Preparation Of Endometrium Research Articles

Progesterone Intramuscularly or Vaginally Administration May Not Change Live Birth Rate or Neonatal Outcomes in Artificial Frozen-Thawed Embryo Transfer Cycles.

BackgroundsPrevious studies suggested that singletons from frozen-thawed embryo transfer (FET) were associated with higher risk of large, post-date babies and adverse obstetrical outcomes compared to fresh transfer and natural pregnancy. No data available revealed whether the adverse perinatal outcomes were associated with aberrantly high progesterone level from different endometrium preparations in HRT-FET cycle. This study aimed to compare the impact of progesterone intramuscularly and vaginally regimens on neonatal outcomes in HRT-FET cycles.MethodsA total of 856 HRT-FET cycles from a fertility center from 2015 to 2018 were retrospectively analyzed. All patients had their first FET with two cleavage-staged embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone intramuscularly 60 mg per day or vaginal gel Crinone 90 mg per day. Pregnancy outcomes including live birth rate, singleton birthweight, large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm delivery rate were analyzed. Student’s t test, Mann-Whitney U-test, Chi square analysis, and multivariable logistic regression were used where appropriate. Differences were considered significant if p < 0.05.ResultsNo significant difference of live birth rate was found between different progesterone regimens (Adjusted OR 1.128, 95% CI 0.842, 1.511, p = 0.420). Neonatal outcomes like singleton birthweight (p = 0.744), preterm delivery rate (Adjusted OR 1.920, 95% CI 0.603, 6.11, p = 0.269), SGA (Adjusted OR 0.227, 95% CI 0.027, 1.934, p = 0.175), and LGA rate (Adjusted OR 0.862, 95% CI 0.425, 1.749, p=0.681) were not different between two progesterone regimens. Serum P level >41.82 pmol/L at 14 day post-FET was associated with higher live birth rate than serum P level ≤41.82 pmol/L in HRT-FET cycles when progesterone was intramuscularly delivered (Adjusted OR 1.690, 95% CI 1.002, 2.849, p = 0.049). But singleton birthweight, preterm delivery rate, SGA and LGA rate were not different between these two groups.ConclusionsRelatively higher serum progesterone level induced by intramuscular regimen did not change live birth rate or neonatal outcomes compared to vaginal regimen. Monitoring serum progesterone level and optimizing progesterone dose of intramuscular progesterone as needed in HRT-FET cycles has a role in improving live birth rate without impact on neonatal outcomes.

ENDOMETRIC FACTOR OF ENDOMETRIOSIS-ASSOCIATED INFERTILITY

BACKGROUND Despite numerous studies and a not decreasing amount of endometriosis and associated infertility, the study of endometriosis- associated infertility does not lose its relevance, and the characteristics of the endometrium is appeared to be central and predictive factors that determine the success of overcoming infertility. OBJECTIVE To reflect the molecular genetic features of the state of the endometrium with endometriosis associated with infertility, expand the understanding of its pathogenesis, substantiate theoretical aspects of the use of hormonal preimplantation preparation of the endometrium in endometriosis-associated infertility. MATERIALS AND METHODS To write this review, we searched for domestic and foreign publications in Russian and international search systems (eLIBRARY, PubMed, MedLine, Crossref, etc.) over the past 1–16 years. RESULTS The model of changes in endometrial receptivity is examined the mechanisms of resistance to progesterone and overproduction of estrogens as key endometrial factors in the pathogenesis of endometriosis-associated infertility and theoretical justification for the use of hormonal therapy for the preimplantation preparation of compromised endometrium is given. CONCLUSION Despite the large number of publications, there is no consensus and the same approaches to determining the receptivity of the endometrium and its role in implantation disorders in endometriosis, as well as clear ideas about the pathogenesis of endometriosis-associated infertility. A personalized approach in the management of patients with endometriosis-associated infertility will lead to a common denominator of many factors affecting reproduction and determine their potential role in both the diagnosis and treatment of a particular patient.

