Improvement instead of stability in embryo quality between day 3-5: A possible extra predictor for blastocyst selection.

OBJECTIVE: The aim of this study was to evaluate the predictive value of the dynamic morphological development process between cleavage-stage and blastocyst-stage embryos. STUDY DESIGN: A retrospective study was executed between 2015 and 2017 at Ghent University Hospital. A total of 996 first fresh IVF/ICSI cycles resulting in a single embryo transfer on day 5 were included. Embryos were scored on day 3 and day 5 as excellent, good, moderate or poor based on Alpha/ESHRE guidelines and Gardner and Schoolcraft scoring-system. If embryos changed category between day 3 and 5, the number of steps (between excellent; good; moderate; poor) in positive and negative direction was expressed. RESULTS: On day 5, the ongoing pregnancy rate (OPR) of excellent embryos was 37.4 %. Univariate analyses showed that on day 5, both a higher cell stage, better inner cell mass and better trophectoderm were significantly associated with an ongoing pregnancy. In case of deterioration in quality of individual embryos between day 3 and day 5, the OPR was significantly lower. Conversely, improvement of embryo quality between day 3 and day 5 showed higher ongoing pregnancy rates (overall OPR of good day-3 embryos improving to excellent day-5 embryos: 30 %; moderate day 3 to excellent day 5: 50 %; poor day 3 to excellent day 5: 42 %; poor day 3 to good day 5: 20 %; poor day 3 to moderate day 5: 16 %). When embryos improved from poor on day 3 to excellent day 5 the OPR was significantly higher in comparison with embryos that did not change in quality scoring during development (steady embryos) (OR: 1.785, p < 0.05). CONCLUSION: Our results suggest that it is more likely to achieve an ongoing pregnancy when transferring an embryo that has improved in quality between days 3 and 5 as opposed to one that has remained stable.

Blind Source Separation for Clutter and Noise Suppression in Ultrasound Imaging: Review for Different Applications.

Blind source separation (BSS) refers to a number of signal processing techniques that decompose a signal into several "source" signals. In recent years, BSS is increasingly employed for the suppression of clutter and noise in ultrasonic imaging. In particular, its ability to separate sources based on measures of independence rather than their temporal or spatial frequency content makes BSS a powerful filtering tool for data in which the desired and undesired signals overlap in the spectral domain. The purpose of this work was to review the existing BSS methods and their potential in ultrasound imaging. Furthermore, we tested and compared the effectiveness of these techniques in the field of contrast-ultrasound super-resolution, contrast quantification, and speckle tracking. For all applications, this was done in silico, in vitro, and in vivo. We found that the critical step in BSS filtering is the identification of components containing the desired signal and highlighted the value of a priori domain knowledge to define effective criteria for signal component selection.

Visual inspection of transvaginal ultrasound videos to characterize uterine peristalsis: an inter-observer agreement study.

PURPOSE: Contractions in non-pregnant uterine can be assessed by visual inspection of transvaginal ultrasound (TVUS). Many authors have used this method to extract features like contraction frequency and direction. However, visual inspection is a subjective method and the outcome is dependent on the sonographers and video analysts. In this study, we wanted to see which uterine feature is reproducible enough, in terms of inter-observer agreement, to serve as a reliable control for future research. METHODS: Six observers assessed 80 TVUS videos, and rated video quality, contraction frequency, direction and timing. One observer assessed operating time. A Fleiss' kappa (κ) or an intra-class correlation (ICC) was calculated to determine the inter-observer agreement of all features. RESULTS: The inter-observer agreement in frequency was substantial (ICC = 0.68). Conversely, there was just slight to fair agreement in contraction timing and direction and in video quality: ICC = 0.26, κ = 0.17 and κ = 0.16, respectively. Overall, agreement among technical engineers was better than between medical professionals. The level of agreement was correlated with video quality, phase of the menstrual cycle and individual patient (all χ2 with p < 0.00). The time to analyze one video ranged between 6 and 20 min. CONCLUSIONS: This study shows that visual inspection of TVUS videos is a fairly reproducible method to assess contraction frequency. However, the operating time is too extensive to implement this method in daily practice. Automated methods could offer a solution for this problem in the future.

Does endometrial scratching increase the rate of spontaneous conception in couples with unexplained infertility and a good prognosis (Hunault > 30%)? Study protocol of the SCRaTCH-OFO trial: a randomized controlled trial.

BACKGROUND: In the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault > 30%) are advised to perform timed intercourse for at least another 6 months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called 'endometrial scratching', has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility. METHOD: A multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception < 12 months (Hunault > 30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6 months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12 months. DISCUSSION: Several small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conception < 12 months. TRIAL REGISTRATION: NTR6687 , registered August 31st, 2017. PROTOCOL VERSION: Version 2.6, November 14th, 2018.

Preconceptional low-dose aspirin for the prevention of hypertensive pregnancy complications and preterm delivery after IVF: a meta-analysis with individual patient data.

