Mid-cycle serum levels of endogenous LH are not associated with the likelihood of pregnancy in artificial frozen-thawed embryo transfer cycles without pituitary suppression

BACKGROUND: The aim of the present study was to evaluate the association between clinical pregnancy and serum luteinizing hormone (LH) levels, assessed after 14 days of endometrial preparation with estradiol (E(2)) in the absence of pituitary suppression during a frozen-thawed embryo transfer (FRET) cycle. METHODS: A total of 513 patients undergoing their first FRET cycle (01/99 to 11/05) participated in this prospective study. Endometrium preparation for FRET was started on cycle day 1 and continued for a fixed period of 14 days with trans-dermal E(2) patches. On day 14, serum LH, progesterone and E(2) levels were assessed. On day 15, progesterone supplementation was initiated and patients underwent embryo transfer on day 17 or day 18. The association between clinical pregnancy and LH levels was evaluated in groups of patients defined according to Tukey's Hinges percentile analysis of LH levels on day 14. In addition, robust logistic regression was performed with the dependent variable clinical pregnancy and independent variables LH, progesterone, embryos score, cycle rank and gravidity. RESULTS: Age, BMI, parity, cycle rank, embryo number, embryo score, endometrial diameter, E(2) and progesterone were not significantly different in cycles with low (0.1-8.1 IU/l; n = 132), intermediate (8.2-19.4 IU/l; n = 238) and high (20.0-78.0 IU/l; n = 143) levels of LH, respectively. Clinical pregnancy rates were not significantly different in cycles with low [12.1%, 95% confidence intervel (CI) 7.6-18.8], intermediate (13.4%, 9.7-18.4) and high levels of LH (16.1%, 11.0-23.0). Robust logistic regression analysis indicated that embryo score [Odds ratios (OR) 1.04, 95% CI 1.02-1.06, P < 0.01] was statistically significantly associated with the likelihood of clinical pregnancy achievement, but not day 14 levels of LH or progesterone, gravidity or cycle rank. CONCLUSIONS: The likelihood of clinical pregnancy is not associated with serum LH levels on day 14 of an artificial FRET cycle. Hormonal monitoring of LH levels does not yield useful information with regard to cycle management and patient prognosis, and should therefore not be conducted.     

Mast Cells Trigger Disturbed Bone Healing in Osteoporotic Mice

Mast cells are important tissue-resident sensor and effector immune cells but also play a major role in osteoporosis development. Mast cells are increased in numbers in the bone marrow of postmenopausal osteoporotic patients, and mast cell–deficient mice are protected from ovariectomy (OVX)-induced bone loss. In this study, we showed that mast cell–deficient Mcpt5-Cre R-DTA mice were protected from OVX-induced disturbed fracture healing, indicating a critical role for mast cells in the pathomechanisms of impaired bone repair under estrogen-deficient conditions. We revealed that mast cells trigger the fracture-induced inflammatory response by releasing inflammatory mediators, including interleukin-6, midkine (Mdk), and C-X-C motif chemokine ligand 10 (CXCL10), and promote neutrophil infiltration into the fracture site in OVX mice. Furthermore, mast cells were responsible for reduced osteoblast and increased osteoclast activities in OVX mice callus, as well as increased receptor activator of NF-κB ligand serum levels in OVX mice. Additional in vitro studies with human cells showed that mast cells stimulate osteoclastogenesis by releasing the osteoclastogenic mediators Mdk and CXCL10 in an estrogen-dependent manner, which was mediated via the estrogen receptor alpha on mast cells. In conclusion, mast cells negatively affect the healing of bone fractures under estrogen-deficient conditions. Hence, targeting mast cells might provide a therapeutic strategy to improve disturbed bone repair in postmenopausal osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Additional luminal area gain by intravascular ultrasound guidance after coronary stent implantation with high inflation pressure

Aims: Studies by intravascular ultrasound demonstrated inadequate expansion in a large number of stents, which lead to the increase of inflation pressures for stenting. The present study examined whether routine use of high-pressure inflation would be sufficient for an optimum stent expansion without sonographic guidance. Methods and results: Two types of single coronary stents (Palmaz-Schatz in 54, and Wiktor in 25) were implanted with inflation pressures of 16–20 atm in 79 nonocclusive coronary lesions. IVUS before stenting was used in 78% to select the adequate stent size. Intravascular ultrasound after stenting was used to assess the minimum stent area and diameter, the reference areas, and the strut apposition to the vessel wall. The difference between the area of the expanding balloon and the stent area was calculated as the luminal deficit of the stent. Completeness of stent expansion required full strut apposition and lesion coverage, and a minimum stent area that was larger than the distal reference, and larger than 60% of the proximal reference. Intravascular ultrasound before stenting lead to an increase of the stent size in 47%. After high-pressure expansion, even with the optimized balloon size, 8% of stents had struts protruding into the lumen. The stent area (6.87 ± 1.93 mm²) was significantly smaller than both the proximal (9.59 ± 2.91 mm²; p<0.001) and distal reference area (8.23 ± 3.03 mm²; p<0.001). The criteria for complete expansion were met in 48%. The expansion with a larger high-pressure balloon in 28 stents lead to an increase of the stent area by 19% (8.19 ± 2.24; p<0.001), and full stent apposition in all cases. The criteria of stent expansion were met in 82%. A wide range of the luminal deficit upto 48% was observed, which was not related to sonographic lesion characteristics, except in lesions with complete circumferential calcifications. The different stent designs were characterized by a slightly lower luminal deficit in slotted-tube stents (23 ± 13% vs. 28 ± 12%; p=0.11) and a better index of stent symmetry as compared with the coil stent (0.87 ± 0.08 vs. 0.82 ± 0.09; p<0.05). Conclusion: Routine use of high-pressure stent expansion did not lead to a sufficient stent expansion, even when the initial stent size had been guided by intravascular ultrasound. Further stent dilatation with larger balloons under ultrasound guidance would be required to optimize the luminal area gain.     

