Suboptimal Pregnancy Outcomes Research Articles

Identify high-risk DOR women ≤ 35 years old following assisted reproduction technology through cutoffs of anti-mullerian hormone and antral follicle counts

BackgroundFemales with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the “high-risk DOR” group.ObjectiveThe primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs).MethodsA total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson’s chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02).ResultsAccording to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL < AMH values < 2.50 ng/mL, with 6 ≤ AFC ≤ 10; n = 682), and their outcomes were further compared to those of DOR patients (positive control, AMH values ≤ 1.2 ng/mL, and/or AFC ≤ 5; n = 1153) and of NOR patients (negative control, 2.5 ng/mL ≤ AMH values ≤ 5.5 ng/mL, and 11 ≤ AFC ≤ 20; n = 2649). Patients in the high-risk DOR group had significantly lower CLBRs than those in the NOR group (p < 0.001) but higher CLBRs than those in the DOR group (p < 0.001). Logistic regression further demonstrated that high-risk DOR was associated with a lower likelihood of cumulative live birth chance (OR 0.401, 95% CI: 0.332–0.486, p < 0.001) than NOR was, with a greater likelihood of cumulative live birth chance (OR 1.911, 95% CI:1.558–2.344, p < 0.001) than DOR was. To investigate the effects of embryo development stage, the outcomes of D3 embryos and blastocysts were analyzed separately. Significant differences in pregnancy outcomes were detected only in D3 embryo ET cycles among the three groups (high-risk DOR vs. NOR, all p < 0.05; DOR vs. NOR, all p < 0.05). DOR/high-risk DOR did not influence the pregnancy loss rates or pregnancy outcomes (clinical pregnancy rates and ongoing pregnancy rates) per positive HCG cycle (all p > 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM.Conclusion(s)Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.

The role of microRNAs in pregnancies complicated by maternal diabetes.

With the global prevalence of diabetes increasing, more people of reproductive age are experiencing hyperglycaemic pregnancies. Maternal Type 1 (T1DM) or Type 2 (T2DM) diabetes mellitus, and gestational diabetes mellitus (GDM) are associated with maternal cardiovascular and metabolic complications. Pregnancies complicated by maternal diabetes also increase the risk of short- and long-term health complications for the offspring, including altered fetal growth and the onset of T2DM and cardiometabolic diseases throughout life. Despite advanced methods for improving maternal glucose control, the prevalence of adverse maternal and offspring outcomes associated with maternal diabetes remains high. The placenta is a key organ at the maternal-fetal interface that regulates fetal growth and development. In pregnancies complicated by maternal diabetes, altered placental development and function has been linked to adverse outcomes in both mother and fetus. Emerging evidence suggests that microRNAs (miRNAs) are key molecules involved in mediating these changes. In this review, we describe the role of miRNAs in normal pregnancy and discuss how miRNA dysregulation in the placenta and maternal circulation is associated with suboptimal placental development and pregnancy outcomes in individuals with maternal diabetes. We also discuss evidence demonstrating that miRNA dysregulation may affect the long-term health of mothers and their offspring. As such, miRNAs are potential candidates as biomarkers and therapeutic targets in diabetic pregnancies at risk of adverse outcomes.

Nutritional Deficiencies and Subfertility: A Comprehensive Review of Current Evidence.

Subfertility, a condition marked by a reduced capacity to conceive naturally, affects a significant proportion of couples globally. Nutrition is a fundamental aspect of reproductive health, with various nutrients essential in maintaining optimal reproductive function. This comprehensive review explores the intricate relationship between nutritional deficiencies and subfertility. It examines key micronutrients such as vitamins D, E, C, and B12, as well as minerals such as zinc, iron, selenium, and magnesium, and their impacts on fertility. The review also considers macronutrients and the importance of a balanced diet in supporting reproductive health. Drawing on an extensive body of clinical evidence and studies, this review highlights how deficiencies in these nutrients can lead to hormonal imbalances, impaired gametogenesis, and suboptimal pregnancy outcomes. It discusses the efficacy of nutritional interventions, including dietary supplements and lifestyle modifications, in improving fertility. Furthermore, it addresses the emerging research on personalized nutrition and its potential to enhance reproductive outcomes. The review underscores the necessity for healthcare providers to assess and address the nutritional status of patients with subfertility. It provides practical recommendations for developing nutritional plans, counseling patients, and integrating nutritional interventions into fertility treatments. By offering a comprehensive synthesis of current evidence, this review aims to inform clinical practice and promote further research into the role of nutrition in enhancing fertility.

