Toxic epidermal necrolysis associated with carvedilol treatment.

OBJECTIVE: To report a case of fatal toxic epidermal necrolysis associated with carvedilol treatment. CASE SUMMARY: Two days after the initiation of carvedilol treatment, a 70-year old woman presented with skin eruptions in the form of maculous rash with blisters that rapidly progressed to epidermal necrolysis. Although the suspected drug was withdrawn, the reaction was extremely rapid in its development with fatal outcome. DISCUSSION: Carvedilol is not a drug commonly associated with TEN. To our knowledge there are no cases of carvedilol related TEN reported in the literature. CONCLUSION: Because of the close temporal relationship between the initiation of carvedilol treatment and the appearance of skin eruptions, and because carvedilol was the only new medication the patient had taken, the etiology of TEN was most likely a reaction to this drug. Physicians should be aware of this extremely rare but serious ADR.

Predicted luteal phase length has no influence on success of vitrified-warmed blastocyst transfer in natural cycle.

BACKGROUND: This study evaluated the influence of menstrual cycle length, menstrual cycle variability and predicted luteal phase length on the success of vitrified-warmed blastocyst transfer in natural menstrual cycle using progesterone for luteal phase supplementation. METHODS: Consecutive women undergoing vitrified-warmed blastocyst transfer in natural menstrual cycle between January 2013 and December 2015 were included in this retrospective study. Patients' characteristics, clinical data and data about menstrual cycle length in the last year were collected from our database. Predicted luteal phase length (LPL) was defined as the period starting at ovulation (one day after positive urinary LH test) and ending on the last day before predicted menses, based on women's usual, minimal and maximal menstrual cycle length data. Logistic regression was used to identify the predictors significantly associated with live-birth. RESULTS: A total of 1195 FETs (frozen-thawed embryo transfers) resulted in 457 (38.24%) clinical pregnancies, 82 (17.94%), miscarriages and 371 live births (31.04%). There were no statistically significant differences in menstrual cycle length, menstrual cycle variability, day of LH surge, day of FET and predicted LPL between FET cycles resulting in live birth and those not resulting in live birth. In the multivariate logistic regression model, only women's age (OR 0.93, 95% CI: 0.90-0.96), transfer of morphologically optimal blastocysts (OR 2.17, 95% CI: 1.59-2.94) and endometrium thickness (OR 1.10, 95% CI: 1.03-1.17) were important independent prognostic factors for live birth. CONCLUSION: Menstrual cycle length, menstrual cycle variability and predicted LPL do not seem to be an important factor influencing live birth after FET in natural cycles with progesterone supplementation. Results of our study suggest that FET should not be cancelled if LH surge is detected before or after the predicted period in natural cycle with progesterone supplementation.

Value of the serum estradiol level on the day of human chorionic gonadotropin injection and on the day after in predicting the outcome in natural in vitro fertilization/intracytoplasmic sperm injection cycles.

OBJECTIVE: To predict the risk of premature ovulation and possibility of pregnancy in natural IVF/ICSI cycles on the basis of the estradiol (E2) level on the day of hCG injection and on the day after. DESIGN: A prospective study. SETTING: Hospital research program. PATIENT(S): One hundred sixty-four women undergoing 305 IVF/ICSI natural cycles. INTERVENTION(S): Serum E2 levels were measured approximately 12 h before (day 0) and 12-17 h after hCG administration (day 1). MAIN OUTCOME MEASURE(S): E2 levels on day 0 and day 1, the ratio of the day 1 to day 0 levels, and cycle outcome. RESULT(S): In cycles with premature ovulation and in conception cycles, the average E2 level on day 0 was statistically significantly higher than in other cycles, whereas the E2 ratio was statistically significantly lower. Multiple logistic regression was used to determine the connection of the E2 level on day 0 (B0 = -0.742, B = 2.147, P =.01) and the E2 ratio (B0 = -0.742, B = -3.135, P<.001) with premature ovulation. Only the E2 ratio (B0 = 0.659, B = -2.209, P =.0068) was significantly connected with conception. CONCLUSION(S): In predicting the outcome of natural IVF/ICSI cycles, the importance lies not in the E2 level on the day of hCG administration or on the day after, but rather in the E2 ratio.

