History Of Recurrent Pregnancy Loss Research Articles

740 Maternal history of recurrent pregnancy loss and placental related complications

740 Maternal history of recurrent pregnancy loss and placental related complications

Metroplasty increases the take-home baby rate by reducing pregnancy loss without changing the chance of conception in women with septate uterus: a retrospective, single-center, observational study

BackgroundAlthough abdominal or hysteroscopic metroplasty for septate uterus is considered to reduce pregnancy loss and increase the take-home baby (THB) rate in women with a history of recurrent pregnancy loss, there exists an inherent risk of impaired fertility. This study aimed to clarify the reproductive outcomes of women with septate uterus who underwent abdominal and hysteroscopic metroplasty in a single center.MethodsThis retrospective observational study enrolled 27 women who underwent metroplasty between 2007 and 2019. The analysis included women with septate uterus [European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) type U2)] or septate-bicornuate uterus (ESHRE/ESGE type U3b) who underwent either abdominal or hysteroscopic metroplasty. Women who did not have an immediate desire to conceive were excluded from the analysis. As a rule, we recommended pregnancy without surgery for women who had not experienced repeated pregnancy loss. Abdominal metroplasty (ABM) was performed using the modified Tompkins’ method and hysteroscopic metroplasty was performed using hysteroscopic transcervical resection of the septum [transcervical metroplasty (TCM)]. The conception ratio was calculated as the number of women who achieved ≥ 1 conception/total number of women, the pregnancy loss ratio was calculated as the number of women who experienced ≥ 1 pregnancy loss/the number of women who conceived, and the THB ratio was calculated as the number of women who achieved ≥ 1 THB/total number of women.ResultsSeventeen women underwent ABM and 10 women underwent TCM. Thirty-three conceptions and 26 babies were taken home after surgery. ABM did not change the ≥ 1 conception ratio (76% vs. 83% before and after surgery, respectively; RR = 1.08, p = 0.80). Meanwhile, ABM decreased the ≥ 1 pregnancy loss ratio (100% vs. 36%, RR = 0.36, p < 0.001) and increased the ≥ 1 THB ratio (12% vs. 71%, RR = 6.00, p < 0.01). Similarly, TCM did not change the ≥ 1 conception ratio, decreased the ≥ 1 pregnancy loss ratio, and increased the ≥ 1 THB ratio.ConclusionsBoth abdominal and hysteroscopic metroplasty for septate uterus increased the THB rate by preventing pregnancy loss without affecting the chance of pregnancy.Trial registrationNot applicable.

Future risk of metabolic syndrome after recurrent pregnancy loss: a cohort study using UK Biobank

To evaluate the risk of metabolic syndrome (MS) after recurrent pregnancy loss (RPL) using UK Biobank data. A history of pregnancy loss is associated with the development of cardiovascular diseases in the future. However, the association between RPL and subsequent MS is poorly understood. Therefore, we aimed to check the risk of MS after RPL. The study population was divided into 2 groups according to reproductive history: women with a history of RPL and women without a history of RPL. Recurrent pregnancy loss was defined as 2 or more spontaneous miscarriages, and MS was defined as at least 3 of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, high-blood pressure, and hyperglycemia. UK Biobank resource. The UK Biobank is a prospective cohort study that enrolled individuals aged between 40 and 69 years whose medical and reproductive histories were retrieved at enrollment. In this cohort, only women with a history of at least one pregnancy were selected. Recurrent pregnancy loss. The primary outcome was the prevalence of MS. The secondary outcomes were 5 diagnostic components of MS. We analyzed 228,674 women, including 15,702 with a history of RPL and 212,972 without a history of RPL. Women with a history of RPL have a higher prevalence of MS between the ages of 40 and 60 years (33.0% vs. 31.5%). After adjusting for covariates (age, race, number of live births, early menopause, smoking, alcohol consumption, and physical activity), the increased risk of MS after RPL remained significant (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.15). Furthermore, in the analysis of the 5 diagnostic components of MS, a history of RPL significantly increased the risk of abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hyperglycemia. Middle-aged women with a history of RPL have an increased risk of MS.