Maternal and Neonatal Complications After Natural vs. Hormone Replacement Therapy Cycle Regimen for Frozen Single Blastocyst Transfer.

Objective: To evaluate the maternal and neonatal complications after frozen-thawed blastocyst transfer cycles utilizing different endometrial preparation regimens.Design: This is a retrospective cohort study and a secondary analysis of a multicenter, randomized, controlled trial comparing live birth rate after fresh vs. frozen single blastocyst transfer (Frefro-blastocyst).Setting: Reproductive medicine centers.Patient(s): A total of 800 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilization after frozen-thawed single blastocyst transfer.Intervention(s): Endometrium preparation was performed with a natural cycle regimen or hormone replacement therapy (HRT) cycle regimen, at the discretion of local investigators. All pregnancies were followed up until delivery.Main Outcome Measure(s): Maternal and neonatal complications.Result(s): 513 infertile patients who underwent natural cycles regimen and 287 who underwent HRT cycles regimen were analyzed. The incidences of maternal and neonatal complications were comparable between the natural cycle and HRT cycle regimen. Regarding the risk of gestational diabetes, gestational hypertension, pre-eclampsia, preterm delivery, small for gestational age and large for gestational age, the HRT cycle was still not a significant risk factor after adjusting for potential confounders. The natural cycle regimen yielded an insignificant higher total live birth rate [59.45 vs. 50.17%, P = 0.001, adjusted odds ratio (AOR) 1.366, 95% confidence interval (CI) 0.975–1.913], clinical pregnancy rate (68.23 vs. 58.89%, P = 0.008, AOR 1.406, 95% CI 0.992–1.991) and ongoing pregnancy rate (62.18 vs. 52.61%, P = 0.008, AOR 1.387, 95% CI 0.988–1.948) than did the HRT cycle regimen. However, compared to natural cycles, HRT cycles were associated with a significantly higher risk of biochemical miscarriage (6.86 vs. 18.18%, P < 0.001, AOR 0.328, 95% CI, 0.176–0.611).Conclusion(s): The incidence of maternal and neonatal complications in natural cycle and HRT cycle regimens after frozen single blastocyst transfer were comparable. Frozen-thawed single blastocyst transfer in a natural cycle was associated with lower biomedical miscarriage than the use of the HRT cycle.Clinical Trial Registration Number: Frefro-blastocyst was registered at Chinese Clinical Trial Registry, ChiCTR-IOR-14005405.

Modified natural protocol seems superior to natural and artificial protocols for preparing the endometrium in frozen embryo transfer cycles.

Although several studies claim higher success rates in natural cycle (NC) and modified natural cycle (mNC) protocols, currently, there is no consensus on the most effective method of endometrium preparation prior to frozen embryo transfer (FET) cycles. We aimed to find out the best protocol by comparing three different protocols for preparing the endometrium in FET cycles. This retrospective cohort study was conducted at a private in-vitro fertilization (IVF) center. Medical records of all patients enrolled in frozen embryo transfer cycles between November 2017 and February 2019 were reviewed. Group I (N.=94) included patients who underwent artificial endometrial preparation (AC), group II (N.=23) confined patients enrolled in mNC and group III (N.=12) included patients who had NC protocol. Main outcome parameters were clinical pregnancy rates, implantation rates and miscarriage rates. There was a tendency towards higher clinical pregnancy rate in mNC group. Clinical pregnancy rates of the three groups were 54.3%, 65.2% and 33.3% respectively (P=0.199). Implantation rate was significantly higher in group II (34%, 50% and 12% respectively, P=0.006). Miscarriage rates were similar for the three groups. Although not reaching a statistically significant level, there is a tendency towards higher implantation rate and pregnancy rate in mNC protocol compared to true NC and AC protocols.

