Poor Reproductive History Research Articles

Prevalence of T-shaped uterus among fertile women based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria

Research questionWhat is the prevalence of T-shaped uteri among fertile women based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria? DesignA prospective cohort study of 258 women of reproductive age with a history of at least one natural pregnancy resulting in live birth. Participants were recruited from the family planning clinic between January 2018 and March 2020. The ESHRE/ESGE classification of congenital anomalies of the female genital tract was used for describing abnormal findings. CUME criteria were also used for diagnosing T-shaped uterus. Uterine cavity volume was measured. ResultsMean age of participants was 35.4 ± 6.2 years. Participants were diagnosed with the following: congenital uterine abnormality (n = 9 [3.6%]); partial septate uterus (n = 5 [2.0%]) and hemiuterus (n = 2 [0.8%]). Two women (0.8%) were diagnosed with T-shaped uterus and borderline T-shaped uterus based on the ESHRE/ESGE criteria and CUME. Mean lateral indentation angle, lateral indentation depth and T-angle were 156.2° ± 9.53°, 2.85 ± 0.93 mm and 73.3° ± 9.85° in patients with normal uterine cavity. In patients with T-shaped and borderline T-shaped uteri, respective figures were 115° versus 121°, 10 mm versus 7.6 mm and 27.5° versus 70°. Median volume of the uterine cavity in patients with normal uterine cavity and T-shaped uterus was 3.71 ml (minimum 2.0 to maximum 9.03 ml, interquartile range 1.93) and 3.2 ml (2.9 and 3.62 ml), respectively. ConclusionsThe prevalence of T-shaped uteri in fertile women is low, which corresponds to previous reports of women with poor reproductive history.

Intralipid therapy and adverse reproductive outcome: is there any evidence?

Controversy exists regarding the benefits of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no evidence to support the effectiveness, utility or safety for this treatment. While individual studies may be perceived as weak, a systematic review and meta-analysis were performed to determine if there is any advantage to patients. PubMed, Embase and Scopus searches were performed with the target populations being either recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) undergoing assisted reproductive technology (ART) and receiving intralipid infusions. These cohorts were compared with either placebo, no intervention or alternative treatments. The most relevant outcome measures were considered to be clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR) and miscarriage rate (MR). Twelve studies encompassing 2676 participants met the criteria for selection and were included and reviewed. Treatment of the target population with intralipid led to an improvement in IR (Odds Ratio (OR): 2.97, 2.05–4.29), pregnancy rate (OR: 1.64, 1.31–2.04), and LBR (OR: 2.36, 1.75–3.17), with a reduction in MR (OR: 0.2, 0.14–0.30). Although intravenous intralipid is not recommended as a routine treatment for recurrent miscarriage or implantation failure, there is enough data to suggest consideration in selected patients where routine testing is unremarkable, standard treatments have failed and immunological risk factors are present. The presence of abnormal uterine natural killer (uNK) cells needs more study as a target marker to determine those who could benefit.Lay summaryThere is controversy regarding the benefits and efficacy of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no credible evidence to support their use. A situation we frequently face as medical professionals is patients asking us to consider immune therapy (such as intralipid) for reproductive failure where good quality embryos have been used. Intralipid infusions have been reported to improve pregnancy rates with IVF, and reduce the miscarriage risk in selected patient groups, but study results are not universally accepted. We have performed a detailed review and analysis of the literature to determine if there is any benefit to this immune treatment in specific patient groups. Our paper identified and analyzed 12 studies, finding that treatment with intravenous intralipid leads to an improvement in implantation, pregnancy and live birth rates, with a decrease in miscarriage rate. This study shows that there is evidence to suggest consideration of intralipid in certain patients where standard treatments have failed.