Pregnancy with uterine didelphys and history of recurrent pregnancy loss: Case report

Link of Video Abstract: https://youtu.be/H7Y7XoPOUAw Background: Uterine didelphys is an embryologic disorder that arises from the failure of Mullerian duct fusion. It is characterized by the presence of two distinct cervices, two vaginas, and two uterine horns. Obstetric complications may arise during pregnancy when uterine didelphys is present; these may include spontaneous abortion, premature labour, and fetal malpresentation. Case Presentation: A 25-year-old woman has been married for three years and had history of six gravid, zero parity, and five abortion. The patient had uterine didelphys. A fully septated uterus with double cervices and vaginas was found on pelvic magnetic resonance imaging. The patient arrived at the hospital at 27/28 weeks. Periodic sonograms demonstrated breech presentation and no (Intrauterine Growth Restriction) IUGR evidence. At 38/39 weeks, the patient was scheduled for cesarean surgery. Uterine didelphys morphology, pregnancy on the left side of the uterus, and the septum separating the left and right uterine cavities were all observed during the caesarean section. The newborn had three umbilical cords wrapped around his neck. The infant was female, 2800 grams, 48 cm, Apgar score 7-8, Ballard score (BS) 38 weeks, Lubchenco score (LS) p25-50. Conclusion: Antenatal care is required for investigating risks of uterine didelphys, including cervical incompetence, spontaneous abortion, and preterm birth, using serial sonograms to assess fetal well-being and cervical length.

Case Report On Abnormal Uterine Bleeding with Multi-System Disorders

Autoimmune disease is a condition that attacks the immune system and leads to multi-system disorders like systemiclupus erythematosus and rheumatoid disorders, which initiates self-directed immune responses that result in clinical diseases,mainly in obstetrics conditions like recurrent pregnancy loss, pre-eclampsia are common. The study aimed to identify therelationship between connective tissue disorders and abnormal uterine bleeding patterns. A rare case of abnormal uterinebleeding with a past history of recurrent pregnancy loss was presented in the casualty with excessive menstrual bleeding in astate of hypovolemic shock. The patient complained of generalised malaise, giddiness, breathlessness, and palpitations for thepast 2 months. She suffered recurrent epistaxis for the past 2 months and experienced symptoms like loss of appetite, recurrentvomiting for the past 15 – 20 days, and rashes over the face and cheeks for 6 months. Her haemoglobin was 2.4g/dL, and theplatelets were less than 10,000 with bicytopenia at the time of admission She was shifted to ICU and haemodynamicallystabilized by packed red blood cells, fresh frozen plasma, and platelets. Following this, she was treated with antifibrinolytics, andsevere anaemia was corrected with multiple PRBC transfusions. Multiple single-donor platelet transfusions were also done. Afterrecovery, the patient was discharged with an advice to continue hydroxychloroquine. Immune dysregulation and inflammationtogether contribute to the development of menstrual disorders among women with Rheumatoid Disorders which can be wellmanaged with systematic therapeutic plans at the initial stage.

Prevalence of Hypothyroidism in Pregnancy and Its Associations with Adverse Pregnancy Outcomes Among Pregnant Women in A General Hospital: A Cross Sectional Study.

Hypothyroidism affects 3-5% of all pregnant mothers, making it the most common thyroid disorder associated with pregnancy. Furthermore, it is associated with adverse outcomes of pregnancy and newborn. Therefore, this research is aimed at determining the magnitude and pregnancy adverse outcomes associated with hypothyroidism among pregnant women having maternity services in a general hospital in Somalia. A cross-sectional study was conducted on pregnant women who delivered in the hospital between December 2022 and May 2023. Subjects were selected through systematic sampling and data collected through an interviewer-based questionnaire. Adjusted odds ratios (AORs) of P values and 95% confidence intervals (CIs) were used to assess the correlation between variables. The prevalence of hypothyroidism was 23.6% (95% CI: [19.4-27.8]). Overt DM (AOR=9.125, CI (3.106-26.812)), History of Recurrent pregnancy loss (AOR=12.938, CI (4.958-33.763), hypertension during pregnancy (AOR=6.718, CI (2.326-19.994)) and preterm delivery (AOR=7.015, CI (3.234-13.958)) were variables associated with hypothyroidism in pregnancy. The study has shown a high prevalence of hypothyroidism during pregnancy at Daruxannan Hospital compared to previous studies around the world. This finding highlights the need for national and regional surveys to identify the prevalence and associated factors that contribute to hypothyroidism in pregnancy to set up interventions and determine policy directions.

What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping?