Exploring perceptions of vulnerability among women facing psychosocial adversity before, during and after pregnancy: A qualitative interview-study using thematic analysis

ObjectiveThe term ‘vulnerable’ is often used to describe women facing psychosocial adversity during pregnancy, implying a heightened risk of experiencing suboptimal pregnancy outcomes. While this label might facilitate the pathway to appropriate care, it can be perceived as stigmatizing by the women it intends to help, which could deter their interaction with healthcare services. This study explores how women facing psychosocial adversity before, during and after pregnancy perceive the concept of vulnerability and experience being labeled as such. MethodsWe conducted a thematic analysis of semi-structured, in-depth interviews. Through purposive sampling targeting maximum variation, ten women of diverse backgrounds were included. ResultsThree central themes emerged: defining vulnerability, embracing vulnerability and the feeling of being stigmatized. Women perceived vulnerability as an inability to adequately care for themselves or their children, necessitating additional support alongside routine antenatal care. Acceptance of the ’vulnerable’ label came when it also acknowledged their proactive efforts and strengths to improve their situation. Conversely, if discussions surrounding vulnerability failed to recognize women’s agency – specifically, their personal journeys and the courage needed to seek support – the label was perceived as stigmatizing. ConclusionsAddressing vulnerability effectively in maternity care requires a nuanced, patient-centered approach, acknowledging both the challenges and strengths of women facing psychosocial adversities. Emphasizing personal narratives and their courage in seeking support can mitigate the stigmatizing effects of the ’vulnerable’ label. Integrating these narratives into maternal healthcare practices can foster deeper connections with the women involved, enhancing the overall quality of care.

Pregnancy experiences of transgender and gender-expansive individuals: A systematic scoping review from a critical midwifery perspective.

Evidence suggests that transgender and gender-expansive people are more likely to have suboptimal pregnancy outcomes compared with cisgender people. The aim of this study was to gain a deeper understanding of the role of midwifery in these inequities by analyzing the pregnancy experiences of transgender and gender-expansive people from a critical midwifery perspective. We conducted a systematic scoping review. We included 15 papers published since 2010 that reported on pregnancy experiences of people who had experienced gestational pregnancy at least once, and were transgender, nonbinary, or had other gender-expansive identities. Three themes emerged from our analysis: "Navigating identity during pregnancy," "Experiences with mental health and wellbeing," and "Encounters in the maternal and newborn care system." Although across studies respondents reported positive experiences, both within healthcare and social settings, access to gender-affirmative (midwifery) care and daily social realities were often shaped by trans-negativity and transphobia. To improve care outcomes of transgender and gender-expansive people, it is necessary to counter anti-trans ideologies by "fixing the knowledge" of midwifery curricula. This requires challenging dominant cultural norms and images around pregnancy, reconsidering the way in which the relationship among "sex," "gender," and "pregnancy" is understood and given meaning to in midwifery, and applying an intersectional lens to investigate the relationship between gender inequality and reproductive inequity of people with multiple, intersecting marginalized identities who may experience the accumulated impacts of racism, ageism, and classism. Future research should identify pedagogical frameworks that are suitable for guiding implementation efforts.