Preparation of endometrium for frozen embryo transfer cycles

Aim. Aim of the study was to the effectiveness of various endometrial preparation protocols in IVF frozen embryo transfer cycles.&#x0D; Materials and methods. The study included 288 women, which were stratified into two groups depending on the onset of pregnancy: group 1 pregnancy + (n=92), group 2 pregnancy - (n=196). Then endometrium preparation features were evaluated.&#x0D; Results. The pregnancy rate after frozen-thawed embryo transfer was a bit higher in the natural menstrual cycle (41.2%) compared to the hormonal replacement therapy (30.0%); p=0.083. There were no significant differences in the use of various estrogen and progestogen drugs, the average estrogen dose, progestogen administration and the endometrium thickness. In the natural cycle, the odds ratio of pregnancy with the duration menstrual cycle from 28 to 30 days was 4.25 (95% CI 1.15; 17.23).&#x0D; Conclusion. Thus, the pregnancy rate is slightly higher in natural cycle frozen-thawed embryo transfer. However, the duration of the menstrual cycle (from 28 to 30 days) has a key effect on the effectiveness of the IVF program in this case.

Increased Risk of Pre-eclampsia After Frozen-Thawed Embryo Transfer in Programming Cycles.

Objective: This study aims to investigate whether obstetric complications and perinatal outcomes after frozen embryo transfer (FET) in the programming cycles differ from that in the natural cycles.Methods: We conducted a retrospective cohort study collecting a total of 14,373 singletons born after frozen embryo transfer at the Center for Reproductive Medicine Affiliated to Shandong University from September 2013 to September 2018. The women were divided into two groups according to the regimens for endometrium preparation: either natural cycles (n = 10,211) or programming cycles (n = 4,162). The primary outcomes were the incidence of obstetric complications consisting of pre-eclampsia, gestational diabetes mellitus, placenta previa, placental abruption, and postpartum hemorrhage. The perinatal outcomes included average birthweight, low birthweight (LBW), very LBW, macrosomia, large for gestational age, and small for gestational age. Multivariable logistic regression analysis was performed to adjust for potential confounders.Results: The incidences of pre-eclampsia (8.6 vs. 3.8%) and postpartum hemorrhage (0.7 vs. 0.2%) in the programming FET cycles were significantly higher than those in the natural FET cycles. The logistic regression analysis showed that, compared to the natural FET cycles, the programming FET cycles were associated with an elevated risk of pre-eclampsia (aOR, 2.55; 95% CI, 2.06–3.16) and postpartum hemorrhage (aOR, 2.94; 95% CI, 1.44–5.99).Conclusion: The women with singleton delivery after frozen-thawed embryo transfer in the programming cycles had an elevated risk of pre-eclampsia and postpartum hemorrhage, which was speculated to be associated with the absence of the corpus luteum.

A comparison of the effects of three different estrogen used for endometrium preparation on the outcome of day 5 frozen embryo transfer cycle.

Objective:To evaluate the effects of three different estrogen used for endometrium preparation on pregnancy rate, as well as hormone profile on day 5 frozen embryo transfer (FET) cycles.Methods:Retrospective, observational study. Setting: A tertiary teaching and research private reproductive medicine center. Patients: Ninety patients who were undergoing endometrium preparation for day five frozen embryo transfer cycle (FET). Intervention(s): The women were divided in three groups according to the administration route of estrogen (E2): oral (Primogyna), transdermal patches (Estradot), or transdermal gel (Oestrogel Pump). These administration routines of estrogen are equivalent to 6mg of estradiol daily. All women received 600mg of vaginal progesterone (P) per day (Utrogestan) for luteal phase support. We drew blood samples on starting P day, as well as on beta hCG day for E2 and P measurements. Main Outcome Measure(s): Clinical pregnancy rates (PR).Results:Patient features in the three groups were comparable. There were no significant differences concerning implantation rate, clinical PR, miscarriage rate, multiple-pregnancy rate, or E2 and P levels on starting P day and on beta hCG day.Conclusions:In FET cycles with oral (Primogyna) or transdermal patches (Estradot), or transdermal gel (Oestrogel Pump), there was no significant difference on pregnancy rates.