Daily practice management of septate uterus: reproductive outcome after septoplasty

Septate uterus is the most common uterine malformation found in women presenting poor reproductive history. Hysteroscopic septoplasty (HS) restores the uterine anatomy in a safe procedure. The goal of our study is to determine the reproductive outcomes after HS of symptomatic septate uterus. In a retrospective observational single centre study the reproductive outcomes and complications after HS were evaluated in 31 women with symptomatic septate uterus. The patients were separated into two groups according to the symptoms - infertility or recurrent pregnancy loss (RPL). were the pregnancy and live birth rate and secondarily the complication rate. Furthermore, the results were analysed depending on the need of assisted reproductive techniques (ART). The treatment has resulted in an overall pregnancy rate of 71% for both groups. The spontaneous pregnancy rate is 45% and 8 pregnancies resulted from ART (26%). The overall first live birth rate is 51.6%. A decrease has been noticed in the miscarriage rate from 95.24% to 24% (p<0.001) in the overall population. In patients with a symptomatic septate uterus hysteroscopic septoplasty is a safe and effective procedure. The favourable results pointing out the benefits of surgery on the reproductive outcomes as well as the relatively simple and safe technique of HS make the intervention attractive.

Use of gestational surrogacy for a patient with recurrent pregnancy loss from early onset of severe pre-eclampsia: Case report.

Introduction: The use of a gestational carrier deserves consideration as a treatment option in patients with poor reproductive histories because of early onset severe pre-eclampsia (PET) and hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP). The case report is of 33 years old woman and 35 years old husband who presented with bad obstetric outcome of 7 pregnancies losses in the second trimester due to severe PET. After the 7th pregnancy loss, the couple opted for gestational surrogacy. In a traditional surrogacy arrangement, the surrogate mother provides the oocyte and the uterus to foster a pregnancy. With a gestational surrogate IVF cycle, the gestational surrogate is not the genetic mother because she does not provide the oocyte. In Vitro Fertilization (IVF) was undertaken using the patients oocytes and her husband’s sperm with the transfer of three embryos to a gestational surrogate where conception occurred with subsequent twin delivery. &#x0D; The objective of this case report is to report a case of gestational surrogate treatment in the prevention of severe early onset pre-eclampsia (PET) with subsequent term twin delivery.

The endometrial immune environment of women with endometriosis.

Endometriosis, a common oestrogen-dependent inflammatory disorder in women of reproductive age, is characterized by endometrial-like tissue outside its normal location in the uterus, which causes pelvic scarring, pain and infertility. While its pathogenesis is poorly understood, the immune system (systemically and locally in endometrium, pelvic endometriotic lesions and peritoneal fluid) is believed to play a central role in its aetiology, pathophysiology and associated morbidities of pain, infertility and poor pregnancy outcomes. However, immune cell populations within the endometrium of women with the disease have had incomplete phenotyping, thereby limiting insight into their roles in this disorder. The objective herein was to determine reproducible and consistent findings regarding specific immune cell populations and their abundance, steroid hormone responsiveness, functionality, activation states, and markers, locally and systemically in women with and without endometriosis. A comprehensive English language PubMed, Medline and Google Scholar search was conducted with key search terms that included endometriosis, inflammation, human eutopic/ectopic endometrium, immune cells, immune population, immune system, macrophages, dendritic cells (DC), natural killer cells, mast cells, eosinophils, neutrophils, B cells and T cells. In women with endometriosis compared to those without endometriosis, some endometrial immune cells display similar cycle-phase variation, whereas macrophages (Mø), immature DC and regulatory T cells behave differently. A pro-inflammatory Mø1 phenotype versus anti-inflammatory Mø2 phenotype predominates and natural killer cells display abnormal activity in endometrium of women with the disease. Conflicting data largely derive from small studies, variably defined hormonal milieu and different experimental approaches and technologies. Phenotyping immune cell subtypes is essential to determine the role of the endometrial immune niche in pregnancy and endometrial homeostasis normally and in women with poor reproductive history and can facilitate development of innovative diagnostics and therapeutics for associated symptoms and compromised reproductive outcomes.