BackgroundBalanced chromosome aberrations are reported in about 1:30 couples with recurrent pregnancy loss (RPL). Karyotyping of both parents is necessary to identify these aberrations. Genome-wide non-invasive prenatal testing (NIPT) in case of recurrent pregnancy loss could be a more efficient way to identify couples at increased risk for carrying a balanced chromosome rearrangement. The aim of this study was to evaluate whether the potential fetal imbalances caused by parental balanced aberrations detected in our center are large enough to be detectable by genome-wide non-invasive prenatal testing (NIPT).Material and methodsFrom January 1970 until May 2020 our laboratory received 30,863 unique requests for karyotyping due to RPL. We have identified 16,045 couples and evaluated all abnormal cytogenetic results to assess the minimal size of the involved chromosomal segments in potential unbalanced products of the rearrangements.ResultsIn the presented cohort we detected 277 aberrant balanced translocations/inversions in females and 185 in males amongst 16,045 couples with RPL, which can be translated to a risk of 1:35 (2.9%, 95% CI 2.6–3.2%). Our study showed that the vast majority (98.7%, 95% CI 97.1–99.5%) of these balanced aberrations will potentially cause a fetal imbalance > 10 Mb, which is detectable with genome-wide NIPT if it was performed during one of the miscarriages.ConclusionsOur study suggests that genome-wide NIPT is able to reveal most unbalanced products of balanced chromosomal rearrangements carried by couples with RPL and therefore can potentially identify balanced chromosomal aberration carriers. Moreover, our data suggest that these couples can be offered NIPT in case they decline invasive testing in future pregnancies.

Depression, anxiety, and stress and adverse pregnancy outcomes in pregnant women with history of recurrent pregnancy loss in Nigeria.

The primary purpose of this study was to examine whether pregnant women with a history of recurrent pregnancy loss (RPL) are more likely to experience moderate-to-severe depression, anxiety, or stress symptoms than pregnant women without a history of RPL. The secondary purpose was to determine whether women with prior RPL experienced more unfavorable pregnancy outcomes if they had depression, anxiety, or stress. A prospective case-control study was conducted that included 47 pregnant women with a history of RPL and 94 pregnant women without prior RPL. Participants 20weeks of gestation or earlier were included. Both groups completed the Depression, Anxiety, and Stress Scale (DASS-21), and were followed up until delivery to determine the pregnancy outcomes. Multivariate logistic regression was used to compare adverse pregnancy outcomes. Among the 47 women with prior RPL, 10 had primary RPL (two or more miscarriages without a successful pregnancy) and 37 secondary RPL (two or more miscarriages with a history of successful pregnancy). RPL was significantly associated with moderate-to-severe levels of depression (P < .001), anxiety (P < .001), and stress (P < .001). Among the RPL group, high stress level was significantly associated with repeat miscarriage (adjusted odds ratio (AOR) = 5.28, 95%CI = 1.25-100.0, P = .03) and preterm labor (AOR = 6.07, 95%CI = 1.61-100.0, P = .04). Depression and anxiety were not associated with adverse pregnancy outcomes. Pregnant women with a history of RPL had considerably higher rates of moderate-to-severe depression, anxiety, and stress. Repeat miscarriage and preterm labor were considerably higher among pregnant women with RPL who were experiencing high stress levels at baseline.

Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder.

Recurrent pregnancy loss (RPL) refers to two or more miscarriages before 20 weeks gestation. Its prevalence is 1-2%; its pathogenesis remains unexplained in more than 50% of cases, in which the cause is thought to be abnormal immune activity during placentation leading to a lack of pregnancy-induced immune tolerance. It is unknown whether immune activity is deranged in the endometrium of women with RPL. We studied the gene expression and the quantitative tissue protein levels of three immune checkpoints (CD276, which enhances cytotoxic T-cell activity, cytotoxic T-lymphocyte-associated antigen-4 [CTL-4], which reduces Th1 cytokine production, and lymphocyte activation gene-3 [LAG-3], which shows suppressive activity on Tregs and CD4+ T-cells) in endometrial samples from 27 women with unexplained RPL and in 29 women with dysfunctional uterine bleeding and previous uneventful pregnancies as controls. RNA isolation, real-time PCR, protein isolation, and ELISA were performed. CD276 gene expression and protein tissue levels were significantly lower in the endometrium of the RPL group than in the controls, whereas both CTL-4 and LAG-3 were significantly higher. This difference suggests defective endometrial immune regulation and overactivation of immune response in women with a history of RPL, at least in relation to controls with dysfunctional uterine bleeding and previous normal reproductive history.

Treatment of recurrent pregnancy loss in women with euthyroid-based thyroid peroxidase antibody syndrome.

