Pretreatment with or without GnRH-agonist before frozen-thawed embryo transfer in patients with PCOS: a systematic review and meta-analysis.

PURPOSE: This study was aimed to systematically evaluate the efficacy of artificial cycle-prepared frozen-thawed embryo transfer (FET) with or without gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment for women with polycystic ovary syndrome (PCOS). METHODS: The analysis was carried out by searching the PubMed, EMBASE, and CNKI databases with a combination of keywords before October 2021. The available studies of the effects of GnRH-a pretreatment or no pretreatment on FET in PCOS patients were considered. The risk ratios (RRs) or standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated with using subgroups and sensitivity analysis. The quality evaluation for this analysis was followed. RESULTS: Seventeen studies including 3646 women were analyzed. GnRH-a pretreatment was significantly associated with a higher implantation rate (RR = 1.12, 95%CI: 1.00-1.24) and clinical pregnancy rate (RR = 1.19, 95%CI: 1.08-1.32) than the placebo. Moreover, in the GnRH-a pretreatment group, significant differences were detected for increasing the endometrium thickness among PCOS patients (SMD = 0.56, 95%CI: 0.20-0.92). However, for RCTs subgroup, no differences were observed, even after sensitivity analyses. In addition, the miscarriage rates, ectopic pregnancy rates, multiple pregnancy rates, and live birth rates were similar in both two groups. CONCLUSIONS: Endometrial preparation using GnRH agonist pretreatment prior to FET seems to be the better choice for PCOS patients. However, well-designed RCTs are required for confirmation.

Proximal tubal occlusion first or oocyte retrieval first for patients with hydrosalpinx?

PURPOSE: Our study aimed to investigate the best time to manage hydrosalpinx to improve pregnancy outcomes during in vitro fertilization-embryo transfer (IVF-ET). METHODS: Patients with hydrosalpinx who received IVF treatment were analyzed retrospectively. And two groups were included to compare the effects of different timing treatment of hydrosalpinx on IVF pregnancy outcomes, "Proximal Tubal Occlusion First Group" (Group Ligation-COH) and "Oocyte Retrieval First Group" (Group COH-Ligation). The main outcome measures included: ovarian response indexes, laboratory indexes and clinical pregnancy outcomes. Univariate and multivariate Logistic regression analysis was performed for outcome indicators, and the odds ratios (OR) and 95% confidence interval (CI) were used. RESULTS: A total of 1490 patients were included (n = 976 Ligation-COH and n = 514 COH-Ligation). The Gn starting dose and MII rate in group Ligation-COH were significantly higher than those in group COH-Ligation (203.33 ± 58.20 vs. 203.33 ± 58.20, 81.58% vs. 80.28%, P < 0.05). The number of oocytes obtained and the number of available D3 embryos in group COH-Ligation were higher than those in group Ligation-COH (15.10 ± 7.58 vs. 13.45 ± 6.42, 10.92 ± 5.81 vs. 9.94 ± 5.15, P < 0.05). Although the number of ET cycles per IVF cycle in group COH-Ligation was higher than that in group Ligation-COH (1.88 ± 1.00 vs. 1.48 ± 0.70, P < 0.05), the biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, live birth rate and cumulative live birth rate in group Ligation-COH were significantly higher than those in group COH-Ligation (60.83% vs. 46.27% for biochemical pregnancy, 55.69% vs. 38.5% for clinical pregnancy, 26.18% vs. 17.74% for multiple pregnancy, 47.08% vs. 25.26% for live birth, 69.47% vs. 47.47% for cumulative live birth, P < 0.05), and the miscarriage rate in group Ligation-COH was lower than that in group COH-Ligation (10.47% vs. 17.20 for early abortion, 4.49% vs. 15.86% for late abortion, P < 0.05). In logistic regression analysis, after adjustment for age and multiple factors, the above results were still statistically significant differences (P < 0.001). For elderly patients, the clinical pregnancy rate, multiple birth rate and live birth rate in group Ligation-COH were also higher than those in group COH-Ligation (P < 0.001). No significant differences were detected for patients with diminished ovarian reserve. CONCLUSIONS: For the choice of ligation operation time, we recommend that patients choose tubal ligation first and then ovulation induction and oocyte retrieval treatment.

Atosiban application in fresh ET cycle is effective for women undergoing repeated embryo implantation failures, especially for advanced-age obese patients.

