Infertility, defined as the inability to conceive within 1 year of unprotected intercourse1, is estimated to affect as many as 186 million people worldwide2. Reproductive medicine aims to help these couples by offering them the best treatment option. As individual perception of the effectiveness of any treatment is affected by bias, it is generally accepted that clinical practice should be based on scientific methods. The definition of evidence‐based medicine was first introduced by Sackett as the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients3-5. To achieve this, knowledge should be sought in the medical literature to inform clinical decisions6. Reporting the most relevant and informative outcomes in clinical research, therefore, is mandatory for effective comparison between different interventions6. In 2003, the European Society for Human Reproduction and Embryology recommended that the outcome measure of assisted reproductive techniques (ART) and non‐ART should be ‘singleton live birth’7. Nothing, however, was stated with respect to the treatment cycle or effectiveness over time. Traditionally, success rates of in‐vitro fertilization (IVF) have been reported in terms of live births per fresh cycle or embryo transfer. However, with the increasing use of embryo freezing and thawing, it is essential that outcomes are reported not only following fresh but also after frozen embryo transfer as a complete measure of success of IVF treatment8. Moreover, evaluations should be extended over treatment strategies that incorporate multiple treatment cycles, even if they are of different types, and should also consider any natural conceptions that occur in between treatments. Here, we advocate that, in both clinical trials and clinical practice, the outcome of fertility treatment should be reported as a function of time and as the outcome of multiple transfers from one cycle or the outcome of multiple cycles in a predefined period.

ABSTRACT Objectives: To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. Methods: We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates). Results: We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles; WMD, −1.39; 95% CI, −2.27 to −0.51; I2 =100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217 cycles; RR, 0.97; 95% CI, 0.90–1.04; I2 =47%), while CC led to a lower pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63–0.95; I2 =43%) and a lower live birth rate (RR, 0.70; 95% CI, 0.49–0.98; I2 =35%). In two RCTs that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were comparable (101 women, 140 cycles; WMD, −0.23; 95% CI, −0.92 to 0.45; I2 =78%; RR, 0.84; 95% CI, 0.67–1.06; I2 =0%; and RR, 0.79; 95% CI, 0.33–1.87; I2 =0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT was lower in the CC group (340 women, 300 cycles; WMD, −1.51; 95% CI, −1.98 to −1.04; I2 =45%). In two studies that compared CC with CC+nitric oxide (NO) donor, EMT was lower in the CC group (120 women, 304 cycles; WMD, −1.75; 95% CI, −2.08 to −1.41; I2 =0%). Compared with CC plus NO donor or NAC, CC showed statistically significant lower ovulation and pregnancy rates. Compared with tamoxifen in three studies, CC showed a tendency towards lower EMT (571 women, 844 cycles; WMD, −1.34; 95% CI, −2.70 to 0.01; I2 =96%) with comparable ovulation and pregnancy rates. Conclusions: In women with WHO group II ovulatory disorders, ovulation induction with CC might result in lower EMT than other ovulation induction regimens. Whether the lower EMT caused the lower pregnancy and live birth rates remains to be elucidated. Letrozole seems to be beneficial for these women. However, our findings should be interpreted with caution as the quality of evidence was very low. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

ABSTRACT Objectives: To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. Methods: We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates). Results: We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles; WMD, −1.39; 95% CI, −2.27 to −0.51; I2 =100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217 cycles; RR, 0.97; 95% CI, 0.90–1.04; I2 =47%), while CC led to a lower pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63–0.95; I2 =43%) and a lower live birth rate (RR, 0.70; 95% CI, 0.49–0.98; I2 =35%). In two RCTs that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were comparable (101 women, 140 cycles; WMD, −0.23; 95% CI, −0.92 to 0.45; I2 =78%; RR, 0.84; 95% CI, 0.67–1.06; I2 =0%; and RR, 0.79; 95% CI, 0.33–1.87; I2 =0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT was lower in the CC group (340 women, 300 cycles; WMD, −1.51; 95% CI, −1.98 to −1.04; I2 =45%). In two studies that compared CC with CC+nitric oxide (NO) donor, EMT was lower in the CC group (120 women, 304 cycles; WMD, −1.75; 95% CI, −2.08 to −1.41; I2 =0%). Compared with CC plus NO donor or NAC, CC showed statistically significant lower ovulation and pregnancy rates. Compared with tamoxifen in three studies, CC showed a tendency towards lower EMT (571 women, 844 cycles; WMD, −1.34; 95% CI, −2.70 to 0.01; I2 =96%) with comparable ovulation and pregnancy rates. Conclusions: In women with WHO group II ovulatory disorders, ovulation induction with CC might result in lower EMT than other ovulation induction regimens. Whether the lower EMT caused the lower pregnancy and live birth rates remains to be elucidated. Letrozole seems to be beneficial for these women. However, our findings should be interpreted with caution as the quality of evidence was very low. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

