Clinical Pregnancy Rate In Women Research Articles

#311 : Intrauterine Administration of Human Chorionic Gonadotropin in Women Undergoing IVF– An Individual Participant Data Meta-Analysis

Background and Aims: Human chorionic gonadotropin (hCG) has been proposed as an intrauterine intervention around embryo transfer period due to its potential to enhance endometrium receptivity and implantation. Existing randomised controlled trials (RCTs) showed inconsistent findings and multiple meta-analyses on this topic showed high unexplained heterogeneity. Individual participant data meta-analysis (IPDMA) is considered the “gold standard” synthesis method due to its ability to standardise and harmonise the data reporting and analysis. In this IPDMA, we aimed to investigate the effectiveness and safety of intrauterine hCG before embryo transfer. Method: We searched Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and PsycINFO without language restrictions up to November 2022. We included RCTs comparing intrauterine administration of hCG before embryo transfer versus placebo or no intervention in women undergoing IVF. The outcomes were live birth, clinical pregnancy and other fertility outcomes. We invited trial authors to share the de-identified IPD and established the IHABT collaboration. We performed a one-stage IPDMA as the main analysis. Results: Eight RCTs including IPD of 2338 participants were included. These RCTs were conducted in 6 different countries, with a dosage of intrauterine hCG between 500 IU and 1000 IU. In women undergoing IVF, compared to the control group, intrauterine administration of hCG before embryo transfer does not improve live birth rates (7 RCTs, 2245 participants, odds ratio [OR] 0.98, 95% confidence interval [CI] 0.82–1.17) or clinical pregnancy rates (8 RCTs, 2338 participants, OR 1.13, 95%CI 0.89–1.43). There was insufficient evidence of a difference between the two groups on any of the other fertility outcomes. Conclusion: Intrauterine administration of hCG does not improve live birth or clinical pregnancy rates in women undergoing IVF. Therefore, it should not be offered as an IVF add-on in clinical practice.

Improved Pregnancy Outcomes and Endometrial Receptivity by Thawed Frozen Embryo Transfer in Mildly Stimulated Cycles with Letrozole Combined with Estrogen in Women with Unresponsive Thin Endometrium Compared to Standard Endometrial Preparation with Estrogen Alone: A Retrospective Study.

Infertile women undergoing frozen embryo transfer (FET) cycles may not show optimal endometrial growth with estrogens alone. To evaluate clinical effect of mild stimulation with letrozole and estrogens on endometrial growth in comparison to standard endometrial preparation with oral and topical estrogens in infertile women with unresponsive thin endometrium undergoing FET. Retrospective observational case-control study. Forty women unresponsive to first AC-FET cycle were given mild stimulation with letrozole and estrogens as second LE-FET cycle for endometrial preparation (LE-FET study group) and compared with 40 historical controls who had received two cycles of AC-FET (AC-FET control group). Responses were assessed by optimal endometrial thickness (≥ 7mm) and clinical pregnancy. Descriptive statistics were elaborated by mean ± SD and percentages. Results were expressed by mean ± SD, unpaired t test for difference in endometrial thickness, chi square and Fisher exact test to compare the difference in pregnancy among both groups. Mean endometrial thickness was significantly increased in LE-FET study group (6.68 ± 2.09mm) versus AC-FET control group (5.35 ± 1.90mm). Higher clinical pregnancy rate was noted in study group as compared to control group (35% versus 12.5%). This study suggests that letrozole with estradiol (LE-FET) compared to estradiol alone (AC-FET) for second cycle significantly increased endometrial thickness and improved clinical pregnancy rates in women with unresponsive thin endometrium after first AC-FET cycle with estradiol alone. Addition of letrozole to estrogen upfront for FET cycles may enhance endometrial receptivity and might improve pregnancy outcomes.

