm function with semen levels of PAEs. Semen samples were obtained from 100 male patients attending the Unit of Andrology and Reproductive Medicine, University Hospital of Padova, (Italy), 22 of which having a recognized history of idiopathic infertility. Compared to fertile subjects, infertile patients showed reduced levels of acrosome reaction (AR), evaluated by CD46 staining upon progesterone (P4) triggering (p < 0.001). Subjects showing positive detection of PAEs in semen, evaluated by liquid chromatography-mass spectrometry (LC-MS), were significantly more represented in those reporting an history of infertility (13 out of 22), compared to fertile subjects (25 out of 78, P = 0.0266). In vitro sperm exposure to PAEs showed that lipophilic PAE representative Di-n-octyl phthalate (DNOP) had higher cell accumulation and inhibition of P4-induced AR than less lipophilic PAE representative Dibutyl phthalate (DBP). Computer-based binding analysis and fluorimetric inhibition assay, showed that both DNOP and DBP had similar Phospholipase-A2 (PLA

Topics: Arachidonic Acid; Calcimycin; Calcium Ionophores; Dibutyl Phthalate; Endocrine Disruptors; Esters; Humans; Infertility; Male; Phospholipases; Phospholipases A2; Progesterone; Semen; Signal Transduction; Spermatozoa

Does calcium ionophore treatment of oocytes improve fertilization rate, embryo development and outcomes in specific groups of infertile couples?. This retrospective cohort study involved 796 couples undergoing oocyte activation with calcium ionophore (A23187) after intracytoplasmic sperm injection (ICSI) between 2016 and 2018. All metaphase II oocytes were exposed to 5 μmol/l ionophore for 15 min immediately after ICSI, cultured in vitro to the blastocyst stage, and transferred to the uteri of recipients on day 5 or cryopreserved for transfer in the next cycle. The previous cycles of the same patients formed the control group.. Among 1261 ICSI cycles and 796 ICSI-artificial oocyte activation (ICSI-AOA) cycles, implantation, positive beta-HCG, clinical pregnancy and live birth rates were significantly (P < 0.05 to P < 0.001) improved for all groups, compared with previous cycles, except live birth rate in women with primary ovarian insufficiency (POI). Compared with previous cycles, rates of blastulation (all P < 0.001) and high-quality blastocysts (P < 0.05 to P < 0.001) were increased significantly for couples with male factor (oligoasthenoteratozoospermia [OAT]), unexplained infertility and couples with both factors in the ICSI-AOA cycles. High-quality blastocyst rate was increased in couples with polycystic ovary syndrome (PCOS) (P = 0.0453). Miscarriage rates were decreased significantly (P < 0.05 to P < 0.001) in couples with OAT, PCOS and unexplained infertility in the treatment cycles. No significant differences were found for fertilization rate, embryo development or live birth rate in patients with POI between both groups.. Artificial oocyte activation was able to 'rescue' the poor reproductive outcomes in certain types of infertile couples with history of failure to achieve pregnancy.

Topics: Adult; Birth Rate; Calcimycin; Calcium Ionophores; Embryo Transfer; Female; Fertilization in Vitro; Humans; Infertility; Live Birth; Male; Oocyte Retrieval; Oocytes; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome

To evaluate the impact of artificial oocyte activation (AOA) in pregnancy and neonatal outcomes in infertile patients undergoing cryopreserved embryo transfer.. This retrospective study included 5686 patients' transferred embryos from routine intracytoplasmic sperm injection (ICSI) and 194 patients' transferred embryos from ICSI combined with AOA (ICSI-AOA) from January 2011 to December 2016. Pregnancy and neonatal outcomes of couples undergoing routine ICSI or ICSI-AOA were analyzed before and after propensity score matching. Artificial oocyte activation was performed with ionomycin.. The pregnancy outcomes showed no significant difference in the rates of biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live births between the routine ICSI and ICSI-AOA groups before and after propensity score matching, respectively. The assessment of neonatal outcomes showed no statistically significant differences in the birth defect rate, birth weight, gestational age, preterm birth rate, early-neonatal death rate, and fetal sex ratio between the two groups, and similar results were also observed in the two matched cohorts.. Artificial oocyte activation with ionomycin does not adversely affect pregnancy and neonatal outcomes in patients undergoing frozen-thawed embryo transfer, which is beneficial to clinicians counseling patients on the risks of artificial oocyte activation.

Topics: Abortion, Spontaneous; Adult; Birth Rate; Calcimycin; Calcium Ionophores; Cell Culture Techniques; Cryopreservation; Embryo Implantation; Embryo Transfer; Female; Humans; Infertility; Live Birth; Male; Oocytes; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Pregnancy, Multiple; Retrospective Studies; Risk Assessment; Sperm Injections, Intracytoplasmic

To assess the effect of two assisted oocyte activation (AOA) protocols with the use of two calcium (Ca(2+)) ionophores, ionomycin and A23187 (calcimycin), on the intracellular Ca(2+) level in mouse and human oocytes and the fertilization rates.. Comparison of two Ca(2+) ionophores, ionomycin and A23187, regarding their capacity to increase the intracellular Ca(2+) level and to support subsequent oocyte activation and development.. University hospital research laboratory.. Patients undergoing intracytoplasmic sperm injection (ICSI) treatment and B6D2F1 mice.. Assisted oocyte activation and microinjection of mouse and human oocytes with sperm.. Measurement of the fertilizing and Ca(2+)-releasing ability of human sperm.. Ionomycin was more potent than A23187 in provoking Ca(2+) increases in both mouse and human oocytes with significantly higher amplitude and area under the receiver operating characteristic curve. The oocyte activation rate was significantly higher when mouse oocytes were activated with the use of the ionomycin- rather than the A23187-based AOA protocol. Furthermore, oocyte activation rate was higher when human in vitro matured oocytes were activated with the ionomycin-based AOA protocol, but the difference did not reach statistical significance.. In both mouse and human oocytes, the AOA protocol that used ionomycin was more efficient than the one that used A23187. Bearing in mind that mammalian fertilization is successful when the total dose of Ca(2+) released reaches a minimal threshold, the use of ionomycin for human AOA might be justified instead of the use of A23187.

