The aromatase inhibitor anastrozole is associated with favorable embryo development and implantation markers in mice ovarian stimulation cycles  Öznur Karaer, M.D., H. Seda Vatansever, M.D., Semra Oruç, M.D., Kemal Özbilgin, M.D., Serap Cilaker, M.D., M. Faik Koyuncu, M.D.  Fertility and Sterility  Volume 83, Issue 6, Pages 1797-1806 (June 2005) DOI: 10.1016/j.fertnstert.2005.01.100 Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Embryos obtained from the three study groups in the preimplantation period. (A) In group I, embryos were in the eight-cell stage; (B) in group II, embryos were in the two-cell stage; (C) no embryo was observed in group III. Original magnification, ×400. Karaer. Effect of anastrozole on implantation. Fertil Steril 2005. Fertility and Sterility 2005 83, 1797-1806DOI: (10.1016/j.fertnstert.2005.01.100) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Histologic evaluation of endometrium in the three groups in the implantation stage by hematoxylin-eosin staining. (A) In group I, embryos were implanted, and polygonal decidual cells containing abundant glycogen and lipid were noted. Although we collected the embryos at the E2.5–3 stage, they were surprisingly consistent with stage E5–5.5 embryos. (B) In group II, although implantation did not take place, a clump of embryonic cells were detected in the horn cavity. Endometrial glands containing glycogen and tortuous coiling were characteristic of the secretory phase. (C) In group III, properties of endometrium were consistent with the late proliferative phase, with thick endometrial epithelium and tubular glands. Original magnification, ×100. Karaer. Effect of anastrozole on implantation. Fertil Steril 2005. Fertility and Sterility 2005 83, 1797-1806DOI: (10.1016/j.fertnstert.2005.01.100) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Immunohistochemistry of TNF-α, LIF, laminin, and collagen IV in embryonic, decidual, and endometrial cells in group I. In group I, although the staining intensity of TNF-α was strong in all compartments (A, B), mild and weak staining of LIF were detected in trophoectoderm and desidual cells, respectively (C, D). Immunoreactivity of laminin and collagen was seen in the embryonal and maternal parts of the implantation region; these immunoreactivities were strongly detected in trophoectoderm and basement membrane of the endometrial epithelium (E-H). Original magnification, × 100 (A, C, E, G) and ×400 (B, D, F, H). Karaer. Effect of anastrozole on implantation. Fertil Steril 2005. Fertility and Sterility 2005 83, 1797-1806DOI: (10.1016/j.fertnstert.2005.01.100) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Immunohistochemistry of TNF-α, LIF, laminin, and collagen IV in group II. (A-D) Weak staining in embryo and uterine epithelium and mild staining in stroma for TNF-α and LIF were detected. (E-H) Clumps of embryonic cells were stained with laminin and collagen IV, which are markers for trophoectoderm cells. Laminin staining was detected in both epithelial and stromal parts of the endometrium, and the intensity of laminin was strong in stroma (E, F). Immunoreactivity of collagen IV was also seen in both the epithelial and stromal parts of the endometrium, and was less than laminin staining (G, H). Original magnification, ×100 (A, C, E, G) and ×400 (B, D, F, H). Karaer. Effect of anastrozole on implantation. Fertil Steril 2005. Fertility and Sterility 2005 83, 1797-1806DOI: (10.1016/j.fertnstert.2005.01.100) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 5 Immunohistochemistry of (A, B) TNFα, (C, D) LIF, (E, F) laminin, and (G, H) collagen IV in group III. Uterine epithelium and stroma were stained with all antibodies. Strong immunoreactivities were observed for LIF and collagen IV (C, D, G, H). Original magnification, ×100 (A, C, E, G) and ×400 (B, D, F, H). Karaer. Effect of anastrozole on implantation. Fertil Steril 2005. Fertility and Sterility 2005 83, 1797-1806DOI: (10.1016/j.fertnstert.2005.01.100) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions