Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen-thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure.

BACKGROUND: To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen-thawed embryo transfer cycles for older patients (aged 36-43 years) with idiopathic recurrent implantation failure (RIF). METHODS: This retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015-December 2020) at Northwest Women's and Children's Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist-HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates. RESULTS: The live birth rate in the GnRH agonist-HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P < 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist-HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381-0.926; P = 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181-0.796; P = 0.010). CONCLUSIONS: The GnRH agonist-HRT protocol improves the live birth rate in frozen-thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist-HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist-HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF. TRIAL REGISTRATION: This research protocol was approved by the hospital institutional ethics committee (No. 2021002).

DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

Recurrent pregnancy loss (RPL) is a common and severe pathological pregnancy, whose pathogenesis is not fully understood. With the development of epigenetics, the study of DNA methylation, provides a new perspective on the pathogenesis and therapy of RPL. The abnormal DNA methylation of imprinted genes, placenta-specific genes, immune-related genes and sperm DNA may, directly or indirectly, affect embryo implantation, growth and development, leading to the occurrence of RPL. In addition, the unique immune tolerogenic microenvironment formed at the maternal-fetal interface has an irreplaceable effect on the maintenance of pregnancy. In view of these, changes in the cellular components of the maternal-fetal immune microenvironment and the regulation of DNA methylation have attracted a lot of research interest. This review summarizes the research progress of DNA methylation involved in the occurrence of RPL and the regulation of the maternal-fetal immune microenvironment. The review provides insights into the personalized diagnosis and treatment of RPL.

FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway.

Recurrent spontaneous abortion (RSA) effects both the physical and mental health of women of reproductive age. Trophoblast dysfunction may result in RSA due to shallow placental implantation. The mechanisms underlying formyl peptide receptor 2 (FPR2) on the biological functions of trophoblasts remain to be elucidated. The present study aimed to explore the potential functions of FPR2, a G protein­coupled receptor, in placental trophoblasts. The location and expression levels of FPR2 in the villi tissue of patients with RSA were detected using immunohistochemical staining, reverse transcription­quantitative PCR and western blotting. Following the transfection of small interfering RNA targeting FPR2 in HTR­8/SVneo cells, a Cell Counting Kit­8 assay was used to determine the levels of cell viability. Flow cytometry was used to examine the levels of cell apoptosis and gap closure and Transwell assays were carried out to evaluate the levels of cell migration and invasion. A tube formation assay was performed to detect the levels of capillary­like structure formation. Western blotting was used to detect the expression levels of proteins in the associated signaling pathways. The expression of FPR2 was present in villi trophoblasts and was markedly increased in patients with RSA. The levels of trophoblast invasion, migration and tube formation were markedly increased following FPR2 knockdown, whereas the levels of apoptosis were markedly decreased. In addition, FPR2 knockdown caused an increase in the phosphorylation levels of AKT and PI3K. Thus, FPR2 may be involved in the regulation of trophoblast function via the PI3K/AKT signaling pathway. The results of the present study provided a theoretical basis for the use of FPR2 as a target for the treatment of trophoblast­associated diseases, such as RSA.

Treatment following hysteroscopy and endometrial diagnostic biopsy increases the chance for live birth in women with chronic endometritis.

PROBLEM: Repeated implantation failure and recurrent pregnancy loss are associated with chronic endometritis, a persistent endometrial inflammation. Its diagnosis and treatment may increase pregnancy and live birth rates. The aim of this study was to assess the effectiveness of endometrial diagnostic biopsy and subsequent antibiotic treatment in cases of chronic endometritis on reproductive outcomes over a long observation period. METHOD OF STUDY: We conducted a historical cohort study (2014-2018) at our University-based infertility center that included women (n = 108) with repeated implantation failure or recurrent pregnancy loss without known pathologies associated with either condition. Forty-one women underwent a hysteroscopy only (reference group); the remaining 67 women underwent, in addition to the hysteroscopy, an endometrial diagnostic biopsy with immunohistochemically staining for CD138 to detect plasma cells (biopsy group). If one or more plasma cells were detected, the women were treated with doxycycline 100 mg twice a day orally for 2 weeks. We performed stratified survival analysis (Kaplan-Meier) and Cox regression. RESULTS: The biopsy group had higher chances of pregnancy (hazard ratio 2.28; 95% confidence interval 1.23-4.24; p = .009) and of live birth (hazard ratio 2.76; 95% confidence interval 1.30-5.87; p = .008) compared with the reference group. In the sensitivity analysis, repeated implantation failure or recurrent pregnancy loss did not affect the outcome. CONCLUSION: Endometrial diagnostic biopsy followed by antibiotic treatment in case of chronic endometritis in women with repeated implantation failure or recurrent pregnancy loss may increase the chances for live birth.

Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models.

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.

Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss.

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5-18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3-11·4%), two miscarriages is 1·9% (1·8-2·1%), and three or more miscarriages is 0·7% (0·5-0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need to be available. We recommend that miscarriage data are gathered and reported to facilitate comparison of rates among countries, to accelerate research, and to improve patient care and policy development.

Uterine factors in recurrent pregnancy losses.

Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal myomas are the primary surgical indications for managing RPLs.

Recurrent pregnancy losses, a lasting cause of infertility.

Recurrent pregnancy loss (RPL), defined as two to three spontaneous pregnancy terminations occurring before 12 weeks of gestation, affects approximately 1% of the general population. The causes may include congenital factors that originate with the quality of the gametes (sperm or oocyte) or the resulting embryo, or factors that originate within the uterus. Alterations of endometrial receptivity from endometriosis and/or endometritis, which are associated with impaired action of progesterone, have also been implicated in RPL. Finally, immunologic factors and thrombophilia, congenital and acquired, have also been suspected to cause RPL.

Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis.

Chronic inflammatory processes affecting the endometrium, as encountered in endometriosis, adenomyosis, and chronic endometritis, alter endometrial receptivity. These disorders are associated with early pregnancy losses and possibly recurrent pregnancy losses (RPL). In the cases of endometriosis, other factors associated with the disease also are susceptible of causing miscarriages and possibly RPL, such as an impact of intrapelvic inflammatory processes affecting the oocyte and embryo in case of natural conception. Conversely these latter effects obviously are bypassed in case of assisted reproductive technology. Chronic inflammation of the endometrium in the condition known as chronic endometritis also causes early pregnancy losses and RPL with beneficial effects achieved when specific treatment is undertaken.

Severe metabolic disorders coexisting with Werner syndrome: a case report.

Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner syndrome is a segmental progeroid syndrome whose presentation resembles accelerated aging. The most common causes of death for WS patients are atherosclerosis and cancer. A 40-year-old female presented with short stature, bird-like facies, canities with alopecia, scleroderma-like skin changes, and non-healing foot ulcers. The patient reported a history of delayed puberty, abortion, hypertriglyceridemia, and juvenile cataracts. A clinical diagnosis of WS was made and subsequently confirmed. We discovered two WRN gene mutations in the patient, Variant 1 was the most common WRN mutation, nonsense mutation (c.1105C>T:p.R369Ter) in exon 9, which caused a premature termination codon (PTC) at position 369. Variant 2 was a frameshift mutation (c.1134delA:p.E379KfsTer5) in exon 9, which caused a PTC at position 383 and has no published reports describing. Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia). Doctors must be cognizant of early manifestations of WS and treatment options.

Role of Slit2 upregulation in recurrent miscarriage through regulation of stromal decidualization.

INTRODUCTION: Knockout mouse model has shown a relationship between Slit2/Robo1 signalling and altered fertility. Altered expression by endometrial epithelium and trophoblast and is associated with the pathogenesis of pregnancy complications but few studies have investigated the expression of decidual Slit2 in miscarriage. METHODS: Expression profiles of Slit2 and Robo1 were measured in human endometrial tissues during the menstrual cycle phases (n = 30), in decidua tissues from recurrent miscarriage (n = 20) and healthy control (n = 20) at 6-8 weeks of gestation. The hormonal regulation of Slit2/Robo1 expression and the role of Slit2/Robo1 signalling in decidualization was investigated in vitro, along with its effects on ß-catenin and MET expression. RESULTS: In human endometrium, Slit2 and Robo1 protein expression in stromal cells were decreased between the late-proliferative and early-secretory phase. In recurrent miscarriage patients, decidual expression Slit2 was increased and associated with lower expression of E-cadherin and higher level vimentin compared to controls. In vitro, the expression of Slit2 was downregulated by cAMP and progesterone in hESCs. Upregulation of Slit2 resulted in inhibition of cell decidualization and ß-catenin translocation to nucleus. DISCUSSION: This study indicates a functional role for Slit2 in endometrial stromal cell decidualization and the pathogenesis of recurrent miscarriage. Aberrant Increase in Slit2 expression may impairs decidualization of endometrial stromal cells leading to recurrent in recurrent miscarriage.

Assessing endometrial receptivity after recurrent implantation failure: a prospective controlled cohort study.

