Outcomes In Infertile Women Research Articles

Using Uterine Biophysical Profile as a Predictor of Endometrial Receptivity and Pregnancy in Stimulated IUI Cycles

Implantation failure and disorders of endometrial receptivity represent an essential cause of infertility; multiple parameters were needed to predict the uterine receptivity understanding that no sole parameter could predict the same. A score was termed as (Uterine Biophysical Profile) could be utilized as a predictor of endometrial receptivity. To evaluate the predictive potential of Uterine biophysical profile of both endometrial receptivity and pregnancy outcome in infertile women undergoing Intrauterine Insemination (IUI). The current cross-sectional study was conducted in the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies in Al Nahrain University, Baghdad, Iraq from the 1st of Oct. 2018 till 1st of May 2019 involving seventy women of infertile couples with the same inclusion and exclusion criteria. Uterine biophysical profile was evaluated using a doppler ultrasound examination and then a score was calculated and correlated to pregnancy outcome. The mean Uterine Artery Pulsatility Index (UAPI) was significantly lower in women with positive pregnancy in comparison to women with negative pregnancy, 2.10±0.19 versus 2.47±0.65, respectively (P=0.032). Moreover, no women with Pulsatility Index (PI) score (0) succeeded to get pregnant and the higher the score, the higher the rate of pregnancy (P=0.006). Furthermore, Spearman correlation showed significant positive correlation between positive pregnancy outcome and UAPI (r=0.365; P=0.002). The mean total score was significantly higher for pregnant women than in women with negative pregnancy, 18.27±1.33 versus 16.35±2.47, respectively (P=0.005). The cutoff value was >17 with an acceptable accuracy level of 74.2. The sensitivity of that cutoff vale was 80 % and the specificity was 65.5%. Uterine artery pulsatility index and total uterine biophysical score are the principal predictors of positive pregnancy outcomes in infertile women undergoing IUI.

The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study.

Thyroid dysfunction and thyroid autoimmunity (TAI) have been reported to be linked to infertility, pregnancy loss and preterm birth. Infertile women undergoing assisted reproductive technology are recommended to maintain thyroid stimulating hormone (TSH) levels below 2.5 μIU/mL. It is unclear, however, whether levothyroxine (L-T4) treatment decreases the effects of TAI on fertility and pregnancy outcome in infertile women. We therefore aimed to clarify the influence of TAI on pregnancy undergoing L-T4 treatment for hypothyroidism. Prospectively recruited to this study were the 595 infertile women who visited the Utsunomiya Ladies Clinic between January 2013 and December 2015. Five patients with Graves' disease were excluded. Clinical profiles of 590 women were as follows: proportion of SCH = 19.6%, thyroid peroxidase antibody (TPOAb) positivity = 10.4%, and thyroglobulin antibody (TgAb) positivity = 15.1%. Fertility was not affected by any thyroid-associated factors. Regarding pregnancy outcomes, TPOAb titers were significantly higher in women who had miscarriage than in those progressed to delivery (46.4 ± 114.1 vs. 18.9 ± 54.6 IU/mL, p = 0.039), notably in those undergoing intrauterine insemination (p = 0.046) and in vitro fertilization (p = 0.023). Multivariate logistic regression analysis revealed that higher age (odds ratio 26.4, p < 0.001) and higher TPOAb titer (odds ratio 11.8, p = 0.043) were risk factors for miscarriage. Higher TPOAb titer should be considered as one of the risk factors for miscarriage in infertile women, even if they have been treated with L-T4 for hypothyroidism.

Evaluation of Reproductive Outcome in Infertile Hypothyroid Women on Thyroxine Therapy.

