Objective: Thin endometrium (TE) represents a huge challenge in assisted reproduction, since it is related to decreased endometrial receptivity and consequent implantation failure, negatively affecting reproductive outcomes. The application of mesenchymal stem cells (MSE) has shown promising results, as its regenerative properties improves thickness and expression of receptivity biomarkers in the endometrium. However, the costs and complex processes involved in these treatments prevent its routine aplication. In this context, there is a need to create strategies to stimulate specific stem cell recruitment and migration to tissue injury sites. AMD3100 is a CXCR4 antagonist receptor that disrupts the CXCL12-CXCR4 axis which is directly related to stem cell migration and has been used in tissue regeneration studies to increase the influx of stem cells to the site of injury. In addition, its combined use with β3 adrenergic agonists receptors leads to selective recruitment of MSC with better regenerative results proved in a recent paper on bone fracture healing. Thus, the objective of this study is to evaluate the regenerative potential of AMD3100 alone or in association with a β3 adrenergic agonist receptor in a murine animal model of TE and its impact on the reproductive outcomes. Methods: Experiments were carried out on female C57Bl/6 mice (age 9 weeks; 20 g). TE was induced by direct application of 50 μl of 95% ethanol in the exposed uterus through an abdominal incision, while Phosphate-buffered saline(PBS) was used in the sham procedure (SH). Mice in each group were randomly divided into 3 treatment subgroups (n = 8 for each): (1)PBS(PL); (2)AMD 3100(5 mg/kg sc) single dose after surgery (AMD); (3)BRL37344(rodent-selective β3 adrenergic receptor agonist)(10 mg/kg sc) for 4 consecutive days previous to surgery plus AMD 3100(5 mg/kg sc) single dose (AMD/B3). Two estrous cycles after modeling and treatment, all the groups were mated with proven male C57BL/6 mice. The pregnancy rate and litter size were evaluated in order to establish the impact on the reproductive outcomes. In addition, a macroscopic anatomic analysis was performed on the offspring to evaluate possible teratogenic effects. Results: In relation to pregnancy rate, 23 out of 24 sham mice got pregnant (despite the treatment group). The TE model reproduced the literature results, with under 30% of failure in inducing endometrial damage, represented by a pregnancy rate of 25%(2/8) in the TE+PL group in comparison to all sham groups(p<0.05). The AMD/B3 treatment completely restored the endometrial function, promoting pregnancy rates similar to all sham groups(p>0.05). There was no difference between the TE+AMD treatment group and all the other groups(p>0.05) in terms of pregnancy, although a clinically relevant difference between TE+PL and TE+AMD groups was found(25% versus 62.5%, respectively). The litter size was similar between the treatment groups, except for the TE+AMD group with a smaller number of newborns. Regarding the JBRA Assisted Reproduction 2022;26(1):162-164 doi: 10.5935/1518-0557.20210106

Maternal and neonatal outcomes after frozen , fresh and ovulation induction cycles : are there any differences ?

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Maternal and neonatal outcomes after frozen , fresh and ovulation induction cycles : are there any differences ?