Research question: Does tailor-made embryo transfer (TmET), timed with respect to embryonic developmental speed, affect pregnancy outcomes in patients with recurrent implantation failure?
Design: Among 741 patients identified as receptive through endometrial receptivity testing, the clinical pregnancy rates and live birth rates were retrospectively compared between those who underwent standard personalized embryo transfer and those who underwent TmET in hormone replacement therapy cycles. Personalized embryo transfer was performed according to endometrial receptivity test results (standard personalized embryo transfer group) or considering embryonic developmental speed (TmET group). For TmET, the expansion grade of warmed blastocysts was estimated based on each patient's previous embryonic developmental pattern. The embryo transfer days were set so that estimated blastocyst grades 3, 4, 5 and 6 were transferred on days P+5, P+5.5, P+6.0 and P+6.5, respectively.
Results: In a propensity score matching analysis, the clinical pregnancy rate was significantly higher in the TmET group than the standard personalized embryo transfer group (P = 0.014), whereas the live birth rates were similar between the two groups (P = 0.65). In a subgroup analysis with euploid embryo transfers, the clinical pregnancy rate was significantly higher in the TmET group than the standard personalized embryo transfer group, although there was no difference in live birth rate between the two groups (P = 0.045 and P = 0.057, respectively).
Conclusions: For patients experiencing recurrent implantation failure and identified as receptive through endometrial receptivity testing, subsequent TmET strategies may further enhance pregnancy outcomes.
Research question: What role, if any, does the extent of lesional fibrosis play in impaired glycolysis leading to adenomyosis-associated heavy menstrual bleeding (ADM-HMB)?
Design: Forty-eight patients with ADM-HMB were recruited, among them 25 reported moderate to heavy bleeding (MHB), and the remaining 23, excessive bleeding (EXB). The full-thickness uterine tissue columns were processed for Masson trichrome staining and immunohistochemistry analyses. The expression levels of HIF-1α, GLUT1, HK2, PFKFB3 and PKM2 proteins that are critically involved in glycolysis in endometrial epithelial cells cultured on substrates of different stiffness, and the levels of glycolysis were quantitated. A mouse experiment with induced adenomyosis and simulated menstrual bleeding was conducted to assess the effect of adenomyosis on immunoexpression of proteins involved in glycolysis and inflammation as well as on endometrial repair and bleeding.
Results: The endometrial staining of HIF-1α, GLUT1, HK2, PFKFB3 and PKM2 was significantly lower in the EXB group as compared with MHB patients, concomitant with higher extent of fibrosis. The expression of HIF-1α, GLUT1, HK2, PFKFB3 and PKM2 was significantly reduced when endometrial epithelial cells were cultured in stiff substrate, concomitant with reduced glycolysis. Mice with induced adenomyosis had reduced immunoexpression of Hif-1α, as well as those proteins each of which plays a vital, rate-limiting role in different steps of the glycolysis pathway, such as Glut1, Hk2, Pfkfb3 and Pkm2, and elevated fibrosis in endometrium, concomitant with disrupted endometrial repair and more bleeding.
Conclusions: Lesional fibrosis results in reduced endometrial glycolysis in eutopic endometrium and subsequent imbalance in pro-inflammatory and anti-inflammatory response, leading to ADM-HMB.