Congenital anomaly and perinatal outcome following blastocyst- vs cleavage-stage embryo transfer: systematic review and network meta-analysis.

OBJECTIVES: To compare the reported rate of any congenital anomaly and perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer using a pairwise meta-analysis and to evaluate the same outcomes following fresh-blastocyst, frozen-blastocyst, fresh-cleavage or frozen-cleavage embryo transfer using a network meta-analysis. METHODS: A literature search was performed in PubMed, Scopus and CENTRAL and registers for ongoing studies, from inception to February 2022, for randomized controlled trials (RCTs) with any sample size and observational studies including at least 100 live births per group, comparing the rates of any congenital anomaly and perinatal outcome of pregnancy following fresh/frozen embryo transfer at cleavage (day 2-3) vs blastocyst (day 5-7) stage. Risk ratios (RRs) along with their 95% CIs were pooled via a random-effects model meta-analysis. Within a frequentist network meta-analysis framework, outcomes of all four treatment modalities (i.e. fresh-blastocyst, fresh-cleavage, frozen-blastocyst, frozen-cleavage) were compared further. Any congenital anomaly constituted the primary outcome, whereas preterm delivery (delivery < 37 weeks), low birth weight (LBW; < 2500 g), gender of the neonate (male), perinatal death and healthy neonate (defined as liveborn neonate, delivered at term, weighing ≥ 2500 g, surviving for at least 28 days postbirth and without any congenital anomaly) were considered as secondary outcomes. Subgroup analyses by plurality (liveborn singleton vs multiple pregnancy) were conducted in the pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool for RCTs and the ROBINS-I tool for non-randomized studies. Certainty of evidence was assessed using GRADE. RESULTS: Through the literature search, 550 studies were retrieved and 33 were included in the systematic review. We found no significant difference in the risk for any congenital anomaly between blastocyst- and cleavage-stage transfer (RR, 0.80 (95% CI, 0.63-1.03); 10 studies; n = 192 442; I2 = 85.5%). An increased probability of a male neonate was observed following blastocyst- vs cleavage-stage transfer (RR, 1.07 (95% CI, 1.06-1.09); 18 studies; n = 227 530; I2 = 32.7%). No significant differences in other secondary outcomes or significant subgroup differences between liveborn singletons and multiple pregnancies were observed. The network meta-analysis showed a significantly lower risk for LBW following frozen-blastocyst vs fresh-blastocyst (RR, 0.76 (95% CI, 0.60-0.95)) or fresh-cleavage (RR, 0.74 (95% CI, 0.59-0.93)) transfer. Frozen-blastocyst transfer was associated with an increased risk for perinatal death compared with the fresh-cleavage method (RR, 2.06 (95% CI, 1.10-3.88)). The higher probability of a male neonate following blastocyst transfer remained evident in the network comparisons. All outcomes were assessed to be of very-low certainty of evidence. CONCLUSIONS: Current very-low certainty of evidence shows that there may be little-to-no difference in the risk for congenital anomaly or adverse perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer, although there was a slightly increased probability of a male neonate following blastocyst transfer. When considering cryopreservation, frozen-blastocyst transfer was associated with a reduction in the risk for LBW compared with both fresh-transfer modalities, and fresh-cleavage transfer may be associated with a reduction in the risk for perinatal death compared with frozen-blastocyst transfer. High-quality RCTs with separate data on fresh and frozen cycles and consistent reporting of culture conditions and freezing methods are mandatory. Individual participant data meta-analyses are required to address the substantial inconsistency resulting from current aggregate data approaches. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Exploring the potential of novel biomixtures and Lentinula edodes fungus for the degradation of selected pesticides. Evaluation for use in biobed systems.

An approach to reduce the contamination of water sources with pesticides is the use of biopurificaction systems. The active core of these systems is the biomixture. The composition of biomixtures depends on the availability of local agro-industrial wastes and design should be adapted to every region. In Portugal, cork processing is generally regarded as environmentally friendly and would be interesting to find applications for its industry residues. In this work the potential use of different substrates in biomixtures, as cork (CBX); cork and straw, coat pine and LECA (Light Expanded Clay Aggregates), was tested on the degradation of terbuthylazine, difenoconazole, diflufenican and pendimethalin pesticides. Bioaugmentation strategies using the white-rot fungus Lentinula edodes inoculated into the CBX, was also assessed. The results obtained from this study clearly demonstrated the relevance of using natural biosorbents as cork residues to increase the capacity of pesticide dissipation in biomixtures for establishing biobeds. Furthermore, higher degradation of all the pesticides was achieved by use of bioaugmented biomixtures. Indeed, the biomixtures inoculated with L. edodes EL1 were able to mineralize the selected xenobiotics, revelling that these white-rot fungi might be a suitable fungus for being used as inoculum sources in on-farm sustainable biopurification system, in order to increase its degradation efficiency. After 120 days, maximum degradation of terbuthylazine, difenoconazole, diflufenican and pendimethalin, of bioaugmented CBX, was 89.9%, 75.0%, 65.0% and 99.4%, respectively.. The dominant metabolic route of terbuthylazine in biomixtures inoculated with L. edodes EL1 proceeded mainly via hydroxylation, towards production of terbuthylazine-hydroxy-2 metabolite. Finally, sorption process to cork by pesticides proved to be a reversible process, working cork as a mitigating factor reducing the toxicity to microorganisms in the biomixture, especially in the early stages.