9 Randel Lecture: In Vivo investigation of pregnancy Physiology

Abstract Pregnancy in any mammal requires the integration of three distinct compartments; the maternal, placental and fetal compartments. Compromised function of any of the three compartments can result in suboptimal pregnancy outcomes, including increased morbidity and mortality at delivery, reduced livestock production efficiency and adult-onset of metabolically-related disease in humans. To accurately understand the progression of both normal and compromised pregnancies, therefore, requires the simultaneous assessment of all three compartments, which for most species is not technically feasible. Consequently, over the past 60 yr the pregnant sheep has been used extensively for in vivo investigation of pregnancy physiology. The ability to place indwelling catheters, within both maternal and fetal vessels, allows the simultaneous steady-state assessment of uterine and umbilical blood flows, hormone secretion, and nutrient uptake and utilization of nutrients by each of the three compartments, under non-stressed and non-anesthetized conditions. This has provided unrivalled insight into the physiology of pregnancy, and the realization that the placenta is a highly metabolic tissue, utilizing the majority of oxygen and glucose taken up by the uterus. However, the deficit in studying pregnant sheep is the lack of genetic models, readily available in rodents, that could help define specific gene function during pregnancy. Consequently, we developed in vivo lentiviral-mediated RNA interference (RNAi) methods to specifically alter the abundance of specific gene transcripts/proteins within the placenta, beginning at 9 d of gestation (dGA). Our lentiviral-mediated approach limits the RNAi to the trophectoderm derivatives of the placenta. Initially we used this approach to determine the importance of PRR15 and LIN28 during the establishment of pregnancies, but turned our efforts towards combining in vivo RNAi with steady-state physiological assessments during late gestation to examine the function of genes involved in placental nutrient transport (SLC2A3) and placenta derived hormones (CSH). By creating a placental deficiency in SLC2A3, not only was the fetus smaller and hypoglycemic at mid-gestation, but by interfering with placental glucose uptake, maternal hormone concentrations were also impacted, yet near-term, a distinctly different phenotype was present. For the placental hormone CSH (a.k.a. placental lactogen), CSH RNAi not only impacts placental and fetal growth, but also reductions in uterine blood flow, nutrient fluxes to the fetus, and produces an altered hormonal environment. Combining these methodological approaches provides new and often unexpected insights into the physiological integration of the maternal, placental and fetal compartments. Supported by NIH-NICHD grants HD093701 and HD094952.

Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes

Aims/hypothesisType 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT).MethodsA total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables.ResultsMaternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks.Conclusions/interpretationAltered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes.Graphical

Assessing male gamete genome integrity to ameliorate poor assisted reproductive technology clinical outcome