Introduction:Thyroid dysfunction is associated with increased risk of infertility. Serum thyroid stimulating hormone (TSH) screening in all women seeking infertility care is recommended and hypothyroid infertile women should be treated with thyroxine until the preconception serum TSH level is <2.5 mU/l.[1] However, insufficient evidence exist to determine if thyroxine therapy improves fertility in subclinical hypothyroid women who are trying to conceive naturally.Objectives:The objective is to study the effect of thyroxine therapy on reproductive outcome in infertile women with clinical and subclinical hypothyroidism (SCH).Materials and Methods:The study is a descriptive cohort study with 72 subjects. Women between 20 and 40 years of age with primary or secondary infertility with hypothyroidism were studied and thyroid profile including free T3, T4, TSH, and thyroid antibodies were done. Thyroxine was given to clinical, subclinical hypothyroid subjects depending on TSH levels such that serum TSH levels are maintained < 2.5 mU/L. Serial thyroid function test was done every 6 weeks until the optimal levels were reached. Once normal TSH levels were reached subjects were followed up for 6 months. Reproductive outcome was analyzed in two groups. Group A included hypothyroid infertile women who conceived and Group B included those who did not conceive following thyroxine therapy.Results:Thirty-eight out of 72 subjects (54%) conceived during thyroxine treatment (Group A) of which 4 cases had miscarriage. Maximum infertile women in Group A (20/38) conceived between 6 and 12 months (52.6%) of thyroxine therapy. Significant decrease was observed in mean TSH levels over a period of 6 months (P < 0.001). The infertility period until pregnancy in Group A reduced significantly from 5.2 ± 1.8 years to 0.5 ± 0.8 years after thyroxine treatment (P = 0.001).Conclusion:Thyroxine therapy enhances fertility in infertile women with clinical and SCH.

In vitro Fertilization with Single-nucleotide Polymorphism Microarray-based Preimplantation Genetic Testing for Aneuploidy Significantly Improves Clinical Outcomes in Infertile Women with Recurrent Pregnancy Loss: A Randomized Controlled Trial

Objective: To evaluate the effect of preimplantation genetic testing for aneuploidy (PGT-A) in infertile patients with recurrent pregnancy loss (RPL). Methods: A prospective randomized clinical trial was performed in a university-affiliated fertility center in Shanghai, China. Patients in the PGT-A group underwent blastocyst biopsy followed by single-nucleotide polymorphism microarray-based PGT-A and single euploid blastocyst transfer, whereas patients in the control group underwent routinein vitro fertilization/ICSI procedures and frozen embryo transfer of 1–2 embryos selected according to morphological standards. Results: Two hundred and seven infertile patients with RPL were included in this study and randomly assigned to either the control or the PGT-A group. Baseline variables and cycle characteristics were comparable between the two groups. The results showed that PGT-A significantly improved the ongoing pregnancy rate (55.34% vs. 29.81%) as well as the live birth rate (48.54% vs. 27.88%) and significantly reduced the miscarriage rate (0.00% vs. 14.42%) on a per-patient analysis. A significant increase in cumulative ongoing pregnancy rates over time was observed in the PGT-A group. Subgroup analysis showed that the significant benefit diminished for patients who attempted ≥2 PGT-A cycles. Conclusions: PGT-A significantly improved the ongoing pregnancy and live birth rate, while reduced miscarriage rate in infertile RPL patients. However, the significance diminished in patients attempting ≥2 cycles; thus, further studies are warranted to explore the most cost-effective number of attempts in these patients to avoid overuse.

To study the effect of autologous platelet-rich plasma instillation on suboptimal endometrium and pregnancy outcomes in infertile women undergoing frozen embryo transfer cycle

Introduction:This pilot study was done to evaluate the effectiveness of intrauterineinstillation of autologous platelet rich plasma in the treatment of infertile woman with ≥2 IVF failures due to thin endometrium not responding to empirical medical therapies. Design: Prospective interventional study. Material and Methods: Intra uterine instillation of PRP was done in 50 women between 23 to 38 years with suboptimal endometrial receptivity, ≥ 2 IVF failures and HRT cycle cancellations over a course of 9 months. Frozen embryo transfer was done when optimal endometrial thickness and vascularity was achieved. Results: The mean endometrial thickness pre PRP was 5.78mm which increased to 7.20mm post-PRP (P value

Role of Vascular Endothelial Growth Factor (VEGF) and Doppler Sub-endometrial Parameters as Predictors of Successful Implantation in Intracytoplasmic Sperm Injection (ICSI) Patients

