Clomiphene citrate and letrozole to reduce follicle-stimulating hormone consumption during ovarian stimulation: systematic review and meta-analysis.

OBJECTIVE: To assess the available evidence comparing effectiveness of ovarian stimulation (OS) using clomiphene citrate (CC) and/or letrozole (LTZ) to reduce follicle-stimulating hormone (FSH) consumption compared with standard OS. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials that compared reproductive outcomes following in-vitro fertilization. We searched 11 electronic databases and hand-searched the reference lists of included studies and related reviews. We stratified the results, separating studies according to the oral agent used (CC or LTZ) and the characteristics of the included women (expected poor ovarian response or other women). When combining the results of the included studies, we assessed the relative risk (RR) for live birth, clinical pregnancy, miscarriage and cycle cancelation, the Peto odds ratio (OR) for ovarian hyperstimulation syndrome (OHSS) and mean difference (MD) for the number of oocytes retrieved and FSH consumption. RESULTS: A total of 22 studies were included in the review. Considering women with expected poor ovarian response, the available evidence suggested that using CC to reduce FSH consumption during OS provided similar rates of live birth (RR, 0.9 (95% CI, 0.6-1.2), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.4), moderate-quality evidence); the use of LTZ did not cause a relevant change in the number of oocytes retrieved (MD, -0.4 (95% CI, -0.9 to 0.1), high-quality evidence). Considering the studies evaluating other women, the available evidence suggested that using CC to reduce FSH consumption during OS reduced the number of oocytes retrieved (MD, -4.6 (95% CI, -6.1 to -3.0), high-quality evidence) and risk of OHSS (Peto OR, 0.2 (95% CI, 0.1-0.3), moderate-quality evidence), while results were similar for rates of live birth (RR, 0.9 (95% CI, 0.7-1.1), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.1), high-quality evidence). The quality of the evidence was low or very low for other outcomes. CONCLUSION: The use of CC to reduce FSH consumption in women with expected poor ovarian response has the advantage of providing similar reproductive outcomes with reduced costs. For the other women, the use of CC for reducing FSH consumption has the additional advantage of reducing OHSS, but also reduces the total number of oocytes retrieved. More studies are needed to evaluate the effect of LTZ for the same purpose. Future studies should focus on cumulative pregnancy per oocyte retrieval, patient dissatisfaction and agreement to repeat the cycle if not pregnant, which are important outcomes for clinical decisions. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Blastocyst vs cleavage-stage embryo transfer: systematic review and meta-analysis of reproductive outcomes.

OBJECTIVES: Blastocyst transfer in assisted reproduction techniques could be advantageous because the timing of exposure of the embryo to the uterine environment is more analogous to a natural cycle and permits embryo self-selection after activation of the embryonic genome on day 3. Conversely, the in-vitro environment is likely to be inferior to that in vivo, and in-vitro culture beyond embryonic genomic activation could potentially harm the embryo. Our objective was to identify, appraise and summarize the available evidence comparing the effectiveness of blastocyst vs cleavage-stage embryo transfer. METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the transfer of blastocysts (days 5-6) with the transfer of cleavage-stage embryos (days 2-3) in women undergoing in-vitro fertilization or intracytoplasmic sperm injection. The last electronic searches were run on 1 August 2016. Abstracts and studies with a mean difference between the two study groups of > 0.5 for the number of embryos transferred were excluded. RESULTS: We screened 1187 records and assessed 33 potentially eligible studies. Twelve studies were included, comprising a total of 1200 women undergoing blastocyst transfer and 1218 undergoing cleavage-stage embryo transfer. We observed low-quality evidence of no significant difference of blastocyst transfer on live birth/ongoing pregnancy (relative risk (RR), 1.11 (95% CI, 0.92-1.35), 10 RCTs, 1940 women, I2 = 54%), clinical pregnancy (RR, 1.10 (95% CI, 0.93-1.31), 12 RCTs, 2418 women, I2 = 64%), cumulative pregnancy (RR, 0.89 (95% CI, 0.67-1.16), four RCTs, 524 women, I2 = 63%) and miscarriage (RR, 1.08 (95% CI, 0.74-1.56), 10 RCTs, 763 pregnancies, I2 = 0%). There was moderate-quality evidence of a decrease in the number of women with surplus embryos after the blastocyst-stage embryo transfer (RR, 0.78 (95% CI, 0.66-0.91)). Overall, the quality of the evidence was limited by the quality of the included studies and by unexplained inconsistency across studies. CONCLUSIONS: Current evidence shows no superiority of blastocyst compared with cleavage-stage embryo transfer in clinical practice. As the quality of the evidence for the primary outcomes is low, additional well-designed RCTs are still needed before robust conclusions can be drawn. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Obstetrical and perinatal outcomes following blastocyst transfer compared to cleavage transfer: a systematic review and meta-analysis.

