GnRH agonist early follicular challenge test as a predictor of ovarian response in antagonist cycles for fertility preservation.

The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and < 5 M2 oocytes was calculated. For GAST E3 levels obtaining < 5 M2 oocytes, an AUC value of 0.79 was found. For GAST E3 levels obtaining > 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain < 5 oocytes. Patients younger than 35 with GAST E3 > 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose.Trial registration number: 0304-20-ASF.

Follicular challenge test to predict suboptimal response to gonadotropin releasing hormone agonist trigger in elective oocyte cryopreservation cycles.

This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10-12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders.

Endometrial compaction is associated with increased clinical and ongoing pregnancy rates in unstimulated natural cycle frozen embryo transfers: a prospective cohort study.

PURPOSE: To investigate the association between endometrial compaction and pregnancy rates in unstimulated natural cycle frozen embryo transfers. DESIGN: A single-center prospective cohort study. Endometrial thickness by transvaginal ultrasound and blood progesterone levels on the day of ovulation and the day of embryo transfer were evaluated in patients undergoing natural cycle frozen embryo transfer. Compaction was defined as > 5% decrease in endometrial thickness between ovulation day and day of transfer. Clinical and ongoing pregnancy rates in cycles with and without compaction were compared. RESULTS: Seventy-one women were included, of which 44% had endometrial compaction, with similar rates when subdividing the patients by day of transfer (day 3 or day 5). Clinical and ongoing pregnancy rates were higher in the compaction group compared to the non-compaction group (0.58 vs. 0.16, P < 0.001; 0.52 vs. 0.13, P < 0.001 respectively). Subdividing by degree of compaction > 10% and > 15% revealed similar pregnancy rates as > 5%, with no added benefit to higher degrees of compaction. CONCLUSIONS: About half the patients in our study undergoing unstimulated natural cycle frozen embryo transfer experienced compaction of the endometrium, occurring as early as day 3 post-ovulation. This was significantly correlated with increased clinical and ongoing pregnancy rates.

[The findings and sequence of events leading to termination of pregnancy due to Down's syndrome--before and after the verge of viability: 10 years experience at a single medical center].

OBJECTIVE: To assess the differences in the sequence of events, leading to termination of pregnancy (TOP) due to diagnosis of Down syndrome (DS). The study compared women who were referred to institutional abortion committees (< 23 weeks) to those who were referred to supreme regional abortion committees (> 23 weeks). METHODS: Cases of singleton pregnancy ending in TOP due to DS in our institute during the period January 2000-December 2010 were retrospectively reviewed. The women were divided into two groups according to the gestational age at the time of the TOP. Group 1 included women who underwent TOP prior to 23 weeks of pregnancy; group 2 included women who had TOP at 23 weeks and onwards. The groups were compared regarding their demographic, sonographic and biochemical parameters during the affected pregnancy. Women in group 2 completed a telephone questionnaire about the circumstances leading to a late TOP after 23 weeks. RESULTS: There were 303 cases of DS, which had TOP during this period of time. All cases were diagnosed by fetal karyotyping. A total of 282 cases (93%) had earlier TOP while 21 cases (7%) had late TOP. The mean gestational age in each group was 18 weeks (range 12-22 weeks] versus 24 weeks (18-34 weeks) respectively (p < 0.001). In group 2, there were significantly more abnormal cardiovascular findings (67% vs. 21% in group 1, p < 0.002). No other significant differences were found between the groups regarding the demographic parameters, biochemical screening results (triple test), nuchal translucency (NT) and early and/or late sonographic anomaly scans. In Group 2 a total of 9 (42.8%) out of 21 women agreed to answer the telephone questionnaire. In this group the triple test, was performed in the upper recommended time limit according to the Ministry of Health. This may have led to the delay in the TOP. CONCLUSION: In our institutional experience we found that the circumstances leading to late TOPs because of DS were maternal dependent and not related to the screening findings. This stresses the efficiency of current screening programs, leading to early karyotyping and diagnosis of DS.

Model predicted Down syndrome detection rates for nuchal translucency screening in twin pregnancies.