Reproductive outcome and gynecologic comorbidities in women with endometriosis in a non-IVF setting: a retrospective study

BackgroundEndometriosis-related infertility is a disease associated with significant morbidity and distress to the couple and requires timely, multidisciplinary, and often high-cost care involving assisted reproductive technologies (ART). Many health care systems in the Middle East do not provide coverage for ART. This study aims to describe the reproductive outcome in a form of a clinical pregnancy rate in women with endometriosis-related infertility in a health care system that does not provide coverage for ART.ResultsThis is a retrospective observational cohort study on women who attended the gynecology clinic in a tertiary center in Oman with the diagnosis of endometriosis from January 2011 to December 2019. Women of reproductive age seeking pregnancy were included in the analysis. Out of total women with endometriosis, (144/262) 55.0% were included in the analysis with a mean age of 31.10 ± 5.73 years. The mean duration of follow-up was 30.18 months and 43/144 (29.9%) of our patients had a follow-up > 60 months. Based on surgical staging, 11.8% had mild disease, 70.1% had moderate to severe disease and 18.1% were not operated. After a thorough assessment, (30.2%) were advised to seek in vitro fertilization (IVF) as a primary treatment for infertility but 23.08% declined the advice. Of the 144, 24.3% achieved a clinical pregnancy. (16/144), 11% conceived spontaneously. 11/144) 7.6% conceived with ovulation induction ± intrauterine insemination (OI ± IUI) and the rest conceived with a self-sponsored IVF. The overall clinical pregnancy rate was not statistically different between those who had surgery and those did not have surgery (P value 0.474). The pregnancy rate based on the management plan were; surgery + IVF (7/25, 28.0%), surgery + OI/IUI (10/47, 21.3%), surgery alone (9/33, 27.3%). The pregnancy rate was not statistically different between the groups (P value 0.782).In addition to endometriosis, a significant proportion (63/144, 43.8%) of these women have a coexisting gynecologic morbidity including 2.1% non-endometrioma ovarian cyst, 13.9% myomas, 4.2% adenomyosis, 8.3% Mullerian anomalies, 2.1% polycystic ovary syndrome, 6.3% pelvic inflammatory disease or tubo-ovarian abscess and 1.4% biopsy-proven endometritis.ConclusionThe reproductive outcome of patients with endometriosis in this study population was generally poorer than what is reported in the literature with an overall pregnancy rate of 24.3% and a spontaneous pregnancy rate of 11%. Several causes can be noted for such an outcome, including advanced disease stage, coexisting gynecologic morbidities, and poor access to advance fertility management.

P-665 Timing of metformin treatment in women with polycystic ovarian syndrome and associated pregnancy outcomes: a systematic review and meta-analysis