Efficacy of endometrium preparation with the help of GnRH antagonist for frozen embryo transfer

Efficacy of endometrium preparation with the help of GnRH antagonist for frozen embryo transfer

HORMONAL SUPPORT OF ENDOMETRIUM IN IVF CYCLES WITH VITRIFIED EUPLOID BLASTOCYST TRANSFER

A total of 100 women with tubal-peritoneal infertility, that were divided into 2 groups, 50 people each, were examined. In the first group, vitrified embryo transfer was carried out in the natural menstrual cycle with minimal LP support. The second group included patients, who underwent endometrial hormonal preparation and LP maintenance. Analysis of the efficiency of embryo transfer (ET) in the cryocycle showed that after the endometrium prepa ration was performed with hormonal preparations (group II) on the ET day, the thickness and structure of the endometrium normalized and practically did not differ from the endometrial thickness in women in the natural menstrual cycle with minimal LF support (I Group). A slight decrease in vascular resistance indices of uterine blood flow during hormonal preparation of the endometrium, compared with the natural cycle, indicates a posi tive effect of hormonal therapy on the structure and function of the endometrium. The results of the analysis of protocols with hormonal preparation of the endometrium and transfer of thawed embryos in the natural menstrual cycle showed the same efficiency in terms of the frequency of preg nancy.

Sex steroids influence organizational but not functional decidualization of feline endometrial cells in a 3D culture system†.

Successful implantation requires complex signaling between the uterine endometrium and the blastocyst. Prior to the blastocyst reaching the uterus, the endometrium is remodeled by sex steroids and other signals to render the endometrium receptive. In vitro models have facilitated major advances in our understanding of endometrium preparation and endometrial-blastocyst communication in mice and humans, but these systems have not been widely adapted for use in other models which might generate a deeper understanding of these processes. The objective of our study was to use a recently developed, three-dimensional culture system to identify specific roles of female sex steroids in remodeling the organization and function of feline endometrial cells. We treated endometrial cells with physiologically relevant concentrations of estradiol and progesterone, either in isolation or in combination, for 1 week. We then examined size and density of three-dimensional structures, and quantified expression of candidate genes known to vary in response to sex steroid treatments and that have functional relevance to the decidualization process. Combined sex steroid treatments recapitulated organizational patterns seen in vivo; however, sex steroid manipulations did not induce expected changes to expression of decidualization-related genes. Our results demonstrate that sex steroids may not be sufficient for complete decidualization and preparation of the feline endometrium, thereby highlighting key areas of opportunity for further study and suggesting some unique functions of felid uterine tissues.

Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus.

What were the risks with regard to the pregnancy outcomes of patients who conceived by frozen-thawed embryo transfer (FET) during a hormone replacement cycle (HRC-FET)? The patients who conceived by HRC-FET had increased risks of hypertensive disorders of pregnancy (HDP) and placenta accreta and a reduced risk of gestational diabetes mellitus (GDM) in comparison to those who conceived by FET during a natural ovulatory cycle (NC-FET). Previous studies have shown that pregnancy and live-birth rates after HRC-FET and NC-FET are comparable. Little has been clarified regarding the association between endometrium preparation and other pregnancy outcomes. A retrospective cohort study of patients who conceived after HRC-FET and those who conceived after NC-FET was performed based on the Japanese assisted reproductive technology registry in 2014. The pregnancy outcomes were compared between NC-FET (n = 29 760) and HRC-FET (n = 75 474) cycles. Multiple logistic regression analyses were performed to investigate the potential confounding factors. The pregnancy rate (32.1% vs 36.1%) and the live birth rate among pregnancies (67.1% vs 71.9%) in HRC-FET cycles were significantly lower than those in NC-FET cycles. A multiple logistic regression analysis showed that pregnancies after HRC-FET had increased odds of HDPs [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.14-1.80] and placenta accreta (adjusted odds ratio, 6.91; 95% CI, 2.87-16.66) and decreased odds for GDM (adjusted odds ratio, 0.52; 95% CI, 0.40-0.68) in comparison to pregnancies after NC-FET. Our study was retrospective in nature, and some cases were excluded due to missing data. The implication of bias and residual confounding factors such as body mass index, alcohol consumption, and smoking habits should be considered in other observational studies. Pregnancies following HRC-FET are associated with higher risks of HDPs and placenta accreta and a lower risk of GDM. The association between the endometrium preparation method and obstetrical complication merits further attention. No funding was obtained for this work. The authors declare no conflicts of interest in association with the present study. Not applicable.