To assess the effect of atosiban in pregnancy outcomes of the fresh embryo transfer (ET), the retrospective cohort study was conducted. Six hundred and eighty-nine cases (using atosiban) and 1377 age and ET cycle-matched controls were collected from the January 2016 to May 2022 to perform the fresh IVF-ET cycle. The essential characteristics and pregnancy outcomes were analyzed. Conditional logistic regression analysis and subgroup analysis were performed. In the whole samples, atosiban had no effects in the pregnancy outcomes. Subgroup analyses suggested that atosiban could improve the clinical pregnancy in more than 3 ET cycles (OR 1.667, 95% CI 1.108-2.509, P = 0.014). Moreover, the improvement of clinical pregnancy was mainly present in the advanced-age women (age ≥ 35 years: OR 1.851, 95% CI 1.136-3.014, P = 0.013), obesity (BMI ≥ 24 kg/m2: OR 2.550, 95% CI 1.105-5.883, P = 0.028) and cleavage stage embryo (D3 embryo: OR 1.721, 95% CI 1.098-2.696, P = 0.018) among the repeated implantation failures (RIF). Atosiban could also improve the live birth for the obese women. Further, in the RIF, atosiban application was strongly recommended for the advanced-age infertility women, who also had the risk of obesity with the implantation of the cleavage stage embryo. In conclusion, atosiban could improve pregnancy outcomes for the advanced-age and obese women in RIF, especially while implanting the cleavage stage embryo in fresh ET cycle.

A prognostic model for ovarian neoplasms established by an integrated analysis of 1580 transcriptomic profiles.

Even after debulking surgery combined with chemotherapy or new adjuvant chemotherapy paired with internal surgery, the average year of disease free survival in advanced ovarian cancer was approximately 1.7 years1. The development of a molecular predictor of early recurrence would allow for the identification of ovarian cancer (OC) patients with high risk of relapse. The Ovarian Cancer Disease Free Survival Predictor (ODFSP), a predictive model constructed from a special set of 1580 OC tumors in which gene expression was assessed using both microarray and sequencing platforms, was created by our team. To construct gene expression barcodes that were resistant to biases caused by disparate profiling platforms and batch effects, we employed a meta-analysis methodology that was based on the binary gene pair technique. We demonstrate that ODFSP is a reliable single-sample predictor of early recurrence (1 year or less) using the largest pool of OC transcriptome data sets available to date. The ODFSP model showed significantly high prognostic value for binary recurrence prediction unaffected by clinicopathologic factors, with a meta-estimate of the area under the receiver operating curve of 0.64 (P = 4.6E-05) and a D-index (robust hazard ratio) of 1.67 (P = 9.2E-06), respectively. GO analysis of ODFSP's 2040 gene pairs (collapsed to 886 distinct genes) revealed the involvement in small molecular catabolic process, sulfur compound metabolic process, organic acid catabolic process, sulfur compound biosynthetic process, glycosaminoglycan metabolic process and aminometabolic process. Kyoto encyclopedia of genes and genomes pathway analysis of ODFSP's signature genes identified prominent pathways that included cAMP signaling pathway and FoxO signaling pathway. By identifying individuals who might benefit from a more aggressive treatment plan or enrolment in a clinical trial but who will not benefit from standard surgery or chemotherapy, ODFSP could help with treatment decisions.

Efficacy of electrical stimulation combined with ultrasound acupuncture therapy on treatment in patients with intrauterine adhesions: Study protocol for a placebo-controlled, single-blind, single-center, randomized trial.

BACKGROUND: Recurrence of postoperative adhesions is one of the most important factors for poor reproductive outcomes after hysteroscopic surgery, particularly in cases diagnosed with severe intrauterine adhesions (IUAs), where the recurrence rate is significantly higher. This study aims to explore the effectiveness of the electrical muscle stimulation combined with ultrasound acupuncture therapy in preventing the recurrence of IUAs and improving reproductive outcomes after operative hysteroscopy. METHODS: This study is a single-center, randomized controlled trial. A total of 210 patients with IUAs will be randomly assigned into 2 groups according to the ratio of 1:1, as the treatment group and the control group. Participants will receive the electrical muscle stimulation combined with ultrasound acupuncture therapy and oral hormone supplementation or receive oral hormone supplementation only. The primary outcome was the clinical response rate. There were 3 menstrual cycles of treatment and 3 menstrual cycles of follow-up in this study. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Reproductive Hospital of Guangxi Zhuang Autonomous Region (approval number: KY-LL-2022-06). This trial will be conducted in accordance with the principles of the Declaration of Helsinki as well as Good Clinical Practice. Study results will be disseminated at academic presentations and publications in peer-reviewed journals. TRIAL REGISTRATION: Registry name: Clinical value of electroultrasonic instrument in the treatment of IUAs and changes of related protein expression; Registry number: ChiCTR2200058901; registration date: April 19th, 2022; http://www.chictr.org.cn/showproj.aspx?proj=166155.

Effects of oral contraceptive for different responder women before GnRH antagonists: a systematic review and meta-analysis.