To assess the role of evaluating sperm chromatin fragmentation (SCF) as a tool to guide treatment in couples who achieved unexpectedly poor clinical outcomes after intracytoplasmic sperm injection (ICSI). We identified couples with an unexpectedly suboptimal clinical outcome after ICSI who were then screened for SCF. Consequently, the same couples were counseled to undergo a subsequent ICSI cycle using either ejaculates processed by microfluidic sperm selection (MFSS) or spermatozoa retrieved from the testis, and clinical outcomes were compared between history and treatment cycles. To confirm the sole effect of a compromised male gamete, we compared the ICSI outcome in cycles where male gametes with abnormal SCF were used to inseminate autologous and donor oocytes. Finally, to eliminate an eventual confounding female factor component, we compared the clinical outcome of ICSI cycles using sibling donor oocytes injected with spermatozoa with normal or abnormal SCF. Academic reproductive medicine center point of care. The patient population consisted of 76 couples with reproductively healthy and relatively young female partners and male partners with compromised semen parameters, but suitable for ICSI. In a subanalysis, we identified 67 couples with abnormal SCF who underwent ICSI cycle(s) with donor oocytes. Furthermore, we identified 29 couples, 12 with normal SCF and 17 with abnormal, uncorrected SCF, and 7 couples with abnormal, corrected SCF vs. a control, who used sibling donor oocytes for their ICSI cycle(s). For couples who resulted in surprisingly low clinical outcomes after ICSI, despite semen parameters adequate for ICSI and a normal female infertility evaluation, a SCF assessment was performed on the semen specimen using the terminal deoxynucleotidyl transferase-mediated fluorescein-deoxyuridine triphosphate nick-end labeling (TUNEL) assay. The couples then underwent a subsequent ICSI cycle with spermatozoa processed by MFSS or surgically retrieved. Moreover, cycles with donor oocytes were used to confirm the sole contribution of the male gamete. Clinical outcomes, such as fertilization, embryo implantation, clinical pregnancy, delivery, and pregnancy loss rates were compared between history and treatment cycle(s) using ejaculated spermatozoa selected by MFSS or from a testicular biopsy, taking into consideration the level of SCF. In a subanalysis, we reported the clinical outcomes of 67 patients who used donor oocytes and compared them with cycles where their own oocytes were used. Furthermore, we compared the ICSI clinical outcomes between cycles using sibling donor oocytes injected with low or high SCF with or without sperm intervention aimed at correcting, or alleviating the degree of SCF. In a total of 168 cycles, 76 couples had in a prior cycle a 67.1% fertilization rate, and clinical pregnancy and pregnancy loss rates of 16.6% and 52.3%, respectively. After testing for SCF, the DNA fragmentation rate was 21.6%. This led to a subsequent ICSI cycle with MFSS or testicular sperm extraction, resulting in clinical pregnancy and delivery rates of 39.2%, and 37.3%, respectively. The embryo implantation rate increased to 23.5%, whereas the pregnancy loss rate decreased to 5% in the treatment cycle. This was particularly significant in the moderate SCF group, reaching embryo implantation, clinical pregnancy, and delivery rates of 24.3%, 40.4%, and 36.2%, respectively, and reducing the pregnancy loss rate to 10.5% in post-sperm treatment cycles. In 67 patients with high SCF who used donor oocytes, a significantly higher fertilization rate of 78.1% and embryo implantation rate of 29.1% were reported, compared with those in couples also with an elevated SCF who used their own. Interestingly, the clinical pregnancy and delivery rates only increased slightly from 28.0%-36.1% and from 23.7%-29.2%, respectively. To further control for a female factor, we observed couples who shared sibling donor oocytes, 17 with normal SCF and 12 with abnormal (uncorrected) SCF. Interestingly, the abnormal SCF group had impaired fertilization (69.3%), embryo implantation (15.0%), and delivery (15.4%) rates. For an additional 15 couples who split their donor oocytes, 8 had normal SCF, and although 7 couples originally had abnormal SCF, 4 used microfluidic processing, 2 used testicular spermatozoa, and 1 used donor spermatozoa to alleviate the degree of SCF, resulting in comparable clinical outcomes with the normal SCF group. A superimposed male factor component may explain the disappointing ICSI outcome in some couples despite reproductively healthy female partners. Therefore, it may be useful to screen couples for SCF to guide treatment options and maximize chances of a successful pregnancy. The improved, but suboptimal pregnancy and delivery outcomes observed in couples using donor oocytes confirmed the exclusive detrimental role that the male gamete exerted on embryo development despite the presence of putative oocyte repair mechanisms.

Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes.

The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes. One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit). HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks' gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63-140 mg/dL [3.5-7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c. HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).

Association between maternal prepregnancy body mass index and pregnancy outcomes following assisted reproductive technology: A systematic review and dose-response meta-analysis.

This systematic review investigated dose-response relationship between maternal prepregnancy body mass index (BMI) and pregnancy outcomes following assisted reproductive technology, including clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR). We searched four major databases and finally included 105 studies involving more than 271,632 pregnant women. We performed linear or nonlinear dose-response meta-analyses using random effects models. At per-woman level, pooling of unadjusted estimates shown an inverted J-shaped relationship between maternal BMI and CPR; pooling of adjusted estimates showed a linear association, suggesting statistical association between higher maternal BMI and lower CPR (adjusted OR [aOR] for 5-unit increase in BMI: 0.96, 95%CI: 0.94-0.98). At per-cycle level, linear dose-response relationship was found between maternal BMI and CPR (crude relative risk, RR, [cRR] for 5-unit increase in BMI 0.97, 0.96-0.98; aOR 0.96, 0.94-0.99). Linear dose-response relationship was established between maternal BMI and the outcomes of MR or LBR (higher BMI associated with higher MR [cRR 1.15, 1.08-1.22] and lower LBR [cRR 0.91, 0.88-0.94] at per-woman level). Sensitivity analyses showed no significant changes. In conclusion, there is dose-response relationship between maternal BMI and pregnancy outcomes following assisted reproductive technology. Higher BMI values may suggest suboptimal pregnancy outcomes.

Approaches to screening for hyperglycaemia in pregnant women during and after the COVID-19 pandemic.

