In vitro inhibition of uterine contractions using electrospun nanofibers loaded with nifedipine and ML7.

OBJECTIVE: To formulate a nanofiber-based controlled drug delivery system that could be effective in preventing uterine contractions and can be used for the treatment of preterm labor. PATIENTS AND METHODS: We utilized uterine tissue samples obtained from ten pregnant women who underwent cesarean section at term to investigate the effect of nanofibers on spontaneous and induced myometrial contractions. We prepared nifedipine and ML7-loaded nanofibers using the electrospinning method with Poly(D,L-lactide-co-glycolide) (PLGA) polymer, resulted in seven groups of nanofibers, including a control group. Group I served as the control, Group II was non-drug loaded nanofiber, Group III was nifedipine (10-5 M) loaded nanofiber, Group IV was ML7 (3x10-5 M) loaded nanofiber, Group V was ML7 (3x10-5 M) and nifedipine (10-5 M) nanofiber, Group VI was ML7 (3x10-5 M) and nifedipine (3x10-5 M) nanofiber, and Group VII was ML7 (3x10-5 M) and nifedipine (10-4 M) nanofiber. To evaluate the contractile response, the nanofibers loaded with different doses of ML7 and nifedipine were applied onto the tissue strips, and in vitro organ bath experiments were performed. Full-thickness uterine samples were cleared of the serosa and surrounding tissues, and eight strips (3x10 mm) were prepared from each sample. The seven different nanofiber formulations were gently placed and sutured onto the strips, with one strip always kept as the time control. We recorded spontaneous, KCl-induced, and stimulated cumulative oxytocin-induced contractions from all samples in all groups. After completing all experiments, the viability of the strips was checked, and weight measurement was recorded. RESULTS: The administration of drug-loaded polymers resulted in a significant decrease in both the frequency and intensity of spontaneous and induced contractions in all groups (p<0.01). No significant difference was observed between the control group and the non-drug-loaded nanofiber group in post hoc analysis (p=0.704). In terms of amplitude and frequency of contractions, the most significant decrease was observed in group VII at cumulative oxytocin doses compared to the control and non-drug-loaded nanofiber groups (p<0.05). Moreover, group VI also showed a significant decrease in contraction intensity and frequency compared to the control and non-drug-loaded nanofiber groups (p<0.05). While the use of nifedipine and/or ML7-loaded nanofibers decreased both intensity and frequency of contraction, this attenuation was not significant compared to the control and empty polymer groups. However, a more significant inhibition was observed when ML7 was used with nifedipine at doses of 3x10-5 M and 10-4 M. CONCLUSIONS: The results indicate that human uterine contractions can be inhibited using calcium channel blocker (nifedipine) and myosin light chain kinase inhibitor (ML7) loaded nanofibers in uterine tissue strips. These results strongly suggested the potential for the development of locally effective and safe controlled drug release systems to prevent premature birth.

Role of telocytes in the pathogenesis of ectopic pregnancy.

OBJECTIVE: The aim of this study is to investigate the effect of telocytes on tubal motility in ectopic pregnancies. PATIENTS AND METHODS: This study included patients with ectopic pregnancy (EP) (n=10) and control patients (n=10) (partial salpingectomy for contraception). Immunohistochemical staining for c-Kit, vimentin, CD34 and S100A was performed to quantify telocytes in the mucosa, muscular layer and serosa of fallopian tubes of control and EP group. Spontaneous and KCl- (80 mM) induced contraction and cumulative progesterone dose-relaxation (10-11-10-5 M) and cumulative oxytocin dose-contraction (10-10-10-4 M) responses were recorded. RESULTS: The groups were comparable in terms of age, gravida, parity, delivery type and gestational week (p>0.05). The homogenous distribution of telocytes in the mucosa and muscular layers of the control group, changed to heterogeneous localization the EP group. Immunohistochemical staining with vimentin, S100A, c-Kit and CD34, revealed increased telocyte counts in the muscular layer and serosa of the tubal tissues of EP. The frequency of the spontaneous contractions was higher in the control group (p<0.001); contrarily, the amplitude of the contractions was higher in ectopic pregnancies (p<0.001). Although the cumulative oxytocin dose-contraction curves were similar at all concentrations (p>0.05), the cumulative progesterone dose-relaxation curves exhibited higher relaxation response in the EP group at all concentrations (p<0.001). CONCLUSIONS: Increased telocyte count in the fallopian tube may decrease tubal motility and may affect the transfer of the blastocyst to the uterus and possibly contribute to the pathogenesis of EP.

Reproductive performance after hysteroscopic metroplasty in infertile women: complete versus partial uterine septum.

OBJECTIVE: To investigate the impact of hysteroscopic metroplasty on pregnancy outcome in women with complete or incomplete uterine septum (US) accompanying infertility. MATERIALS AND METHODS: Seventy-three patients who had hysteroscopic metroplasty for complete and incomplete US with primary and secondary infertility were reviewed. Obstetric outcomes (number of pregnancies, live births, and miscarriages) up to 36 months follow up period were investigated. RESULTS: Twenty-five patients in complete US and 28 patients in incomplete US became pregnant in 36 months follow up. Postoperative miscarriage rate was significantly lower in patients with complete US (p = 0.0001,p = 0.0001, respectively). The mean gestational week at the time of birth and mean birth weight of the in- fants were significantly lower in patients with complete US compared to the incomplete US cases (p = 0.026, p = 0.049, respectively). Postoperative pregnancy rate was significantly lower in incomplete US patients with primary infertility compared with secondary in- fertility (p = 0.037). CONCLUSION: Hysteroscopic metroplasty improves fertility and pregnancy performance. This improvement is more prominent in patients with complete US, and incomplete US patients with secondary infertility.