Pregnancy Outcomes in Double Stimulation versus Two Consecutive Mild Stimulations for IVF in Poor Ovarian Responders

To compare pregnancy outcomes between double stimulation (DouStim) and two consecutive mild stimulations in poor ovarian responders, this study retrospectively analyzed 281 patients diagnosed as having poor ovarian response (POR) who underwent oocytes retrieval for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) from January 2018 to December 2020. They were divided into two groups: the DouStim group (n = 89) and the two consecutive mild stimulations group (n = 192). The results illustrated that there were no significant differences in the number of oocytes and 2PNs between the two groups. The number of frozen embryos [1 (0, 2) versus 1(0, 2)] was significantly lower and the proportion of patients without frozen embryos (39.3% versus 26.0%) was significantly higher in the DouStim group than in the two consecutive mild stimulations group (p p > 0.05). The intra-subgroup comparison showed that in young POR patients under 35 years old, there were no significant differences in clinical indicators and pregnancy outcomes (p > 0.05). In elderly POR patients aged 35 years and above, the number of frozen embryos [1 (0, 1.5) versus 1 (0.25, 2)] (p p > 0.05). In conclusion, the DouStim protocol is inferior to the two consecutive mild stimulations protocol in terms of the number of frozen embryos, which mainly occurs in elderly patients, but there is no difference in pregnancy outcomes between the two protocols

Timing of Hepatectomy for Resectable Synchronous Colorectal Liver Metastases: For Whom Simultaneous Resection Is More Suitable - A Meta-Analysis

<div><p>Background</p><p>The optimal timing of resection for synchronous colorectal liver metastases is still controversial. Retrospective cohort studies always had baseline imbalances in comparing simultaneous resection with staged strategy. Significantly more patients with mild conditions received simultaneous resections. Previous published meta-analyses based on these studies did not correct these biases, resulting in low reliability. Our meta-analysis was conducted to compensate for this deficiency and find candidates for each surgical strategy.</p><p>Methods</p><p>A systemic search for major databases and relevant journals from January 2000 to April 2013 was performed. The primary outcomes were postoperative mortality, morbidity, overall survival and disease-free survival. Other outcomes such as number of patients need blood transfusion and length of hospital stay were also assessed. Baseline analyses were conducted to find and correct potential confounding factors.</p><p>Results</p><p>22 studies with a total of 4494 patients were finally included. After correction of baseline imbalance, simultaneous and staged resections were similar in postoperative mortality (RR = 1.14, P = 0.52), morbidity (RR = 1.02, P = 0.85), overall survival (HR = 0.96, P = 0.50) and disease-free survival (HR = 0.97, P = 0.87). Only in pulmonary complications, simultaneous resection took a significant advantage (RR = 0.23, P = 0.003). The number of liver metastases was the major factor interfering with selecting surgical strategies. With >3 metastases, simultaneous and staged strategies were almost the same in morbidity (49.4% vs. 50.9%). With ≤3 metastases, staged resection caused lower morbidity (13.8% vs. 17.2%), not statistically significant.</p><p>Conclusions</p><p>The number of liver metastases was the major confounding factor for postoperative morbidity, especially in staged resections. Without baseline imbalances, simultaneous took no statistical significant advantage in safety and efficacy. Considering the inherent limitations of this meta-analysis, the results should be interpret and applied prudently.</p></div

Baseline imbalance in studies included in the meta-analysis.

<p>Y: significant imbalance of baseline; N: no significant imbalance of baseline; NA: data not available.</p><p>Location was compared as: (right-sided vs. left-sided vs. rectum)^a or (colon vs. rectum)^b. When compared as (right-sided vs. left-sided vs. rectum)^a, the transverse colon was included in the right-sided, the sigmoid colon was included in the left-sided.</p><p>T stage was compared as T1+T2 vs. T3+T4.</p><p>N stage was compared as N0 vs. N+.</p><p>Number of metastases was compared as: (single vs. multiple)^c or (≤3 vs. >3)^d or (mean ± SD)^e or others with no superscript.</p><p>Maximum diameter of metastases was compared as: (≤5 cm vs. >5 cm)^f or (mean ± SD)^g or others with no superscript.</p><p>Major hepatectomy was defined as resection with ≥3 segments.</p><p>Preoperative chemotherapy included chemotherapy before both primary resection and hepatectomy.</p><p>The study Vassiliou 2007 enrolled only patients with ≤3 liver metastases.</p

Pooled analyses of baseline imbalances.

<p>Forest plots displayed the potential confounding factors found by baseline analyses. M-H: Mantel-Haenszel method. IV: Inverse Variance method. Random: In some subgroups there were significant heterogeneity, and random effect model was used. CI: confidence interval. <b>A</b>) Baseline analysis on number of liver metastases. Staged/Sim. favours lower: more patients in staged/simultaneous group had lower number of metastases. <b>B</b>) Baseline analysis on size of liver metastases. Staged/Sim. favours small: more patients in staged/simultaneous group had smaller size of metastases. <b>C</b>) Baseline analysis on distribution of liver metastases. Staged/Sim. faours unilobar: more patients in staged/simultaneous group had unilobar liver metastases. <b>D</b>) Baseline analysis on scope of hepatectomy. Staged/Sim. favours minor: more patients in staged/simultaneous group received minor hepatectomy. <b>E</b>) Baseline analysis on primary tumor location. Staged/Sim. favours right-sided: more patients in staged/simultaneous group had primary tumor located at right-sided colon.</p

Study search process.

<p>Study search process.</p

Subtype analyses of pooled postoperative morbidity.

<p>Forest plots displayed the results of the meta-analysis comparing overall survival following simultaneous resection vs. staged resection for SCRLMs. IV: Inverse Variance method. Fixed: The heterogeneity test showed no significant heterogeneity, and fixed effect model was used. CI: confidence interval. Favours Simultaneous: With results on this side, simultaneous group had longer overall survival. Favours Staged: With results on this side, staged group had longer overall survival.</p

Characteristics of studies included for Meta-analysis.

<p>* Means were converted from medians. NOS: Newcastle-Ottawa Scale.</p

Postoperative morbidity with different number of liver metastases.

<p>CI: confidence interval.</p

Pooled postoperative morbidity.

<p>Forest plots displayed the results of the meta-analysis comparing postoperative complication morbidity following simultaneous resection vs. staged resection for SCRLMs. M-H: Mantel-Haenszel method. Fixed: The heterogeneity test showed no significant heterogeneity, and fixed effect model was used. CI: confidence interval. Favours Simultaneous: With results on this side, simultaneous group had lower postoperative mortality. Favours Staged: With results on this side, staged group had lower postoperative mortality.</p