Abstract Study question Does giving women with polycystic ovarian syndrome (PCOS) preconception metformin and continuing it through at least the first trimester improve pregnancy outcomes? Summary answer Giving women with PCOS preconception metformin and continuing throughout the first trimester significantly reduces the risk of early miscarriage, and can improve pregnancy outcomes. What is known already Metformin, either alone or in combination with other ovulation induction agents, can improve ovulation and clinical pregnancy rates in women with PCOS. Its impact on miscarriage and live birth rate are less well understood. Furthermore the impact of both the timing and duration of metformin treatment on subsequent pregnancy outcomes, in women with PCOS, is unknown. We sought to evaluate the role that preconception metformin, continued until at least the point of positive pregnancy test, may have on pregnancy outcomes in women with PCOS and the effect that stopping metformin once pregnant might have. Study design, size, duration We conducted a systematic review and meta-analysis. A search within MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for studies listed from database inception to 13th October 2022 was conducted. Potentially eligible studies identified through other sources (such as the reference lists of the selected primary studies and review articles) were also screened for inclusion. We adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for determining the quality of the evidence. Participants/materials, setting, methods The full-text of studies identified as being potentially suitable for inclusion were obtained. Those meeting the study selection criteria, outlined, were included in the systematic review and meta-analysis. Studies were included if they were prospective randomised controlled trials, comparing the use of metformin in women with PCOS, which had been started pre-conceptually and continued at least until pregnant (confirmed urinary pregnancy test), to either placebo or no treatment. Main results and the role of chance A total of 12 studies (1517 women) were included in the systematic review and meta-analysis. Women who were given preconception metformin which was continued until at least the end of the first trimester showed a significantly reduced risk of early miscarriage [OR 0.51 95% CI (0.27-0.96), 6 studies, n = 294, I2=0%], compared to either placebo or no treatment. Continuing preconception metformin until at least the end of first trimester also significantly increased clinical pregnancy rates [OR 1.92 95% CI (1.43-2.59), 5 studies, n = 793, I2=67%]. Only 3 studies, looked at live birth outcome which showed an increased odds of live birth in the metformin group, but this was not statistically significant [OR 1.38 95% CI (0.65-2.92), 3 studies, n = 212, I2=0%]. In women who stopped taking metformin following a positive pregnancy test, there was a suggestion of improvement in clinical pregnancy [OR 1.36 95% CI (0.99-1.87), 6 studies, n = 663, I2=45%] and live birth rates [OR 1.15 95% CI (0.57-2.35), 5 studies, n = 244, I2=0%]; but these were not statistically significant. Conversely, there was an increased odds of early miscarriage [OR 1.22 95% CI (0.59-2.52), 6 studies, n = 244, I2=0%], but this was also not statistically significant. Limitations, reasons for caution Whilst a role for commencing metformin pre-conceptually and continuing until at least the end of the first trimester has been demonstrated to be effective in improving clinical pregnancy rates and reducing miscarriage risk, the effectiveness and safety of continuing it throughout the remainder of the pregnancy remains unclear. Wider implications of the findings Continuing metformin treatment until at least the end of first trimester can increase the clinical pregnancy rate and reduce the risk of miscarriage. Stopping metformin once pregnant could be harmful and increase the risk of miscarriage. These findings should be considered when managing women with PCOS wishing to conceive. Trial registration number CRD42017073976

Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond.

During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

Is glucocorticoid use associated with a higher clinical pregnancy rate of in vitro fertilization and embryo transfer? A meta-analysis

BackgroundIt has been reported that the use of glucocorticoids may be able to improve clinical pregnancy rates in patients receiving in vitro fertilization and embryo transfer (IVF-ET). The purpose of this study was to investigate the association between glucocorticoid use and clinical pregnancy rate in IVF-ET patients. MethodsThis study has been registered on the International Register of Prospective Systems Evaluation (PROSPERO) (ID: CRD42022375427). A thorough and detailed search of databases including PubMed, Web of Science, Embase, and Cochrane Library was conducted to identify eligible studies up to October 2022. Quality assessment was conducted on the modified Jadad Scoring Scale and Newcastle-Ottawa Scale, and the inter-study heterogeneity was estimated by Q test and I2 test. Combined hazard ratios with 95% CI were calculated using random effects or fixed effects models based on heterogeneity. Meanwhile, Begg's and Egger's tests were used to detect the existence of publication bias, the leave-one-out method was used for sensitivity analysis and multiple subgroup analyses were conducted. ResultsSeventeen studies involving 3056 IVF-ET cycles were included. We found that glucocorticoid use was associated with a higher IVF-ET pregnancy rate (OR = 1.86, 95% CI = 1.27–2.74, P = 0.002). In the subgroup analysis, studies of different regions and different study types all showed similar results that glucocorticoid is beneficial to improve the clinical pregnancy rate of patients with IVF-ET, and patients with positive autoantibodies and patients receiving IVF-ET multiple times also showed the same results. However, there was no significant change in clinical pregnancy rates in the seven studies with negative autoantibodies and in the seven studies with initial IVF-ET treatment. The results of the 12 medium-acting glucocorticoids and 4 long-acting glucocorticoids were also generally consistent with each other. There was no statistical difference in subgroup analysis of whether patients had endometriosis or not. ConclusionAppropriate use of glucocorticoids is beneficial for improving the clinical pregnancy rate in women receiving IVF-ET, but this result still needs to be verified by more high-quality and large sample size randomized controlled trials (RCTs).

Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience.

Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today's approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide.

Relationship between advanced maternal age and decline of endometrial receptivity: a systematic review and meta-analysis.

Female fertility decreases with age. A decline in oocyte quality plays a key role in reproductive problems in older women. Whether advanced maternal age (AMA) is associated with a decline in endometrial receptivity (ER) remains controversial. A systematic review and meta-analysis were conducted to evaluate the relationship between AMA and ER. Eighteen eligible studies were included in this meta-analysis. Of the 18 studies, 17, 8, 14, and 9 studies reported the impact of AMA on clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR), respectively. The combined results showed a trend (without significance) toward lower CPR in women with AMA than in younger women. A similar trend of worse outcomes in terms of IR was observed in women with AMA. A significantly higher MR and lower LBR were observed in infertile women with AMA than in younger women. In conclusion, there was a slightly lower IR and CPR without significance; however, significantly increased MR and decreased LBR were observed in women with AMA than in younger women, indicating that AMA is related to the decline of ER. Further prospective cohort studies with a preimplantation genetic testing for aneuploidy model are needed to observe the relationship between AMA and ER and explore the possible mechanisms.

The effect of Nifedipine on embryo transfer outcomes: A randomized clinical trial.

Endometrial receptivity is crucial for embryo implantation, and excessive uterine contraction reduces success. Nifedipine which is a calcium channel blocker, could decrease uterine contraction and improve pregnancy outcomes. This study aimed to assess the effect of Nifedipine before embryo transfer on the pregnancy outcome in women undergoing in vitro fertilization (IVF) in a tertiary center in Iran. 150 women who were candidates for IVF were randomly assigned into 2 groups: group 1 received 20 mg Nifedipine 30 min before embryo transfer, and group 2 received no intervention. Blood pressure of the participants was monitored every 10 min for 1 hr under the supervision of an anesthesiologist. Finally, implantation rate and chemical and clinical pregnancy rates were compared between groups. At the end of the study, 140 participants were included in the final analyses. No significant difference was observed in clinical pregnancy rates between groups (20% vs. 22%, p = 0.51). Nifedipine administration before embryo transfer does not improve the implantation and clinical pregnancy rates in women undergoing IVF.

Efficacy of In-utero Infusion of Autologous Platelet Rich Plasma Therapy in Women with Recurrent Implantation Failure: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Introduction: In-utero infusion of autologous Platelet Rich Plasma (PRP) is found to be a novel approach to address the thin, non receptive endometrium leading to recurrent implantation failure. Aim: To estimate the efficacy of intrauterine PRP infusion in subfertile females affected with recurrent implantation failure via the conduction of a systematic review and meta-analysis of the available Randomised Controlled Trials (RCTs). Materials and methods: A systematic literature search was done in electronic databases like Medline (through PubMed), Embase, Scopus, Web of Science, and Cochrane database from January 2000 to November 2020 using keywords like “In-vitro Fertilisation” OR “IVF” OR “Intracytoplasmic sperm injection” OR “ICSI” OR “Embryo transfer” AND “Platelet rich plasma” OR “PRP” OR “Autologous platelet rich plasma” OR “Platelet rich plasma” and “recurrent implantation failure”. The randomised controlled trials, comparing intrauterine infusion of PRP versus no intervention or placebo in a study population of subfertile women with recurrent implantation failure and having medically confirmed pregnancy outcomes like live birth, clinical pregnancy, chemical pregnancy, and miscarriage were included in this systematic review. Studies with inadequate details in the methodology or result section were excluded from this analysis. This meta-analysis involved a pooled data analysis of 335 participants (174 cases and 161 controls) from four RCTs. Results: Compared with the control group, patients in the PRP group were found to have more beneficial effects in terms of implantation rate (Relative risks: 1.51, 95% Confidence interval: 0.94, 2.44; Heterogeneity: Tau²=0.08; I²=44%; Test for overall effect: Z=1.69, p-value=0.09) and clinical pregnancy (Relative risk: 1.88, 95% CI: 1.17, 3.03; Heterogeneity: Tau²=0.12; I²=51%; Test for overall effect: Z=2.62; p-value=0.009). Conclusion: Intrauterine PRP infusion increases the implantation rate and clinical pregnancy rate in women undergoing the frozen embryo transfer cycle.