RESEARCH QUESTION: What is the prevalence of disrupted markers of endometrial function among women experiencing recurrent implantation failure (RIF), and does the prevalence differ from a control cohort? DESIGN: Prospective controlled cohort study. In total, 86 women with a history of RIF and 37 women starting their first fertility treatment were recruited for this study. Endometrial and blood profiling were carried out in a hormone-substituted cycle using oestradiol and progesterone. Endometrial biopsies were analysed by histology, immune cell profiling, and the endometrial receptivity array (ERA®) test (Igenomix, Valencia, Spain). The vaginal microbiome was analysed using a NGS-based technology (ArtPRED, Amsterdam, the Netherlands). Blood tests included oestradiol, progesterone, prolactin, thyroid-stimulating hormone, vitamin D and anti-phospholipid antibody levels. RESULTS: Patients who had experienced RIF produced a range of test abnormalities. Compared with controls, women with RIF had a higher prevalence of chronic endometritis (24% versus 6%), a lower vitamin D level and a borderline lower progesterone level. Women who had experienced RIF had a more favourable vaginal microbiome compared with controls. Although the RIF cohort was older than the controls (mean age 33.8 years versus 30.2 years), no differences between the groups were observed in immune cell profiling and the ERA test. CONCLUSION: These data demonstrate that a single test or treatment for the endometrial factor in RIF is unlikely to be clinically effective. Diagnosing the endometrium in women with RIF permits targeted rather than blind interventions. Relative vitamin D deficiency, lower mid-luteal progesterone and chronic endometritis are ready targets for treatment. Understanding the role and treatment of an unfavourable vaginal microbiome in RIF needs further investigation.

Uterine disorders affecting female fertility: what are the molecular functions altered in endometrium?

OBJECTIVE: To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. DESIGN: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. SETTING: Infertility research department affiliated with a university hospital. PATIENT(S): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II-IV endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genomewide gene expression and altered molecular functions in the endometrium of each uterine disorder. RESULT(S): Using robust analysis methods, we identified statistically significantly altered endometrial functions in all the uterine disorders. Cell cycle alterations were shared among all the pathologies investigated. Endometriosis was characterized by the down-regulation of ciliary processes. Among the endometriosis, ADC, and RIF samples, mitochondrial dysfunction and protein degradation were shared dysregulated processes. In addition, RPL had the most distinct functional profile, and 95% of affected functions were down-regulated. CONCLUSION(S): The most robust functions dysregulated in the endometrium of patients with uterine disorders across sample cohorts implicated an endometrial factor at the gene expression level. This shared endometrial factor affects endometrial receptivity processes.

The AGT Haplotype of the ESR2 Gene Containing the Polymorphisms rs2077647A, rs4986938G, and rs1256049T Increases the Susceptibility of Unexplained Recurrent Spontaneous Abortion in Women in the Chinese Hui Population.

BACKGROUND Estrogen has an important role in unexplained recurrent spontaneous abortion (URSA). Polymorphisms of the ESR1 gene and the ESR2 gene have been identified as risk factors for URSA, but with varied associations in Chinese populations. This study aimed to compare the role of gene polymorphisms of ESR1 and ESR2 and the risk of URSA in the Chinese Hui and Chinese Han populations. MATERIAL AND METHODS Chinese Hui women (n=171) and Chinese Han women (n=234) with URSA were compared with healthy controls (n=417) matched by ethnicity and age. Genotyping was performed using direct sequencing and identified three polymorphisms of the ESR1 gene (rs9340799, rs2234693, and rs3798759) and three polymorphisms of the ESR2 gene (rs207764, rs4986938, and rs1256049). The association between ESR1 and ESR2 gene polymorphisms and the risk of URSA was evaluated statistically using the odds ratio (OR) and 95% confidence interval (CI). RESULTS No association was detected between the allelic, dominant, and recessive models of ESR1 and ESR2 gene polymorphisms and the risk of URSA in Chinese Han and Hui populations (p>0.05). The distribution of the AGT haplotype containing ESR2 gene polymorphisms rs2077647A, rs4986938G, and rs1256049T was significantly reduced in patients with URSA compared with controls in the Chinese Hui population (OR, 0.29; 95% CI, 0.14-0.62; p=0.0009; padj=0.005). CONCLUSIONS The AGT haplotype of the ESR2 gene containing the polymorphism rs2077647A, rs4986938G, and rs1256049T (ESR2 hapAGT) was a protective factor for URSA in women in the Chinese Hui population when compared with the Chinese Han population.

Association of IL-1ß, IL-6, TNF-α, and TGFß1 Gene Polymorphisms with Recurrent Spontaneous Abortion in Polycystic Ovary Syndrome.

