The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats†.

A decellularized uterine scaffold (DUS) prepared from rats permits recellularization and regeneration of uterine tissues when placed onto a partially excised uterus and supports pregnancy in a fashion comparable to the intact uterus. The underlying extracellular matrix (ECM) together with an acellular, perfusable vascular architecture preserved in DUS is thought to be responsible for appropriate regeneration of the uterus. To investigate this concept, we examined the effect of the orientation of the DUS-preserving ECM and the vascular architecture on uterine regeneration through placement of a DUS onto a partially defective uterine area in the reversed orientation such that the luminal face of the DUS was outside and the serosal face was inside. We characterized the tissue structure and function of the regenerated uterus, comparing the outcome to that when the DUS was placed in the correct orientation. Histological analysis revealed that aberrant structures including ectopic location of glands and an abnormal lining of smooth muscle layers were observed significantly more frequently in the reversed group than in the correct group (70% vs. 30%, P < 0.05). Despite the changes in tissue topology, the uteri regenerated with an incorrectly oriented DUS could achieve pregnancy in a way similar to uteri regenerated with a correctly oriented DUS. These results suggest that DUS-driven ECM orientation determines the regenerated uterus structure. Using DUS in the correct orientation is preferable when clinically applied. The disoriented DUS may deteriorate the tissue topology leading to structural disease of the uterus even though the fertility potential is not immediately affected.

Impact of borderline-subclinical hypothyroidism on subsequent pregnancy outcome in women with unexplained recurrent pregnancy loss.

AIM: Because subclinical hypothyroidism (thyroid-stimulating hormone [TSH] > 4.5 IU/mL) is associated with adverse pregnancy outcome, including early pregnancy loss, TSH is recommended to be titrated to ≤2.5 mIU/L in levothyroxine-treated women before pregnancy. The purpose of this study was to determine whether borderline-subclinical hypothyroidism (borderline-SCH; 2.5 < TSH ≤ 4.5 IU/mL) affects the outcome of subsequent pregnancies in women with unexplained recurrent pregnancy loss (uRPL). METHODS: After workup for antinuclear antibody (ANA), anti-phospholipid syndrome, thrombophilia, uterine abnormalities, hormone disorders, and/or chromosomal abnormalities, 317 women with a history of uRPL were enrolled. The women were classified into two groups: borderline-SCH, and euthyroidism (0.3 ≤ TSH ≤ 2.5 IU/mL). All women had normal serum free thyroxine (T4) and did not receive levothyroxine before or during the subsequent pregnancy. RESULTS: There were no significant differences in age, number of previous pregnancy losses, number of live births, or body mass index between the borderline-SCH (n = 56) and the euthyroid (n = 261) groups, but the rate of ANA positivity differed significantly (53.6% vs 33.7%, respectively; P = 0.005). The subsequent pregnancy rate did not differ between the two groups (55.4%, 31/56 vs 51.3%, 134/261, respectively). The pregnancy loss rate (<22 weeks of gestation) tended to be higher in the borderline-SCH than the euthyroid group (29.0%, 9/31 vs 17.9%, 24/134), although not significantly so (P = 0.16). CONCLUSIONS: Although some subset of uRPL is though to be due to as-yet-unidentified cause(s), borderline-SCH is unlikely to be involved in uRPL.

Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial.

PURPOSE: Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC. METHODS: This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy. RESULTS: Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events. CONCLUSIONS: Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

How to Create an Embryo Penetration Route.

Numerous past investigations into human implantation have tended to pay attention to the mechanism of embryo adhesion to endometrial cells or embryo invasion into endometrial stromal tissue. For successful pregnancy, however, embryo penetration through the endometrial epithelial cell (EEC) sheet is also absolutely required. To improve the performance of assisted reproductive technology, implantation studies should also focus on EEC dynamics, in particular, the action of EECs during embryo penetration. Although only EEC apoptosis has been proposed as a mechanism for the formation of the embryo penetration route, we have also recently reported that characteristic EEC collective motion, regulated by the epithelial to mesenchymal transition, also plays a key role in permitting embryo penetration. We review here how EECs form embryo penetration routes in light of our findings.