Ultrasound guidance during embryo transfer: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To summarize the current evidence on the effect of using ultrasound (US) guidance during embryo transfer (ET). METHODS: In this systematic review, we included randomized controlled trials examining the effect of the use of US guidance during ET; data from studies using the same catheter type in study arms were not pooled with the results from studies that used different catheter types. RESULTS: Twenty-one studies were included in the quantitative analysis: 18 compared 'US guidance' with 'clinical touch', of which one was subsequently excluded from the quantitative meta-analysis owing to a lack of available data, three studies compared transvaginal US guidance with transabdominal US guidance, and one study compared 'hysterosonometry before ET' with US guidance. Comparison of the use of US guidance with clinical touch, in studies that used the same catheter type in the study arms, indicated a benefit of using US guidance during ET on the rates of live birth (relative risk (RR), 1.48 (95% CI, 1.16-1.87)), based on two studies involving 888 women with moderate-quality evidence, and on the rates of clinical pregnancy (RR, 1.32 (95% CI, 1.18-1.46)), based on 13 studies involving 3641 women with high-quality evidence. However, when comparing the use of US guidance with clinical touch in studies that used different catheter types, the results suggest that using US guidance during ET has no effect on the rates of reproductive outcome: live birth (RR, 0.99 (95% CI, 0.83-1.19)), based on one study involving 1649 women with moderate-quality evidence; clinical pregnancy (RR, 1.04 (95% CI, 0.89-1.21)), based on five studies involving 2949 women with moderate-quality evidence. The estimates for the rate of miscarriage and for the other identified comparisons were imprecise. CONCLUSIONS: The available evidence suggests that there is a benefit of using US guidance during ET. However, both US-guided transfer and clinical touch should be considered acceptable, as the benefit of US is not large and should be balanced against the increased cost and need to change the catheter type. More studies are required before conclusions can be drawn regarding the effect of other techniques on reproductive outcome.

Ovarian hyperstimulation syndrome: pathophysiology, staging, prediction and prevention.

OBJECTIVE: To identify, appraise and summarize the current evidence regarding the pathophysiology, staging, prediction and prevention of ovarian hyperstimulation syndrome (OHSS). METHODS: Two comprehensive systematic reviews were carried out: one examined methods of predicting either high ovarian response or OHSS and the other examined interventions aimed at reducing the occurrence of OHSS. Additionally, we describe the related pathophysiology and staging criteria. RESULTS: Seven studies examining methods of predicting OHSS and eight more examining methods of predicting high ovarian response to controlled ovarian stimulation were included. Current evidence shows that the best methods of predicting high response are antral follicle count and anti-Müllerian hormone levels, and that a high ovarian response (examined by the number of large follicles, estradiol concentration or the number of retrieved oocytes) is the best method of predicting the occurrence of OHSS. Ninety-seven randomized controlled trials examining the effect of several interventions for reducing the occurrence of OHSS were included. There was high-quality evidence that replacing human chorionic gonadotropin by gonadotropin-releasing hormone agonists or recombinant luteinizing hormone, and moderate-quality evidence that antagonist protocols, dopamine agonists and mild stimulation, reduce the occurrence of OHSS. The evidence for the effect of the other interventions was of low/very low quality. Additionally, we identified and described 12 different staging criteria. CONCLUSIONS: There are useful predictive tools and several preventive interventions aimed at reducing the occurrence of OHSS. Acknowledging and understanding them are of crucial importance for planning the treatment of, and, ultimately, eliminating, OHSS while maintaining high pregnancy rates.

Impact of endometriosis and its staging on assisted reproduction outcome: systematic review and meta-analysis.