Recurrent spontaneous abortion (RSA) is a common pregnancy-associated complication of polycystic ovary syndrome (PCOS) which is an endocrine malfunction disease. Patients with PCOS may have several underlying contributing and interrelated factors, which have been reported in women with RSA. The incidence rate between PCOS and RSA remains uncertain. The aim of this study is to determine the possible association of IL-1ß-511C/T, IL-6-174G/C, TNF-α-1031T/C, and TGFß1-509T/C with RSA patients with or without PCOS. A total of 140 RSA patients, 70 of which were PCOS patients, and 140 healthy females with no history of RSA or PCOS were included in this study. PCR amplification, genotyping, and sequence analysis were employed to investigate the presence of the polymorphisms. The genotypic and allelic frequencies were calculated separately for each subject. Out of the four studied polymorphisms, the IL-1ß-511C/T genotype in RSA without PCOS patients (12.7%) was significantly different compared with that in control subjects (p = 0.047). For IL-6-174C/G, there was a tendency towards more CC carriers among RSA with PCOS patients (10%) than in controls (3%). The GG genotype in RSA women with PCOS (60%) was significantly different compared with that in control subjects (p = 0.033), and the GC genotype in RSA with PCOS patients (30%) showed a marginal significant difference compared with that in control subjects (p = 0.050). Significant difference was identified in the allelic frequencies in RSA patients with PCOS compared to controls (p = 0.025). IL-6-174G/C and TNF-α-1031T/C polymorphisms are significantly associated with RSA patients in Saudi patients with PCOS, while the IL-1ß-511C/T polymorphism is significantly associated with RSA patients without PCOS.

Low-dose aspirin improves endometrial receptivity in the midluteal phase in unexplained recurrent pregnancy loss.

OBJECTIVE: To evaluate differences in Doppler parameters and pregnancy outcomes, if any, and to determine the predictive accuracy of such indices, as well as the effects of low-dose aspirin (LDA) in unexplained recurrent pregnancy loss (URPL). METHODS: An observational study was conducted at Ren Ji Hospital, Shanghai, China, from May 2015 to December 2016. The endometrial thickness, and the pulsatility index (PI), resistive index (RI), and systolic-to-diastolic ratio (S/D) values of endometrial and uterine artery blood flow were collected. Receiver operating characteristic (ROC) curve analysis was used to analyze data from URPL patients (three or more first-trimester spontaneous abortions with unknown etiology) and patients with normal fertility. A second ultrasonography examination was performed in URPL patients who had received daily LDA for 2 months. RESULTS: There were 190 URPL patients and 35 control patients. Endometrial thickness was significantly thinner in URPL patients than control patients (P=0.005). The PI, RI, and S/D values for endometrial blood flow and the mean PI, RI, and S/D values for uterine arteries were significantly higher in URPL patients (P<0.001). The predictive accuracy of the indices mentioned above were 0.660, 0.802, 0.852, 0.837, 0.784, 0.929, and 0.929, respectively. Following LDA supplementation, URPL patients showed a significant reduction in resistance to endometrial and uterine artery blood flow (P<0.001). CONCLUSION: URPL patients had impaired uterine perfusion. Doppler parameters are valuable in predicting women at high risk of URPL. LDA could be effective in improving endometrial receptivity.

Abnormal uterine inflammation in obstetric syndromes: molecular insights into the role of chemokine decoy receptor D6 and inflammasome NLRP3.

The adaptation of the uterine environment into a favorable immunological and inflammatory milieu is a physiological process needed in normal pregnancy. A uterine hyperinflammatory state, whether idiopathic or secondary to hormonal or organic uterine disorders (polycystic ovary syndromes, endometriosis/adenomyosis and fibroids), negatively influences the interactions between decidua and trophoblast, early in gestation, and between chorion and decidua later in pregnancy. Abnormal activation of uterine inflammatory pathways not only contributes to the pathogenesis of the obstetric syndromes, i.e. recurrent pregnancy loss (RPL), pre-term delivery (PTD) and pre-eclampsia (PE), but also to correlates with severity. In this review, we summarize recent advances in the knowledge of uterine molecular mechanisms of inflammatory modulation in normal pregnancy and obstetric syndromes (RPL, PTD and PE). In particular, we focus on two regulators of uterine/placental inflammation: the NLRP3 inflammasome and the chemokines decoy receptor D6. We performed comprehensive review of the literature in PubMed and Google Scholar databases from 1994 to 2018. The available evidence suggests that: (i) the expression of inflammasome NLRP3 is increased in the endometrium of women with unexplained RPL, in the chorioamniotic membranes of women with PTL and in the placenta of women with PE; (ii) there is a role for abnormal expression and function of D6 decoy receptor at the feto-maternal interface in cases of RPL and PTD and (iii) the function of placental D6 decoy receptor is impaired in PE. A wider comprehension of the inflammatory molecular mechanisms involved in the pathogenesis of the obstetric syndromes might lead to the identification of new potential therapeutic targets.

