Rie Ozaki

Association between uterine repair at laparoscopic myomectomy and postoperative adhesions

Objective. To determine whether uterine repair at laparoscopic myomectomy influences postoperative adhesions. Design. Retrospective study. Setting. University‐affiliated hospital. Population. A total of 108 patients who underwent second‐look laparoscopy after laparoscopic myomectomy without concomitant pelvic surgery between January 2006 and May 2010. Methods. Absorbable cellulose adhesion barriers were used for uterine repair at initial surgery in all women. The presence of adhesions was evaluated by second‐look laparoscopy. Main outcome measures. The influence of background factors (diameter of largest myoma, number of myomas, incision sites and number of suture layers) and the uterine status immediately after uterine repair at laparoscopic myomectomy (number, length and location of wounds, as well as wound appearance classified as virtually normal, swollen or protruding) on adhesion formation were analysed in 108 women with 296 uterine wounds. Data were analysed by logistic regression analysis. Results. Forty‐one (38.0%) women had adhesions to their uterus at follow up. We identified 48 (16.2%) adhesions among 296 wounds in all women. A protruding wound was significantly associated with postoperative wound adhesion (odds ratio, 2.53; p=0.02). The number of enucleated subserosal myomas (odds ratio, 3.29; p<0.001) and the diameter of the largest myoma (odds ratio, 1.05; p<0.001) were significantly associated with wound protrusion, which was a critical factor influencing adhesion. Conclusions. Postoperative wound adhesion formation seems to depend on uterine status immediately after laparoscopic myomectomy.

Feasibility of laparoscopically assisted extracorporeal cystectomy via single suprapubic incision using an adjustable-view laparoscope to treat large benign ovarian cysts: comparison with conventional procedure

OBJECTIVE To demonstrate the feasibility of minimally invasive surgery using a novel optical device to treat large benign ovarian cysts and to compare the safety of the procedure with that of conventional laparoscopically assisted multiport extracorporeal cystectomy. STUDY DESIGN Twenty-one patients with large benign ovarian cysts underwent laparoscopically assisted extracorporeal ovarian cystectomy via a single suprapubic incision using a novel 10-mm rigid laparoscope with an adjustable direction of view and a multiport device, between October 2010 and July 2012. The surgical outcomes were retrospectively compared between these patients (Group A) and 32 patients who underwent the conventional 3-port laparoscopically assisted extracorporeal procedure between January 2009 and September 2010 (Group B). Data were statistically analyzed using the Mann-Whitney U-test or Fishers exact test. RESULTS None of Group A required conversion to conventional multiport laparoscopy. The total duration of surgery, elapsed time between skin incision and the start of pneumoperitoneum, and time required for intra- and extra-corporeal manipulations did not significantly differ between the groups. The time required for skin closure, however, was significantly decreased in Group A compared with Group B (13.0 ± 3.5 vs. 20.2 ± 4.8 min, P=0.005). The volume of blood loss and postoperative blood findings were similar to those associated with the conventional procedure. Postoperative visual analog pain scales at 3h were significantly lower in Group A than in Group B (3.7 ± 2.6 vs. 4.8 ± 2.0, P=0.04). Postoperative complications did not arise after either procedure. CONCLUSION Laparoscopically assisted extracorporeal cystectomy via a single suprapubic incision is a feasible and safe alternative to conventional multiport cystectomy for treating large benign ovarian cysts.

Reprogramming of the retinoic acid pathway in decidualizing human endometrial stromal cells

Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively. Furthermore, the expression of RAR, the receptor that mediates the pro-apoptotic effects of RA, was also inhibited. By contrast, PPARβ/δ, which transduces the differentiation responses of RA, was upregulated. Decidualization was also associated with increased expression of retinol-binding protein 4 (RBP4) and various enzymes involved in the metabolism of RA and its precursor, retinaldehyde (Rald), including CYP26A1, DHRS3, and RDH12. Exposure of differentiating HESCs to RA or Rald reversed the inhibition of the CRABP2-RAR pathway, perturbed the expression of decidual marker genes and triggered cell death. Taken together, the data demonstrate that decidualizing HESCs silence RA signaling by downregulating key cytoplasmic binding proteins and by increasing retinoid metabolism. However, excessive RA exposure is toxic for decidual cells and triggers a response that may lead to pregnancy failure.

Minimum ovarian stimulation involving combined clomiphene citrate and estradiol treatment for in vitro fertilization of Bologna‐criteria poor ovarian responders

The aim of this study was to assess the efficacy of a minimal ovarian stimulation involving combined clomiphene citrate (CC) and estradiol (E2) administration for poor responders with diminished ovarian reserve (DOR).

Vitamin D Regulates Maternal T-Helper Cytokine Production in Infertile Women

Vitamin D (VD) deficiency is associated with reproductive failure. However, the relationship between VD and maternal immunity remains unclear. We investigated the clinical efficacy of VD in maternal T-helper (Th) cytokines in 276 infertile women and examined for Th1 and Th2 cells based on the deficient, insufficient, and sufficient serum 25-hydroxyvitamin D3 (25[OH]VD) levels (<12, 12–30, and >30 ng/mL, respectively). Most infertile women had a low-level of VD (87.3%). Immunological tests of pre-/post-VD supplementation were performed in patients who were deficient and insufficient in VD. Of 23 patients, 11 (47.8%) exhibited sufficient VD levels after supplementation. Th1/Th2 cell ratio in patients with insufficient VD was significantly decreased after supplementation (p = 0.004). After supplementation, serum 25(OH)VD levels of the patients: 11 in the sufficient group showed significant decreases in Th1 cell level and Th1/Th2 cell ratio (p = 0.032 and 0.010, respectively), whereas no significant differences in Th1/Th2 cell ratio were recognized in the insufficient group. Furthermore, mid-luteal endometrial biopsies (n = 18) were processed for primary cultures and measured interferon [IFN]-γ and interleukin [IL]-4 in condition media. Decidualizing cultures with 1,25-dihydroxvitamin D3 (1,25[OH]2VD) decreased IFN-γ. Sufficient VD supplementation in women with insufficient VD may optimize maternal T-helper cytokines during pregnancy via rebalancing the Th1/Th2 cell ratio.

Surgical Treatments for Adenomyosis

The objective of this prospective study performed at Juntendo University School of Medicine was to evaluate a novel method of laparoscopic adenomyomectomy (LA). The subjects were 76 women with adenomyosis who wished to conserve fertility.

Reciprocal changes of H3K27ac and H3K27me3 at the promoter regions of the critical genes for endometrial decidualization

AIM Decidualization is essential for embryo implantation and placental development. We aimed to obtain transcriptome and epigenome profiles for primary endometrial stromal cells (ESCs) and in vitro decidualized cells. MATERIALS & METHODS ESCs isolated from human endometrial tissues remained untreated (D0), or decidualized for 4 days (D4) and 8 days (D8) in the presence of 8-bromo-cAMP and progesterone. RESULTS Among the epigenetic modifications examined (DNA methylation, H3K27ac, H3K9me3 and H3K27me3), the H3K27ac patterns changed most dramatically, with a moderate correlation with gene expression changes, upon decidualization. Subsets of up- and down-regulated genes upon decidualization were associated with reciprocal changes of H3K27ac and H3K27me3 modifications at their promoter region, and were enriched with genes essential for decidualization such as WNT4, ZBTB16, PROK1 and GREB1. CONCLUSION Our dataset is useful to further elucidate the molecular mechanisms underlying decidualization.