OBJECTIVE: To estimate the Down syndrome detection rate for nuchal translucency (NT) screening in twins when fetus-specific risk allows for between-fetus NT correlation. METHODS: The between-fetus correlation coefficient of log NT, in multiples of the median (MoM), was estimated from a series of 977 unaffected twins scanned at a single centre. Results were expressed in multiples of the normal median using a curve derived from 515 unaffected singleton pregnancies at the same centre. A screening result was classified as positive if the risk for at least one fetus exceeded the cut-off. Detection rates were estimated for a fixed 1-5% false-positive rate, at different gestational weeks, separately for risk calculation using an algorithm which takes account of between-fetus NT correlation or not. RESULTS: The correlation coefficient in unaffected pregnancies was 0.43 (P < 0.0001) and estimated to be 0.23 and 0.11 in discordant and concordant twins. At 12 weeks of gestation, the model predicted detection rate for a 3% false-positive rate was 68% when between-fetus correlation is not taken into account, increasing to 73% when it is applied. Similarly, for other false-positive rates and gestational weeks there was a predicted 4-6% increase in detection. CONCLUSION: Using a fetus-specific Down syndrome risk algorithm leads to a worthwhile increase in detection.

Intra-arterial infusion of nitric oxide (NO) - first animal trial.

OBJECTIVE: Nitric oxide (NO) is an important signaling molecule that acts in many tissues to regulate a diverse range of physiological processes. NO has been implicated in a number of cardiovascular diseases. Reduced basal NO synthesis or function may lead to: vasoconstriction, elevated blood pressure and thrombus formation. By contrast, overproduction of NO results in vasodilatation, hypotension, vascular leakage, and disruption of cell metabolism. The purpose of this study was to determine the effects of NO gas directly infused into the arteries. METHODS: The study was performed on 28 rabbits and 10 pigs. We developed a device that enables quantitatively controlled infusion of NO gas, directly into the arteries. RESULTS: We found that administration of NO gas via arteries caused widening of the blood vessels as well as increasing blood flow in the extremity. It emerges that. These effects persist up to 2-3 h after the NO infusion ceased. Although the NO breaks down when diffused in blood, its influence commences rapidly and continues for a relatively long time. CONCLUSIONS: Our findings indicate that, administration of NO into blood vessels causes a long lasting vasodilatation and enhanced blood flow. Despite the fact that NO is broken down rapidly.

A reasonable mechanism for visible light-induced skin rejuvenation.

In recent years, much research has been done in the field of non-ablative skin rejuvenation. This comes as a response to the continuous demand for a simple method of treating rhytides, UV exposure, and acne scars. Numerous researches involve visible light-pulsed systems (20-30 J/cm(2)). The mechanism of action is believed to be a selective heat-induced denaturalization of dermal collagen that leads to subsequent reactive synthesis (Bitter Jr., Dermatol. Surg., 26:836-843, 2000; Fitzpatrick et al., Arch. Dermatol., 132:395-402, 1996; Kauvar and Geronemus, Dermatol. Clin., 15:459-467, 1997; Negishi et al., Lasers Surg. Med., 30:298-305, 2002; Goldberg and Cutler, Lasers Surg. Med., 26:196-200, 2000; Hernandez-Perez and Ibeitt, Dermatol. Surg., 28:651-655, 2002). In this study, we suggest a different mechanism for photorejuvenation based on light-induced reactive oxygen species (ROS) formation. We irradiated collagen in vitro with a broadband of visible light (400-800 nm, 24-72 J/cm(2)) and used the spin trapping coupled with electron paramagnetic resonance spectroscopy to detect ROS. Irradiated collagen resulted in hydroxyl radicals formation. We propose, as a new concept, that visible light at the energy doses used for skin rejuvenation (20-30 J/cm(2)) produces high amounts of ROS, which destroy old collagen fibers, encouraging the formation of new ones. On the other hand, at inner depths of the skin, where the light intensity is much weaker, low amounts of ROS are formed, which are well known to stimulate fibroblast proliferation.

Burns in inpatients by simultaneous use of cigarettes and oxygen therapy.

Two inpatients with chronic obstructive pulmonary disease (COPD), treated with oxygen in the respiratory intensive care unit (RICU), sustained burns from explosion of oxygen delivery system while illicitly smoking. The authors discuss incidence and possible etiology with literature review.