Recurrent pregnancy loss (RPL) due to thyroid peroxidase antibody (TPOAb) syndrome remains a significant challenge in pregnancy. The current study offers better insights into miscarriages that occur due to the presence of TPOAb with euthyroid in pregnant women with a history of RPL. Out of the 347 women confirmed with unexplained RPL, only 70 (20.2%) tested positive for TPOAb (215±53). After eight women were excluded from the study due to failure to follow up, 62 participants (age range: 33±4.8 years; body mass index (BMI):25-30kg/m2 (58%) and >30kg/m2 (42%)) were included. The TPOAb-dependent RPL patients were divided according to their RPL types into 23 (30.7%) nulliparous (1˚) and 39 (69.3%) multiparous (2˚) patients, respectively. Out of the sample, 69.2% and 30.8% had a history of miscarriages during the 1st and 2nd trimesters, respectively. For treatment purposes, while screening for the TPOAb, the women received 50µg/day of L-thyroxine (LTx) for three months prior to pregnancy and during the first three months of pregnancy and were followed up until giving birth or miscarriage. Thyroxine treatment was correlated to successful normal births in 56.6% and 21.2% of pregnant women after 36 and during 28-36 weeks of gestation, respectively. However, miscarriages occurred in 18.1% and 4.1% of patients during 14-28 weeks and before 14 weeks of gestation, respectively. The current findings show the promising use of thyroxine in the control of RPL caused by euthyroid-based thyroid peroxidase antibody syndrome. This treatment has led to a significant number of women experiencing successful full-term pregnancies and giving birth to healthy babies.

11:20-11:30 - Soluble HLA-G blood levels are not increased during ongoing pregnancy in women with a history of recurrent pregnancy loss

11:20-11:30 - Soluble HLA-G blood levels are not increased during ongoing pregnancy in women with a history of recurrent pregnancy loss

P-540 Improper placentation due to skewed Oct4-Cdx2 expression may be a leading factor in idiopathic recurrent pregnancy loss (RPL) cases from Assam, India.

Abstract Study question Does the differential expression of key embryonic stem cell (ESC) markers due to upstream signaling cascade(s) deregulation influence RPL pathogenesis in the studied population? Summary answer Imbalanced Oct4-Cdx2 expression linked differential ESCs polarization due to β-catenin signaling deregulation during the peri-implantation period impacts RPL pathogenesis in the studied population. What is known already RPL affects approximately 2-5% of women globally and around 7% Indian women in reproductive age group; with 50% of case etiology being unclear. Proper placentation is indispensable for establishment, continuation, and success of a pregnancy; and it depends largely on a healthy balance between apoptosis and stem cell differentiation that aids proper trophoblast invasion. These differentiation events are tightly controlled by the interplay of oxygen tension, hormones, growth factors, other signaling molecules and most importantly by transcription factors including those deciding the stem cell lineage like Oct4, NANOG, and Cdx2, wherein, β-catenin is known to enhance Oct-4 activity in ESCs. Study design, size, duration The sample size was predicted using Raosoft software utilizing the prevalence rate of RPL. Overall 87 women with 2 or more pregnancy losses before completion of 20 weeks of gestation were enrolled as RPL cases with informed consent, whereas, for the control group, 107 women volunteers undergoing medical termination of pregnancy (MTP) were enrolled as gestation-week-matched comparative study group for experimental data analysis. Participants/materials, setting, methods Products of conception (POC) was collected from the MTP and RPL cases. POCs were collected in 2vials for every subject: (i) 4% buffered formalin for fixation and preparation of microscopic slides for immunofluorescence (IF) based protein expression of Oct4 and Cdx2; (ii) RNA later solution for site specific transcriptional analysis of Oct4, NANOG, Cdx2, and β-catenin utilizing Realtime PCR. The difference in expression was analyzed using SPSS statistical software. Main results and the role of chance IF based site specific protein expression data confirmed higher expression of OCT4 in RPL cases compared to MTP controls, whereas CDX2 expression was found to be low in RPL compared to MTP subjects. The Realtime PCR amplification of cDNA using β-actin as internal normalization control for Oct4 (25.76 ± 10.17 folds) and NANOG (18.32 ± 6.67folds) showed increased expression whereas the Cdx2 expression was downregulated (0.487 ± 0.186 folds) in RPL cases compared to MTP controls, indicating a shift towards pluripotency which is a non-favorable environment for the ongoing pregnancy since cell polarization for initiation of differentiation to different cell lineages is required at that time of gestation. The cdx2 and oct4 expression correlated inversely and significantly {Pearson’s correlation= −0.838, p = 0.009; Spearman’s rho= −0.786; p = 0.016}. The realtime PCR amplification of β-catenin, the key molecule involved in direct enhancing of Oct4 expression during gestation was found to be increased in RPL cases compared to MTP controls. Statistically, the β-catenin-Oct4 expression correlated positively significantly. Limitations, reasons for caution Being a patient based study, the present study is limited to being an associative study only; and therefore secondary validation of the data for causal association using cell lines or suitable model system futuristically may add valuable scientific inputs and aid clinical intervention modalities for controlling RPL. Wider implications of the findings As the majority of RPL pathogenesis etiology is undefined limiting the possibilities of clinical interventions therefore we presume the present data can layout possible therapeutic interventions by regulating key regulators influencing skewed ESC profile aiding proper placentation leading to successful pregnancy in a subpopulation of cases with RPL history. Trial registration number Not applicable