Objective: to investigate the expression of vascular endothelial growth factor (VEGF) in patients having infertility due to low endometrial acceptance, and to correlate it to non-invasive ultrasound variables, endometrial thickness, and sub-endometrial Doppler parameters (PI, RI, Vs/Vd). Methods: 80 women all under the age of 40 underwent ICSI-ET; all patients were exposed to ovarian stimulation protocols. The oocytes were retrieved using an ultrasound guide, and were fertilised via injection of sperm inside the follicle (ICSI). VEGF serum level was analysed at day of embryo transfer by ELIZA test, and sub-endometrial evaluation was conducted via two-dimension power Doppler ultrasound (2D PD-US), by measuring resistance index (RI) and pulsatility index (PI) on the day of embryo transfer. Results: There was a significantly higher VEGF level and endometrial thickness in pregnant (433± 207 and 9.72± 1.35) women, compared to non-pregnant (276± 165 and 8.95 ± 1.21) respectively as p -values were (0.001 and 0.01)). Additionally, there were significantly lower RI and PI in pregnant (0.584 ± 0.124 and 0.829 ± 0.301) women compared to non-pregnant (0.651±0.132 and 1.006±0.335) women, as p -values were (0.02 and 0.02, respectively). The level of E2 was on the day of embryo transfer and Vs/Vd in pregnant women (1402± 524 and 3.14 ± 3.75) and in the non-pregnant group (1296± 611 and 3.82 ± 3.07), as p -values were 0.41 and 0.38, respectively. Conclusion: The combined analysis of endometrial receptivity was completed, and the serum level of VEGF and sub-endometrial evaluation with 2D PD-US was defined by measuring resistance index (RI) and pulsatility index (PI) on the day of embryo transfer. These can serve as useful prognostic methods for the detection of endometrial receptivity and pregnancy outcomes in infertile women undergoing ICSI protocols, and will be helpful for candidate counselling about postponing embryo transfer and cryopreservation, which may serve as a better option, to be recommended for the next cycle, when achieving better endometrial Doppler parameters.

Association Between Systemic and Local Oxidative Stress of Infertile Women Undergoing Ivf/Icsi

Oxidative stress (OS) may affect in vitro fertilization (IVF) outcomes in infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The aim of this study is to explore the possible relationships between OS parameters in serum and follicular fluid (FF) from infertile women with male cause infertility (n=40), women with polycystic ovary syndrome (PCOS) (n=40), and women with unexplained infertility (UI)(n=45) undergoing IVF/ICSI. The collection of blood and FF samples was done at the day of oocyte aspiration. Total peroxide (TPX) level, total antioxidant capacity (TAC), and malondialdehyde (MDA) level were measured in serum and FF; whereas, glutathione-s-transferase (GST) activity and superoxide dismutase (SOD) activity were measured in FF. Also, oxidative stress index (OSI) that is the percentage ratio of TPX to TAC, was calculated. In the control group, correlation analysis reveals the presence of a significant positive association between FF OSI with serum OSI, FF TPX with FF OSI, and serum TPX with FF GST activity. In the PCOS group, there was a significant negative association between: FF TPX and serum TAC level. However, non-significant relationship was found between serum and FF OS status parameters in the UI group. It’s concluded from the present study that systemic OS may give valuable information about local OS occurrence (blood OS reflects FF OS) only in control group and PCOS group. Such information could be useful for a better understanding of the pathological OS mechanisms involved in IVF failure for patients with different causes of infertility.

The effect of interleukin 6 on controlled ovarian stimulation results and IVF outcome in infertile women with adenomyosis undergoing IVF

To investigate the effect of serum interleukin 6 (IL-6) on controlled ovarian stimulation (COS) results and IVF outcome in infertile women with adenomyosis undergoing IVF. Retrospective cohort study. A total of 59 infertile women with adenomyosis who had their blood taken for analysis of serum IL-6 on the day of hCG injection in IVF cycle between May 2018 and March 2019 was included in this study. COS results and IVF outcome were compared among the three groups (group 1;<1.5 pg/ml, group 2;1.5-7.0 pg/ml, group 3;>7.0 pg/ml) according to the serum IL-6 levels. Analysis of variance (ANOVA) was used to compare the mean values among three groups. Chi-square test and Fisher's exact test were used for the comparisons of fraction. Statistical significance was defined as P<.05. Serum IL-6 levels on the day of hCG injection was significantly higher in infertile women with adenomyosis than in patients without adenomyosis who underwent IVF during the same period (P=.01). The demographic characteristics of patients with adenomyosis were comparable among the three groups according to the serum IL-6 levels. There were also no differences in the three groups with respect to the number of oocytes retrieved, mature oocytes retrieved and fertilized oocytes. However, the number of grade 1 or 2 embryos was significantly lower in group 3 (P<.05). Clinical pregnancy rate was significantly lower in group 3, compared with group 1 or 2 (P<.001, P<.023, respectively). None of the patients with serum IL-6 levels more than 8.0 achieve pregnancy following the corresponding IVF cycle. High serum IL-6 levels in infertile women with adenomyosis can have an adverse effect on the IVF outcome including embryo quality and clinical pregnancy rate.