Moving from peripheral blood to local uterine immunophenotype analysis in patients with poor reproductive history: pilot study of a novel technique.

A complete reproductive immunophenotype is poorly described, with most focus on peripheral blood natural killer cells rather than uterine populations. There is debate regarding normal endometrial levels, with no consensus, and much controversy on correlation with implantation/miscarriage. Development and validation of a rapid endometrial assessment flow cytometry (FCM) technique, allowing determination of local lymphocyte subset ranges, comparison to peripheral blood, and patient subgroup analysis. Prospective pilot, assessing patients with prior implantation, failure offered endometrial biopsy before subsequent ART cycle, functioning as therapeutic scratch. HRT regime administered to standardise environment, and progesterone-primed mid-luteal biopsy (five completed days progestogen, P+5) analysed using comprehensive flow panel to identify lymphocyte subsets. Two hundred patients were recruited in a tertiary university-affiliated ART centre. FCM identified differing lymphocyte ranges between peripheral blood and biopsy. Uterine/decidual natural killer cells are the dominant endometrial subtype. Patients with repeated implantation failure had higher uNK levels (52.4 vs 43.7%, p = 0.01). Conversely, B lymphocytes (0.87 vs 0.72%, p = 0.032), pNK (1.21 vs 0.8%, p = 0.041), and NK-T (2.68 vs 2.26, p = 0.031) cells were higher in recurrent pregnancy loss. FCM is widely used to assess cellular populations, but not typically employed for endometrial evaluation. FCM provides a rapid, detailed, and quantitative analysis and reduces inter-observer subjectivity bias. Detailed understanding of the normal endometrial immunophenotype, and associated deviations, may provide insight into the aetiology of infertile patients labelled "unexplained". Failure despite transfer of high grade, or proven euploid blastocysts, is a difficult problem, and endometrial profiling may help identify research areas to determine potential future therapeutic interventions for this difficult to treat population.

Surgical correction of T-shaped uteri in women with reproductive failure: Long term anatomical and reproductive outcomes

ObjectiveTo evaluate the long term anatomical and reproductive outcomes of hysteroscopic treatment for T shaped uterus in patients presenting with reproductive failure. MethodsThis prospective cohort study included 56 patients with a history of long-standing unexplained infertility, recurrent implantation failure (RIF), and/or recurrent pregnancy loss (RPL) who were eligible for metroplasty by office hysteroscopy. Office hysteroscopy under conscious sedation was performed. Anatomical outcomes were assessed with pre- and postoperative measurements of the transostial, isthmic and myometrial diameters and the uterine volume using three-dimensional transvaginal sonography (3D-TVS). Reproductive outcome was assessed after spontaneous or assisted conception. ResultsHysteroscopic treatment significantly increased the volume of the uterus from a mean of 2.5+1mL before surgery to 3.2±1mL by the end of 1 year as measured by 3D-TVS. According to the main indication to perform metroplasty, 20 of 32 (62.5%) patients with long standing unexplained infertility, 9 of 14 (64%) patients with RIF, and 8 of 10 (80%) patients with RPL conceived either spontaneously or with assisted reproduction. ConclusionsOffice hysteroscopic metroplasty results in a significant long-term expansion of the uterine cavity and improved reproductive outcomes in women presenting with a T shaped uterus and poor reproductive history.