AimTo evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA1c, during the COVID‐19 pandemic.MethodsRetrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004–2008; 826 consecutive gestational diabetes pregnancies, 2014–2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large‐for‐gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver‐operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA1c performance.ResultsGestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver‐operating characteristic curve for both criteria 0.81 (95% CI 0.79–0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver‐operating characteristic curve 0.75 (95% CI 0.65–0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver‐operating characteristic curve 0.92 (95% CI 0.85–0.98)] and HbA1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75–0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77–0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2–5.4 mmol/l (sensitivity 18–41%; specificity 97–98%).ConclusionsRandom plasma glucose at 12 weeks, and fasting plasma glucose or HbA1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.

PREIMPLANTATION GENETIC TESTING FOR ANEUPLOIDY DOES NOT IMPROVE OUTCOME IN YOUNG PATIENTS UNDERGOING IVF TREATMENT: A SART CORS STUDY

Preimplantation genetic testing for aneuploidy (PGT-A) is associated with significant improvement in ongoing pregnancy rates per transfer, reduction of multiple pregnancies using elective single embryo transfer (eSET), and reduced miscarriage rates in women > 35 years or older. As these improvements have not been observed in women < 35 years old, we sought to investigate whether offering PGT-A to favorable prognosis young women can be counterproductive and lead to suboptimal pregnancy outcomes.

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

Motivators and challenges to research recruitment – A qualitative study with midwives

ObjectiveTo explore midwives’ experiences of recruiting participants to research studies conducted by other researchers. DesignAn inductive qualitative study. MethodsIndividual face-to-face or telephone interviews using a semi-structured interview guide. Interviews were analysed thematically. SettingsOne large urban maternity hospital in Ireland. ParticipantsA purposive sample of 19 midwives FindingsThree co-dependent themes emerged: intrinsic motivations, extrinsic motivations and challenges. Intrinsic motivations included midwives’ personal beliefs about the value of research in general, its potential to improve practice, and their perceptions of how robust a particular study was and how it might impact on an individual woman and her baby. This included an inherent desire to shield some women, those who were perceived to have ongoing health issues or be anticipating a sub-optimal pregnancy outcome, from being offered study information. Extrinsic motivations related to the complexity of a research study and a specific researcher's characteristics. Challenges to offering potential participants research study information and, therefore, to successful recruitment included time constraints, workload and the volume of research being conducted simultaneously. Key conclusionsParticipants navigated the two, sometimes competing, worlds of clinical practice and clinical research. Set in the context of workload and the volume of research being conducted simultaneously, midwives’ perceptions of a study's robustness, clarity, its potential impact on individual women and ability to improve practice governed their motivation to offer information on research studies to potential participants. Implications for practiceInviting clinicians to assess the study information may improve its clarity and create opportunities to discuss the potential value and recruitment bias. Researchers should be available to address clinicians’ questions about particular research studies. At an organisational level, a system for managing the volume of research activity is required.

Brief Report: Maternal Opioid Prescription from Preconception Through Pregnancy and the Odds of Autism Spectrum Disorder and Autism Features in Children.

Opioid use during pregnancy is associated with suboptimal pregnancy outcomes. Little is known about child neurodevelopmental outcomes. We examined associations between maternal opioid prescriptions preconception to delivery (peri-pregnancy) and child's risk of ASD, developmental delay/disorder (DD) with no ASD features, or ASD/DD with autism features in the Study to Explore Early Development, a case-control study of neurodevelopment. Preconception opioid prescription was associated with 2.43 times the odds of ASD [95% confidence interval (CI) 0.99, 6.02] and 2.64 times the odds of ASD/DD with autism features (95% CI 1.10, 6.31) compared to mothers without prescriptions. Odds for ASD and ASD/DD were non-significantly elevated for first trimester prescriptions. Work exploring mechanisms and timing between peri-pregnancy opioid use and child neurodevelopment is needed.