Impact of maternal ethnicity on pregnancy outcome in infertile women with polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is the most prevalent endocrine pathology seen among women of reproductive age. The objective of the study is to investigate the impact that ethnic background has on pregnancy outcomes, including live birth rates in infertile women with PCOS going through IVF compared to women without PCOS. Retrospective cohort study in an academic IVF center. This study used a coded REDCap data set of 486 women, 18-45 years of age who underwent IVF and embryo transfer between 1/1/2010 and 12/31/2015 at an academic IVF Center after IRB approval (IRB 2015-0623). Patients underwent their 1st IVF cycle following progestogen withdrawal (norethindrone acetate) using GnRH agonist or antagonist protocols with mixed gonadotropins and demographic data, including race and ethnicity was obtained. Data collected during the IVF process included peak estradiol, number of mature oocytes, fertilization rate, number of top quality embryos on Day 3 of development, number of embryos transferred, implantation rate, clinical pregnancy rate, live birth rate, clinical miscarriage rate, and ectopic pregnancy rate. In women, whose pregnancy resulted in a live birth, additional maternal and neonatal variables were collected, including estimated gestational age (EGA) at delivery, mode of delivery, and weight at birth. Using R analytics software, data was analyzed using logistic regression and linear models. For logistic regression, the estimated coefficient was the log-odds-ratio. A significant p value was considered <0.05. Of the 486 initial women, 360 women were included in the final analysis. Only women with known/reported ethnicity were included. Not Hispanic is the referent cohort for ethnicity and non-PCOS is the referent group when comparing PCOS status. There was no significant difference found for implantation rate (p=0.53) and pregnancy rate (p=0.99) when comparing women without PCOs with the women with PCOS. When taking into account the ethnicity factor in PCOS and the women who conceived and had a live birth, there was no significant difference between being Hispanic with PCOs and the referent non-Hispanic group. However, when evaluating women who started the IVF cycle, women with PCOS are less likely to have a pregnancy that leads to a live birth compared to women without PCOS (p=0.046). Being Hispanic by itself does not seem to affect live birth (p= 0.81). Hispanic women with PCOS have the same probability of having a vaginal delivery compared to the referent group (p=0.935). Women with PCOS are more likely to deliver ∼2 weeks earlier than non-PCOS patients (p=0.038). Being Hispanic and having PCOS did not affect the EGA at delivery (p= 0.83) or affected fetal weight compared to the referent group (p=0.58). This pilot study did not find a significant difference in most of the variables studied comparing Hispanic PCOS women with non-Hispanic women without PCOS. However, further studies with a larger number of subjects are needed to assess the impact of ethnicity and PCOS on IVF pregnancy outcomes.

Effect of dehydroepiandrosterone (DHEA) supplementation on intracytoplasmic sperm injection outcome in infertile women with anticipated normo-ovarian response

Effect of dehydroepiandrosterone (DHEA) supplementation on intracytoplasmic sperm injection outcome in infertile women with anticipated normo-ovarian response

Chronic Endometritis in Fertile and Infertile Women Who Underwent Hysteroscopic Polypectomy

To evaluate the prevalence of chronic endometritis (CE) among fertile and infertile women who underwent hysteroscopic polypectomy. A retrospective cohort study. University-affiliated tertiary hospital. A total of 277 women who underwent hysteroscopic polypectomy in the period from 2015 to 2018. Endometrial polyp samples were obtained after hysteroscopy for histopathologic analysis using hematoxylin-eosin and immunohistochemistry staining with CD138 antibodies for plasma cell detection. All infertile women diagnosed with CE were treated with oral doxycycline 100 mg twice daily for 14 days before infertility treatment. The prevalence of CE in infertile women (n = 137) was significantly higher than in those with no history of infertility (n = 140) (22.6% vs 8.6%; p = .001). The prevalence of CE between women with primary infertility and those with secondary infertility was similar (25.0% vs 19.3%; p = .43). Clinical pregnancy (32.3% vs 41.5%; p = .35), live birth (29.0% vs 38.7%; p = .33), and miscarriage (10.0% vs 6.8%; p = .73) rates were similar between infertile women with treated CE and those without CE. A multivariate model showed that diagnosis of infertility was significantly associated with the diagnosis of CE (odds ratio, 3.16; 95% confidence interval, 1.53-6.49). In women with endometrial polyps, the prevalence of CE in infertile women is higher than that in fertile women. Pregnancy outcome in infertile women with treated CE was similar to those who were infertile and without CE.