ART implantation failure and miscarriage in patients with elevated intracellular cytokine ratios: response to immune support therapy

BackgroundThe origins of adverse reproductive outcome can be multifactorial, but the contribution of the maternal immune system is considered debatable. Elevated intracellular cytokine ratios have been proposed, although not universally supported, as a marker for immunological dysfunction in implantation and early pregnancy. Poor patient selection or inadequate treatment or testing may be confounding factors. Specific immunomodulation, in carefully selected sub-populations of ART patients with poor reproductive history, despite transfer of good quality blastocysts, may potentially improve clinical outcomes.MethodsIntracellular cytokine ratios (CKR) were prospectively assessed in 337 patients presenting with a history of implantation failure and/or pregnancy loss, prior to further treatment, and were found to be elevated in 150 (44.5%). Of this group, 134 agreed to initiate a standardised immunotherapy regime (nutraceuticals, prednisolone & intralipids) to evaluate the efficacy of this proposed therapy. Of the intervention population, a small cohort (n = 70) delayed commencing ART for ~ 10 weeks to assess if extended pre-treatment nutraceutical supplementation could normalise CKRs prior to starting ART, and if this conferred additional benefit.ResultsBaseline assessment in the intervention population (n = 134) identified 160 miscarriages from 180 total pregnancies (89% miscarriage rate, MR), conceived both spontaneously and by assisted reproduction. Post-treatment analysis of subsequent ART cycles revealed a significant improvement in both implantation (OR 3.0, 2.0–4.5) and miscarriage rates (41/97, 42.2% MR, P < 0.001). Interestingly, pre-treatment normalisation of CKRs appeared to impart marginal extra benefit prior to subsequent fertility treatment with immunotherapy.ConclusionsFollowing immunomodulation, significant improvements in both implantation rate and miscarriage rate were seen in this poor prognosis population. This suggests a possible role for both detailed immuno-evaluation of patients with poor reproductive history with good embryo quality, and application of personalised immunotherapy regimes alongside ART in selected cases. Future randomised controlled trials are needed to definitively evaluate this potentially promising therapeutic approach.

Differential Associations of Adverse Childhood Experience on Maternal Health

The current study examined whether three distinct antecedent factors related to maternal adverse childhood experiences were differentially associated with maternal health and psychosocial outcomes in the antepartum period. It was hypothesized that all three adverse childhood experience factors would be positively associated with poor health prior to pregnancy, poor reproductive health history, and health complications and psychosocial difficulties during pregnancy. Data from 1,994 women (mean age=30.87 years) and their infants were collected from a prospective longitudinal cohort from 2008 to 2011. Pregnant women completed self-report questionnaires and a healthcare professional assessed the mothers' health prior to pregnancy, reproductive history, and pregnancy complications. Data analyses were conducted from December 2016 to March 2017. Path analysis demonstrated that women who had experience with physical/emotional abuse in childhood were significantly more likely to enter pregnancy with a chronic health condition (AOR=1.25, 95% CI=1.02, 1.54) and to have psychosocial difficulties in their pregnancy (AOR=1.60, 95% CI=1.34, 1.89). Women who were exposed to household dysfunction in childhood were also significantly more likely to experience psychosocial difficulties during pregnancy (AOR=2.33, 95% CI=1.49, 3.65). There was no association between exposure to sexual abuse and maternal health or mental health outcomes. Adverse childhood experience categories differentially predicted maternal health and psychosocial outcomes prior to and during pregnancy. The overall variance accounted for by adverse childhood experiences was small (3%-19%), suggesting that factors other than childhood adversity likely contribute to maternal health.

The role of transabdominal cervical cerclage techniques in maternity care

Key content The transabdominal cerclage procedure aims to strengthen the cervix by placing a suture at the level of the internal os. The main indications for transabdominal suture are a grossly disrupted cervix, an absent vaginal cervix, and previous failed elective vaginal cerclage. The transabdominal cerclage was first described in 1965 and the laparoscopic modification was first reported in 1998. Published reports suggest very high neonatal survival rates with both approaches. Laparoscopic cerclage has the general advantages of minimal access surgery, such as avoiding a large abdominal incision, short hospital stay and quick recovery. Potential complications include bleeding from uterine vessels and loss of pregnancy for non‐interval procedures. The other reported complications, such as suture migration, rectouterine fistula, uterine rupture and intrauterine growth restriction, are rare. The place of transabdominal cerclage in preventing pregnancy loss and preterm birth remains a subject of debate and there is a need to audit the outcomes. Learning objectives To better understand the role of the cervix in miscarriage. To understand the indications for referral for transabdominal cervical cerclage. To understand the obstetric and neonatal outcomes of women after this procedure. Ethical issues To consider the place of this invasive procedure, with its consequent possible complications, in the management of cervical weakness in women who often have poor reproductive histories. To consider the lack of national and international availability of this potentially valuable procedure. To consider an effective system of assessment of this procedure in a referral context, and the future of this procedure.