Progestin-primed milder stimulation with clomiphene citrate yields fewer oocytes and suboptimal pregnancy outcomes compared with the standard progestin-primed ovarian stimulation in infertile women with polycystic ovarian syndrome

BackgroundOral progestin has recently been used to prevent premature LH surges in ovarian stimulation, and this progestin-primed ovarian stimulation (PPOS) is effective and safe in patients with different ovarian reserves. The current data are lacking regarding how to individualize the gonadotropin dose and regimen for women with polycystic ovarian syndrome (PCOS). A retrospective cohort trial was performed to evaluate the efficacy of progestin-primed milder stimulation with clomiphene citrate (CC) compared to the standard progestin-primed ovarian stimulation (PPOS) protocol for infertile women with PCOS.MethodsA total of 220 PCOS women were collected and classified into the study group (HMG 150 IU/d + CC 50 mg/d + MPA 10 mg/d) and control group (HMG 225 IU/d + MPA 10 mg/d). Ovulation was triggered by GnRH agonist 0.1 mg and hCG 1000 IU when dominant follicles matured. Viable embryos were cryopreserved for later transfer. The primary endpoint was the ongoing pregnancy rate. Secondary outcomes included the cycle characteristics and the live birth rate.Result(s)The study group consumed less HMG (1470.0 ± 360.1 IU vs 1943.8 ± 372.0 IU, P < 0.001) and harvested fewer oocytes than the control group (12.2 ± 7.4 vs 18.2 ± 9.7, P < 0.001). The study group showed a higher mid-follicular LH concentration (4.49 ± 2.49 mIU/ml vs 2.52 ± 2.09 mIU/ml, P < 0.05) but no endogenous LH surge. No between-group difference was found in the incidence of ovarian hyperstimulation syndrome (OHSS) (0.91% vs 0.91%, P > 0.05). The cumulative ongoing pregnancy rate and live birth rate per patient were lower but did not reach significance compared with the control group (71.8% vs 81.8 and 64.5% vs 75.5%, respectively, both P > 0.05).Conclusion(s)The milder PPOS with CC in PCOS women led to lower oocyte yields and suboptimal pregnancy outcomes compared to the standard PPOS treatment. The two regimens both achieved a low incidence of OHSS. The results from the CC combination regimen provide a new insight for developing a more patient-friendly protocol for PCOS women.

Managing obesity in pregnancy: Are psychological dimensions of behavioural change important to midwives and women?

Currently a quarter of British women are obese. It is well known that maternal obesity increases the risk of suboptimal pregnancy outcomes. The National Institute for Health and Care Excellence (NICE) in the UK recommends that pregnant women should be given advice and support on achieving appropriate weight gain during pregnancy. However, evidence suggests that such advice relating to diet and physical activity in pregnancy is inconsistent, as well as sometimes being ineffectual. Recent research shows that many midwives at the forefront of maternity care lack the confidence to discuss weight gain during pregnancy with obese women, and midwives recognise that further training concerning weight gain would enhance their ability to support obese women. Concerns include offending and potentially disengaging women from health services. This paper considers the policy position on diet and activity for obese, pregnant women and the evidence for nutrition and lifestyle intervention for controlling gestational weight gain. It is suggested that the inclusion of a psychological dimension may increase the efficacy of interventions relating to obesity during pregnancy. Recommendation is made for a controlled trial for community midwives examining the efficacy of behaviour change intervention, underpinned by psychological theory that would enable community midwives to offer specific advice and support for obese, pregnant women.

Nutritional status of pre-pregnant and pregnant women residing in Bogor district, Indonesia: a cross-sectional dietary and nutrient intake study.

