Wellington P. Martins

Ovarian hyperstimulation syndrome: pathophysiology and prevention

PurposeTo review and discuss the pathophysiology and prevention strategies for ovarian hyperstimulation syndrome (OHSS), which is a condition that may occur in up to 20% of the high risk women submitted to assisted reproductive technology cycles.MethodsThe English language literature on these topics were reviewed through PubMed and discussed with emphasis on recent data.ResultsThe role of estradiol, luteinizing hormone, human chorionic gonadotropin (hCG), inflammatory mediators, the renin-angiotensin system and vascular endothelial growth factor is discussed in the pathophysiology of OHSS. In addition we consider the prevention strategies, including coasting, administration of albumin, renin-angiotensin system blockage, dopamine agonist administration, non-steroidal anti-inflammatory administration, GnRH antagonist protocols, reducing hCG dosage, replacement of hCG and in vitro maturation of oocytes (IVM).ConclusionsAmong the many prevention strategies that have been discussed, the current evidence points to the replacement of hCG by GnRH agonists in antagonist cycles and the performance of IVM procedures as the safest approaches.

Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND Assisted hatching (AH) is a manipulation of zona pellucida aiming to facilitate embryo implantation. METHODS Systematic review and meta-analysis of medical literature was used to evaluate the effect of AH on assisted reproduction outcomes: clinical pregnancy, live birth, multiple pregnancy and miscarriage. Additional analysis was performed in these subgroups: (i) fresh embryos transferred to unselected or non-poor prognosis women; (ii) fresh embryos transferred to women with previous repeated failure; (iii) fresh embryos transferred to women of advanced age; (iv) frozen-thawed embryos transferred to unselected or non-poor prognosis women. Analyses were based on risk ratio and 95% confidence intervals (RR, 95% CIs) using Mantel-Haenszel random effects model. RESULTS There were 28 studies (5507 participants) included. AH was related to a trend toward increased clinical pregnancy for all participants (RR = 1.11, 95% CI = 1.00-1.24), with a significant increase in subgroups 2 (RR = 1.73; 95% CI = 1.37-2.17) and 4 (RR = 1.36; 95% CI = 1.08-1.72, P< 0.01), but not for subgroups 1 and 3. For multiple pregnancy, a significant increase was observed for all participants (RR = 1.45; 95% CI = 1.11-1.90) and for subgroups 2 (RR = 2.53; 95% CI = 1.23-5.21) and 4 (RR = 3.40; 95% CI = 1.93-6.01). No significant heterogeneity was observed in subgroup analysis. CONCLUSIONS AH was related to increased clinical pregnancy and multiple pregnancy rates in women with previous repeated failure or frozen-thawed embryos. However, AH is unlikely to increase clinical pregnancy rates when performed in fresh embryos transferred to unselected or non-poor prognosis women or to women of advanced age. Due to the small sample evaluated by the pool of included studies, no proper conclusions could be drawn regarding miscarriage or live birth.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements : A consensus opinion from the International Deep Endometriosis Analysis (IDEA) group

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright

Quantitative three-dimensional power Doppler angiography: a flow-free phantom experiment to evaluate the relationship between color gain, depth and signal artifact

To evaluate the presence of false flow three‐dimensional (3D) power Doppler signals in ‘flow‐free’ models.

Endometrial scratching performed in the non-transfer cycle and outcome of assisted reproduction: a randomized controlled trial

To investigate the effect of endometrial scratching, performed during oral contraceptive pill (OCP) pretreatment, on reproductive outcome and on ultrasound markers of endometrial receptivity, and to assess the pain involved in the procedure, in unselected women undergoing assisted reproductive techniques (ART).

Increased arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS) without comorbidities: one more characteristic inherent to the syndrome?

Background  Polycystic ovary syndrome (PCOS) is associated with adverse metabolic effects. Some cardiovascular disease (CVD) risk markers are increased in women with PCOS. However, early markers of atherosclerosis are also associated with obesity and insulin resistance, which are related to PCOS. These markers may result either directly from PCOS or indirectly as a consequence of the comorbidities associated with the syndrome.