C-reactive protein and the treatment of pelvic inflammatory disease.

OBJECTIVE: The significance of C-reactive protein (CRP) in assessing the treatment of pelvic inflammatory disease (PID) was established and compared with body temperature (BT), erythrocyte sedimentation rate (ESR) and serum leukocyte concentration (L). METHOD: In 51 patients with PID, 20 (39%) of them with tubo-ovarial abscess (TOA), measurement of BT and laboratory investigations were carried out on admission and during treatment on days 3-4, 6-8 and 18-21. The changes in these values were compared with the changes in clinical condition. RESULT: Prior to treatment, the majority--49 patients or 96.1%--had increased CRP values. In successful treatment, the CRP values decreased significantly in PID patients without TOA on day 3-4, in patients with TOA on day 6-8 and reached normal values in both groups on day 18-21. Changes in clinical condition were most concurrent with changes in CRP. CONCLUSION: In assessing PID treatment, the determination of CRP has precedence over L, ESR and BT as the percentage of patients with increased CRP is higher and because the changes in value follow the changes in clinical condition more reliably.

Monitoring parameters in the management of patients with tubo-ovarian complexes.

OBJECTIVE: The aim of the study was to determine which of the monitored parameters is most suitable for following the treatment of tubo-ovarian complex (TOC). METHODS: In 35 patients treated conservatively for TOC, serum levels of C-reactive protein (CRP), erytrocyte sedimentation rate (ESR) and tumor-associated antigen 125 (CA-125) were determined at the beginning as well as on days 5, 10, 15 and 20 of treatment. TOC size was measured ultrasonographically prior to and on day 20 of treatment. We compared the dynamics of these parameters. Spearman's correlation test was used to establish the connection between levels of CRP, ESR, CA-125 and the size of the TOC. RESULTS: CRP follows the course of acute inflammation quickly, ESR and CA-125 with some delay. The correlation between the size of the tumor on admission and the CRP levels was established on days 5-10, ESR from the beginning until day 15 and the CA-125 levels on days 10-20 of treatment. On day 20, only the levels of CA-125 correlated with the size of the TOC measured on the same day (R = 0.49, P = 0.01) and only the difference between its levels correlated with the difference in TOC (R = 0.41, P = 0.01). CONCLUSION: Determination of CRP, and somewhat less ESR, is more suitable for following the treatment of TOC in the acute phase while CA-125 and measuring of TOC size is more suitable in the subacute phase.

Simplification of the clinical phase of IVF and ICSI treatment in programmed cycles.

OBJECTIVE: To evaluate the success of a protocol for controlled ovarian hyperstimulation allowing patient self-selection into groups for ovulation stimulation planned 8 weeks and more in advance following cycle synchronization, drug self-administration as well as a reduced number of folliculometries. METHODS: A total of 714 patients received the same stimulation protocol. In 260 cases GnRH-a was applied daily and in 454 as depot. In all patients FSH-HP was self-administered subcutaneously for ovarian stimulation. In 316 patients IVF and in 398 patients ICSI was performed. RESULTS: The delivery rate per started cycle was higher in patients receiving depot GnRH-a in the IVF and ICSI group (30.2 vs. 23.4) than in those receiving subcutaneous GnRH-a (20.2 vs. 22.1). CONCLUSION: Programming of the IVF/ICSI cycle greatly simplifies treatment. A comparison of pregnancy rate and delivery rate per cycle between depot and subcutaneous daily application of GnRh-a did not confirm any statistically significant difference.

Number of oocytes retrieved and resulting pregnancy. Risk factors for ovarian hyperstimulation syndrome.