CLINICAL IMPACT OF MATERNAL-EMBRYONIC COMMUNICATION AT IMPLANTATION

The endometrium is a hormonally regulated organ that is non-adhesive to embryos throughout most of the menstrual cycle in humans. Endometrial receptivity refers to a hormone-limited period in which the endometrial tissue acquires a functional and transient ovarian steroid-dependent status allowing blastocyst adhesion. Functional genomic studies of human endometrium in natural cycles have demonstrated that endometrial receptivity is an active process involving up- and down-regulation of hundreds of genes ( 1 ). Personalized medicine is a well-accepted concept in reproductive medicine except for the endometrial factor that is still neglected. Our group has developed the endometrial receptivity array (ERA) ( 2 ), a customized array of 238 genes now performed using Next Generation Sequencing (NGS) coupled to a computational predictor capable of diagnosing the window of endometrial receptivity regardless of its histological appearance ( 2 ). The accuracy of the diagnostic tool ERA has been demonstrated to be superior to endometrial histology and results are completely reproducible 29 to 40 months later ( 3 ). The aim of this presentation is to demonstrate the diagnostic and therapeutic efficiency of ERA in patients with implantation failure (IF), through personalization of the day of embryo transfer (pET) ( 4 , 5 , 6 , 7 , 8 ). We are conducting an international RCT to investigate the reproductive outcome of infertile women under 38 year (BMI of 18.5-30 and AFC>8) s in their first IVF/ICSI cycle with elective blastocyst transfer randomly allocated to be performed in a fresh cycle, after freezing all embryos or after identification of the personalized WOI with the ERA test (pET). According to a preliminary analysis after recruiting 356 patients of the 546 planned, the pET group had a higher pregnancy rate per ET, and a trend to a higher implantation rate and ongoing pregnancy rate ( 9 ). Finally, the investigation of endometrial bacterial communities has revealed that the endometrial cavity is not sterile. The presence of a Non-Lactobacillus-dominated microbiota (NLD) ( 10 ) or pathogens responsible for chronic endometritis ( 11 ) in infertile patients are associated with decrease reproductive outcome in terms of implantation, pregnancy and live birth rates.

Implantation failures in women with infertility associated endometriosis

Endometriosis is currently considered as one of the most common diseases associated with infertility. A controversial issue is whether endometriosis per se exerts a detrimental effect on IVF outcomes. Failure of implantation due to endometriosis-associated infertility is a contradictory and widely discussed burden nowadays. The purpose of the study is to assess the quality of embryos and implantation rate in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 26 and 40 years who underwent IVF and ICSI procedures. The patients were divided into two groups: group I (n = 70) involved 70 patients with recurrent unilateral endometriomas, II control group (n = 50) with tubal factor infertility. The quality of the retrieved embryos was assessed according to the generally accepted classification of Gardner, indicating the rate of implantation in each group. Embryo transfer was performed in case of high quality embryos. Assessing the ovarian reserve indicators, in the group I patients with recurrent unilateral endometriomas the serum level of AMH was significantly lower (2.1 ± 1.75 vs. 3.2 ± 1.4, p < .005), as well as the number of retrieved oocytes (8.1 ± 3.9 and 10.1 ± 6.8, p < .005). The analysis of the results demonstrated that the duration of stimulation in the group patients with recurrent unilateral endometriomas was significantly higher in comparison with the group II (12.2 ± 1.8 and 10.2 ± 1.6 days, p < .001). Nevertheless, the number of good quality embryos retrieved was comparable in both groups (2.2 ± 1.5 and 2.8 ± 1.8). In the group I patients with recurrent unilateral endometriomas, there was a statistically significant decrease of implantation rate (17.1% vs. 24% p < .005). The results of the study revealed no statistical difference in embryo quality in the study cohort. However, it is important to note that a statistically significant difference in implantation rate in the group of endometriosis-associated infertility compared was obtained 1.5 times lower than in the control group (15.8% vs. 24.0% p < .005). The achieved results demonstrated an adverse IVF outcome in infertile women with recurrent endometrioma compared to the control group.

