The inclusion of blastomeres into the inner cell mass in early-stage human embryos depends on the sequence of cell cleavages during the fourth division

The fate of the ICM in humans is still unknown, due to the ethical difficulties surrounding experimentation in this field. In this study we have explored the existing time-lapse recording data of embryos in the early stages of development, taking advantage of the large refractile bodies (RBs) within blastomeres as cellular markers. Our study found that the cellular composition of the ICM in humans is largely determined at the time of the fourth division and blastomeres which cleave first to fourth, during the fourth division from 8 cells to 16 cells, have the potential to be incorporated in the ICM

A Novel Concept of Fundus-Ovary-Salpinx-Para-Aorta Implantation Promoting Unit during Human Embryo Implantation

Human embryo implantation is mainly regulated by the endocrine system. Since the ovary, fallopian tube, and fundus can directly communicate through the mesosalpinx and ovarian ligament, the local concentration of progesterone in the pathway of the developing embryo is considered to be higher than in systemic blood circulation. The immune system promotes embryo implantation by stimulating progesterone production of the ovary and by inducing endometrial differentiation. The recognition of the developing embryo in the fallopian tube by the immune system is achieved through the para-aortic lymph nodes. On the basis of the above evidence, the autologous immune cells activated in vitro were demonstrated to improve clinical pregnancy rates in patients with repeated implantation failures. In addition, the autonomic nerve system that innervates the fundus, the ovary, and the fallopian tube from the para-aortic region is proposed to regulate the environment of the pathway of the developing embryo. From these findings, we suppose that a unique unilateral functional unit to promote human embryo implantation exists in the pathway of the developing embryo including the para-aortic regions and propose naming this novel functional unit the Fundus-Ovary-Salpinx-Para-aorta Implantation Promoting unit (FOSPa-IP unit)

Effectiveness of high‐dose transvaginal progesterone supplementation for women who are undergoing a frozen‐thawed embryo transfer

Abstract Purpose To evaluate the effectiveness of high‐dose progesterone supplementation for women who are undergoing a frozen‐thawed embryo transfer (FET). Methods Among the 2010 FET cycles that were included in the present study, 1188 were 1200 mg/d of vaginal progesterone, while 822 were 900 mg/d. The dose of progesterone that was used was decided by the treatment period and additional progesterone supplementation was used when the serum progesterone levels were <9 ng/mL on luteal day 5. Results The clinical pregnancy rate was higher in the 1200 mg group than in the 900 mg group. The mean serum progesterone level on luteal day 5 in the 1200 mg and 900 mg groups was 12.6 ng/mL and 13.4 ng/mL, respectively. The rate of additional progesterone supplementation was higher in the 1200 mg group. A logistic regression analysis identified a younger age (≤37 years) and the use of 1200 mg progesterone as independent predictive factors for the clinical pregnancy outcome. The analysis of the infant outcomes revealed no significant difference in the distribution of birth ages and weights. Conclusion High‐dose transvaginal progesterone of 1200 mg/d as luteal support contributed to good pregnancy outcomes

Clinical outcome of intrauterine infusion of platelet‐rich plasma in patients with recurrent implantation failure

Abstract Purpose This study aimed to evaluate the effectiveness of intrauterine infusion of platelet‐rich plasma (PRP) before embryo transfer (ET) in recurrent implantation failure (RIF) cases. Methods The authors retrospectively analyzed 54 ET cycles involving frozen and thawed high‐quality blastocysts after intrauterine PRP infusion between September 2019 and November 2020. All patients had a history of at least two times of implantation failure on ET. A total of 54 patients were categorized into two groups: thin endometrium (39 patients) and unexplained implantation failure (15 patients). In the thin‐endometrium group, the endometrial thickness (EMT) was <8.0 mm at cycle days 12–14 in the prior ET cycle. Results Among the 54 ET cycles after PRP infusion, 31 (57.4%) were positive for human chorionic gonadotropin (hCG) and 27 (50%) achieved clinical pregnancy, which was significantly better than that in prior ET cycles without PRP infusion (27.2% and 9.6%, respectively). The EMT was not increased at ET date on the PRP cycle compared with that in the prior ET cycle in both patient groups. Moreover, EMT was not different between the hCG‐positive and hCG‐negative groups. Conclusion Although intrauterine PRP infusion had no superior effect on increasing the EMT than conventional therapeutic agents, it resulted in high pregnancy rates in patients experiencing RIF with or without thin endometrium