Value of Intrauterine Injection of HCG (Human Chorionic Gonadotropin) before Fresh Embryo Transfer on Clinical Pregnancy Rate in Women with Previous Failed One or Two ICSI (Intra Cytoplasmic Sperm Injection) Trials

Value of Intrauterine Injection of HCG (Human Chorionic Gonadotropin) before Fresh Embryo Transfer on Clinical Pregnancy Rate in Women with Previous Failed One or Two ICSI (Intra Cytoplasmic Sperm Injection) Trials

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome.

Chronic Endometritis in Infertile Women: Impact of Untreated Disease, Plasma Cell Count and Antibiotic Therapy on IVF Outcome-A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.

Transcutaneous electrical acupoint stimulation improves endometrial receptivity resulting in improved IVF-ET pregnancy outcomes in older women: a multicenter, randomized, controlled clinical trial

ObjectiveTo examine the effects and mechanisms of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization (IVF)-embryo transfer (ET).Design, setting, and participantsThis efficacy study was a multicenter, randomized, controlled clinical trial (RCT) in women receiving IVF-ET. The mechanistic study was a single-center RCT.InterventionsThe participants received TEAS vs. no TEAS treatment.Main outcome measuresIn the efficacy study, the primary outcomes were the rates of clinical pregnancy, embryo implantation, and live birth. In the mechanistic study, sex hormones and endometrial protein expression were examined.ResultsUltimately, 739 participants were enrolled (367 and 372 in the TEAS and control groups, respectively). The clinical pregnancy rate was higher in the TEAS group than in the controls (55.1% vs. 46.7%, P = 0.03). There were no significant differences in embryo implantation, biochemical pregnancy, and live birth rates between the two groups (all P > 0.05) in the study population. In women > 35 years, the clinical pregnancy rates, embryo implantation rates and live birth rates in the TEAS and control groups were 48.9% vs. 23.7% (P = 0.004),30.8 vs. 13.9% (P = 0.001) and 34.0% vs. 19.7% (P = 0.06) respectively. In the mechanistic study with 120 participants, on the theoretical embryo implantation day, better developed endometrial pinopodes, elevated endometrial integrin α1β1/αVβ3, leukemia inhibitory factor, and elevated serum progesterone levels were found in the TEAS group compared with controls.ConclusionTEAS significantly improved the clinical pregnancy rate in women undergoing IVF-ET, especially in women of older age. It might be due to improved endometrial receptivity.Trial registrationChiCTR-TRC-13003950.

Effect of vaginal/oral tadalafil on endometrial thickness in IVF patients: a double-blind, placebo controlled RCT: a pilot study.

To investigate the effect of tadalafil (a long working phosphodiesterase type 5 inhibitor) on the endometrial thickness, biochemical pregnancy rates and clinical pregnancy rates in women in an in vitro fertilization treatment. This study investigates the use of vaginal and oral administration of tadalafil. This is a prospective double-blind placebo-controlled randomized controlled trial with 58 patients in an in vitro fertilization treatment with a short antagonist stimulation protocol. The study population is divided into three equal groups comparing oral and vaginal administration of tadalafil to a control group. No significant difference in endometrial thickness and number of biochemical and clinical pregnancies was found between the three groups. This study could not show a significant benefit of administration of tadalafil. However, a trend towards more pregnancies in the group treated with oral tadalafil is seen, more research in specific subgroups is needed.