The Cycle Characteristics and Outcomes of Infertile Nonclassic 21-Hydroxylase Deficiency Patients Undergoing Ovarian Stimulation for In Vitro Fertilization.

The objective of the work was to investigate the cycle characteristics and outcomes of infertile women with nonclassic 21-hydroxylase deficiency (21-OHD) undergoing in vitro fertilization (IVF). Twenty-five infertile nonclassic 21-OHD patients were retrospectively observed. From cycle day 3, patients were given human menopausal gonadotropin (HMG) 150 IU/d or 225 IU/d daily. Dexamethasone was administered orally at 0.75 mg/d. Ovulation was co-triggered by human chorionic gonadotropin (hCG) and triptorelin. Binary logistic regression was performed to quantify the effect of IVF parameters on embryo transfer cycle outcomes. The receiver operating characteristic (ROC) curve was used to determine cutoff points of the selected confounders for predicting pregnant probabilities. In controlled ovarian hyperstimulation (COH) cycles, there was a trend that the viable embryos group consisted of more polycystic ovary (PCO) patients. In embryo transfer (ET) cycles, differences were detected in the usage rate of dexamethasone and the minimum progesterone (P4) and total testosterone (TT) values between the non-pregnant group and the biochemical pregnant group. Binary logistic regression analysis confirmed that decreasing minimum P4 and body mass index (BMI) value was respectively correlated with increasing pregnancy probability. ROC analysis proved that the cutoff values for minimum P4 and BMI were 0.45 ng/ml and 23.36 kg/m2. In COH cycles, the ultrasonographic appearance of ovary helps to predict the number of viable embryos. In ET cycles, dexamethasone obviously improves the pregnancy rate. If the minimum P4 value before endometrial transformation cannot be kept below 0.45 ng/ml, we may consider cycle cancellation. Moreover, it is suggested that BMI of nonclassic 21-OHD women is regulated below 23.36 kg/m2.

Effect of Vaginal Low Dose Sildenafil on the Outcome of ICSI after ICSI Failures Attributed to Poor Endometrial Development

Background: Endometrial thickness is a marker of endometrial receptivity and a prognostic factor for embryo transfers (ET). Poor endometrium is a multifactorial condition; so, its management should be cause-related. One of the treatment options is Sildenafil citrate intake. It causes uterine vascularity improvement. Objectives: The aim of the current work was to evaluate the effects of vaginally administered doses of sildenafil on endometrial lining and ICSI outcome in infertile women with poor endometrial development. Patients and Methods: This study included a total of thirty infertile women with at least one prior ICSI failure attributed to inadequate endometrial development, undergoing ICSI procedure attending at a private assisted reproductive center. All patients underwent ICSI using a long GnRH-a protocol with the addition of sildenafil vaginal suppositories (20 mg, 4 times per day) for 10 days beginning with ovulation induction and continued until trigger day. Results: The results showed that increased endometrial thickness due to treatment with sildenafil to reach 12-14 mm in 28 out of 30 cases and was associated with a pregnancy rate of 60.7% if compared to the same group thickness. Also, another effect of sildenafil citrate was increasing the endometrial trilaminar pattern in 27 case and subsequently with high pregnancy rate. Conclusion: Increased endometrial thickness due to sildenafil therapy was associated with high pregnancy rat and its intake was associated with increased trilaminar endometrial pattern in 90% of patients which causes high pregnancy rate.