OBJECTIVE: To test whether the risk of developing clinically significant ovarian hyperstimulation syndrome (OHSS) is related to the number of oocytes retrieved by puncture and the resulting pregnancy and to determine the most suitable cutoff limit of the number of oocytes in predicting OHSS. STUDY DESIGN: The study included 973 patients who underwent ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. Using the classification of Schenker and Weinstein, we identified patients who developed moderate and severe OHSS. By multiple logistic regression we established the risk of moderate or severe OHSS development in relation to the number of oocytes retrieved and the resulting pregnancy. A receiver operator characteristic curve was constructed to describe the relation between sensitivity and the false positive rate for the number of oocytes retrieved in the prediction of OHSS. RESULTS: We identified 35 (3.6%) patients who developed OHSS, 8 (0.8%) severe and 27 (2.8%) moderate. The risk of developing OHSS increased with the number of oocytes retrieved (odds ratio = 1.14) and with pregnancy (odds ratio = 1.14). The most suitable limit for predicting OHSS was 10 oocytes, with 81.9% specificity and 48.6% sensitivity. The risk of OHSS development in cycles with < or = 10 oocytes and no conception was 1.31% and, with conception, 5.12%. The risk of OHSS development in cycles with > 10 oocytes and no conception was 4.43% and with conception, 15.93%. CONCLUSION: The risk of OHSS development increases with the number of oocytes retrieved and with pregnancy. The most suitable limit for predicting OHSS is 10 oocytes; however, due to low sensitivity, it is also necessary to consider other factors when establishing the increased risk of OHSS.

Three protocols for monitoring follicle development in 587 unstimulated cycles of in vitro fertilization and intracytoplasmic sperm injection. A comparison.

OBJECTIVE: To test the adequacy of unstimulated cycles for intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) and to evaluate implantation and pregnancy rates in three monitoring protocols. STUDY DESIGN: A retrospective chart review of 587 patients undergoing IVF and ICSI in unstimulated cycles was performed. In the first group (protocol A), all cycles were monitored by ultrasound only. Human chorionic gonadotropin (hCG) was given when the mean follicle diameter reached 18 mm. In protocol B, hCG was given when serum estradiol (E2) or follicle diameter reached the critical value (0.91 nmol/L and 18 mm). With a smaller follicle diameter, the E2 level had to be higher, and vice versa. In protocol C, hCG was administered when the serum E2 was > 0.49 nmol/L and follicle diameter at least 15 mm. Cycles with positive luteinizing hormone in urine before hCG was given were cancelled. RESULTS: The cancellation rate was lower in protocol C (33/335, 9.8%) than protocol B (42/151, 27.8%) and A (41/101, 40.5%). In protocol C the pregnancy rate per cycle was higher with IVF (n = 219) and ICSI (n = 116) cycles (10.5% and 12.1%) than when protocol B was used (3.8% and 4.3%). The pregnancy rate per transfer was highest when protocol C was used in the IVF (23/105, 21.9%) and ICSI group (14/53, 26.4%). CONCLUSION: Unstimulated cycles monitored by serum E2, urinary luteinizing hormone and ultrasound can produce an acceptable pregnancy rate after IVF and ICSI.

The value of serum CA 125 for the management of tubo-ovarian abscesses.

OBJECTIVE: The aim of this study was to compare the value of CA 125, ESR and CRP in predicting the outcome of tubo-ovarian abscess (TOA) treatment and to investigate whether TOA treatment could be improved by following the dynamics of CA 125 serum levels. STUDY DESIGN: This prospective study included 36 patients with unilateral TOA, confirmed on the basis of history and physical examination, laboratory findings, and ultrasound (US) investigation. Venous blood samples for estimation of serum CA 125, CRP, and ESR were taken on hospital admission and then every 5 days. On day 20, the success of treatment was evaluated by clinical and sonographical re-assessment, and the patients were divided into two groups: those with complete regression of the TOA and those with residual inflammatory disease. Statistical analysis was performed by nonparametric Mann-Whitney U-test with multiple regression. RESULTS: On admission, CA 125 levels were increased (> 16.7 U/ml) in 32 patients (88.9%). The CA 125 level amounted to 55.7 U/ml on the average. A significant difference in CA 125 values between the above mentioned two groups was observed from day 10 of treatment onwards (p = 0.00015). On comparison of ESR, CRP, and CA 125, the latter had the highest predictive value for disease outcome after day 10 (p < 0.0011), while at the time of diagnosis, ESR proved more reliable in predicting the outcome. CONCLUSIONS: The dynamics of serum CA 125 allow an objective evaluation of the course and outcome of TOA, in combination with clinical parametres and US investigation.