Re: Three‐dimensional power Doppler: validity and reliability

In an Opinion in the September 2008 issue of this Journal, Alcazar stated that ‘more than 100 papers have been published analyzing the role of 3D power Doppler ultrasound in almost all areas of obstetrics and gynecology and, despite this abundance of literature on the application of 3D power Doppler ultrasound, it seems that so far few have stopped to ask what we are measuring’1. He was alluding to our 10-year experience of 3D power Doppler indices and commented on three articles published in that issue which, using in-vitro models, evaluated limitations of 3D power Doppler and its relationship with true flow2–4. Two of these three studies were conducted by the same group and used complex experimental models: a computer-controlled gear pump connected to different test tanks which were evaluated by 3D ultrasonography. Each test tank was designed for a specific purpose, but all contained tubes perfused with blood-mimicking fluid. Using this model, the authors evaluated the effect of flow rate, vessel number, attenuation, concentration of particles in the fluid3 and machine settings2 on the 3D power Doppler indices: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The other study evaluated two simpler models: a flow-free model using a tissue-equivalent phantom and a flow model, using a syringe infusion pump connected to a polyurethane tube that passed through a test tank, also evaluated by 3D ultrasonography. Using the models, the authors also evaluated the effect of certain machine settings (e.g. gain, pulse repetition frequency (PRF), wall motion filter) and fluid velocity on VI, FI and VFI. The three articles demonstrated that 3D power Doppler indices are highly dependent on both flow and machine settings as well as on the concentration of particles in the fluid and on attenuation. Their publication probably raised awareness and confidence in this technology: over 100 papers involving 3D power Doppler in obstetrics or gynecology have been published in just the last 2 years. After reading these three studies I tried to reproduce the model described by Schulten-Wijman et al.4. However, I stopped when I observed an intense attenuation caused by the tube wall, which clearly reduced the detection of flow by Doppler ultrasonography. This limitation of inorganic models has doubtless been observed by others and, aiming to better correlate 3D power Doppler indices with true perfusion, researchers went further. Jones et al.5 created an ingenious experimental model consisting of a human placental lobule exposed to dual perfusion (from both maternal and fetal sides) with a solution containing human erythrocytes. Using the model, the authors evaluated the influence of flow and erythrocyte concentration (0.5% and 5.0%) in a solution running within actual human vessels. The results of this work confirmed previous findings3 and demonstrated a strong association between flow and the 3D power Doppler indices (all R2 values exceeded 0.95, indicating that more than 95% of the variation observed in the indices could be attributed to variation in flow rate), a dependence of 3D power Doppler indices on erythrocyte concentration, and, by using agarbased tissue-mimicking material of different thicknesses (1–7 cm), that attenuation reduces all of these 3D power Doppler indices. In this issue of the Journal, we learn that researchers have gone still further in the quest to evaluate placental perfusion by 3D power Doppler and have developed an in-vivo model based on the pregnant sheep6. With the exception of the common uterine artery supplying the pregnant horn, which was dissected to apply occlusion and measure flow, all arterial supplies to the uterus were ligated and the 3D power Doppler indices within placentomes were evaluated. Different flow rates in the dissected uterine artery were applied in seven pregnant sheep. Ten datasets per sheep were obtained but 22 were excluded due to artifactual images, resulting in only 48 analyzed volumes. The authors observed a significant positive correlation between the 3D power Doppler indices and blood flow. The authors were very careful to consider the limitations of 3D power Doppler, especially the effect of attenuation, and they standardized their technique to evaluate only those placentomes situated 3–5 cm from the probe. The effect of attenuation can also be accounted for by normalizing the Doppler signal7 using ‘fractional moving blood volume’ (FMBV)8–10. Some believe that without this normalization 3D power Doppler indices should only be obtained using transvaginal gynecological ultrasonography, when the transducer is in close proximity to the organ under investigation11,12. However, I would argue that standardizing power Doppler evaluation is more important than is the normalization performed during FMBV, because the latter is not able to correct for all the consequences of attenuation or machine settings. The measures performed during FMBV evaluation are dependent on both presence/absence of Doppler signals and intensity (similar to VFI in 3D power Doppler7) but only the information related to Doppler signal intensity is normalized. However, previous studies clearly demonstrated that attenuation and machine settings interfere not only with signal intensity (represented in 3D power Doppler by FI),

Reliability and validity of tissue volume measurement by three-dimensional ultrasound: an experimental model

To determine the validity and the intra‐ and interobserver reliability of volume measurements of an endometrium‐like model using a three‐dimensional (3D) ultrasound rotational technique.

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

To evaluate whether the presence or severity of endometriosis affects the outcome of assisted reproductive techniques (ART).

Cabergoline for the prevention of ovarian hyperstimulation syndrome: systematic review and meta-analysis of randomized controlled trials

OBJECTIVE To evaluate the efficacy and safety of using cabergoline for reducing the risk of ovarian hyperstimulation syndrome (OHSS). DESIGN Systematic review and meta-analysis of randomized clinical trials (RCTs). PATIENTS Women submitted to controlled ovarian stimulation (COS) for assisted reproduction. INTERVENTIONS Cabergoline. SETTING Fertility centers. MAIN OUTCOME MEASURES Moderate-severe OHSS, live birth, clinical pregnancy, number of retrieved oocytes, miscarriage, congenital abnormalities. Comparisons were performed with the use of risk ratios (RRs) or mean differences (MDs) and their respective 95% confidence intervals (CIs). RESULT(S) Eight RCTs were considered to be eligible; data from seven studies could be extracted and included in the meta-analysis. Cabergoline reduces the risk of moderate-severe OHSS (RR 0.38, 95% CI 0.29-0.51, 7 studies, 858 women) and probably has no clinically relevant negative impact on clinical pregnancy (RR 1.02, 95% CI 0.78-1.34, 4 studies, 561 women) or on the number of retrieved oocytes (MD 1.15, 95% CI -0.76 to 3.07, 5 studies, 628 women). However, our estimates were imprecise for distinguishing between substantial harm, no effect, and substantial benefit considering live birth (RR 1.03, 95% CI 0.71-1.48, 1 study, 200 women), and miscarriage (RR 0.69, 95% CI 0.27 to 1.76, 3 studies, 194 pregnant women). No studies reported congenital abnormalities. CONCLUSION(S) Cabergoline reduces the occurrence of moderate-severe OHSS. Cabergoline is unlikely to have a clinically relevant negative impact on clinical pregnancy or on the number of retrieved oocytes. However, we are still uncertain of its impact on live birth, miscarriage, and congenital abnormalities.