STUDY QUESTION: Is blastocyst transfer safe when compared to cleavage stage embryo transfer regarding obstetric and perinatal outcomes? SUMMARY ANSWER: The clinical equipoise between blastocyst and cleavage stage embryo transfer remains as the evidence associating blastocyst transfer with some adverse perinatal outcomes is of low/very low quality. WHAT IS KNOWN ALREADY: Extended embryo culture to the blastocyst stage provides some theoretical advantages and disadvantages. While it permits embryo self-selection, it also exposes those embryos to possible harm due to the in vitro environment. Both effectiveness and safety should be weighed to permit evidence-based decisions in clinical practice. STUDY DESIGN, SIZE, DURATION: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies reporting perinatal outcomes for singletons comparing the deliveries resulting from blastocyst and cleavage stage embryo transfer. Observational studies were included because the primary outcomes, perinatal mortality and birth defects, are rare and require a large number of participants (>50 000) to be properly assessed. The last electronic searches were last run on 11 March 2016. PARTICIPANTS/MATERIALS, SETTING, METHOD: There were 12 observational studies encompassing 195 325 singleton pregnancies included in the study. No RCT reported the studied outcomes. The quality of the included studies was evaluated according to the Newcastle-Ottawa Scale and the quality of the evidence was evaluated according to GRADE criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst stage transfer was associated with increased risks of preterm birth (<37 weeks), very preterm birth (<32 weeks), large for gestational age and perinatal mortality, although the latter was only identified from one study. Conversely, blastocyst stage transfer was associated with a decrease in the risks of small for gestational age and vanishing twins, although the latter was reported by only one study. LIMITATIONS, REASONS FOR CAUTION: The observational nature of the included studies and some inconsistency and imprecision in the analysis contributed to decreasing our confidence in the estimates. WIDER IMPLICATIONS OF THE FINDINGS: Due to the overall low quality of available evidence, the clinical equipoise between cleavage stage and blastocyst transfer remains. More large well-conducted studies are needed to clarify the potential risks and benefits of blastocyst transfer. As this review was initiated to support global recommendations on best practice, and in light of the challenges in lower resource settings to offer extended culture to blastocyst stage, it is critical to take into consideration these obstetric and neonatal outcomes in order to ensure any recommendation will not result in the overburdening of existing maternal and child health care systems and services. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no competing interests to declare. PROSPERO REGISTRATION NUMBER: CRD42015023910.

High miscarriage rate in women treated with Essure® for hydrosalpinx before embryo transfer: a systematic review and meta-analysis.