Dependence of the in-vitro fertilization capacity of the oocyte on perifollicular flow in the preovulatory period of unstimulated cycles.

BACKGROUND: One method to economize on monitoring cycles for IVF and improving its outcome is follicular selection. The purpose of our study was to determine whether quantitative indices of perifollicular blood flow allow the prediction which follicles contain a fertilizable oocyte and which do not. METHODS: This prospective study included 178 unstimulated cycles for IVF in patients treated for tubal infertility, endometriosis and unknown causes of infertility that ended with follicular aspiration. All male partners had a normal spermiogram. Cycles were monitored using ultrasound folliculometry and estimation of serum estradiol concentrations. On the day of hCG administration (day 0), day +1 and prior to follicular aspiration (day +2), perifollicular blood flow was measured using color and pulsed Doppler. The pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV) between the group in which fertilization occurred (group A) and that in which no fertilization occurred (group B) were compared. Student's t-test and ANOVA were used for statistical analysis. RESULTS: The oocyte recovery rate was 71.5% and the fertilization rate 74.8%. Comparison of RI and PI between group A (N = 95) and group B (N = 32) revealed a decline in PI and RI after hCG administration in both groups. Only on day 0 was PI in group A significantly lower than that in group B. The difference in RI and PSV between the two groups was not statistically significant. ANOVA showed that there was no significant difference in serial Doppler measurements between the two groups. CONCLUSION: We confirmed an increased perifollicular blood flow in the preovulatory period. Quantitative indices of perifollicular blood flow are of limited value as parameters for cycle monitoring and decision-making in unstimulated cycles for IVF.

The significance of crown-rump length measurement for predicting adverse pregnancy outcome of threatened abortion.

OBJECTIVES: To determine if in women with threatened miscarriage the measurement of fetal crown-rump length (CRL) is a useful predictor of spontaneous miscarriage and small for gestational age (SGA) infants. METHODS: Fetal CRL was measured in 310 singleton pregnancies with live fetuses, presenting with threatened miscarriage before 13 weeks of gestation. The relationship between fetal CRL and pregnancy outcome was investigated. RESULTS: In fetuses with CRL < 18 mm there was a significant positive association between the deficit in CRL for gestation and the incidence of subsequent spontaneous miscarriage. In those cases with CRL deficit more than 2 standard deviations (SDs) the incidence of miscarriage was 13.7%, whereas if the CRL was between the mean and -2 SDs the incidence of miscarriage was 8.3%. In fetuses with CRL > or = 18 mm there was a significant positive association between the deficit in CRL for gestation and the incidence of SGA. In those cases with CRL deficit of more than 2 SD the incidence of SGA was 27.3%, whereas if the CRL was between the mean and -2 SDs the incidence of SGA was 18.9%. CONCLUSIONS: The findings of this study suggest that the measurement of fetal CRL may be a useful predictor of spontaneous miscarriage and SGA in pregnancies with threatened miscarriage.

The preovulatory serum estradiol pattern in natural IVF/ICSI cycles.

PURPOSE: The aim of the study was to find whether inferences to the possible success of natural IVF/ICSI cycles could be drawn from the estradiol (E2) pattern. METHODS: Sixty-eight women who underwent oocyte recovery in 98 natural cycles were recruited for the study. Daily serum E2 was measured in the preovulatory phase (-3 to +2 day). The E2 pattern was compared among four groups: Group A, unsuccessful egg retrieval; Group B, no fertilization; Group C, no implantation; and Group D, implantation. RESULTS: There was no difference in mean E2 levels between groups. Only the ratio of E2 on day +1/E2 on day 0 was significantly lower in conception cycles in comparison with nonconception cycles. In cycles with a decreased E2 level on day +1, only the implantation rate was significantly higher in comparison with cycles with an increasing E2 level. CONCLUSIONS: From the E2 pattern it is possible to make inferences about the likelihood of implantation but not the fertilization or oocyte recovery success.