The AUGMENTSM Treatment: Physician Reported Outcomes of the Initial Global Patient Experience

Background: Egg precursor cells can be readily isolated from the protective outer lining of the ovarian cortex. Studies have demonstrated that mitochondria isolated from these cells are of high quality. The AUGMENTSM treatment is a proprietary new technology based on previous clinical use demonstrating that the addition of mitochondria during in vitro fertilization (IVF) is safe, improves embryo quality, and increases the success of IVF. Subsequent published animal studies also confirmed the role of mitochondria in improved outcomes. This report represents the earliest global observations of the AUGMENTSM treatment in routine clinical practice from two distinct international centers. Methods and results: The AUGMENTSM treatment was initially used in a population of difficult-to-treat patients with a poor prognosis for success with standard IVF who were likely moving to donor egg as a next step. Each group reported marked improvements in pregnancy rates above the historic IVF success rate for these patients (e.g., 11- and 18- fold increase in ongoing clinical pregnancy rates in the UAE and Canada, respectively). In a 25 patient subset, retrieved eggs from each woman were allocated to two treatment groups; one group underwent the AUGMENTSM treatment at the time of ICSI while the other group underwent conventional ICSI. Embryos were selected for fresh-embryo transfer based on standard criteria including embryo morphology and the results of preimplantation genetic testing. Morphogenetic embryo selection and transfer from the AUGMENTSM treatment group was significantly higher, suggesting that improved embryo quality may have resulted in the improved pregnancy rates observed in these women. Conclusions: Based on these findings, the AUGMENTSM treatment may be a viable treatment option to address an unmet need for women with poor reproductive histories, history of poor egg quality, poor embryo development, previously failed IVF, and those seeking—despite repeated failures-to conceive genetically-related offspring.

Predicting birth outcomes: Together, mother and health care provider know best

ObjectiveTo examine contributors to perceived risk in pregnancy and its utility in predicting lower birth weight and earlier delivery in conjunction with health care providers' assessment of obstetric risk. Methods165 pregnant women at high (n=34) or low (n=131) obstetric risk completed assessments of perceived risk, stress, optimism, and health behaviors using well-validated instruments and measures designed for this study. Medical charts were abstracted for gestational age at delivery and birth weight. Results40% of the sample perceived their risk status differently than their health care provider. Stress, poor reproductive history, provider assigned risk, and unhealthful behaviors were significant, independent predictors of perceived risk (R2=.37). The greatest difference in birth weight (p=.003) and gestational age (p=.05) was between women considered at low risk by both self and provider and women considered at high risk by both. Perceived risk improved prediction of adverse birth outcomes, especially lower birth weight, in women considered by providers to be at low risk. ConclusionWomen's perceptions of risk are an important contributor to prediction of birth outcomes, but the combination of information from both a woman and her health care provider is superior. Incorporating women's perceptions into obstetric risk determination may help to reduce the number of women identified as high risk who subsequently have a normal birth outcome (false positives), and more importantly, the number of women considered to be at low risk who ultimately experience an adverse outcome (false negatives).

Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Highly significant improvement in embryo implantation and increased live birth rate achieved after comprehensive chromosomal screening: implications for single embryo transfer

OBJECTIVE: To improve the identification of viable embryos for uterine transfer with a view to increasing implantation and birth rates. DESIGN: Prospective clinical trial. MATERIALS AND METHODS: Comparative genomic hybridization (CGH) was used to screen all 23 pairs of chromosomes for aneuploidy in over 500 blastocysts derived from 115 patients. The patients were of advanced maternal age (mean 39 years) and in most cases had at least one previous failed IVF attempt (mean failed cycles 2). RESULTS: The CGH approach underwent extensive validation prior to clinical application, confirming concordance between the biopsied trophectoderm (TE) cells and the inner cell mass. A full chromosome screen was obtained for 93% of blastocysts tested. Almost all patients (96%) had at least one normal embryo available for transfer. Currently, 42 patients have had their blastocysts transferred, with the remaining patients scheduled to receive transfers in the coming weeks. The clinical pregnancy rate stands at 86% (36/42). Fifteen cycles have now gone to term, giving a birth rate per cycle of 80% (versus 60% in control blastocyst transfer cycles). Even more impressive was the implantation rate (fetal heart detected) which was increased from 28% in controls to 66% (54/82) in cases with CGH screening (2.4 fold increase, P<0.0003). CONCLUSIONS: We report the first births following comprehensive chromosome screening of blastocyst stage embryos. The sampling of several TE cells led to a robust diagnosis, less susceptible to problems such as chromosomal mosaicism than previous screening methods. Implantation and birth rates were exceptional (66% per embryo and 80% per cycle started respectively). These results were especially good given the poor reproductive history of the patients and were significantly better than cycles without chromosome screening. The dramatic improvement in implantation rate provides a clear indication that methods such as this will allow high pregnancy and birth rates in cycles involving single embryo transfer.

High pregnancy rate after comprehensive chromosomal screening of blastocysts

OBJECTIVE: Traditionally, preimplantation genetic screening has involved the biopsy of a single blastomere at the cleavage stage followed by limited chromosomal assessment using fluorescent in situ hybridization (FISH). The objective of this study was to clinically apply a novel strategy for aneuploidy detection, based upon comprehensive chromosome screening of trophectoderm (TE) cells biopsied at the blastocyst stage. DESIGN: Clinical evaluation of a new approach for embryo viability assessment. MATERIALS AND METHODS: All 23 pairs of chromosomes were screened for aneuploidy in 106 blastocysts derived from 17 patients. The patients were of advanced maternal age (mean 37 years), with a history of multiple failed IVF attempts and/or multiple abortions. 3-10 TE cells were biopsied from each blastocyst and subjected to whole genome amplification and comparative genomic hybridization (CGH). Blastocysts were cryopreserved using vitrification while CGH analysis took place. Chromosomally normal blastocysts were warmed and transferred in a subsequent FET. RESULTS: The CGH approach underwent extensive validation prior to clinical application, confirming accuracy and cytogenetic concordance between the TE and inner cell mass. Clinically, CGH succeeded in producing a full chromosome screen for 91% of blastocysts tested. The aneuploidy rate was 43.8%. Embryo survival after biopsy and warming were excellent (100%). To date, 10 patients have undergone blastocyst FET, resulting in an implantation rate of 55% per embryo and an ongoing clinical pregnancy rate (fetal heart) of 70% per cycle. Further transfers are in progress. CONCLUSIONS: We report the first clinical application of a novel approach for preimplantation genetic screening, involving assessment of all chromosomes at the blastocyst stage. The sampling of several cells resulted in a robust diagnosis and greatly reduces the risk of misdiagnosis due to chromosomal mosaicism. Implantation and clinical pregnancy rates were high (55% and 70%), especially given the poor reproductive history of the patients, and compare very favorably with non-PGS cycles matched for maternal age (30% and 60% respectively). Despite the high implantation potential of blastocysts it is clear that many still harbor lethal aneuploidies. It is likely that accurate, comprehensive chromosomal screening will significantly improve embryo selection and may be key to maintaining high pregnancy rates in cycles involving elective single blastocyst transfer.

