Current therapeutic medicines for endometriosis cannot be administered during assisted reproductive technology (ART) because they have bad effects during pregnancy. In this study, we created an animal model of endometriosis and evaluated the therapeutic effect of progestin (Dienogest), dopamine agonist (Cabergoline), and their combination (Dienogest + Cabergoline). We established a mouse model mimicking human endometriosis. The mice with endometriosis were then treated with a single drug (Dienogest or Cabergoline) or both drugs (Dienogest + Cabergoline) for 14 days. An immunohistological study was then performed to analyze inflammatory lesions in the recipient mice. Real-time polymerase chain reaction (RT-PCR) and Western blotting were also performed to determine the levels of genes and proteins in inflammatory lesions to assess the recovery of endometriosis. Histologic staining showed that all medication groups showed a clear decrease in the inflammatory phenotype in the uterus, peritoneum, and intestine. Gene and protein expression analysis showed a therapeutic effect in all medication groups. In conclusion, Cabergoline had a therapeutic effect similar to that of Dienogest and could be used as an alternative to Dienogest during ART for patients with infertility; compared to the individual drugs, the combination treatment has a synergistic effect on endometriosis.

This study is designed to investigate the effects of increased progesterone (P4) levels on the quality of retrieved oocytes and embryos during IVF. This retrospective analysis included 982 all-freezing in vitro fertilization (IVF) cycles (conducted between November 2019 and June 2020 at CHA Fertility Center Bundang, South Korea) in which serum P4 levels were measured on the day of human chorionic gonadotropin (hCG) administration. Our study revealed that the serum P4 levels on the day of hCG administration are strongly associated with the rates of oocyte maturation, displaying a positive correlation in patients with serum P4 < 2.25 ng/mL (p = 0.025). Moreover, patients with serum P4 < 1.25 ng/mL showed relatively low fertilization rates (p = 0.037), and the rates of good embryo retrieval were significantly increased with the serum P4 level < 1.5 ng/mL (p = 0.001). Interestingly, serum P4 level on the day of hCG administration affects the rate of good-quality embryo development, especially at the cleavage stage, and is associated with the status of ovarian responses. Our current study suggests that serum P4 level on the day of hCG administration negatively affects the rates of oocyte maturation, fertilization, and the development of good embryos.

Objective: Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation.Methods: Morphological alterations depending on the status of PFN1 expression were assessed in PFN1-depleted or control cells grown on Matrigel-coated cover glass. Day-5 mouse embryos were cocultured with Ishikawa cells. Comparisons of the rates of F-actin formation and embryo attachment were performed by measuring the stability of the attached embryo onto PFN1-depleted or control cells.Results: Depletion of PFN1 in endometrial epithelial cells induced a significant reduction in cell-cell adhesion displaying less formation of colonies and a more circular cell shape. Mouse embryos co-cultured with PFN1-depleted cells failed to form actin cytoskeletal networks, whereas more F-actin formation in the direction of surrounding PFN1-intact endometrial epithelial cells was detected. Furthermore, significantly lower embryo attachment stability was observed in PFN1-depleted cells than in control cells. This may have been due to reduced endometrial receptivity caused by impaired actin cytoskeletal networks associated with PFN1 deficiency.Conclusion: These observations definitively demonstrate an important role of PFN1 in mediating cell-cell adhesion during the initial stage of embryo implantation and suggest a potential therapeutic target or novel biomarker for patients suffering from implantation failure.

We aimed to assess the efficacy of accumulated embryo transfer (ACC-ET) through several controlled ovarian hyperstimulation (COS) cycles to increase the rates of pregnancy in patients with poor ovarian response (POR). We retrospectively reviewed the medical records of 588 patients with POR under 43-years old who underwent embryo transfer from January 2010 to December 2015. We compared the pregnancy rate (PR), clinical pregnancy rate (CPR), and live birth rate (LBR) between ACC-ET (frozen-thawed: 47; fresh + frozen-thawed: 24) group (n = 71) and fresh ET groups (n = 517). Characteristics of ACC-ET patients were similar to those of fresh ET groups (Age: 38.1 ± 3.5 vs. 38.2 ± 3.7, p = 0.88; Anti Müllerian Hormone (AMH; ng/mL): 0.5 ± 0.4 vs. 0.6 ± 0.6, p = 0.38; follicle stimulating hormone (FSH: mIU/mL): 11.9 ± 8.0 vs. 10.8 ± 9.0, p = 0.35). The total number of transferred embryos (3.1 ± 0.9 vs. 1.5 ± 0.7, p = 0.00), PR (29.6% (21/71) vs. 18.8% (97/517), p = 0.040), and CPR (23.5% (16/68) vs. 14.0% (71/508) p = 0.047) were significantly higher in the ACC-ET group than in the fresh ET group. In addition, PR, CPR, and LBR increased with the number of ET in the fresh ET group. However, there were no significant differences observed in LBR between ACC-ET and fresh ET groups (14.9% (10/67) vs. 9.8% (50/508), p = 0.203). From our knowledge, there is no clinical evidence reported to prove that transfer of multiple embryos of adequate quality obtained through multiple cycles can compensate for the limited number of retrieved oocytes from POR patients. We concluded that ACC-ET from several COS cycles could be an alternative method to increase PR and CPR in <43-year-old patients with POR.

Baeck JH, et al. Investig Clin Urol. 2022 Nov;64:e2. https://doi.org/10.4111/icu.20220253