ADministration of Clotrimazole prior to Frozen Embryo Transfer (FET) Cycles May Improve Implantation Rate

Introduction We hypothesized 2 years ago that the presence of candidiasis whether clinical or sub- clinical may impact negatively on implantation and pregnancy rates. On this basis, we decided to put our patients prophylactically on clotrimazole (Canestan) one week prior to the embryo transfer. We found a trend to higher pregnancy and implantation rate in patients administered with Canestan as opposed to those who were not ( Lee et al., PGDIS, 2017 ). It is of interest that vaginal candidiasis has been associated with a reduced number of lactobacilli ( Hillier et al., 1992 ). Moreover, Moreno et al. (2016) also reported a significantly reduced implantation rate in IVF patients with a non-Lactobacillus- dominant endometrial microbiota. In this retrospective study, we review the effect of Canesten in the clinical outcome of FET patients. Material and Methods A total of 342 patients (age range=23-44) with blastocysts screened using Preimplantation Genetic Screening (PGS) underwent FET cycles in Alpha Fertility Centre, Malaysia, between July 2016 and October 2017. Oocyte donors were excluded from the study. These patients were divided into 2 groups: 290 patients with 362 euploid blastocysts transferred in the treatment group (Group A), and 52 patients with 64 euploid blastocysts transferred in the control group (Group B). All patients were administered with oestrogen (Progynova) and progesterone (Cyclogest or Crinone 8%) for endometrium preparation. In Group A, patients were given Canesten 500 mg pessary 7 days prior to embryo transfer. The mean age of patients in Group A was 34.3 while the mean age of patients in Group B was 35.3 (p>0.05). All thawed blastocysts survived with morphologically intact inner cell masses and trophectoderm cells. The mean number of blastocysts transferred was 1.2 each for Group A and B. Clinical pregnancy and number of gestational sacs were determined by ultrasound. Results The implantation rate was significantly higher in patients treated with Canesten (67.0%) compared to those who were not (53.1%) with a p value of 0.05). Conclusion Based on our preliminary result and this study with a larger sample size, it is suggestive that the use of Canesten pessaries in FET cycles is promising in improving implantation rate and this appears to apply to all age groups. Nevertheless, further studies which are controlled needs to be undertaken to confirm the above.

Should single embryo transfer be used in patients with any kind of infertility factor? Preliminary outcomes.

Objective:Multiple embryos have been transferred to compensate for low implantation rates, which in turn, increase the likelihood of multiple pregnancies. Despite the publication of clinical guidelines and a reduction in the number of embryos transferred, double embryo transfer still is the most common practice. There is no clear evidence of who should receive the single embryo transfer (SET), and it is more commonly indicated for patients of good prognosis. However, it is not clear how much the presence of other infertility factors can affect the SET prognosis. The aim of this study was to evaluate differences in clinical pregnancy rates (CPR) of frozen-thawed SET cycles for women presenting with different infertility factors.Methods:Retrospective cohort study evaluating 305 frozen-thawed SET cycles performed in the last 10 years in a private IVF center. We included patients undergoing ovarian stimulation cycles, using ejaculated sperm and a frozen-thawed ET. Embryos were routinely vitrified and warmed up, and the blastocysts were transferred after endometrium preparation. The cycles were categorized according to the infertility factor classified by the Society for Assisted Reproductive Technologies (SART) as anatomic female factor (n=55), endocrine female factor (n=26), endometriosis (n=37), male factor (n=60), ovarian insufficiency (n=26), unexplained (n=24), multiple factors (n=45) and other (n=32). CPR were compared between the groups and the multivariate analysis was performed to evaluate the association of each infertility factor and the CPR, adjusted for confounders.Results:The women varied in age from 18 to 44 years (35.9±3.8), presented Body Mass Index of 22.4±3.1kg/m2, baseline serum FSH of 7.4±8.3 IU/ml, and had a mean of 11.0±8.4 MII oocytes recovered and 6.4±5.3 embryos cryopreserved. The CPR, according to infertility factors were: anatomic female factor (25.9%), endocrine female factor (30.8%), endometriosis (27.8%), male factor (20.7%), ovarian insufficiency (21.7%), unexplained (9.5%), multiple factors (17.1%) and other (20.7%). Multivariate analysis did not show significant association of infertility factors and CPR adjusted for confounders.Conclusions:Patients presenting different infertility factors seem to have a satisfactory CPR for a SET cycle, except those with unexplained infertility. This is a preliminary outcome and the number of patients by category is small; in addition, the retrospective characteristics of the study are its limitations. Overall, our findings suggest that patients presenting any infertility factor, except unexplained infertility, are suitable to receive a SET with satisfactory outcomes.