Variable aneuploidy mechanisms in embryos from couples with poor reproductive histories undergoing preimplantation genetic screening

Preimplantation genetic screening (PGS) is used to determine the chromosome status of human embryos from patients with advanced maternal age (AMA), recurrent miscarriage (RM) or repeated implantation failure (RIF). Embryos from 47 such couples were investigated for chromosomes 13, 15, 16, 18, 21 and 22 using fluorescence in situ hybridization with two rounds of hybridization. The investigation included parental lymphocyte work-up, the screening of blastomeres on day 3 and full follow-up on day 5/6 of untransferred embryos. The outcome of 60 PGS cycles is described, in which 523 embryos were biopsied; 91% gave results, of which 18% were diploid for all the chromosomes tested and 82% were abnormal. The pregnancy rate per cycle that reached the biopsy stage was 27%, and 30% per embryo transfer. Satisfactory follow-up was obtained from 353 embryos; all those diagnosed as abnormal were confirmed as such, although two false-positives were detected in relation to specific chromosome abnormalities. Meiotic errors were identified in 16% of embryos. Between the RM, AMA and RIF groups, there was a significant difference in the distribution of embryos that were uniformly abnormal and of those with meiotic errors; with an almost 3-fold increase in meiotic errors in the first two groups compared with the RIF group. This complete investigation has identified significant differences between referral groups concerning the origin of aneuploidy in their embryos.

Perceptions of parent–staff communication in Neonatal Intensive Care: The findings from a rating scale

A rating scale has been developed assessing parental perceptions of the quality of communication received at two time points during the first 2 weeks following birth (see [Reid, T., Bramwell, R., Booth, N., Weindling, M., 2007. Perceptions of parent-staff communication in Neonatal Intensive Care: The development of a rating scale. Journal of Neonatal Nursing 13 (1), 24–35]). This paper explores the findings according to various parental and infant characteristics, for example parental gender, infant illness, transfer status and mode of birth. There were no differences in mothers' and fathers' communication ratings, and infant illness did not appear to influence ratings significantly. Parents who were transferred from their planned place of birth had more negative ratings at the later assessment. Previous negative experiences such as previous preterm birth, poor reproductive history or history of previous poor outcome did not appear to unduly influence communication ratings, though the numbers of such parents were relatively small in this study. Mode of birth appeared to influence communication ratings for mothers at the early assessment, as ratings were more positive for elective caesarian birth compared to those giving birth normally or by emergency caesarian section. Analyses which explored differences in subscale scores according to socioeconomic status, birth order, pregnancy risk, maternal or paternal age, cohabitation status or presence of congenital anomaly revealed no significant influence on communication scores. The study also examined ratings between the earlier and later assessments, and results revealed significantly increased negative ratings over time. There were also differences in ratings between nurses, nurse practitioners and medical staff, revealing that parents were able to discriminate differing clinical roles in NICU.

Antiphospholipid antibodies and infertility: The importance of anti-phosphatidylserine antibody