Perinatal pathology for women with reproductive losses in anamnesis

Perinatal aspects of miscarriage, despite progress in the study of pathogenetic mechanisms, continue to be leading in modern obstetrics. The presence of even one case of miscarriage in a woman’s anamnesis negatively affects her further reproductive function, affects the course and outcome of the next pregnancy, and even pre-pregnancy correction of detected disorders does not always allow to achieve the desired result - the birth of a healthy child. The issues of prediction, prevention, and prevention of perinatal complications require a clear understanding of the mechanism of influence of the threat of spontaneous abortion and premature birth on the fetus. Placental dysfunction can have serious consequences during pregnancy, affecting both mother and baby. Therefore, it is very important to study the relationship between potential risk groups, such as women with a history of recurrent pregnancy loss, and placental dysfunction. Perinatal pathology for women with reproductive losses in anamnesis. Based on the germination of a pathogeny of unmaturing of pregnancy and violations of placenta dysfunction, previous abortions in anamnesis can be related to the enhanced able risk of violations of placenta dysfunction. Comparing primiparous women, in which there were abortions in anamnesis, to the control group of women giving birth, can bring the overvalue of risks, as for the primiparous women of violation of placenta dysfunction more widespread, than for women giving birth. It is set that the most closely-coupled interface from preeclampsia was observed for patients with premature births of &lt;37 weeks of gestation, but not in those, who gave in a term. Found out the theenhanceable risk of preeclampsia at the repeated losses of pregnancy, but only at the presence of an anamnesis of auxiliary genesial technologies. Other research it was not succeeded to find out the higher risk of preeclampsia for women with repeated loss of pregnancy, that it is possible to explain the small population and absence of a clear determination of the sequence of abortions. The repeated loss of pregnancy is a studied not enough problem, which causes serious disturbance in pair which try to create a family. Separate patients can have isolated infertility, repeated spontaneous abortions, or repeated losses in the ІІ and ІІІ trimesters. However much epidemiology information testify to strong intercommunication between these unfavorable results. The set reasons for the repeated loss of pregnancy include a hormonal disbalance, anomalies oogenesis highway, genetic or chromosomal anomalies, psychosocial, autoimmune diseases, and, possibly, immunological incompatibility of mother and fetus.

C4d Staining Is Present in Normal Placentas From Pregnancies Prior to Pregnancy Loss Associated With Chronic Histiocytic Intervillositis and Is Reduced by Immunomodulatory Therapy in Subsequent Pregnancies.

Chronic histiocytic intervillositis (CHI) is associated with adverse pregnancy outcomes and high recurrence risk. Recent studies suggest that CHI may represent a host-vs-graft rejection, and that C4d immunostain can be used as a marker for complement activation and antibody-mediated rejection in the CHI. This retrospective cohort study focused on 5 fetal autopsy cases associated with CHI (5 index cases) from 5 women. We analyzed placentas from the index cases (fetal autopsy cases associated with CHI) and placentas from the women's previous and subsequent pregnancies. We assessed the presence and extent of CHI and C4d immunostaining in these placentas. We evaluated each available placenta and graded the severity of CHI as either <50% or ≥50%. Additionally, we conducted C4d immunostaining on one representative section from each placenta and graded the staining levels as follows: 0+ for staining <5%; 1+ for staining between 5% and <25%; 2+ for staining between 25% and <75%; and 3+ for staining ≥75%. Three of the 5 women had pregnancies prior to their index cases (fetal autopsy cases associated with CHI). Despite the absence of CHI in their initial pregnancies, the placentas displayed positive C4d staining with grades of 1+, 3+, and 3+, respectively. These results suggest the presence of complement activation and antibody-mediated rejection in placentas from their prior pregnancies without CHI. Three of the 5 women received immunomodulatory therapy after experiencing pregnancy losses associated with CHI. After treatment, 2 of these women had live births at 35 and 37 gestational weeks, respectively, while the third had a stillbirth at 25 gestational weeks. The severity of CHI and the degree of C4d staining in the placentas decreased in all 3 cases following immunomodulatory therapies. Specifically, the level of C4d staining decreased from 3+ to 2+, 2+ to 0+, and 3+ to 1+ in these 3 cases, respectively. In women with a history of recurrent pregnancy loss associated with CHI, C4d immunostaining was present in the placentas from their previous non-CHI pregnancies, suggesting activation of the classical complement pathway and antibody-mediated reaction in their prior non-CHI pregnancies before the development of CHI in subsequent pregnancies. Immunomodulatory therapy may improve pregnancy outcomes by reducing complement activation, as shown by the reduction of C4d immunopositivity in the placentas after immunomodulatory treatment. Although we believe that the study provides valuable insights, we acknowledge that there are limitations to the findings. Therefore, to further elucidate the pathogenesis of CHI, additional research efforts with a collaborative and multidisciplinary approach are necessary.