Endometrial Receptivity, what time is ideal to transfer

The endometrium is a hormonally regulated organ that is non-adhesive to embryos throughout most of the menstrual cycle in humans. Endometrial receptivity refers to a hormone-limited period in which the endometrial tissue acquires a functional and transient ovarian steroid-dependent status allowing blastocyst adhesion. Functional genomic studies of human endometrium in natural cycles have demonstrated that endometrial receptivity is an active process involving up- and down-regulation of hundreds of genes ( Riesewijk et al., 2003 ). Personalized medicine is a well-accepted concept in reproductive medicine except for the endometrial factor that is still neglected. Our group has developed the endometrial receptivity array (ERA) ( Diaz-Gimeno et al., 2011 ), a customized array of 238 genes now performed using Next Generation Sequencing (NGS) coupled to a computational predictor capable of diagnosing the window of endometrial receptivity regardless of its histological appearance ( Diaz-Gimeno et al., 2011 ). The accuracy of the diagnostic tool ERA has been demonstrated to be superior to endometrial histology and results are completely reproducible 29 to 40 months later ( Diaz-Gimeno et al., 2013 ). The aim of this presentation is to demonstrate the diagnostic and therapeutic efficiency of ERA in patients with implantation failure (IF), through personalization of the day of embryo transfer (pET) ( Ruiz-Alonso et al., 2013 , Ruiz-Alonso et al., 2014 , Hashimoto et al., 2017 Jun 27 , Mahajan, 2015 Jul-Sep , Tan et al., 2018 Jan 11 ). We are conducting an international RCT to investigate the reproductive outcome of infertile women under 38year (BMI of 18.5-30 and AFC>8) s in their first IVF/ICSI cycle with elective blastocyst transfer randomly allocated to be performed in a fresh cycle, after freezing all embryos or after identification of the personalized WOI with the ERA test (pET). According to a preliminary analysis after recruiting 356 patients of the 546 planned, the pET group had a higher pregnancy rate per ET, and a trend to a higher implantation rate and ongoing pregnancy rate ( Simon et al., 2016 ). Finally, the investigation of endometrial bacterial communities has revealed that the endometrial cavity is not sterile. The presence of a Non-Lactobacillus-dominated microbiota (NLD)( Moreno et al., 2016 ) or pathogens responsible for chronic endometritis ( Moreno et al., 2018 ) in infertile patients are associated with decrease reproductive outcome in terms of implantation, pregnancy and live birth rates.

Influence of metabolic syndrome on female fertility and in vitro fertilization outcomes in PCOS women

With a high incidence of insulin resistance, central obesity and dyslipidemia, women with polycystic ovary syndrome are susceptible to metabolic syndrome (MetS). Our objective was to explore whether metabolic syndrome had an effect on overall female fertility and invitro fertilization outcomes in infertile women with polycystic ovary syndrome. This was a secondary analysis of a multicenter randomized trial in 1508 women with polycystic ovary syndrome, which was originally designed to compare the live birth rate after fresh-embryo transfer vs frozen embryo transfer (Frefro-PCOS). At baseline, metabolic parameters, including body mass index, waist and hip circumference, blood pressure, lipid profile, fasting, and 2 hour glucose and insulin levels after a 75 g oral glucose tolerance test were measured. All subjects were divided into a metabolic syndrome group (metabolic syndrome) and absence of metabolic syndrome group (nonmetabolic syndrome) according to diagnostic criteria. Descriptive statistics and logistic regression models tested the association between metabolic syndrome and overall fertility and invitro fertilization cycle stimulation characteristics and clinical outcomes. Metabolic syndrome was identified in 410 of 1508 infertile women with polycystic ovary syndrome (27.2%). Patients with metabolic syndrome had longer infertility duration (4.0 ± 2.2 vs 3.7 ± 2.2, P= .004) compared with those without metabolic syndrome. During ovarian stimulation, those with metabolic syndrome required significantly higher and longer doses of gonadotropin and had lower peak estradiol level, fewer retrieved oocytes, available embryos, a lower oocyte utilization rate, and ovarian hyperstimulation syndrome than those with nonmetabolic syndrome. The cumulative live birth rate did not show a significant between-group difference (57.8% vs 62.2%, P= .119). Multivariate logistic regression analysis adjusted for age, duration of infertility, body mass index, thyroid-stimulating hormone, metabolic syndrome group, homeostatic model assessment of insulin resistance, metformin utilization, number of available embryos, and embryos transferred showed that the number of embryos transferred and the number of available embryos were positively but metabolic syndrome negatively associated with the cumulative live birth rate (odds ratio, 2.18, 1.10, and 0.70, respectively, P < .05). Women with polycystic ovary syndrome with metabolic syndrome have a negative impact from female fecundity, and this suggests an adverse effect on invitro fertilization cycle stimulation characteristics and clinical outcomes.

Vitamin D improves in-vitro fertilization outcomes in infertile women with polycystic ovary syndrome and insulin resistance.