A Modern Approach to Progesterone Supplementation

At the end of December 2017, some colleagues and I reported results from a prospective cohort study (N=211) into the relationship between serum progesterone (P) and endometrial volume on the day of embryo transfer (ET) and ongoing pregnancy rates (OPR) in artificial endometrium preparation cycles.1

The effect of artificial cycle scheme after long-acting GnRH agonist down regulation in endometrium preparation in frozen embryo transfer cycle in patient with polycystic ovarian syndrome

Objective To assess the effects of artificial cycle after long-acting gonadotropin-releasing hormone (GnRH) agonist down regulation scheme and artificial cycle only scheme in preparation of endometrium before frozen embryo transfer in polycystic ovary syndrome (PCOS) patients on pregnancy outcome. Methods A retrospective analysis was made on the frozen embryo transfer of 132 PCOS patients in the reproductive center of Hunan Maternal and Child Health Hospital from November 2016 to October 2017. The patients were divided into GnRH-a down regulation + artificial cycle group (n=66) and simple artificial cycle group (n=66) according to the different endometrial preparation schemes before frozen embryo transplantation. The transplantation cycle and pregnancy outcome of the two groups were compared. Results ⑴ There was no statistically significant difference in age, primary infertility rate, infertility years and body mass index (BMI) between the two groups (P>0.05). ⑵ In the artificial cycle group, 4 cases in which the transplantation was cancelled, including 2 cases who were cancelled due to breakthrough bleeding and 2 cases due to endometrial thickness that were less than 7 mm. There was a statistically significant difference in the cancellation rate between the two groups (χ2=4.13, P=0.04). There were no statistically significant difference in embryo frozen storage time, retrieved oocytes in fresh embryo cycle, frozen thawed embryos in the survival rate, graftage embryonic number, high-quality embryonic rate, endometrium thickness in conversion day (P>0.05). Estrogen level, luteinizing hormone (LH) levels on endometrium conversion day in GnRH-a down regulation plus artificial cycle group and artificial cycle group were respectively as [(1 439.38±357.43)nmol/ml vs (1 580.54±479.69)nmol/ml and (2.32±0.94)mIU/ml vs (9.46±1.52)mIU/ml], with statistically significant difference (χ2=53.64, P<0.001; χ2=14.32, P<0.001). ⑶ The biochemical pregnancy rates of the patients in the GnRH-a down regulation plus artificial cycle group and artificial cycle group were 72.73% and 53.23% respectively, with statistically significant difference (χ2=5. 23, P=0.036). The clinical pregnancy rate (65.15%) in GnRH-a down regulation plus artificial cycle group was higher than that of the artificial cycle group (46.77%), with statistically significant difference (χ2=4.39, P=0.022). There was no statistically significant difference in early abortion rate and ectopic pregnancy rate between the two groups. Conclusions In frozen embryo transplantation cycle, long-term GnRH-a down regulation after artificial cycle scheme is superior to simple artificial cycle scheme with significantly reduced cycle cancellation rate, low estrogen and LH levels in endometrium transformation day and higher biochemical pregnancy rate and clinical pregnancy rate. Key words: Gonadotropin-releasing hormone; Polycystic ovary syndrome; Embryo transfer; Endometrium