Undetected Maternal Cell Contamination in Products of Conception Analysis May Mask Recurrence Risks for Future Pregnancies: A Case Report and Discussion [ID: 1377203

INTRODUCTION: Maternal cell contamination (MCC) in products of conception (POC) tissue is common; some studies report 59% of 46,XX results represent MCC. METHODS: Products of conception tissue and maternal blood samples were shipped to a laboratory for genotyping using Illumina CytoSNP-12b microarrays and bioinformatics (IRB E&amp;I 19040-03A). Patient informed consent was obtained for submission of a case report. RESULTS: A 25-year-old woman with a family history of recurrent pregnancy loss (RPL) was first offered POC analysis after her second loss. The result was normal female; however, MCC could not be ruled out because a maternal sample was not provided. Thus, the result was presumed normal, and the patient was informed her testing did not identify a genetic cause for her loss. The patient's third miscarriage was sent for POC analysis with a parental sample, which identified a maternally derived 26.8-Mb terminal deletion and 39.3-Mb terminal duplication of chromosome 4. The submitted maternal sample allowed for reanalysis of the second loss confirming MCC. Maternal karyotype analysis revealed an abnormal result: 46,XX,inv(4)(p15.2q31.3). The patient was referred to reproductive endocrinology for discussion of options, including in vitro fertilization with preimplantation genetic testing. CONCLUSION: Undetected MCC can lead to erroneous normal female results, masking fetal findings that could affect recurrence risks. Since 5% of couples with RPL have a balanced chromosome rearrangement, almost six couples for every 1,000 losses are at risk for undetected MCC masking recurrence risks (calculated using a 50% expected aneuploidy rate and 59% of 46,XX results actually representing MCC).

Can circulating levels of transforming growth factor-β1 in early pregnancy serve as a predictive marker of unfavourable outcome?

IntroductionTransforming Growth Factor (TGF-β1) is an anti-inflammatory pleiotropic cytokine, crucial for maternal immune tolerance towards semi-allograft. It acts as a mediator in achieving successful implantation and maintenance of pregnancy. MethodsA total of 300 samples; 150 with Recurrent Pregnancy Loss (RPL) and 150 with no pregnancy loss, in their first trimester were evaluated for circulating levels of TGF-β1 using Enzyme-Linked Immunosorbent Assay (ELISA). Further, the Receiver Operating Characteristics (ROC) analysis was performed to assess the potential of TGF-β1 in the risk prediction of RPL and the prognostic importance in the form of favourable and unfavourable outcome in the existing pregnancy. ResultsThe results showed significant elevated levels in women without the history of RPL compared to those with the history of RPL (4783.60 ± 522.95 vs. 4252.18 ± 672.26 pg/mL, p < 0.0001).Further evaluation of follow up data of women with the history of RPL, based on favourable (78%) and unfavourable (22%) outcome of the existent pregnancy showed significantly higher TGF-β1 in women with favourable pregnancy outcome in comparison with those who had a foetal loss (4877.12 ± 460.04 vs. 4075.91 ± 616.17 pg/mL, <0.0001). Furthermore, the Receiver Operating Characteristics (ROC) analysis revealed sufficient importance for risk assessment and very good marker to predict unfavourable event (AUC-0.85, SE = 67%, SP = 88%, p < 0.0001). ConclusionCertainly TGF-β1 appears to have predictive importance; however additional studies with large sample size are warranted for further validation.

The risk factors of progestational anxiety, depression, and sleep disturbance in women with recurrent pregnancy loss: A cross-sectional study in China.