The aim of f this study is to investigate the effect of vitamin D supplementation upon the outcome of in-vitro fertilization (IVF) in infertile women with polycystic ovarian syndrome (PCOS) and insulin resistance (IR). Three hundred and five infertile patients with PCOS and insulin resistance undergoing IVF were included in this study. All participants underwent oral glucose tolerance test (OGTT). Insulin resistance was calculated by homeostasis model assessment. Vitamin D status was measured by assessing circulating levels of 25OH-VD in serum samples by radioimmunoassay. All the patients were then divided into four groups according to their relative levels of serum 25OH-VD (levels of 25OH-VD≥20 ng/mL were defined as being normal) and whether treatment had been administered prior to COH: Group I (deficiency group without treatment [25OH-VD<20 ng/mL]); Group II (normal group [25OH-VD≥20 ng/mL]), Group III (normal group after treatment), Group IV (deficiency group after treatment). In total, 305 women were included in this study. Implantation rates across the four groups were 8.5% (9/106) in Group I, 49% (24/49) in Group II, 49.1% (55/112) in Group III and 14.3 (18/126) in Group IV, respectively. Clinical pregnancy rates were 19.3% (11/57), 65.2 (15/23), 66.7% (38/57) and 23.5% (16/68) in the four groups, respectively. Both the implantation rate and clinical pregnancy rate in groups in which serum 25OH-VD was normal (Groups II and III) were significantly higher (P<0.05) than the other two groups. Serum levels of 25OH-VD were highly correlated with clinical pregnancy and implantation rates (P<0.01).There also were significant differences among the four groups in terms of fertilization rate (80±16%, 93±10%, 90±12%, and 79±23%), two pronucleus (2PN) fertilization rate (59±21%, 72±14%, 76±17% and 66±24%) and cleavage rate (76±20%, 91±10%, 89±24% and 76±25%). Particularly marked differences were observed in the number of high-quality embryos (20±16%, 63±25%, 55±22%, and 32±19%) and the available embryos which could be transferred (2.5±1.8, 5.8±2.8, 5.2±2.4, and 3.6±1.9) (all P<0.01). Much higher rates of implantation and clinical pregnancy were observed among the 25OH-VD deficient patients who had received vitamin D supplements and 25OH-VD levels returned to normal compared to patients in which 25OH-VD levels did not return to normal. Group III, which had normal 25OH-VD levels following Vitamin D supplementation produced the same number of high-quality embryos as Group II which had normal 25OH-VD levels (Group III versus Group II; 7.6±4.1 vs. 10.6±5.2, 55±22% vs. 63±25%; P<0.05). Our data indicate that vitamin D supplementation can help return serum vitamin D levels in infertile women with PCOS and IR to normal levels leading to an improvement in the quality of embryos and a significantly higher clinical pregnancy rate. Maintaining a normal serum vitamin D level in PCOS women is very important in achieving a successful clinical pregnancy following in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

The Role of Serum and Follicular IL-1Beta in Predicting the ICSI Outcome in Infertile Women

The Role of Serum and Follicular IL-1Beta in Predicting the ICSI Outcome in Infertile Women

Role of Dehydroepiandrosterone Supplementation in Improving Intracytoplasmic Sperm Injection Outcome for Women with Expected Poor Ovarian Response

Background: As regard to adjuvant supplementations, nowadays dehydroepiandrosterone (DHEA) is widely used all over the world and is considered to be a potential agent to ameliorate the assisted reproduction technologies outcomes of infertile women with poor ovarian reserve. Objective: To find out the role of DHEA supplementation in improving intracytoplasmic sperm injection (ICSI) outcome for infertile women with expected poor ovarian response in controlled ovarian stimulation. Setting: Assisted reproduction unit of Obstetrics and Gynecology Department, Faculty of Medicine, South Valley University, Egypt. Duration: From April 2016 to May 2018. Study Design: A randomized double-blinded controlled trial. Methods: One hundred and forty infertile women with expected poor ovarian response prepared for ICSI procedure were included in this study. Patients were divided into two groups; group I (DHEA group) included 70 patients received 25 mg DHEA 12 weeks prior to ICSI cycle and group II (placebo group) included 70 patients received a placebo. Results: There was a highly statistically significant difference in basal AFC at start of ICSI cycle in group I (who received DHEA supplementation for 12 weeks prior to ICSI procedure) than in group II (13.8 ± 5.3 versus 10.7 ± 4.6 respectively) with P 0.05). Conclusions & Recommendations: DHEA supplementations improved basal AFC, increased the number & quality of oocytes and increased quality of embryos in infertile patients with expected poor ovarian response in ICSI procedure. So DHEA supplementations could be an important adjuvant for infertile women with expected poor ovarian response in ICSI procedure.