ABSTRACT Objectives: To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. Methods: We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates). Results: We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles; WMD, −1.39; 95% CI, −2.27 to −0.51; I2 =100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217 cycles; RR, 0.97; 95% CI, 0.90–1.04; I2 =47%), while CC led to a lower pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63–0.95; I2 =43%) and a lower live birth rate (RR, 0.70; 95% CI, 0.49–0.98; I2 =35%). In two RCTs that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were comparable (101 women, 140 cycles; WMD, −0.23; 95% CI, −0.92 to 0.45; I2 =78%; RR, 0.84; 95% CI, 0.67–1.06; I2 =0%; and RR, 0.79; 95% CI, 0.33–1.87; I2 =0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT was lower in the CC group (340 women, 300 cycles; WMD, −1.51; 95% CI, −1.98 to −1.04; I2 =45%). In two studies that compared CC with CC+nitric oxide (NO) donor, EMT was lower in the CC group (120 women, 304 cycles; WMD, −1.75; 95% CI, −2.08 to −1.41; I2 =0%). Compared with CC plus NO donor or NAC, CC showed statistically significant lower ovulation and pregnancy rates. Compared with tamoxifen in three studies, CC showed a tendency towards lower EMT (571 women, 844 cycles; WMD, −1.34; 95% CI, −2.70 to 0.01; I2 =96%) with comparable ovulation and pregnancy rates. Conclusions: In women with WHO group II ovulatory disorders, ovulation induction with CC might result in lower EMT than other ovulation induction regimens. Whether the lower EMT caused the lower pregnancy and live birth rates remains to be elucidated. Letrozole seems to be beneficial for these women. However, our findings should be interpreted with caution as the quality of evidence was very low. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

ABSTRACT Objectives: To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. Methods: We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates). Results: We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles; WMD, −1.39; 95% CI, −2.27 to −0.51; I2 =100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217 cycles; RR, 0.97; 95% CI, 0.90–1.04; I2 =47%), while CC led to a lower pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63–0.95; I2 =43%) and a lower live birth rate (RR, 0.70; 95% CI, 0.49–0.98; I2 =35%). In two RCTs that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were comparable (101 women, 140 cycles; WMD, −0.23; 95% CI, −0.92 to 0.45; I2 =78%; RR, 0.84; 95% CI, 0.67–1.06; I2 =0%; and RR, 0.79; 95% CI, 0.33–1.87; I2 =0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT was lower in the CC group (340 women, 300 cycles; WMD, −1.51; 95% CI, −1.98 to −1.04; I2 =45%). In two studies that compared CC with CC+nitric oxide (NO) donor, EMT was lower in the CC group (120 women, 304 cycles; WMD, −1.75; 95% CI, −2.08 to −1.41; I2 =0%). Compared with CC plus NO donor or NAC, CC showed statistically significant lower ovulation and pregnancy rates. Compared with tamoxifen in three studies, CC showed a tendency towards lower EMT (571 women, 844 cycles; WMD, −1.34; 95% CI, −2.70 to 0.01; I2 =96%) with comparable ovulation and pregnancy rates. Conclusions: In women with WHO group II ovulatory disorders, ovulation induction with CC might result in lower EMT than other ovulation induction regimens. Whether the lower EMT caused the lower pregnancy and live birth rates remains to be elucidated. Letrozole seems to be beneficial for these women. However, our findings should be interpreted with caution as the quality of evidence was very low. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Statement of the problem: Although peripartum cardiomyopathy (PPCM) is a rare disease, its frequency is higher in some regions including Egypt. It can result in morbidity and mortality of 5- 32%. Identifying prognostic indicators of women with PPCM is of paramount importance. Speckle tracking echocardiography (STE) was found helpful to assess early changes of left ventricular function and mechanics; however its prognostic value is still under investigation. Methodology & Theoretical Orientation: This is a case-control prospective study that included 25 PPCM patients admitted to the cardiology and woman health hospitals of Assiut University, Egypt from September 2016 – December 2018 and 20 control pregnant women. Clinical assessment, 2-D echocardiography & STE were done to study population upon inclusion, and at scheduled quarterly visits. Findings: Patients age was 29.9±7.68 years, 75% presented in the postpartum period. At presentation, LVEF was impaired in patients vs. controls (33.2±8.84 % vs. 62.65±5.61 %, P 0.001), STE showed reduction of GLS (-10.08±6.76 vs.-19.49±2.82) , GCS (-11.65±3.34 % vs.-23.63±2.93%) (P0.001). Patients were followed-up for a median of 13.5 months where 9 improved (LVEF ≥ 50%), 7 partially improved (LVEF =40-49%), 4 had persistent LV dysfunction (LVEF40%), 4 died. Along the study; GLS & GCS increased significantly (-13.03±4.53% to -20.18±1.75), (-13.28±3.37% to -22.53±4.82%) in improved patients. Patients who died had significantly impaired GLS and GCS vs. those improved (-9.07±0.65 vs.-16.09±2.57%, -8.17±3.1 vs. -14.02±2.62 %, P0.01)). More reduction was noted in apical GCS (-6.97±4.67 vs. -17.43±6.75%). Patients with persistent LV dysfunction and those who died were presented later than improved (18±11.79 vs.7.5±4.93 days postpartum) Conclusion & Significance: Longitudinal and circumferential strains are depressed in PPCM patients. 2D-STE can be used as an objective marker of LV dysfunction in PPCM patients at long term. Recommendation: A larger multicenter study is recommended. Meanwhile, STE is advised whenever PPCM is suspected.