The risk factors of progestational anxiety, depression, and sleep disturbance in women with a history of recurrent pregnancy loss (RPL) remain controversial, additional study is needed to investigate the incidence and risk factors of progestational anxiety, depression, and sleep quality in RPL women. A cross-sectional study was conducted among 663 non-pregnant RPL women in Northeast China from October 2019 to July 2022. We assessed the state of anxiety, depression, and sleep quality before pregnancy using structured questionnaires, including sociodemographic characteristics, state-trait anxiety scale (STAI), center for epidemiological survey, depression scale (CES-D), Pittsburgh sleep quality index (PSQI), and symptom self-rating scale (SCL-90). Logistic regression was used to evaluate the association between sleep quality and anxiety, depression. Pearson's correlation was used to evaluate the correlation between anxiety and depression. Multivariate logistic regression analysis was used to find the risk factors of depression symptoms. The receiver operating characteristic curve (ROC) was used to evaluate the predictive value of the model. The incidence of state anxiety, trait anxiety, depression, and sleep disturbance in RPL women were 60.3, 51.7, 33.9, and 31.2%, respectively. The level of anxiety and depression in RPL women varied at different stages of treatment. In a longitudinal study (25 pairs), we found the level of state anxiety and trait anxiety were significantly lower after the cause was identified. Sleep disturbance is positively correlated with anxiety and depression. Logistic regression showed that the number of miscarriages ≥4 (Odds ratio (OR) = 2.268, 95%CI 1.300-3.956), Low household family income (OR = 1.613, 95%CI 1.036-2.513/OR = 2.361, 95%CI 1.095-5.092), interval since last miscarriage <6 months (OR = 2.154, 95%CI 1.246-3.726) and sleep disturbance (OR = 5.523, 95%CI 3.542-8.614) were associated with the occurrence of depressive symptoms. At the same time, anxiety can be used as a predictor of depression. Recurrent pregnancy loss women have a certain degree of anxiety, depression, and sleep disturbance. Education level, interval since the last miscarriage <6 months, and sleep disturbance are risk factors for anxiety and depression. A history of pregnancy loss after 14 weeks and no living birth are also closely related to anxiety. Therefore, it is necessary to pay close attention to the psychological state of RPL women and provide appropriate psychosocial support to reduce the occurrence of negative emotions.

Array Comparative Genomic Hybridization Analysis of Products of Conception in Recurrent Pregnancy Loss for specific anomalies detected by USG.

To evaluate the proportion of chromosomal abnormalities in recurrent pregnancy loss (RPL) assisted by array comparative genomic hybridization (aCGH) bright out with higher detection rate, more accuracy, and less sample failure as compared with conventional cytogenetic analysis. In this study, product of conception samples with abnormal USG findings of the fetus and clinical history of RPL were first processed for karyotyping and Fluorescence In Situ Hybridization analysis. Normal results given by Karyotype and FISH samples with major anomalies detected by Ultrasound with RPL were divided into six groups and aCGH was performed to detect the gain or loss and copy number variations (CNVs) of a particular gene present in chromosomal segments. Among a total of 300 POC samples, 100 abnormal samples were identified either by karyotype (n=70) or by FISH (n=30). From the remaining 200 samples, 5 showed the presence of maternal cell contamination excluded. aCGH analysis revealed (n=195) that 74 (38%) samples with copy number variations (CNVs) and two samples with variants of unknown clinical significance (VOUS) were clinically associated with the clinical findings and 121(62%) samples showed no change in CNVs. The most frequent CNVs were loss of chromosome regions at 2q33.1, 7q11.21, 15q11.1, 16p11.2, Xp22.33, and Yp11.32. CNVs at arr[GRCh37]7p22.3,p21.2(830852-15124702)×1,7q34q36.3(141464180_158909738)×3, 14.2Mbp deletion of 7p22.3p21.2 (SUN1 gene) and 17.4Mbp duplication of 7q34q36.3 (KCNH2, CNTNAP2, and SHH genes) in one sample, CNVs at arr[GRCh37]8p22.2q22.3 (86326349_105509986)×1, 2.48Mbp deletion of 8p22.2q22.3 (GRHL1 gene) were found in another sample.

Prevalence, causes, and impact of non-visualized pregnancy losses in a recurrent pregnancy loss population.