STUDY QUESTION: Does preconceptionally started low-dose aspirin prevent hypertensive pregnancy complications and preterm delivery in IVF patients? SUMMARY ANSWER: The current data do not support the use of preconceptionally started low-dose aspirin treatment for the prevention of hypertensive pregnancy complications and preterm delivery in IVF women. WHAT IS KNOWN ALREADY: Studies starting low-dose aspirin treatment as prevention in the second trimester of pregnancy found no or only moderate reductions in the relative risk of developing pre-eclampsia. Low-dose aspirin was possibly started too late, that is after the first episode of trophoblast invasion. STUDY DESIGN, SIZE, DURATION: We performed a meta-analysis with individual patient data (IPD), in which four authors could provide IPD on a total of 268 pregnancies (n = 131 treated with aspirin, n = 137 placebo). Data on hypertensive pregnancy complications and preterm delivery were collected. PARTICIPANTS/MATERIALS, SETTING, METHODS: All separate databases were merged into a summary database. Treatment effect of aspirin on the incidence of hypertensive pregnancy complications (n = 187) and preterm delivery (n = 180) were estimated with odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: There were significantly fewer twin pregnancies in the aspirin group (OR 0.55 95% CI 0.30-0.98), but no significant differences for hypertensive pregnancy complications and preterm delivery: for singletons OR 0.62 (95% CI 0.22-1.7) and OR 0.52 (95% CI 0.16-1.7), respectively, as well as for twin pregnancies OR 1.2 (95% CI 0.35-4.4) and OR 1.6 (95% CI 0.51-5.0), respectively. LIMITATIONS, REASONS FOR CAUTION: We have to bear in mind that the included studies showed clinical heterogeneity; there was variation in the duration of low-dose aspirin therapy and degree of hypertension between the different studies. Although we combined IPD from four studies, we have to realize that the studies were not powered for the outcome of the current IPD meta-analysis. WIDER IMPLICATIONS OF THE FINDINGS: Based on the current meta-analysis with IPD we found no confirmation for the hypothesis that preconceptionally started low-dose aspirin reduces the incidence of hypertensive pregnancy complications or preterm delivery in IVF women. Larger studies are warranted.

Is aspirin effective in women undergoing in vitro fertilization (IVF)? Results from an individual patient data meta-analysis (IPD MA).

BACKGROUND: Aspirin is believed to improve the outcome of IVF, but previous conventional meta-analyses on the subject are conflicting. Therefore, we performed a meta-analysis with individual patient data (IPD MA) of randomized clinical trials (RCTs) on the subject. METHODS: A systematic literature search was conducted to identify RCTs assessing the effectiveness of aspirin in IVF. Authors were asked to share their original data. In a one step meta-analytic approach, the treatment effect of aspirin was estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression, based on the intention to treat principle. RESULTS: Ten studies fulfilled the inclusion criteria. Authors of six studies provided IPD, including 1119 patients (562 placebo and 557 aspirin). There were 160 clinical pregnancies in the aspirin (28.8%) and 179 (31.9%) in the placebo group [OR 0.86, 95% CI (0.69-1.1)]. There were 129 ongoing pregnancies in the aspirin (23.6%) and 147 in the placebo group (26.7%) [OR 0.85, 95% CI (0.65-1.1)]. Whereas the conventional meta-analysis limited to studies that could provide IPD showed an OR of 0.89 (95% CI 0.69-1.2), the conventional meta-analysis limited to the eight studies of which method of randomization could be confirmed showed an OR of 0.94 (95% CI 0.76-1.17) and the conventional meta-analysis including all 10 eligible RCTs identified with our search changed the OR to 1.07 (95% CI 0.81-1.41). This difference in direction of effect, derived from the studies not able to share IPD of which quality of randomization could not be confirmed. CONCLUSIONS: Aspirin does not improve pregnancy rates after IVF.

Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility.

In a double-blind, placebo-controlled, randomized study, 55 anovulatory subjects received a single s.c. injection of placebo (n = 10) or recombinant long-acting FSH [FSH-carboxy terminal peptide (CTP), ORG 36286, corifollitropin alfa; NV Organon, The Netherlands] in doses of 7.5 (n = 13), 15 (n = 10), 30 (n = 11), or 60 microg (n = 11). The injection was given 2 or 3 d after the onset of a spontaneous or progestagen-induced withdrawal bleed. After drug administration, the induced follicular response varied widely among subjects in each dose group. The percentage of subjects with a follicular response (at least one follicle > or = 10.0 mm) increased with the dose (P < 0.01) and was 10, 31, 70, 73, and 82% in the placebo and 7.5-, 15-, 30-, and 60-microg treatment groups, respectively. In responding subjects, the average maximum number of follicles was 4.0, 7.6, 13.4, and 20.0, respectively, which was reached at 6.5, 6.9, 6.6, and 8.2 d after a single dose of 7.5, 15, 30, and 60 microg FSH-CTP, respectively. The dose-response for the number of follicles was statistically significant within the dose range tested (P < 0.01). Peak serum inhibin-B levels were significantly correlated with serum estradiol (E2) levels (r = 0.84, P < 0.01), and peak concentrations of inhibin-B and E2 correlated with the number of follicles observed at the same time point (for both hormones; r = 0.47, P < 0.01). Overall per treatment group, serum E2 and inhibin B concentrations significantly increased only in the two highest FSH-CTP dose groups, reaching peak concentrations at d 3 in the 30-microg group and at d 5 in the 60-microg group. Thereafter these hormone values declined rapidly, returning to baseline within 1 wk after FSH-CTP administration. In total, nine of the 55 treated subjects (16.4%) ovulated after drug administration: one subject in the placebo group, two subjects in the 7.5-microg group, three subjects in the 15-microg group, two in the 30-microg group, and one in the 60-microg group. Three subjects had monofollicular ovulation after placebo (n = 1) and a single dose of 15 microg FSH-CTP (n = 2). In two subjects with too many preovulatory follicles, (multiple) ovulation was prevented by GnRH antagonist administration. Thus, a single low dose of long-acting FSH-CTP was able to induce one or more follicles to grow up to ovulatory sizes, but the anovulatory status was not reversed because the incidence of subsequent (mono)ovulations was low.