The diet of Indonesian women of childbearing age is relatively poor, posing increased risk for suboptimal pregnancy outcome. In a cross-sectional study including 403 women in three economic quintiles (Q), we investigated differences in dietary intake and nutrition sufficiency according to economic status and whether regular dietary intakes of pregnant women (PW, n 203) differ from that of pre-pregnant women (PPW, n 200). Dietary intake data were collected using 2×24 h dietary recall and FFQ. Energy, protein, Fe, Ca, Zn, vitamin A and vitamin C intakes were calculated utilising Food Composition Tables and compared with Indonesian recommendations for adequacy. Energy and protein intakes <70 % and Fe, Ca, Zn, vitamin A and vitamin C intakes <77 % of the local recommendation were considered insufficient. A higher intake of milk/dairy products (Q3, Q4), fruits and vegetables (Q2) and snacks (Q3) in PW was observed compared with PPW, but insufficient to meet nutrient requirements. Nutrient intake calculations showed insufficiency in 26 % of PPW for protein and up to 70 % for Fe. Deficient nutrient intakes in PW were found in 49 % of the subjects for energy and up to 85 % for Fe. Energy and protein intakes decreased with decreasing economic quintiles in PPW and PW. Ca and vitamin A intakes were lower in Q2 compared with Q4. The proportion of animal protein in Q2-PW was low (31 %). Biochemical status parameters in a subset showed that anaemia and Fe and Zn deficiencies were prevalent among PPW and PW. Habitual diets in the study area did not meet the nutrient requirements for both PPW and PW across the investigated economic groups.

Acute neonatal immune challenge: Lipopolysaccharide exposure alters neonatal ovarian inflammatory pathways and mediators

Early ovarian development is driven by immune mediators. Local ovarian immune mechanisms promote processes critical for normal ovarian function, including follicular assembly, proliferation, maturation and apoptosis. Immune disturbances at this time may perturb follicular development and permanently alter reproductive functioning. We have previously demonstrated that rats exposed to lipopolysaccharide (LPS, 0.05 mg/kg; i.p.) on post-natal day (PND) 3 and 5 display activation of circulating and ovarian immune pathways, follicular depletion, advanced senescence, and suboptimal pregnancy outcomes. In the current study, we began to investigate the ovarian expression of early immune mechanisms induced by LPS challenge. Ovaries were collected 2 hours post injection on PND5 and analysed using quantitative real-time (qRT) PCR for genes associated with ovarian maturation and immune activation. Neonatal LPS exposure significantly downregulated the expression of toll-like receptor (TLR) 4, the receptor for LPS. Inflammatory markers involved in establishment of ovarian function, including tumour neurosis factor (TNF)-alpha, protein kinase C and MAP Kinase (MAPK8/JNK1) were significantly upregulated. Downregulation of TLR4 may be associated with an immediate tolerance or protective effect after PND 3 exposure. Upregulation of inflammatory pathways may prematurely accelerate ovarian maturation, leading to follicular depletion, advanced senescence and inflammatory alterations. Therefore, our findings indicate that immune activation in early life acutely alters the ovarian inflammatory milieu during a critical period of gonadal development, potentially increasing the risk of future reproductive dysfunction.

Comparison of immuno-fluorescence microscopy and optical microscopy after Giemsa staining in the diagnosis of malaria during pregnancy in Buea, Cameroon

Malaria in pregnancy remains a significant threat in sub-Saharan Africa as it is associated with suboptimal pregnancy outcomes. Due to the fact that the current standard diagnostic method is cumbersome, we assessed the diagnostic performance of an alternate method-fluorescent microscopy, compared to optical microscopy after Giemsa staining- the current standard.Venous blood samples were collected from 407 consenting pregnant women and tested by optical microscopy (OM) after Giemsa staining and by fluorescent microscopy (FM) using the Partec-Cyscope (Partec GmbH, Munster, Germany). All participants were asymptomatic at the time of enrollment. Of the 407 samples tested by OM, 255 (62.5%) were plasmodiumpositive. Of the 255 OM positive samples, 207 were also plasmodium-positive by FM, thus a sensitivity of 81.1% (95% confidence interval (CI): 75.8, 85.8%). Of the 152 samples negative by OM, 75 were also negative by FM, thus a specificity of 49.3% (95%CI: 41.1, 57.6%). The positive and negative predictive values of FM were respectively 72.9% (95%CI: 67.3, 78.0%) and 61.0% (95%CI: 51.8, 69.6%). The percentage agreement between both methods was 69.3% (Kappa=0.32, p-value<0.01). There was moderate agreement between FM and OM results. The low specificity and negative predictive value of FM suggest a high likelihood of false negative results if FM is used in place of OM. OM after Giemsa staining remains the gold standard. Keywords : Diagnostic performance, sensitivity, specificity, positive predictive value, negative predictive value, Cameroon.