Does the occurrence of non-visualized pregnancy loss (NVPL) affect future reproductive outcomes in patients with recurrent pregnancy loss (RPL)? The number of previous NVPLs is a significant predictor of subsequent live birth in patients with RPL. The number of preceding miscarriages is a strong indicator for future reproductive outcomes. However, NVPL particularly has been sparsely addressed in previous literature. We performed a retrospective cohort study of 1981 patients attending a specialized recurrent pregnancy loss clinic (RPL) from January 2012 to March 2021. A total of 1859 patients met the inclusion criteria of the study and were included in the analysis. Patients with a history of RPL, defined as ≥2 pregnancy losses before 20 weeks gestation, who attended a specialized RPL clinic in a tertiary care center were included. Patients' evaluation included parental karyotyping, antiphospholipid antibodies screening, uterine cavity assessment with hysterosalpingography (HSG) or hysteroscopy, maternal thyroid stimulating hormone (TSH) testing, and serum hemoglobin A1C testing. Other investigations were performed only when indicated such as testing for inherited thrombophilias, serum prolactin, oral glucose tolerance test, and endometrial biopsy. Patients were divided into three groups; patients who experienced NVPLs only (pure NVPLs group), patients with only visualized pregnancy losses (pure VPLs group), and patients with history of both NVPLs and VPLs (mixed group). Statistical analysis was performed using Wilcoxon rank-sum tests for continuous variables and Fisher's exact tests for categorical variables. Significance was detected when P values <0.05. A logistic regression model was used to determine the impact of NVPLs and VPLs numbers on any live birth subsequent to the initial RPL clinic visit. The prevalence of patients with pure NVPLs, pure VPLs, and mixed losses was 14.7% (274/1859), 31.8% (591/1859), and 53.5% (994/1859), respectively. The prevalence of acquired and congenital uterine anomalies diagnosed by HSG or hysteroscopy was significantly different between pure NVPLs, pure VPLs, and mixed groups (16.8% versus 23.7% versus. 20.7%, respectively P = 0.05). There were no significant differences in the results of other RPL investigations or baseline demographics between the three groups. A logistic regression model controlling for maternal age at the initial RPL clinic visit and the follow-up duration showed that the numbers of NVPLs (odds ratio (OR): 0.77, CI: 0.68-0.88) and VPLs (OR: 0.75, CI: 0.64-0.86) are strong predictors for subsequent live births after the initial RPL clinic visit (P < 0.001). The odds of having a live birth decreased by 23% and 25% with each additional NVPL and VPL, respectively. This study may be limited by its retrospective design. Some of our data, including home pregnancy tests and obstetric history, are based on patient self-reporting, which could have overstated the true prevalence of NVPLs. Another limitation is the lack of available live birth data for all patients at the time of the analysis. To our knowledge, this is the first study to examine and analyze the reproductive outcomes of patients with pure NVPLs in a substantial cohort of patients with RPL. NVPLs seem to affect future live births the same way as clinical miscarriages, which supports their inclusion in RPL definitions. This study was supported in part by Canadian Institute Heath Grant (CIHR): Reference Number/W11-179912 and Women's Health Research Institute (WHRI), Vancouver, BC, Canada. M.A.B: Research grants from Canadian Institute for Health Research (CIHR) and Ferring Pharmaceutical. M.A.B. is on the advisory board for AbbVie and Baxter. N/A.

Effect of state insurance mandates on racial/ethnic disparities in the utilization and outcomes of donor oocyte–assisted reproductive technologies

To characterize racial/ethnic disparities in donor oocyte-assisted reproductive technology (ART) nationwide and examine the impact of state insurance mandates on disparities in utilization and outcomes. Retrospective cohort study. Donor oocyte ART cycles in the United States (US). Women who underwent donor oocyte ART in 2014-2016, as reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Race/ethnicity of oocyte recipients. Live birth through 1 or more donor oocyte ART cycles in 2014-2016 per recipient. We analyzed 44,033 donor ART cycles performed for 28,157 oocyte recipients, 99.2% (27,919/28,157) of whom were aged 25-54 years. Race/ethnicity data were reported for 61.4% (17,281/28,157) of the recipients. Among recipients aged 25-54 years with race data, 65.8% (11,264/17,128) identified as non-Hispanic White, whereas 58.9% were White among women aged 25-54 in the 2016 US census. In contrast, Black recipients comprised 8.3% of those aged 25-54 years with race data, compared with 13.7% nationwide. Among White recipients, 7.0% (791/11,356) lived in states with donor ART mandates (Massachusetts/New Jersey), compared with 6.5% (93/1,439) of Black recipients, 8.1% (108/1,335) of Hispanic recipients, and 5.8% (184/3,151) of Asian recipients. Black recipients had a higher median age and body mass index and were more likely to have uterine factor infertility. White recipients had the highest cumulative probability of live birth in the nonmandate (64.6%, 6,820/10,565) and mandate (69.5%, 550/791) states, followed by Asian recipients (nonmandate, 63.4% [1,881/2,967]; mandate, 65.2% [120/184]), Hispanic recipients (nonmandate, 60.5% [742/1,227]; mandate, 68.5% [74/108]), and Black recipients (nonmandate, 48.7% [655/1,346]; mandate, 48.4% [45/93]). The multivariable Poisson regression adjusting for donor's age and recipient's age, body mass index, nulliparity, history of recurrent pregnancy loss, diminished ovarian reserve, tubal factor and uterine factor infertility, prior ART treatment, use of preimplantation genetic testing, cumulative number of embryos transferred, use of blastocysts, and frozen-thawed transfers, demonstrated that Black recipients had a lower cumulative probability of a live birth than White recipients (relative risk [RR], 0.82; 95% confidence interval [CI], 0.77-0.87), as were Hispanic recipients (RR, 0.93; 95% CI, 0.89-0.99) and Asian recipients (RR, 0.96; 95% CI, 0.93-0.99). These disparities were not modified by state mandate for donor ART. State mandates for donor oocyte ART in their current forms are insufficient in decreasing racial/ethnic disparities.