OBJECTIVES: Essure® has been tested as an alternative treatment for hydrosalpinx before embryo transfer (ET) in women undergoing assisted reproduction techniques. However, the persistence of a foreign body inside the uterine cavity might have a negative impact on the outcome of pregnancy. The present systematic review aimed at identifying, appraising and summarizing the available evidence regarding the effectiveness and safety of using Essure prior to ET for women with hydrosalpinx. METHODS: We searched for studies in PubMed, Scopus, CENTRAL, Web of Science and ClinicalTrials.gov and the reference lists of eligible studies. All studies including at least 10 women with hydrosalpinx who received Essure, any other intervention or no treatment prior to ET were considered eligible. Study selection, data extraction and evaluation of the risk of bias were performed independently by two authors. Study outcomes were miscarriage per clinical pregnancy, singleton preterm birth per singleton live birth and live birth/ongoing pregnancy and clinical pregnancy per ET. The pooled results for each outcome and intervention were summarized as proportions with their respective 95% CIs, using a random-effects model. RESULTS: Our electronic search of databases was performed on 7 November 2015, and 26 studies with 43 study arms were considered eligible: eight study arms evaluating Essure; seven assessing tubal aspiration; seven appraising effects of no treatment; 12 evaluating salpingectomy; two assessing tubal division; and seven evaluating tubal occlusion. When compared with women who had no intervention, women with Essure had a higher clinical pregnancy rate per ET (36% (95% CI, 0-43%) vs 13% (95% CI, 9-17%)). When compared with women who had other interventions, women with Essure had a higher miscarriage rate per clinical pregnancy (38% (95% CI, 27-49%) vs 15% (95% CI, 10-19%)). CONCLUSIONS: The available evidence suggests that, although Essure prior to ET in women with hydrosalpinx improves the chance of achieving a clinical pregnancy compared with no intervention, it is associated with a higher rate of miscarriage when compared with the other interventions. Although this evidence is based on observational studies, we believe that salpingectomy should be the first option for women who are eligible for videolaparoscopy. However, it is still premature to make recommendations for women who are not eligible for surgery, and randomized controlled trials are needed to clarify which is the best treatment alternative in such a scenario. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Dydrogesterone vs progesterone for luteal-phase support: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To compare the effects of dydrogesterone and progesterone for luteal-phase support (LPS) in women undergoing assisted reproductive techniques (ART). METHODS: We performed a systematic review to identify relevant randomized controlled trials (RCTs) by searching the following electronic databases: Cochrane CENTRAL, PubMed, Scopus, Web of Science, ClinicalTrials.gov, ISRCTN Registry and WHO ICTRP. RESULTS: The last search was performed in October 2015. Eight RCTs were considered eligible and were included in the review and meta-analyses. There was no relevant difference between oral dydrogesterone and vaginal progesterone for LPS with respect to rate of ongoing pregnancy (risk ratio (RR), 1.04 (95% CI, 0.92-1.18); I(2) , 0%; seven RCTs, 3134 women), clinical pregnancy (RR, 1.07 (95% CI, 0.93-1.23); I(2) , 34%; eight RCTs, 3809 women) or miscarriage (RR, 0.77 (95% CI, 0.53-1.10); I(2) , 0%; seven RCTs, 906 clinical pregnancies). Two of the three studies reporting on dissatisfaction of treatment identified lower levels of dissatisfaction among women using oral dydrogesterone than among women using vaginal progesterone (oral dydrogesterone vs vaginal progesterone capsules: 2/79 (2.5%) vs 90/351 (25.6%), respectively; oral dydrogesterone vs vaginal progesterone gel: 19/411 (4.6%) vs 74/411 (18.0%), respectively). The third study showed no difference in dissatisfaction rate (oral dydrogesterone vs vaginal progesterone capsules: 8/96 (8.3%) vs 8/114 (7.0%), respectively). CONCLUSIONS: Oral dydrogesterone seems to be as effective as vaginal progesterone for LPS in ART cycles, and appears to be better tolerated . Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

GnRH agonist during luteal phase in women undergoing assisted reproductive techniques: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To identify, evaluate and summarize the available evidence regarding the effectiveness and safety of administering a gonadotropin releasing hormone (GnRH) agonist during the luteal phase in women undergoing assisted reproductive techniques. METHODS: In this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) comparing the addition of a GnRH agonist during the luteal phase, compared with standard luteal-phase support. We searched seven electronic databases and hand-searched the reference lists of included studies and related reviews. Our primary outcome was live birth or ongoing pregnancy per randomized woman. Our secondary outcomes were clinical pregnancy per randomized woman, miscarriage per clinical pregnancy, adverse perinatal outcome and congenital malformations. RESULTS: The evidence from eight studies examining 2776 women showed a relative risk (RR) for live birth or ongoing pregnancy of 1.26 (95% CI, 1.04-1.53; I(2) = 58%). Sensitivity analysis when excluding the studies that did not report live birth and those at high risk of bias resulted in one study examining 181 women with an RR of 1.07 (95% CI, 0.73-1.58). Subgroup analysis separating the studies by single/multiple doses of GnRH agonists or by ovarian stimulation with GnRH agonist/antagonist was unable to explain the observed heterogeneity. The quality of the evidence was deemed to be very low: it was downgraded because of the limitation of the included studies, imprecision, inconsistency across the studies' results, and suspicion of publication bias. None of the included studies reported adverse perinatal outcomes or congenital malformations. CONCLUSIONS: There is evidence that adding GnRH agonist during the luteal phase improves the likelihood of ongoing pregnancy. However, this evidence is of very low quality and there is no evidence for adverse perinatal outcome and congenital malformations. We therefore believe that including this intervention in clinical practice would be premature.

Ovarian response is a better predictor of clinical pregnancy rate following embryo transfer than is thin endometrium or presence of an endometrioma.