Endurance exercise training in orthostatic intolerance: a randomized, controlled trial

Orthostatic intolerance is a syndrome characterized by chronic orthostatic symptoms of light-headedness, fatigue, nausea, orthostatic tachycardia, and aggravated norepinephrine levels while standing. The aim of this study was to assess the protective effect of exercise endurance training on orthostatic symptoms and to examine its usefulness in the treatment of orthostatic intolerance. 2768 military recruits were screened for orthostatic intolerance by questionnaire. Tilt-table testing identified 36 cases of orthostatic intolerance out of the 2768 soldiers. Subsequently, 31 of these subjects with orthostatic intolerance entered a randomized, controlled trial. The patients were allocated randomly to either a "training" (3 months jogging) or a "control" group. The influence of exercise training on orthostatic intolerance was assessed by determination of questionnaire scores and tilt-table testing before and after intervention. After training, only 6 individuals of 16 still had orthostatic intolerance compared with 10 of 11 in the control group. The Fisher exact test showed a highly significant difference in diagnosis between the 2 groups (P=0.008) at the end of the study. Analysis of the questionnaire-score showed significant interaction between time and group (P=0.001). The trained subjects showed an improvement in the average symptom score from 1.79+/-0.4 to 1.04+/-0.4, whereas the control subjects showed no significant change in average symptom score (2.09+/-0.6 and 2.14+/-0.5, respectively). Our data demonstrate that endurance exercise training leads to an improvement of symptoms in the majority of patients with orthostatic intolerance. Therefore, we suggest that endurance training should be considered in the treatment of orthostatic intolerance patients.     

Strong impact of estrogen environment on Doppler variables used for differentiation between benign and malignant breast lesions.

OBJECTIVES: To analyze the impact of an estrogen environment on the Doppler variables usually used for differentiation between benign and malignant lesions. METHODS: A total of 142 malignant and 107 benign breast lesions was demonstrated (in 91 premenopausal and 152 postmenopausal patients) by B-mode ultrasound. Intratumoral vessels were visualized by color Doppler and blood flow velocity waveforms were analyzed by pulsed Doppler. The number of intratumoral vessels and the Doppler variables, peak systolic velocity, resistance and pulsatility indices and the peak systolic/diastolic ratio were evaluated in different endocrine milieus represented by menopausal status, phase of the menstrual cycle, intake of oral contraceptives or hormone replacement therapy. RESULTS: In malignant tumors the Doppler variables resistance and pulsatility indices and the systolic/diastolic ratio were significantly higher in postmenopausal women than in premenopausal women. In benign tumors significantly higher values of resistance and pulsatility indices were also detected in post- compared to premenopausal women (P < or = 0.05). In premenopausal patients with benign tumors taking oral contraceptives the number of intratumoral vessels was significantly higher, while resistance index and systolic/diastolic ratio values were decreased compared to patients with spontaneous menstrual cycles. In postmenopausal patients hormone replacement therapy did not influence Doppler variables in the benign or the malignant groups. CONCLUSION: Our results demonstrate a robust influence of menopausal status and oral contraceptives on Doppler variables of breast lesions. We believe it is likely that some of the differences in the Doppler variables found in reports comparing benign and malignant breast lesions were caused by their association with a pre- or postmenopausal status.     

Mesio-marginal findings at tilted molars. A histological-histomorphometric study

The aim of this study was to investigate the mesio-marginal findings at tilted molars (TM) by means of histological-histomorphometric evaluation. Eight lateral tooth bone segments with TM (six mandibular, two maxillary) from males aged 20-32 years were compared with those of eight samples with non-tilted molars (NTM) in males aged 18-35 years. In comparison with the NTM samples, the TM revealed a higher amount of supra- and subgingival plaque, a significantly higher total number of inflammatory cells (P < 0.05) and blood vessels (P < 0.05) in the connective tissue adjacent to the junctional epithelium, and a lower density and corono-apical width of gingival fibres. No significant differences (P > 0.05) were found between the mesio-marginal bone level of the TM (mean: 978 microns) and that of the NTM (mean: 1222 microns). In contrast, indications were found that TM may affect the disto-marginal bone level of the mesial tooth.