P-350 Endometrial receptivity analysis (ERA) and microbiome testing for recurrent implantation failure (RIF): a matched case control study

Abstract Study question Does the use of ERA, EMMA (endometrial microbiome metogenomic analysis) or ALICE (analysis of infectious chronic endometritis) improve implantation rate and clinical pregnancy? Summary answer The use of ERA significantly improves the clinical pregnancy rate in women with recurrent implantation failure, no difference was observed for EMMA or ALICE. What is known already The ability of ERA to utilise endometrial tissue transcriptomics to detect asynchronous cycles is controversial. Retrospective studies have demonstrated significantly lower implantation rates for the non-receptive cohort and improved pregnancy rates by personalising the embryo transfer (pET). An RCT reported comparable clinical outcomes for pET and standard FET. There have also been multiple reports of the endometrium being dominated by Lactobacillus, prevalence of this species without bacterial vaginosis leads to positive outcomes in IVF. That said, there is a scarcity of good quality evidence to advocate the use of antibiotics and/or probiotics to treat dysbiosis or pathogens in the subfertile population. Study design, size, duration From Jan 2017 to August 2021 202 patients underwent one or more of ERA (n = 202), EMMA (n = 101), and/or ALICE (n = 97) at CARE Fertility UK. The cycle subsequent to the test was compared to 404 age matched control cycles. Participants/materials, setting, methods This study included patients from all 22 clinics across CARE Fertility UK. Rates of positive pregnancy test and clinical pregnancy were compared between patients with normal and abnormal test results using Chi-squared statistic. Binary logistic regression analysis and odds ratios were used to test for improvements in clinical outcomes by adjusting for the following covariates: age, BMI, parity, 2 or more previous implantation failures, donor eggs and frozen embryos. Main results and the role of chance ERA testing resulted in a normal result in 42.3% of patients, 30.6% were pre-receptive and 17% were early receptive. EMMA resulted in a normal result in 36% of patients, 22% were abnormal, 17% had ultra-low biomass and 25% mild dysbiosis. Only 4% of patients using the ALICE tested positive, therefore this was not included in any modelling due to low event rates. The implantation rate and clinical pregnancy rates showed no statistical significance between those with an abnormal result vs. those who had a normal test. When comparing those tested to matched controls and adjusting for the above covariates, the use of the ERA test was significantly associated with improved implantation rate (OR 3.08, 95% CI 1.57-6.03, p = 0.001) and clinical pregnancy rate (OR 2.7, 95% CI 1.38-5.28, p = 0.004). The use of the EMMA test did not improve implantation (OR 0.42, 95% CI 0.051-3.437, p = 0.418) or clinical pregnancy rate (OR 0.48, 95% CI 0.039-5.89, p = 0.566). When comparing those with an abnormal ERA (i.e. presumed intervention) to matched controls the ERA test was significantly associated with improved clinical pregnancy (OR 5.4, 95% CI 2.007-14.85, p &amp;lt; 0.001). On the other hand, EMMA was not associated with any improvements (p = 1.0). Limitations, reasons for caution The data collection process had limitations since minimal information was available for patients who underwent previous cycles at other clinics. The number of patients with receptive ERA and abnormal EMMA is small (n = 25) vs. those with a normal EMMA and ERA (n = 10). Therefore, a significant limitation is sample size. Wider implications of the findings ERA can be more confidently offered to patients and has been demonstrated to significantly improve clinical pregnancy rates. Further research is needed before we can determine whether EMMA or ALICE is a useful test, particularly when considering very few patients show evidence of chronic endometritis. Trial registration number Not applicable