Topics: Adult; Animals; Calcimycin; Calcium Ionophores; Calcium Signaling; Cells, Cultured; Embryo Culture Techniques; Female; Fertility; Fertility Agents, Female; Fertilization; Humans; In Vitro Oocyte Maturation Techniques; Infertility; Ionomycin; Male; Mice; Oocytes; Sperm Injections, Intracytoplasmic; Time Factors; Treatment Failure

To investigate the relationship between sperm acrosome reaction (AR) and the clinical pregnancy rate of intrauterine insemination (IUI).. We detected the sperm spontaneous AR rate and Ca2+ ionophore A23187-induced AR rate in 128 patients who accepted IUI treatment, collected their clinical data and analysed the relationship between sperm AR rate and clinical pregnancy rate of IUI.. There was no statistical difference between the spontaneous AR rates in the pregnant group and the non-pregnant group (7.7% vs. 7.0%, P>0.05), but there was statistical difference between the induced AR rates(51.9 % vs. 43.5%, P<0.05). There was statistical difference in the clinical pregnancy rate among the 3 IUI groups divided by induced AR rate (≤20.0%, 20.1%-49.9%, and ≥50.0%; 4.8% vs. 12.5% vs. 18.6%, P<0.05).. The spontaneous AR rate has nothing to do with the clinical pregnancy rate of IUI, but the induced AR rate is associated with the clinical pregnancy rate of IUI.

Topics: Acrosome Reaction; Adult; Calcimycin; Female; Humans; Infertility; Insemination, Artificial, Homologous; Male; Pregnancy; Pregnancy Rate; Spermatozoa

Fertilization failure following standard in vitro fertilization in couples with normozoospermic men is an as yet unexplained phenomenon. A wide range of gametic disorders as well as environmental factors might contribute to this pathologic condition. One crucial condition appears to be the inability of the spermatozoa to undergo the acrosome reaction (AR). A discriminative test to distinguish fertile from non-fertile spermatozoa would be of utmost interest. In a prospective study, semen samples from men with normal semen parameters and fertilization failure were compared with semen samples from men with normal semen parameters and normal fertilization as to their capacity to undergo the AR. AR was induced using calcium ionophore as well as the physiologic stimuli progesterone and prostaglandin E(1). Discriminance analyses were undertaken to help identify patients with probable fertilization failure. Our data show that in patients with fertilization failure, the capacity of spermatozoa to undergo induced AR is greatly reduced using both unphysiologic and physiologic stimuli. However, physiologic stimuli are more suitable to identify patients with fertilization failure. Using physiologic stimuli, a formula was established to identify patients likely to fail at fertilization.

Topics: Acrosome Reaction; Alprostadil; Calcimycin; Case-Control Studies; Contraindications; Female; Fertilization in Vitro; Humans; Infertility; Male; Progesterone; Sperm Injections, Intracytoplasmic; Spermatozoa; Treatment Outcome

To examine whether fertilization rates after intracytoplasmic sperm injection can be increased by artificial oocyte activation.. Oocytes that failed to fertilize spontaneously by 24 hours after intracytoplasmic sperm injection were treated either with calcium ionophore to induce activation or with solvent only to serve as control. The ability of ionophore-treated and control oocytes to achieve delayed fertilization was compared.. Private hospital and public research center.. Infertile couples treated by intracytoplasmic sperm injection.. Intracytoplasmic sperm injection.. Fertilization and cleavage rates.. The mean rate of spontaneous fertilization after intracytoplasmic sperm injection was 32%, but 88% of the oocytes that failed to fertilize spontaneously did so after subsequent exposure to calcium ionophore. Most of these oocytes underwent at least one apparently normal cleavage division. In contrast, delayed fertilization of oocytes not treated with ionophore was an exceptional finding. If only oocytes remaining intact after intracytoplasmic sperm injection are taken into account, the mean global fertilization rate of ionophore-enhanced intracytoplasmic sperm injection was 91%.. These results show that the failure of oocyte activation is the main cause of fertilization failure after intracytoplasmic sperm injection. If an appropriate, clinically applicable treatment is found to overcome this problem, intracytoplasmic sperm injection can be expected to yield fertilization rates far exceeding those of standard IVF with normal spermatozoa.

Topics: Adult; Calcimycin; Cytoplasm; Female; Fertilization in Vitro; Humans; Infertility; Male; Microinjections; Middle Aged; Oocytes; Spermatozoa; Zygote

Topics: Acrosome; Animals; Biological Assay; Calcimycin; Colloids; Cricetinae; Cytoplasm; Ficoll; Humans; Infertility; Insemination, Artificial; Male; Microinjections; Pentoxifylline; Povidone; Silicon Dioxide; Sperm Motility; Zona Pellucida