This analysis aimed to compare the efficacy of oral contraceptive pill (OCP) pretreatment for gonadotropin-releasing hormone antagonist (GnRH-ant) protocol, especially for different responder women. The PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for trials on with and without OCP pretreatment before stimulation with gonadotropins. The standardized mean differences (SMDs) or pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used for statistical analysis. Fifteen studies with 5326 in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were summarized. The clinical pregnancy rate, moderate or severe ovarian hyper-stimulation syndrome (OHSS) rate, and miscarriage rate was not found to be significantly different between patients with and those without OCP pretreatment, even after sensitivity analyses. In addition, there were still no statistically significant differences for the subgroups analyses of hyper-responders, poor responders, and normal responders. No significant differences were detected in the duration of ovarian stimulation, gonadotropin dose consumed, endometrial thickness on day of oocyte collection, or number of oocytes. This meta-analysis did not find an unequivocally beneficial effect of OCP pretreatment for different responder women with using a GnRH-ant protocol. The clinician should weigh the advantages and disadvantages of OCP pretreatment and guide the treatment scheduling considering the patient's own situation.

Association between AKT2 gene polymorphism and polycystic ovary syndrome: a case-control study.

OBJECTIVE: This study was conducted to understand the association between the AKT2 (AKT serine/threonine kinase 2) gene polymorphism (rs2304186) and PCOS. METHODS: In total, 1287 participants were included. Six genotype models (Dominant model: TT + TG vs. GG; Recessive model: TT vs. TG + GG; Over-dominant model: TT + GG vs. TG; Co-dominant model: TT vs. TG; Co-dominant TT vs. GG; Allele analysis: T vs. G) were applied in the analysis. According to the races and obesity, subgroup analyses were also performed. RESULTS: No significant association between rs2304186 and PCOS was identified in the whole sample or the Han groups, even after multi-adjustments. Only in the Zhuang groups was it suggested that rs2304186 might promote the risk of PCOS to some extent (Unadjusted: Over-dominant TT + GG vs. TG, OR = 1.522, 95%CI = 1.076-2.152, p = .018; Age-adjusted: Over-dominant TT + GG vs. TG, OR = 1.543, 95%CI = 1.069-2.228, p = .021; Multi-adjusted: OR = 1.497, 95%CI = 1.024-2.188, p = .037). The risk effect was also detected in the non-obesity group (BMI <24.0 kg/m2) for the Co-dominant model (TT vs. TG: OR = 1.355, 95%CI = 1.001-1.835, p = .050). CONCLUSIONS: In summary, we first discovered that rs2304186 might significantly elevate the PCOS risk, especially in the Chinese Zhuang population and the non-obesity group. Further studies are needed to confirm these results.

Potential Positive Association between Cytochrome P450 1A1 Gene Polymorphisms and Recurrent Pregnancy Loss: a Meta-Analysis.

In order to discover the potential genetic risks associated with recurrent pregnancy loss (RPL), this meta-analysis was conducted to assess the association between CYP1A1 gene polymorphism and RPL. Studies were retrieved from the databases PubMed, Embase, HuGENet, and CNKI. Four models were then applied. Seven studies, including three datasets for the rs1048943 and five for the rs4646903 single-nucleotide polymorphism (SNP), were included in this analysis, involving 613 cases and 398 controls for the rs1048943; and 864 cases and 842 controls for the rs4646903 SNP. After comprehensive analysis, we found that rs4646903 was significantly associated with RPL [recessive (OR = 1.72, 95%CI: 1.13-2.61); codominant (CC vs TT; OR = 1.74, 95%CI: 1.12-2.71), (CC vs CT; OR = 1.67, 95%CI: 1.07-2.62) and allele analysis (OR = 1.27, 95%CI: 1.07-1.50)]. In the following subgroup analysis, a positive association was also discovered among people of Asian descent, especially South Asians. However, there was no obvious association between rs1048943 and RPL. In summary, our results suggest that CYP1A1 gene polymorphism (particularly for rs4646903) might be associated with RPL risk, especially among South Asians. Further studies are required to confirm this association.

The effect of G-CSF on infertile women undergoing IVF treatment: A meta-analysis.

Evidence for the effect of granulocyte colony stimulating factor (G-CSF) on infertile women undergoing in vitro fertilization (IVF) remains inconsistent. This study aimed to evaluate the effectiveness of G-CSF on infertile women undergoing IVF. PubMed and EMBASE databases were searched before August 2016. Comparing the transvaginal perfusion of G-CSF and placebo or no treatment, the available studies were considered. The pooled risk ratio (RR) with 95% confidence intervals (CIs) was used in the analysis and six studies were included. Transvaginal perfusion of G-CSF was significantly associated with a higher clinical pregnancy rate versus the placebo (RR=1.563, 95%CI: 1.122, 2.176), especially for the Asian population. Among patients with a thin endometrium or repeated IVF failure, the implantation and biochemical pregnancy rates were also significantly increased in patients with the use of G-CSF (implantation rate: RR = 1.887, 95% CI: 1.256, 2.833; biochemical pregnancy rate: RR = 2.385, 95% CI: 1.414, 4.023). However, no statistical significance in increasing endometrial thickness was detected. Transvaginal perfusion of G-CSF for infertile women may play a critical role in assisting human reproduction, especially for patients with a thin endometrium or repeated IVF failure in the Asian population.