Antiphosphplipid antibodies (aPL) have been linked to poor reproductive performance for almost 20 years. Although many different types of antibodies may be present in the so-called antiphospholipid syndrome, the majority of the studies have been focused on anti-cardiolipin and lupus anticoagulant antibodies. However, many other antibodies have been described, among which anti-phosphatidylserine (aPS) is known to have adhesive properties essential for placentation. Therefore, previously unidentified patients with aPS+ may be at increased risk, even in the absence of the classical aPL. The aim of this study was to describe the incidence of aPS in patients with poor reproductive history and compare the results with other abnormal immunological findings. 102 patients with history of either repeated IVF failures (group 1) or recurrent miscarriage (group 2) were submitted to a protocol of immunological evaluation. Recurrent miscarriage was defined as antecedent of ≥ 2 spontaneous previous miscarriages and repeated IVF failures was defined as ≥2 previous failed IVF attempts. The patients were submitted to the following immunological evaluation: group 1: anti-nuclear antibody (ANA), anti-phospholipid antibodies—anti-cardiolipin (aCL) and anti-phosphatidylserine (aPS)—anti-thyroid antibodies (anti-tireoglobulin and anti-microsomal) and natural killer (CD3- CD16+ CD56+) cells count; group 2: the above mentioned exams for group 1 plus cross-match for HLA-sharing assessment, homocysteine level and genetic tests for detection of inherited thrombophilias (data not shown). Fisher’s exact test was used for statistical analysis and a p<0.05 was considered significant. Fifty-three patients (52%) had positive anti-phospholipid tests.Thirty-three patients (32.4%) had aCL and 41 patients (40.2%) presented positive aPS. When the 2 groups were compared, we found an equivalent prevalence of positive aCL: 30.6% (19/62) in group 1 and 35% (14/40) in group 2; p=0.67. The prevalence of positive aPS, however, was significantly higher in group 2: 55% (22/40) vs 30.6% (19/62); p=0.022. Also, 36.4% (12/33) of patients with aCL were negative for aPS. Contrarily, 53.7% (22/41) of patients with positive tests for aPS were negative for aCL. When other immunological abnormalities were studied for aPS positive patients (n=41), we found association with high NK cells in 36.6% (15/41), anti-thyroid antibodies in 9.8% (4/41) and ANA in 29.3% (12/41). Positive aPS and aCL were the only abnormal findings in 8.8% (9/102) and 3.9% (4/102) of all patients, respectively. We found a high prevalence of positive aPS in patients with poor reproductive history (40.2%). Our findings of a higher percentage of aPS positive women in group 2 (55% vs 30.6%) strengthens the importance of phosphatidylserine as a trophoblastic constitutive phospholipid. Autoantibodies against PS might therefore impair placentation and lead to miscarriage. It is noteworthy that neither aCL nor aPS shall be performed alone, because there is a significant number of patients in whom only one or another will be found. Finally, the significant association with other abnormalities in patients aPS+, especially high activated NK cells count (36.6%) and ANA (29.3%), highlights the need of a global immunological evaluation for patients with poor reproductive history, since different abnormalities may indicate distinct and specific treatments.

Immunological abnormalities and infertility

Immunological abnormalities and infertility

Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients

Objective To examine whether there are characteristic histological features in placentas from ongoing pregnancies of patients with a history of recurrent miscarriage, with and without primary antiphospholipid antibody syndrome, in relation to clinical pregnancy outcome. Methods Patients attending a recurrent miscarriage clinic were investigated and treated according to an established protocol. One hundred twenty-one consecutive patients achieving a potentially viable pregnancy (at least 24 completed weeks’ gestation), including 60 primary antiphospholipid antibody syndrome–positive cases and 61 primary antiphospholipid antibody syndrome–negative cases were included. After delivery, placental pathologic examination was carried out by a pathologist unaware of the clinical details. Histological sections were examined by two pathologists independently. Pregnancy outcome and placental findings were reviewed in relation to the maternal antiphospholipid antibody status. Results Pregnancy outcome was similar in primary antiphospholipid antibody syndrome–positive and primary antiphospholipid antibody syndrome–negative groups regarding gestation at delivery and antepartum obstetric complications. Several histological placental abnormalities were identified in both groups, but most pregnancies were clinically uncomplicated, with no significant placental abnormalities. In cases with pregnancy complications, the placental pathology was primarily that of uteroplacental vasculopathy, such as placental infarction and preeclampsia, but there were no specific placental lesions or patterns of abnormalities characteristic of primary antiphospholipid antibody syndrome–positive patients. A small subgroup of primary antiphospholipid antibody syndrome–positive patients may be at increased risk of development of maternal floor infarction or massive perivillus fibrin deposition. Conclusion There are no specific histopathologic placental abnormalities characteristic of treated patients with antiphospholipid antibody syndrome and poor reproductive history, but complications of uteroplacental disease are more common.