The ex utero intrapartum treatment (EXIT) procedure in fetal neck masses: a case report and review of the literature.

Large fetal neck masses can cause airway obstructions with potential fetal demise after delivery. The relationship of the neck mass to airway structures can be defined prenatally with ultrasound and magnetic resonance imaging (MRI). The ex utero intrapartum treatment (EXIT) procedure can be used to obtain a fetal airway while feto-maternal circulation is preserved to optimise fetal outcome. We present a case in which prenatally a large fetal neck mass was diagnosed on ultrasound and a successful EXIT procedure was performed. A review of the literature is given and the prenatal use of ultrasonography and MRI in case of fetal neck masses is discussed.

Circulating immunoreactive and bioactive follicle stimulating hormone concentrations in anovulatory infertile women and during gonadotrophin induction of ovulation using a decremental dose regimen.

Our purpose was to determine whether decreased follicle stimulating hormone (FSH) activity, either systemic or at the follicular level, is involved in impaired follicle growth associated with normogonadotrophic anovulation. To differentiate between the possible levels of disturbance, bioactive (BIO-FSH; using the in-vitro rat granulosa cell aromatase bioassay) and immunoreactive (IRMA-FSH) FSH serum concentrations of three groups of subjects were compared: (i) 172 normogonadotrophic anovulatory infertile women during baseline conditions, (ii) 22 clomiphene-resistant polycystic ovary syndrome patients undergoing ovulation induction by exogenous gonadotrophins using a decremental dose regimen, and (iii) nine regularly cycling controls. BIO-FSH [13.2 (range 0.8-29.5) IU/l] and IRMA-FSH [4.4 (range 1.2-9.3) IU/l] concentrations in anovulatory women during baseline conditions were significantly lower than maximum concentrations reached during the follicular phase in controls [18.7 (13.2-23.4) and 6.4 (5.7-10.0) IU/l respectively], but were not significantly different from initial concentrations in controls [10.4 (7.2-19.6) and 4.8 (2.8-8.2) IU/l respectively]. Moreover, concentrations of IRMA-FSH and BIO-FSH were negatively correlated (r = -0.25, P = 0.01, and r = -0.24, P = 0.02 respectively) with the interval between last vaginal bleeding and blood sampling. Maximum concentrations of IRMA-FSH [7.6 (3.9-10.9) IU/l] during ovulation induction by gonadotrophins were not significantly different from maximum [6.4 (5.7-10.0) IU/l] concentrations in controls, whereas maximum BIO-FSH concentrations [13.5 (8.7-17.4) versus 18.7 (13.2-23.4) IU/l] were significantly lower. Our findings suggest that (i) circulating FSH does not reach concentrations that are sufficient to induce normal follicle development in anovulatory women during baseline conditions, and (ii) the FSH threshold for ovarian stimulation of this patient group is not different from normal.

[Regret after sterilization in women]. / Spijt na sterilisatie bij de vrouw.

PIP: Feelings of regret seem to occur frequently after sterilization, but are mostly short-lived. Women in a test group who asked for reversal did so, on the average, after 3.8 years. This is a major operation and should be discussed thoroughly and, if possible, avoided, to keep requests from increasing. 118 patients who asked for reversal were compared with 116 control patients matched by sterilization date. The reversal group was sterilized at a much younger age, and over 8 times as many had other gynecological procedures at the same time as the control group. The reversal group altered their marital status after sterilization at a higher rate than the control group; both groups had the same number of children at the time of sterilization. Out of the control group, only 1 patient out of 88 reported guilt feelings to the family doctor after a child died. 1/5 of the reversal patients were operated on at the time of other gynecological or obstetrical surgery: 12 abortions, 6 prolapse operations, 4 cesarean sections, and 2 operations due to extrauterine pregnancy. These occurred in only 3 women in the control group. This combination of sterilization and gynecological problems should be avoided, with patients following their doctors' advice. However, patients should have more time to think things over and should not be pressured into sterilization, especially since sterilization can be performed in a clinic under local anesthesia. Reversal should not be encouraged.^ieng