OBJECTIVES: To examine whether endometrial thickness and the presence of endometrioma are independent predictors of clinical pregnancy rate or simply associated with poor ovarian response (POR). METHODS: This was a retrospective cohort study assessing the first cycle of all women undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in a university hospital in Brazil between January 2011 and December 2012. Only the first cycle of each woman within the study period was considered. Women over 40 years of age and those who used clomiphene citrate during controlled ovarian stimulation (COS) or did not undergo embryo transfer were excluded from analysis. POR was defined as ≤ three oocytes retrieved and a thin endometrium was defined as endometrial thickness ≤ 7.0 mm on the day of human chorionic gonadotropin (hCG) administration. We performed a multiple regression analysis to identify which of the following parameters were independent predictors of clinical pregnancy: age, number of oocytes retrieved, endometrial thickness or the presence of endometrioma. RESULTS: Within the study period, 787 women began COS, but 270 were excluded from analysis. Among the 517 women analyzed, those who achieved pregnancy were younger and yielded more oocytes. The proportion of POR was higher in women with a thin endometrium (17/57 (29.8%) vs 80/460 (17.4%); P = 0.03) and in women with endometrioma (15/39 (38.5%) vs 82/478 (17.2%); P = 0.002). The results of regression analysis showed that only age and the number of oocytes retrieved were independent predictors of pregnancy. Additionally, we observed higher clinical pregnancy rates in women with a thin endometrium from whom ≥ seven oocytes were retrieved (11/25 (44.0%)) compared to women with normal endometrial thickness (99/241 (41.1%)). Considering only women from whom ≥ four oocytes were retrieved, we observed reasonable pregnancy rates in those with a thin endometrium (14/40 (35.0%)) and in those with endometrioma (9/24 (37.5%)). CONCLUSION: Both a thin endometrium and the presence of endometrioma are associated with POR but are not important independent predictors of clinical pregnancy. Good pregnancy rates can be observed when these conditions are present in women with a good ovarian response.

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.

Assessment of ovarian reserve by antral follicle count in ovaries with endometrioma.

OBJECTIVE: To evaluate whether the antral follicle count (AFC) is underestimated in the presence of an endometrioma. METHODS: This was a retrospective cohort study assessing all women undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at our clinic between January 2011 and December 2012 who had both ovaries and unilateral endometrioma. The primary outcome of the study was the difference between AFC and the number of oocytes retrieved per ovary. RESULTS: Within the study period 787 women underwent IVF/ICSI at our clinic. Sixty of these women had at least one endometrioma, but 23 were excluded from the analysis as six had only one ovary and 17 had bilateral endometriomas. Therefore a total of 37 women were included in this study and analysis. Compared with the contralateral ovaries, ovaries with an endometrioma were significantly larger in volume (median, 10.3 (interquartile range (IQR), 4.7-18.9) cm(3) vs median, 3.6 (IQR, 2.7-6.5) cm(3); P < 0.001) and presented a significantly lower AFC (median, 3.0 (IQR, 1.0-6.0) vs median, 5.0 (IQR, 2.0-6.5); P = 0.001). However, the median number of oocytes retrieved was similar (P = 0.60) between ovaries with an endometrioma (2.0 (IQR, 0.5-5.0)) and the contralateral ovaries (2.0 (IQR, 0.0-4.0)). Accordingly, the median difference between AFC and number of oocytes retrieved was significantly smaller (P = 0.005) for ovaries with an endometrioma (0.0 (IQR, -1.0 to 1.5) than for those without (2.0 (IQR, 0.0-4.0)). CONCLUSIONS: Although the AFC is reduced in ovaries with an endometrioma, the number of oocytes retrieved is similar, suggesting that the AFC is underestimated in such ovaries. We believe that this is a consequence of an impaired ability to detect small follicles in the presence of an endometrioma.

True Reproducibility of UltraSound Techniques (TRUST): systematic review of reliability studies in obstetrics and gynecology.

OBJECTIVES: To examine the quality of methods used and the accuracy of the interpretation of agreement in existing studies that examine the reliability of ultrasound measurements and judgments in obstetrics and gynecology. METHODS: A systematic search of MEDLINE was performed on 25 March 2014, looking for studies that examined the reliability of ultrasound measurements and judgments in obstetrics and gynecology with evaluation of concordance (CCC) or intraclass (ICC) correlation coefficients or kappa as a main objective. RESULTS: Seven hundred and thirty-three records were examined on the basis of their title and abstract, of which 141 full-text articles were examined completely for eligibility. We excluded 29 studies because they did not report CCC/ICC/kappa, leaving 112 studies that were included in our analysis. Two studies reported both ICC and kappa and were counted twice, therefore, the number used as the denominator in the analyses was 114. Only 16/114 (14.0%) studies were considered to be well designed (independent acquisition and blinded analysis) and to have interpreted the results properly. Most errors occurring in the studies are likely to overestimate the reliability of the method examined. CONCLUSIONS: The vast majority of published studies examined had important flaws in design, interpretation and/or reporting. Such limitations are important to identify as they might create false confidence in the existing measurements and judgments, jeopardizing clinical practice and future research. Specific guidelines aimed at improving the quality of reproducibility studies that examine ultrasound methods should be encouraged.

