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Background: The positive effects of growth hormone (GH) on IVF are often attributed to improvements in oocyte and embryo quality. While emerging evidence emphasizes GH-induced improvements in the endometrium, these results are controversial.Objective and Rationale: This meta-analysis aimed to evaluate whether GH administration improved endometrial function and reproductive outcomes during IVF cycles and to thus guide clinical practice.Search Methods: A literature search in the Cochrane Central Register of Controlled Trials, PubMed and Embase was performed through to 30 November 2021, without language restrictions. Randomized controlled trials (RCTs) evaluating the effects of GH on IVF outcomes were included. Risk of bias and quality of evidence (QoE) were assessed according to the Cochrane Collaboration's tool and the Grading of Recommendations Assessment, Development and Evaluation system. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed by random-effects models.Outcomes: A total of 25 trials with 2424 women were included. Seventeen RCTs with poor responders (n = 1723) showed that GH administration significantly increased endometrial thickness (EMT) (MD = 0.38, 95% CI: 0.18-0.59; moderate QoE), which contributed to an improved live birth rate (OR = 1.67, 95% CI: 1.13-2.49; very low QoE) and clinical pregnancy rate (CPR) (OR = 1.97, 95% CI: 1.43-2.72; low QoE). Subgroup analyses showed a dose- and time-dependent relationship between GH cotreatment and IVF outcomes; the optimal recommendation for improving CPR was consistent with that for EMT, rather than for oocytes and embryos. Hence, GH might improve fertility via effects on the endometrium. Administration of GH daily from the follicular phase of previous cycle until the hCG trigger with < 5 IU/day led to a thicker endometrium and a greater chance of becoming pregnant, while 5-10 IU/day or administration from the luteal phase of the previous cycle until the hCG trigger resulted in higher oocyte and embryo quality. Poor responders might benefit from cotreatment with the GnRH agonist long protocol more than other stimulation protocols. Pooled data from four trials (n = 354) on women with a thin endometrium indicated that improved endometrial function might be critical for improving reproductive outcomes during GH treatment, as no improvements in embryo quality were found. GH administration not only increased EMT (MD = 1.48, 95% CI: 1.21-1.75; moderate QoE) but also promoted endometrial morphology (OR = 2.67, 95% CI: 1.36-5.23; low QoE) and perfusion (OR = 5.84, 95% CI: 1.30-26.17; low QoE), thereby improving the CPR (OR = 2.71, 95% CI: 1.69-4.34; P < 0.0001; low QoE). There was insufficient evidence to reach a conclusion regarding the effects of GH in normal responders (n = 80). Due to obvious improvements in the CPR, women with a thin endometrium might be the most appropriate population to benefit from GH administration.Wider Implications: Improving endometrial function might be another vital mechanism by which GH improves IVF outcomes. Optimal treatment should be offered to the target population according to their personal conditions and needs. The QoE was moderate to very low, due to limited sample sizes and methodological problems; thus, the results should be interpreted with caution. More rigorous RCTs with large sample sizes are needed to confirm the effects and determine optimal GH protocols. [ABSTRACT FROM AUTHOR]

Purpose: Hysterosalpingo-contrast sonography (HyCoSy) is the preferred method for evaluating fallopian tubal patency, and it is associated with improved rates of natural pregnancy among infertile patients. However, the mechanism underlying the improvement in pregnancy rates following HyCoSy remains unclear. This study aimed to investigate the effect of HyCoSy examination on endometrial receptivity as well as pregnancy rates among infertile women. Methods: This prospective study included 120 women with unexplained infertility who visited our department between June 2018 and February 2021. These patients were classified into the study group (n = 60) and the control group (n = 60) depending on their willingness to undergo three-dimensional HyCoSy in the present cycle (study group) or 6 months later (control group). Endometrial characteristics, including endometrial thickness and pattern as well as the endometrial blood flow distribution pattern, were measured twice by transvaginal Doppler ultrasonography in the preovulatory phase before and after HyCoSy examination. Participants were followed for 6 months to observe the outcome of spontaneous conception. Results: Compared with the control group, the study group had a significantly higher cumulative pregnancy rate at 6 months after HyCoSy (21.6% [13/60] vs 5.0% [3/60], P = 0.007). More patients in the study group showed improved endometrial blood flow distribution (P = 0.021, χ2 = 7.699), but no differences in endometrial thickness and pattern were observed between the groups (P > 0.05). Conclusion: HyCoSy examination may improve endometrial perfusion and has a therapeutic effect on improving spontaneous pregnancy among women with unexplained infertility. [ABSTRACT FROM AUTHOR]