Activation of CCL20 and its receptor CCR6 promotes endometrium preparation for implantation and placenta development during the early pregnancy period in pigs

The success of implantation and placentation during early pregnancy depends on the intrauterine environment of diverse histotrophs, including nutrients, growth factors, cytokines, and chemokines. Here, we determined the functional role and signal transduction of CC-motif chemokine 20 (CCL20) in the porcine endometrium during pregnancy. The expression of CCL20 and its receptor CCR6 was abundant in the glandular epithelium (GE) and luminal epithelium (LE) of the porcine endometrium during early pregnancy. Administration of CCL20 to porcine endometrial LE cells increased cellular proliferation with strong PCNA expression by activation of PI3K and MAPK signaling. Blocking PI3K and MAPK decreased the CCL20-mediated elevated proliferation of pLE cells. Moreover, the proliferation of pLE cells was enhanced by inhibiting the LPS-induced cytokines and tunicamycin-induced endoplasmic reticulum (ER) stress response proteins. Overall, these results suggest that CCL20 may improve the endometrial receptivity through inducing proliferative signal transduction in the porcine endometrium during the early gestational period.

Vaginal bioelectrical impedance determines uterine receptivity in mice.

Can vaginal bioelectrical impedance (VZ) electrophysiologically determine alterations of the endometrium in preparation for implantation? VZ can electrophysiologically detect the sulfation and sialylation changes in the uterine glycocalyx in preparation for implantation. Uterine receptivity is associated with various glycosylation changes that affect negative charge density at the luminal epithelial cell surface. VZ has been used to monitor the oestrous cycle. Pathogen-free Jcl:ICR mice, aged 8-10 weeks, were used in this study. We conducted the following three steps to test our hypothesis that VZ may be used to determine uterine receptivity. First, to investigate whether VZ could determine alteration of sulfation and sialylation in the uterine glycocalyx, VZ was measured in mice with induced artificial sulfation and sialylation changes in the uterine glycocalyx (galactose-3-O-sulfotransferase 2 (GP3ST) + α(1,3/1,4) fucosyltransferase gene (FucT-III)-transferred group (n = 15) and in LacZ (encoding for β-galactosidase)-transferred mice as a control group (n = 12)). Second, to investigate whether VZ could determine alterations of the endometrium in preparation for implantation, we measured VZ during the early stage of pregnancy (n = 12 each). Third, to investigate whether VZ could be used to evaluate uterine receptivity prospectively, VZ was measured in an implantation failure model mice. In 21 mice, local and transient suppression of signal transducer and activator of transcription-3 (Stat3) in the uterus were evaluated 1 day before implantation began, and 23 scramble decoy-transferred mice were used as a control group. The VZ was measured at a frequency of 1 kHz in Jcl:ICR mice. Data were analysed using the Kruskal-Wallis test with Dunn's multiple comparisons, or the Student's t-test or Wilcoxon's rank-sum test with the Shapiro-Wilk normality test. The values of VZ were analysed using receiver operating characteristic (ROC) curve analysis to identify the optimal cut-off point to determine if this parameter predicted non-pregnancy. Sulfation and sialylation changes induced in the luminal epithelial glycocalyx decreased the value of VZ. VZ showed a significant daily decrease during the early stage of pregnancy (Day 1.5 versus 2.5 p.c.: P < 0.005; Student's t-test, Day 2.5 versus 3.5 p.c.: P < 0.001; Wilcoxon's rank-sum test, Day 3.5 versus 4.5 p.c.: P < 0.005; Student's t-test, Day 4.5 versus 5.5 p.c.: P < 0.05; Student's t-test). One day before implantation began, VZ in the implantation failure model mice was significantly higher than in the control mice (P < 0.001, Wilcoxon's rank-sum test). The ROC curve analysis of VZ as a predictor of non-conception showed areas under the ROC curve of 0.91 (95% CI: 0.83-0.99). Although it is influenced by surface charge in the uterine epithelium, the mechanism whereby VZ changes during early pregnancy is still unexplained. Local bioelectrical impedance may help to prospectively evaluate uterine receptivity in women. Including the measurement of local bioelectrical impedance as part of a frozen-thawed embryo transfer strategy may improve the efficiency of ART. This work was supported in part by the Japan Society for the Promotion of Science JSPS KAKENHI Grant (Nos. 19390429, 21390453, 16K11086 and 16K11087) from the Ministry of Education, Science and Culture of Japan (Tokyo, Japan) and Suzuken Memorial Foundation (Nagoya, Japan). The authors declare that they have no conflict of interest.