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.

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.

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

OBJECTIVES: 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). METHODS: Women undergoing ART were randomly allocated to undergo either endometrial scratching with a pipelle de Cornier or a sham procedure, 7-14 days before starting controlled ovarian stimulation (COS). We evaluated subsequent rates of clinical pregnancy, live birth, implantation, miscarriage and multiple pregnancy. Pain during the procedure was evaluated using a 10-cm visual analog scale. Endometrial thickness and volume and three-dimensional power Doppler (3D-PD) indices (vascularization index (VI), flow index (FI) and vascularization flow index (VFI)) were assessed during COS when there was at least one follicle ≥ 17 mm in diameter. RESULTS: We included 158 women. Endometrial scratching was associated with higher rates of live birth (41.8% vs 22.8%, P = 0.01) and clinical pregnancy (49.4% vs 29.1%, P = 0.01) and higher pain score (6.42 ± 2.35 cm vs 1.82 ± 1.52 cm, P < 0.001), endometrial VI (3.71 ± 1.77 vs 2.95 ± 1.56, P < 0.01) and VFI (0.97 ± 0.51 vs 0.76 ± 0.40, P < 0.01). There was no significant effect of endometrial scratching on rate of miscarriage (15.4% vs 21.7%, P = 0.53) or multiple pregnancy (22.5% vs 25.0%, P = 0.79), or on endometrial thickness (10.12 ± 1.55 mm vs 9.98 ± 1.62 mm, P = 0.59), endometrial volume (6.18 ± 1.63 cm(3) vs 6.01 ± 1.48 cm(3) , P = 0.51) or FI (26.12 ± 2.82 vs 25.91 ± 2.72, P = 0.65). CONCLUSIONS: Endometrial scratching performed once, during OCP pretreatment 7-14 days before starting COS, increases the chance of live birth and clinical pregnancy, but might cause considerable pain.

Clomiphene combined with gonadotropins and GnRH antagonist versus conventional controlled ovarian hyperstimulation without clomiphene in women undergoing assisted reproductive techniques: systematic review and meta-analysis.

PURPOSE: To compare the effectiveness and safety of controlled ovarian hyperstimulation (COH) using clomiphene citrate associated with gonadotropin and GnRH antagonist (CC + Ant) versus conventional COH without clomiphene citrate (Non-CC) for women undergoing assisted reproductive techniques (ART). METHODS: Systematic review and meta-analysis of randomized controlled-trials comparing CC + Ant versus non-CC. The last search was performed in Apr 13 2012. The following outcomes were retrieved from included trials and compared between CC + Ant versus non-CC: live birth, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), miscarriage, multiple pregnancy, endometrial thickness, total oocytes retrieved, MII oocytes retrieved, total gonadotropin used, and duration of COH. RESULTS: Seven trials (702 participants) were included. There was no significant difference in live birth (55/182 = 30.2 % vs. 47/181 = 26.0 %, p = 0.26, CC + Ant vs. non-CC, respectively), clinical pregnancy (98/346 = 28.3 % vs. 84/356 = 23.6 %, p = 0.12), miscarriage (6/35 = 17.1 % vs. 7/32 = 21.9 %, p = 0.42), endometrial thickness, and on the number of oocytes retrieved. There was a significant reduction in OHSS (1/216 = 0.5 % vs. 9/217 = 4.1 %, p = 0.01), consumption of gonadotropins, and duration of COH. CONCLUSIONS: Compared to non-CC, CC + Ant is likely to reduce the risk of OHSS, medication costs, and the duration of COH without evidence of effect on live birth and clinical pregnancy. More trials are still needed to improve the quality of the evidence. Future studies should evaluate women with PCOS or at increased risk of OHSS, quality of life, satisfaction with the treatment, total cost per live birth, and frequency of congenital anomalies.

Biometry and fetal weight estimation by two-dimensional and three-dimensional ultrasonography: an intraobserver and interobserver reliability and agreement study.

