The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical outcome.

In this prospective cohort study of 286 women undergoing fresh embryo transfer after IVF, uterine contraction frequency and direction were measured before (-5 min), 5 min after (+5 min) and 60 min after (+60 min) embryo transfer. Mean ± SD uterine contraction frequency at -5 min was 1.8 ± 1.1 contractions per min, increasing significantly (P < 0.05) to 2.0 ± 1.1 at +5 min, and returning back to baseline 1.8 ± 1.1 at +60 min. At -5 min, the proportion of women the with retrograde, antegrade, indeterminate direction and absent contractions were 33%, 44%, 17% and 6%; at +5 min, 40%, 42%, 13% and 5%, and at +60 min, 42%, 38%, 14% and 6%. No significant change was observed in the proportion of direction at these three time points. Logistic regression analysis showed live birth rate was significantly reduced in older women (P = 0.035) and in those with higher uterine contraction frequency at +5 min (P = 0.006). Frequency of uterine contraction immediately after embryo transfer (+5 min) seemed to be a significant predictor of IVF outcome and may help to identify women who could benefit from the use of muscle relaxant therapy to improve outcome.

Assessment of the embryo flash position and migration with 3D ultrasound within 60 min of embryo transfer.

STUDY QUESTION: Does the air bubble (embryo flash) position and migration as visualized with 3D ultrasound (US) within 60 min of embryo transfer correlate with clinical outcome following fresh ART transfer cycles? SUMMARY ANSWER: The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, are associated with clinical pregnancy. WHAT IS KNOWN ALREADY: Studies assessing the relation between the pregnancy rate and the position of the catheter tip and/or the position of the air bubbles following embryo transfer show conflicting results to date. STUDY DESIGN, SIZE AND DURATION: This was a prospective cohort study including 277 infertile women undergoing ART between July 2011 and August 2013. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Good prognosis patients undergoing fresh ART cycles within a single tertiary University unit were assessed by 3D US at 1, 5 and 60 min after embryo transfer. The distance of the embryo flash from the fundus was measured at these time points, along with the direction of the embryo flash movement within 60 min of transfer. MAIN RESULTS AND THE ROLE OF CHANCE: Within 60 min of embryo transfer, 76.4% (198/259) of the embryo flashes migrated towards the fundus, 12.4% (32/259) migrated towards the cervix and 11.2% (29/259) remained static. There was no significant association between the embryo position or movement and the pregnancy rate at 1 and 5 min. At 60 min, however, the pregnancy and implantation rates among subjects with embryo flashes located <15 mm from the fundus was significantly higher than those with embryo flashes located >15 mm from the fundus (46.5 and 32.8% versus 25.8 and 18.2%, respectively; P < 0.05). The pregnancy and implantation rates when the embryo flash was seen moving towards the cervix (25.0 and 15.0%) was significantly lower (P < 0.05 and P < 0.01, respectively) compared with those remaining static (55.2 and 37.7%) or moving towards the fundus (45.5 and 32.8%). LIMITATIONS AND REASONS FOR CAUTION: Although the air bubbles seen at the time of embryo transfer are thought to represent the position of the embryo, they are in fact a surrogate marker of the embryo itself, as this cannot be directly visualized by US. WIDER IMPLICATIONS OF THE FINDINGS: Following embryo transfer the majority, but not all, embryo flashes undergo significant migration towards the fundus. The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, is associated with clinical outcome. These findings may challenge the traditional notion that the exact position of the embryo flash immediately following embryo transfer is related to clinical outcome. STUDY FUNDING/COMPETING INTERESTS: The authors have no relevant funding or conflicts of interest to disclose.

Do uterine natural killer cell numbers in peri-implantation endometrium predict hypertensive disorder in pregnancy in women with a history of reproductive failure?

The aim of this study was to investigate whether or not increased uterine natural killer (uNK) cell numbers in the peri-implantation endometrium are associated with an increased risk of hypertensive disorders in a subsequent pregnancy. This is a retrospective study including 80 women with a history of unexplained recurrent miscarriage or recurrent implantation failure. Precisely timed endometrial biopsies were obtained from women 7-9 days after the luteinising hormone surge. uNK cells were immunostained for CD56+ and expressed as a percentage of total stromal cells. Patients were defined as having a high uNK cell count if the percentage of total stromal cells was more than 13.9%. Five out of 29 (17.2%) women in the high uNK cell count group and 5 out of 51 (9.8%) women in the normal uNK cell count group developed gestational hypertension. Pre-eclampsia was diagnosed in 2 (6.9%) patients in the high uNK cell count group and 1 (2.0%) patient from the normal uNK cell count group. There was no significant difference in the incidence of either gestational hypertension (P=0.483) and pre-eclampsia (P=0.296) between groups. The overall incidence of hypertensive disease in women with high uNK cell count (24.1%) was two times higher than women with normal uNK cell count (11.8%), but it was not statistically significant (P=0.208). An increased uNK cells count in the peri-implantation period in a cycle prior to conception did not appear to significantly increase the likelihood of hypertensive disease of pregnancy.

Vascular endothelial growth factor C is increased in endometrium and promotes endothelial functions, vascular permeability and angiogenesis and growth of endometriosis.

Endometriosis is an angiogenesis-dependent disease. Many studies demonstrated inhibition of angiogenesis leads to inhibition of endometriotic growth, however underlying mechanism is still not fully understood. Our previous study suggested vascular endothelial growth factor C (VEGF-C) as a target of anti-angiogenesis therapy for endometriosis. In this study, VEGF-C in endometrium and its role in angiogenesis of endometriosis were studied. Human endometrium were obtained from women with and without endometriosis for molecular studies. VEGF-A, VEGF-B, VEGF-C and VEGF-D mRNA and proteins in eutopic and ectopic endometrium were measured. Human endothelial cells were transfected with VEGF-C siRNA in vitro, effects of VEGF-C on endothelial cell migration, invasion and tube formation were investigated in vitro. Angiogenesis was inhibited in wild type mice, vascular permeability in dermal skin was determined in vivo. Transplanted endometrium were inhibited by VEGF-C siRNA in immunocompromised mice, development, growth and angiogenesis of the experimental endometriosis were compared in vivo. The results showed that VEGF-C mRNA and protein were increased in eutopic and ectopic endometrium of endometriosis patients. VEGF-C siRNA significantly inhibited endothelial cell migration and tube formation. VEGF-C siRNA significantly inhibited development and angiogenesis of the experimental endometriotic lesions in mice. Supplementation and over-expression of VEGF-C significantly reversed the inhibitory effects on the endothelial functions, vascular permeability and endometriotic growth. In conclusion, VEGF-C is increased in endometrium and it promotes endothelial functions, vascular permeability and development of experimental endometriosis. VEGF-C is important for angiogenesis in endometriosis.