OBJECTIVE: To evaluate whether the presence or severity of endometriosis affects the outcome of assisted reproductive techniques (ART). METHODS: In this systematic review, all studies comparing the outcome of ART in women with and those without endometriosis, or at different stages of the disease, were considered eligible. We used either risk ratio (RR) or mean difference (MD) and their 95%CIs for comparisons. The primary outcome was live birth; the secondary outcome was clinical pregnancy. Miscarriage and the number of oocytes retrieved were examined as additional outcomes. RESULTS: We included 92 studies in the review and 78 in the meta-analysis: 20,167 women with endometriosis were compared with 121,931 women without endometriosis, and 1703 women with Stage-III/IV endometriosis were compared with 2227 women with Stage-I/II endometriosis. The following results were observed for the comparison of women with endometriosis vs women without endometriosis: live birth, RR = 0.99 (95%CI, 0.92-1.06); clinical pregnancy, RR = 0.95 (95%CI, 0.89-1.02); miscarriage, RR = 1.31 (95%CI, 1.07-1.59); number of oocytes retrieved, MD = -1.56 (95%CI, -2.05 to -1.08). The following results were observed for the comparison of women with Stage-III/IV vs Stage-I/II endometriosis: live birth, RR = 0.94 (95%CI, 0.80-1.11); clinical pregnancy, RR = 0.90 (95%CI, 0.82-1.00); miscarriage, RR = 0.99 (95%CI, 0.73-1.36); number of oocytes retrieved, MD = -1.03 (95%CI, -1.67 to -0.39). CONCLUSIONS: Women with endometriosis undergoing ART have practically the same chance of achieving clinical pregnancy and live birth as do women with other causes of infertility. No relevant difference was observed in the chance of achieving clinical pregnancy and live birth following ART when comparing Stage-III/IV with Stage-I/II endometriosis. The quality of the evidence for the additional examined outcomes was very low, not allowing meaningful conclusions to be drawn.

Ultrasound for monitoring controlled ovarian stimulation: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of monitoring controlled ovarian stimulation (COS) using ultrasonography. METHODS: We performed a search in April 2013 for randomized controlled trials (RCTs). Studies that compared different methods for monitoring COS, including ultrasound assessment of follicles (alone or combined with hormonal assessment), in at least one group were considered eligible. RESULTS: The search retrieved 1515 records, six of which were eligible. Five studies were included that compared ultrasonography alone with ultrasonography and hormonal assessment (estradiol and/or progesterone) and one study compared 2D and 3D ultrasound monitoring. None of the included studies reported on live birth. Four of the five studies reported on clinical pregnancy (RR, 0.95; 95% CI, 0.78­1.16; n = 611); the confidence interval (CI) was somewhat wide, but allowed us to conclude that ultrasonography alone differs little from ultrasonography combined with hormonal assessment. Three studies reported on the number of oocytes retrieved (mean difference (MD), 0.8 oocytes; 95% CI, ­0.4 to 2.0; n = 474); the CI was somewhat wide and did not permit us to conclude whether ultrasonography alone is better than or similar to ultrasonography and hormonal assessment for this outcome. All five studies reported on ovarian hyperstimulation syndrome (OR, 1.02; 95% CI, 0.47­2.25; n = 725) and only one study reported on miscarriage (RR, 0.37; 95% CI, 0.07­1.79; n = 45); for these two outcomes, the CI was very wide and did not permit us to conclude whether ultrasonography alone is better, similar or less effective than ultrasonography combined with hormonal assessment. For the study comparing 2D and 3D ultrasound, the reported outcomes were clinical pregnancy (RR, 1.00; 95% CI, 0.58­1.73, n = 72) and the number of oocytes retrieved (MD, ­0.4 oocytes; 95% CI, ­3.6 to 2.9; n = 72); for both, the CI was very wide and did not permit us to conclude whether use of 3D ultrasound is better, similar or less effective than use of 2D ultrasound. CONCLUSIONS: Current evidence suggests that monitoring COS only with ultrasonography is unlikely to substantially alter the chances of achieving a clinical pregnancy and the number of oocytes retrieved is similar to that when monitoring with ultrasonography and hormonal assessment. For the other outcomes and comparisons, the available data are inconclusive. We believe that more studies evaluating the optimal procedure for monitoring COS are needed.

Visceral larva migrans and tropical pyomyositis: a case report.

We report a case of tropical pyomyositis in a boy who presented with a severe febrile illness associated with diffuse erythema, and swelling in many areas of the body which revealed on operation extensive necrotic areas of various muscles that required repeated débridement. The patient gave a history of contact with dogs, and an ELISA test for Toxocara canis was positive. He also presented eosinophilia and high serum IgE levels. Staphylococcus aureus was the sole bacteria isolated from the muscles affected. We suggest that tropical pyomyositis may be caused by the presence of migrating larvae of this or other parasites in the muscles. The immunologic and structural alterations caused by the larvae, in the presence of concomitant bacteremia, would favour seeding of the bacteria and the development of pyomyositis.