• Uterine contractions at embryo transfer (ET) negatively correlate with pregnancy rates • Uterine blood flow at ET is a predictor of uterine receptivity • Oxytocin receptor antagonists, such as nolasiban, increase pregnancy rates after ET • Nolasiban lowers contractions, alters endometrial genomics and increases perfusion What are the effects of the oxytocin receptor (OTR) antagonist nolasiban on uterine contractions, endometrial perfusion and endometrial mRNA expression? Randomized, double-blind, parallel-group, mechanism-of-action study with nolasiban. Forty-five healthy, pre-menopausal women were treated with placebo, 900 mg or 1800 mg nolasiban on the day corresponding to blastocyst transfer. Ultrasonographic uterine contraction frequency and endometrial perfusion were assessed, and endometrial biopsies analysed by next-generation sequencing. Both doses of nolasiban showed decreased contraction frequency and increased endometrial perfusion depending on the time point assessed. At 1800 mg, 10 endometrial genes (DPP4, CNTNAP3, CNTN4, CXCL12, TNXB, CTSE, OLFM4, KRT5, KRT6A, IDO2) were significantly differentially expressed (adjusted P < 0.05). Of these, OLFM4, DPP4 and CXCL12 were regulated in the same direction as genes involved in implantation during the window of implantation. In addition, three genes (DPP4, CXCL12 and IDO2) were associated with decidualization and endometrial receptivity. These data expand our knowledge of the mechanism of action of nolasiban in increasing pregnancy rates after embryo transfer. The results suggest more marked effects of nolasiban 1800 mg compared with the 900 mg dose, supporting testing at higher doses in IVF patients. [ABSTRACT FROM AUTHOR]

The objective was to determine endometrial blood perfusion and hormone enzyme activity contralateral and ipsilateral to both the corpus luteum (CL) and developing dominant follicle (DF). Fourteen Angus cows were subjected to an Ovsynch + CIDR estrous synchronization protocol with d 0 corresponding to day of estrus. Equine AI rods were passed through the cervices, which provided a canal for the laser Doppler probe (PeriFlux 5000 LDPM, Perimed Inc., Ardmore, PA) to collect endometrial blood perfusion and microvascular flow of tissue surfaces without traumatizing the endometrium. Optimal perfusion was obtained by selecting 10 s of relatively constant perfusion for measurement, as measured by arbitrary Perfusion Units (PU) following calibration. After perfusion was collected, cattle were subjected to an endometrial biopsy utilizing a mare uterine biopsy punch with a sample collected from each horn and snap frozen. Perfusion and uterine biopsies were collected on d 12, 15, 18, and 21 of the estrous cycle. Data were analyzed using repeated measures ANOVA of the MIXED procedure of SAS (SAS Inst. Inc., Cary, NC), using the Wilcoxon rank sum test, and significance was declared at P ≤ 0.05. The model statement included day of estrous cycle, CL and DF location (respective to each uterine horn), the respective interactions with day, and CL and DF size with their respective interactions with day as covariants. Cattle were subjected to ultrasonography on d 11 and 19 of the estrous cycle to determine CL and follicular locations and size. Uterine biopsies were homogenized and activity of uridine 5'-diphospho-glucuronosyltransferase (UGT) was determined via luminogenic substrates (expressed per mg of protein). No differences (P ≥ 0.15) in endometrial perfusion were observed based on the location of the CL. However, endometrial perfusion was greater (P < 0.01) on the ipsilateral side to the DF. No differences (P ≥ 0.34) in endometrial perfusion were observed within day. Finally, no differences (P ≥ 0.38) were observed for UGT activity. In conclusion, endometrial perfusion relative to location of the DF were different whereas the CL location did not influence blood perfusion or UGT activity. This alteration in endometrial perfusion could be due to an increase in estrogen due to the presence of the DF. [ABSTRACT FROM AUTHOR]