High-sensitivity C-reactive protein levels and pregnancy outcomes in women with unexplained infertility after ovarian stimulation with intrauterine insemination in a multicenter trial

ObjectiveTo determine if chronic inflammation, assessed by basal high-sensitivity C-reactive protein (hs-CRP) levels, is associated with pregnancy outcomes in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination.DesignProspective cohort analysis of the Reproductive Medicine Network’s Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial.SettingMulticenter university-based randomized controlled trial.Patient(s)A total of 781 couples with unexplained infertility.Intervention(s)Secondary analysis.Main Outcome Measure(s)Adjusted risk ratios of live birth, clinical pregnancy, and pregnancy loss rates by hs-CRP levels.Result(s)Associations between hs-CRP levels and clinical pregnancy rates were not observed after adjustment for baseline body mass index. There were fewer live births among women with higher hs-CRP levels, although confidence intervals crossed 1.0. The risk of pregnancy loss was greater in women with increased hs-CRP levels (1–3 mg/L: risk ratio [RR], 1.67; 95% confidence interval [CI], 1.00–2.79; >3–10 mg/L: RR, 1.84; 95% CI, 1.06–3.20; and >10 mg/L: RR, 2.14; 95% CI, 1.05–4.36 compared to women with hs-CRP <1 mg/L).Conclusion(s)This investigation suggests that chronic inflammation may increase the risk of pregnancy loss but not impact the clinical pregnancy rate in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination. Associations between inflammation and pregnancy outcomes in women with infertility merit further investigation.Clinical Trial Registration Numberclinicaltrials.gov NCT01044862.

Impact of mechanical endometrial injury on clinical pregnancy rates in women with clomiphene-resistant polycystic ovary syndrome

Impact of mechanical endometrial injury on clinical pregnancy rates in women with clomiphene-resistant polycystic ovary syndrome

Letrozole promotes the expression of integrin αvβ3 and HOXA10 in endometrium of endometriosis

ABSTRACT Endometriosis is a common estrogen-dependent chronic inflammatory disease that leads to infertility in women of reproductive age. Perhaps infertility reflects the reduced expression of integrin αvβ3 and HOXA10 in endometriosis. Previous studies have shown that administration of letrozole, a non-steroidal aromatase inhibitor for cancer treatment, increased the clinical pregnancy rate in women with endometriosis, but the mechanisms remain to be determined. In this communication, a rat model of endometriosis was established. Animals were treated with letrozole at 2ug/kg of body weight, intragastric administration for 15 consecutive days. Letrozole increased the expression of αvβ3 and HOXA10 in the endometriosis model and endometrial receptivity. Abbreviations: WOI: window of implantation; RGD: Arg-Gly-Asp; HOX: homeobox; E2: estradiol; SPF: specific pathogen-free.

The Current Role of Induced Endometrial Trauma (Endometrial Scratch) in Women Undergoing Infertility Treatment.

Induced endometrial trauma, otherwise known as endometrial scratch is a simple technique that has been rapidly adopted into clinical practice, mainly for women having IVF treatment, in an attempt to increase pregnancy rates. The introduction of endometrial scratch followed early reports of improved clinical pregnancy rates in women with repetitive implantation failure after having the procedure and follows on from evidence from animal models in the early 20th century suggesting that mechanical trauma to the endometrium can induce decidual changes. Due to the ease and low cost of the procedure, it has been rapidly adopted as an add-on to fertility treatments, in many cases where evidence is still lacking. Despite the initial publication of a large number of studies that demonstrated encouraging improvements in pregnancy rates in women who underwent this procedure, these studies were mainly limited by the small sample sizes and heterogeneity of their study populations, leading to limited validity of the evidence provided by these studies. More recently, three large randomized controlled studies have been published that paint a different picture regarding the value of this procedure. This article explores the evolution of the evidence and the current state of endometrial scratch as an adjuvant therapy for women undergoing IVF treatment.