Basal Serum Anti-Müllerian Hormone Level as a Predictor of Clinical Outcomes in Freezing-all Embryo Transfer Program.

As a novel biomarker, there is inconsistent evidence regarding the association between anti-Müllerian hormone (AMH) and live birth rate in freezing-all embryo transfer cycles. We aim to assess the prognostic effect of baseline AMH on clinical outcomes, especially live birth rate in freezing-all embryo transfer cycles. A total of 828 non-polycystic ovary patients that underwent their first frozen-thawed embryo transfers in our center between January 2010 and January 2015 were recruited in this retrospective analysis. Patients were stratified into three groups based on their baseline AMH concentration: low AMH group (<1.4 ng/mL), middle AMH group (1.4-5.8 ng/mL) and high AMH group (>5.8 ng/mL). The results showed that low AMH level was associated with adverse clinical outcomes. The differences in implantation rate (21.9% vs. 43.2% vs. 58.8%, P<0.001), clinical pregnancy rate (32.0% vs. 55.2% vs. 65.7%, P<0.001), live birth delivery rate (21.8% vs. 43.6% vs. 52.7%, P<0.001) and miscarriage rate (31.8% vs. 17.5% vs. 15.4%, P=0.014) among the three groups were statistically significant. After adjusting confounders (i.e. age, baseline FSH level, AFC, endometrium thickness, endometrium preparation protocols, number of embryos transferred, etiologies of infertility), differences in live birth rate, clinical pregnancy rate and implantation rate between groups remained significant. The further age subgroup analysis demonstrated that low AMH concentration was significantly associated with poor outcomes both in young and advanced patients. The area under the curve for serum AMH, age, AFC and FSH were 0.635, 0.634, 0.615 and 0.543 respectively, for predicting live birth. In conclusion, baseline AMH was an independent prognostic factor of live birth rate of freezing-all embryo transfers, but its predictive value on live birth rate was of limited clinical value.

Normal Menstrual Cycle

A normal menstrual cycle is the end result of a sequence of purposeful and coordinated events that occur from intact hypothalamic-pituitary-ovarian and uterine axes. The menstrual cycle is under hormonal control in the reproductively active female and is functionally divided into two phases: the proliferative or follicular phase and the secretory or luteal phase. This tight hormonal control is orchestrated by a series of negative and positive endocrine feedback loops that alter the frequency of the pulsatile secretion of gonadotropin-releasing hormone (GnRH), the pituitary response to GnRH, and the relative secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary gonadotrope with subsequent direct effects on the ovary to produce a series of sex steroids and peptides that aid in the generation of a single mature oocyte and the preparation of a receptive endometrium for implantation to ensue. Any derailment along this programmed pathway can lead to an abnormal menstrual cycle with subsequent impact on the ability to conceive and maintain a pregnancy. This review contains 7 figures and 26 references Key words: follicle-stimulating hormone, follicular phase, gonadotropin-releasing hormone, luteal phase, luteinizing hormone, menstrual cycle, ovulation, progesterone, proliferative phase, secretory phase

Methods of preparation of endometrium in patients with ovarian hyperstimulation syndrome before the transfer of vitrified / warmed embryos

Methods of preparation of endometrium in patients with ovarian hyperstimulation syndrome before the transfer of vitrified / warmed embryos