OBJECTIVE: To evaluate and compare the intraobserver and interobserver reliability and agreement for the biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) obtained by two-dimensional ultrasound (2D-US) and three-dimensional ultrasound (3D-US). METHODS: Singleton pregnant women between 24 and 40 weeks were invited to participate in this study. They were examined using 2D-US in a blinded manner, twice by one observer, intercalated by a scan by a second observer, to determine BPD, AC and FL. In each of the three examinations, three 3D-US datasets (head, abdomen and thigh) were acquired for measurements of the same parameters. We determined EFW using Hadlock's formula. Systematic errors between 3D-US and 2D-US were examined using the paired t-test. Reliability and agreement were assessed by intraclass correlation coefficients (ICCs), limits of agreement (LoA), SD of differences and proportion of differences below arbitrary points. RESULTS: We evaluated 102 singleton pregnancies. No significant systematic error between 2D-US and 3D-US was observed. The ICC values were higher for 3D-US in both intra- and interobserver evaluations; however, only for FL was there no overlap in the 95% CI. The LoA values were wider for 2D-US, suggesting that random errors were smaller when using 3D-US. Additionally, we observed that the SD values determined from 3D-US differences were smaller than those obtained for 2D-US. Higher proportions of differences were below the arbitrarily defined cut-off points when using 3D-US. CONCLUSION: 3D-US improved the reliability and agreement of fetal measurements and EFW compared with 2D-US.

A standardized measurement technique may improve the reliability of measurements of endometrial thickness and volume.

OBJECTIVE: To investigate whether standardization of the multiplanar view (SMV) when evaluating the uterus using three-dimensional ultrasonography (3D-US) improves intra- and interobserver reliability and agreement with regard to endometrial measurement. METHODS: Two-dimensional (2D) and 3D-US was used to measure endometrial thickness by two observers in 30 women undergoing assisted reproduction treatment. Endometrial volume was measured with Virtual Organ Computer-aided AnaLysis (VOCAL(™)) in the longitudinal (A) and coronal (C) planes using an unmodified multiplanar view (UMV) and a standardized multiplanar view (SMV). Measurement reliability was evaluated by intraclass correlation coefficient (ICC) and agreement was examined using Bland-Altman plots with limits of agreement (LoA). The ease of outlining the endometrial-myometrial interface was compared between the A- and C-planes using subjective assessment. RESULTS: Endometrial volume measurements using the SMV and A-plane were more reliable (intra- and interobserver ICCs, 0.979 and 0.975, respectively) than were measurements of endometrial thickness using 2D-US (intra- and interobserver ICCs, 0.742 and 0.702, respectively) or 3D-US (intra- and interobserver ICCs, 0.890 and 0.784, respectively). The LoAs were narrower for SMV than for UMV. Reliability and agreement were not much different between the A- and C-planes. However the observers agreed that delineating the endometrial-myometrial interface using the A-plane was easier (first and second observer, 50.0 and 46.7%, respectively) or 'comparable' (50 and 53.3%, respectively), but never more difficult than using the C-plane. CONCLUSIONS: Endometrial volume measurements are more reliable than endometrial thickness measurements and are best performed using SMV and the A-plane.

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

OBJECTIVES: To evaluate the presence of false flow three-dimensional (3D) power Doppler signals in 'flow-free' models. METHODS: 3D power Doppler datasets were acquired from three different flow-free phantoms (muscle, air and water) with two different transducers and Virtual Organ Computer-aided AnaLysis was used to generate a sphere that was serially applied through the 3D dataset. The vascularization flow index was used to compare artifactual signals at different depths (from 0 to 6 cm) within the different phantoms and at different gain and pulse repetition frequency (PRF) settings. RESULTS: Artifactual Doppler signals were seen in all phantoms despite these being flow-free. The pattern was very similar and the degree of artifact appeared to be dependent on the gain and distance from the transducer. False signals were more evident in the far field and increased as the gain was increased, with false signals first appearing with a gain of 1 dB in the air and muscle phantoms. False signals were seen at a lower gain with the water phantom (-15 dB) and these were associated with vertical lines of Doppler artifact that were related to PRF, and disappeared when reflections were attenuated. CONCLUSIONS: Artifactual Doppler signals are seen in flow-free phantoms and are related to the gain settings and the distance from the transducer. In the in-vivo situation, the lowest gain settings that allow the detection of blood flow and adequate definition of vessel architecture should be used, which invariably means using a setting near or below the middle of the range available. Additionally, observers should be aware of vertical lines when evaluating cystic or liquid-containing structures.