Uterine artery flow velocity waveform (FVW) type and subednometrial vascularity in recurrent pregnancy loss.

Purpose: To assess the subendometrial and uterine artery blood flow and pattern of the waveform of the uterine artery in cases of recurrent pregnancy loss compared with normal controls.Subjects and methods: Fifty women with a history of two or more successive pregnancy losses were investigated by Doppler transvaginal ultrasound to assess the subendometrial blood flow resistance index (RI), type of Doppler waveform of the uterine artery, and uterine artery pulsatility index (PI) in the mid-luteal phase. Fifty normal women acted as controls.Results: Subendometrial blood flow RI and uterine artery PI were higher in cases than controls. The majority of cases of recurrent pregnancy loss had a waveform pattern of A, or loss of diastolic flow, whereas the controls were mainly C wave.Conclusions: Some sort of endometrial and subendometrial ischemia can be suggested in cases of recurrent pregnancy loss, waveform pattern of uterine artery changes may be used to monitor changes in vascularity of endometrium if vascular enhancers are given in such cases.

Polymorphisms in interleukin genes and their association with the risk of recurrent pregnancy loss.

Interleukins play important roles in pregnancy. Altered expression and splicing of various interleukins have been linked to the pathophysiology of recurrent pregnancy loss. Polymorphisms in interleukin genes can affect the expression and/or splicing of their respective genes and thus influence the risk of recurrent pregnancy loss. In this work, we examined the association between the IL1B rs16944, IL1B rs1143634, IL6 rs1800795, IL6 rs1800796, IL10 rs1800896 and IL18 rs187238 polymorphisms and recurrent pregnancy loss risk in a Chinese population. Study subjects comprised 598 idiopathic recurrent pregnancy loss patients and 603 controls. The genotyping was accomplished by PCR-RFLP. Regression analysis was performed to evaluate the disease association. After adjustment by Bonferroni correction, only the IL1B rs16944 and IL6 rs1800796 polymorphisms were significantly associated with risk of recurrent pregnancy loss. The heterozygous TC genotype of IL1B rs16944 had an adjusted odds ratio (aOR) of 1.4209 (1.1302-1.8929) (P = 0.0019), while the homozygous CC genotype had an aOR of 1.7398 (1.2133-2.3203) (P = 0.0008). A significant association was also observed for the C allele [aOR = 1.3747 (1.1296-1.8972)] (P = 0.0003). For IL6 rs1800796, the heterozygous CG genotype, the homozygous GG genotype and the G allele had aORs of 0.7342 (0.4412-0.8423) (P = 0.0016), 0.5424 (0.1768-0.7865) (P = 0.0014) and 0.7009 (0.4511-0.8034) (P = 0.0007), respectively. In summary, the IL1B rs16944 and IL6 rs1800796 variants were associated with an increased and a decreased recurrent pregnancy loss risk, respectively.

Improved in vitro fertilization success and pregnancy outcome with autologous platelet-rich plasma treatment in unexplained infertility patients that had repeated implantation failure history.

Repeated implantation failure (RIF) due to suboptimal endometrial lining is a major challenge in reproductive medicine. The study aims to evaluate effect of intrauterine platelet-rich plasma (PRP) treatment on frozen-thawed embryo transfer (FET) cycles in patients whose endometrium was unable to achieve optimal lining in unexplained infertility patients with history of RIF. We retrospectively analyzed the charts of a total of 302 cycles performed in 273 patients attending Diyar Life ART Centre between January 2014 and January 2017. After excluding 232 cycles, we compared pregnancy outcomes of 34 patients who had suboptimal endometrial lining and underwent PRP + FET and 36 patients who had optimal endometrial lining and underwent only FET. We observed that, endometrial thickness was higher after 48 hours from PRP when compared to endometrial thickness before PRP (10 mm vs. 6.25 mm, p < .001). Clinical pregnancy rate, and importantly live birth rate were also significantly higher in PRP group than the control group. Based on this information, we showed that intrauterine autologous PRP infusion is a safe, inexpensive adjuvant treatment for optimizing endometrium especially in patients with RIF history and intrauterine PRP infusion improved not only endometrial lining but also in vitro fertilization success and pregnancy outcome.