Subendometrial contractility is not predictive for in vitro fertilization (IVF) outcome.

OBJECTIVES: The aim of the study was to investigate whether endometrial thickness, endometrial pattern, endometrial movement and serum estradiol and progesterone affect the outcome of in vitro fertilization. METHODS: Prospectively collected data of endometrial thickness, endometrial pattern and subendometrial activity were analyzed in 122 consecutive in vitro fertilization cycles. All measurements were made on the day of hCG administration (day -2), day of embryo transfer (day +2), day +6 and day +12. RESULTS: It would appear that pregnant women tend to have a thicker endometrium on day +12 than non-pregnant women. There appears to be no appreciable difference between pregnant and non-pregnant women in endometrial movement and thickness, nor in serum estradiol and progesterone on day +2 and day +6. In combining three echographic variables (thickness, pattern and movement) and hormone level (estradiol and progesterone), only progesterone on day +12 could be used to predict the outcome. CONCLUSIONS: Subendometrial contractility plays no important role in implantation on the day of embryo transfer or 4 days later.

Measurement of perifollicular blood flow of the dominant preovulatory follicle using three-dimensional power Doppler.

OBJECTIVE: To establish whether we might predict the outcome of unstimulated in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with quantitative indices of perifollicular blood flow assessed with three-dimensional (3D) reconstruction of power Doppler images. METHODS: This prospective study included an analysis of 52 unstimulated cycles. Color and power Doppler ultrasound examinations of a single dominant preovulatory follicle were performed on the day of oocyte pick-up. With 3D reconstruction and processing, quantitative indices were obtained i.e. the percentage of volume showing a flow signal (VFS) inside a 5-mm capsule of perifollicular tissue and the percentage of VFS of each of the three largest vessels in this capsule. These indices as well as pulsed Doppler indices were compared between the groups of cycles with different outcomes using a one-way ANOVA test. RESULTS: In nine cycles no oocyte was retrieved (Group A), in seven cycles no fertilization occurred (Group B) and in 30 cycles no implantation occurred (Group C). Six cycles resulted in pregnancy (Group D). There were no statistically significant differences in pulsed and power Doppler indices between these groups. However, the percentage of VFS in the capsule was higher than average in cycles with implantation (19.22 +/- 16.82 vs. 12.42 +/- 8.89, NS) and the percentage of VFS in the main vessel exhibited lower than average values in cycles with implantation (20.66 +/- 10.05 vs. 39.84 +/- 20.15), but only reached borderline statistical significance (F = 2.457, P = 0.074). CONCLUSION: It can be hypothesized that the follicles containing oocytes able to produce a pregnancy have a distinctive and more uniform perifollicular vascular network.

Is there any benefit from the culture of a single oocyte to a blastocyst-stage embryo in unstimulated cycles?

BACKGROUND: The aim of the study was to test the influence of 2- and 5-day cultivation of a single oocyte on the pregnancy rate in a non-stimulated cycle. METHODS: A retrospective chart review of 391 consecutive patients undergoing IVF and intracytoplasmic sperm injection in unstimulated cycles was performed. The embryos were kept in MediCult universal IVF medium for day 2 transfers and in BlastAssist System for day 5 transfers. RESULTS: The oocyte recovery rate in the group for 2-day cultivation and in the group for 5-day cultivation was similar, being 79.4 (162/204) and 83.6% (154/187) respectively. The same is true of the fertilization rate (73.8 versus 77.7%). The blastulation rate was 52.8%. The embryo transfer rate per cycle was higher when day 2 embryos were transferred: 64.8% (105/162) compared with 35.7% (55/154) if blastocyst-stage embryos were transferred. The pregnancy rate per transferred embryo was higher when a blastocyst was transferred (40.0%) instead of a day 2 embryo (23.8%). CONCLUSION: The expected pregnancy rate calculated per embryo available on day 2 of cultivation was similar in both groups (23.8 versus 22.2%) and it was not affected by oocyte culture to the blastocyst stage.