Statement of the problem: Although peripartum cardiomyopathy (PPCM) is a rare disease, its frequency is higher in some regions including Egypt. It can result in morbidity and mortality of 5- 32%. Identifying prognostic indicators of women with PPCM is of paramount importance. Speckle tracking echocardiography (STE) was found helpful to assess early changes of left ventricular function and mechanics; however its prognostic value is still under investigation. Methodology & Theoretical Orientation: This is a case-control prospective study that included 25 PPCM patients admitted to the cardiology and woman health hospitals of Assiut University, Egypt from September 2016 – December 2018 and 20 control pregnant women. Clinical assessment, 2-D echocardiography & STE were done to study population upon inclusion, and at scheduled quarterly visits. Findings: Patients age was 29.9±7.68 years, 75% presented in the postpartum period. At presentation, LVEF was impaired in patients vs. controls (33.2±8.84 % vs. 62.65±5.61 %, P 0.001), STE showed reduction of GLS (-10.08±6.76 vs.-19.49±2.82) , GCS (-11.65±3.34 % vs.-23.63±2.93%) (P0.001). Patients were followed-up for a median of 13.5 months where 9 improved (LVEF ≥ 50%), 7 partially improved (LVEF =40-49%), 4 had persistent LV dysfunction (LVEF40%), 4 died. Along the study; GLS & GCS increased significantly (-13.03±4.53% to -20.18±1.75), (-13.28±3.37% to -22.53±4.82%) in improved patients. Patients who died had significantly impaired GLS and GCS vs. those improved (-9.07±0.65 vs.-16.09±2.57%, -8.17±3.1 vs. -14.02±2.62 %, P0.01)). More reduction was noted in apical GCS (-6.97±4.67 vs. -17.43±6.75%). Patients with persistent LV dysfunction and those who died were presented later than improved (18±11.79 vs.7.5±4.93 days postpartum) Conclusion & Significance: Longitudinal and circumferential strains are depressed in PPCM patients. 2D-STE can be used as an objective marker of LV dysfunction in PPCM patients at long term. Recommendation: A larger multicenter study is recommended. Meanwhile, STE is advised whenever PPCM is suspected.

Statement of the problem: Although peripartum cardiomyopathy (PPCM) is a rare disease, its frequency is higher in some regions including Egypt. It can result in morbidity and mortality of 5- 32%. Identifying prognostic indicators of women with PPCM is of paramount importance. Speckle tracking echocardiography (STE) was found helpful to assess early changes of left ventricular function and mechanics; however its prognostic value is still under investigation. Methodology & Theoretical Orientation: This is a case-control prospective study that included 25 PPCM patients admitted to the cardiology and woman health hospitals of Assiut University, Egypt from September 2016 – December 2018 and 20 control pregnant women. Clinical assessment, 2-D echocardiography & STE were done to study population upon inclusion, and at scheduled quarterly visits. Findings: Patients age was 29.9±7.68 years, 75% presented in the postpartum period. At presentation, LVEF was impaired in patients vs. controls (33.2±8.84 % vs. 62.65±5.61 %, P 0.001), STE showed reduction of GLS (-10.08±6.76 vs.-19.49±2.82) , GCS (-11.65±3.34 % vs.-23.63±2.93%) (P0.001). Patients were followed-up for a median of 13.5 months where 9 improved (LVEF ≥ 50%), 7 partially improved (LVEF =40-49%), 4 had persistent LV dysfunction (LVEF40%), 4 died. Along the study; GLS & GCS increased significantly (-13.03±4.53% to -20.18±1.75), (-13.28±3.37% to -22.53±4.82%) in improved patients. Patients who died had significantly impaired GLS and GCS vs. those improved (-9.07±0.65 vs.-16.09±2.57%, -8.17±3.1 vs. -14.02±2.62 %, P0.01)). More reduction was noted in apical GCS (-6.97±4.67 vs. -17.43±6.75%). Patients with persistent LV dysfunction and those who died were presented later than improved (18±11.79 vs.7.5±4.93 days postpartum) Conclusion & Significance: Longitudinal and circumferential strains are depressed in PPCM patients. 2D-STE can be used as an objective marker of LV dysfunction in PPCM patients at long term. Recommendation: A larger multicenter study is recommended. Meanwhile, STE is advised whenever PPCM is suspected.

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