Subsequent Pregnancy Research Articles

Comparison of Stroke Recurrence, Cardiovascular Events, and Death Among Patients With Pregnancy-Associated vs Non–Pregnancy-Associated Stroke

Women with pregnancy-associated stroke might have different risks of stroke recurrence, including during subsequent pregnancies, and other cardiovascular events due to pregnancy-specific stroke risk factors, such as gestational hypertension, preeclampsia, or gestational diabetes. To estimate the rate of stroke recurrence, cardiovascular hospitalization, and death in women with pregnancy-associated stroke compared with women with non-pregnancy-associated stroke. This cohort study included all women aged 15 to 49 years in France who were affiliated with the general scheme of French health care insurance (94% of women) and had a first hospitalization for stroke between January 1, 2010, and December 31, 2018. Women were followed up until December 31, 2020, with the registration of stroke recurrence, hospitalization for cardiovascular conditions, and death. Data were from the French health care database Système National des Données de Santé. Statistical analyses were conducted between December 2021 and September 2022. Pregnancy status at the time of stroke. Poisson regressions were used to estimate incidence rates of these events with 95% CIs. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) of each event during the follow-up for women with a pregnancy-associated stroke vs women with a non-pregnancy-associated stroke. Among women aged between 15 and 49 years between 2010 and 2018 and living in France, 1204 had a pregnancy-associated stroke at a mean (SD) age of 31.5 (5.8) years, and 31 697 had a non-pregnancy-associated stroke at a mean age of 39.6 (8.2) years. Among the 1204 women with a pregnancy-associated stroke, the incidence rate was 11.4 (95% CI, 9.0-14.3) per 1000 person-years, with 2 recurrent events during a subsequent pregnancy. Compared with women with non-pregnancy-associated stroke, women with pregnancy-associated stroke had lower risks of ischemic stroke (adjusted HR, 0.53; 95% CI, 0.36-0.77), cardiovascular events (adjusted HR, 0.58; 95% CI, 0.49-0.69), and death (adjusted HR, 0.42; 95% CI, 0.22-0.79). In contrast, the risk of recurrent intracerebral hemorrhage and cerebral venous thrombosis did not differ significantly, whereas the risks of venous thromboembolism (HR, 2.02; 95% CI, 1.14-3.58) and acute coronary syndrome with ST-segment elevation (HR, 3.93; 95% CI, 1.10-14.0) were increased. In this cohort study, although the risks of ischemic stroke, overall cardiovascular events, and mortality were lower after a pregnancy-associated stroke than after a non-pregnancy-associated stroke, the risks of venous thromboembolism and acute coronary syndrome with ST-segment elevation were higher. Recurrent stroke during a subsequent pregnancy remained rare.

Persistence of long-term insulin independence after islet transplantation and two subsequent pregnancies.

Pregnancy increases metabolic demand for insulin and may lead to the exhaustion of intraportally transplanted islets and post-gestational hyperglycemia. To prevent these complications, we implemented preemptive insulin supplementation during two subsequent pregnancies in an insulin-independent islet transplant recipient. This strategy resulted in optimal blood glucose control during the pregnancies, the preservation of the optimal islet graft function and the postpartum maintenance of long-term insulin independence.

Subsequent fertility, pregnancy, and gynaecological and psychological outcomes after maternal-fetal surgery for open spina bifida: A prospective cohort study.

To determine the medium-term maternal impact of open fetal spina bifida repair. Prospective cohort study. University Hospitals Leuven, Belgium. Mothers who had open maternal-fetal spina bifida repair between March 2012 and December 2021. A patient-reported survey on subsequent fertility, pregnancy, and gynaecological and psychological outcomes. Complications during subsequent pregnancies, and gynaecological and psychological problems. Seventy-two out of 100 invited women completed the questionnaire (72%). Despite being advised not to, seven of 13 women attempting to conceive became pregnant within 2 years after fetal surgery and one woman delivered vaginally. Two of the 16 subsequent pregnancies were complicated by an open neural tube defect. One pregnancy was complicated by a placenta accreta and one pregnancy was complicated by a uterine rupture, both with good neonatal outcomes. Nearly half of respondents who did not attempt to conceive reported that this was because of their experience of the index pregnancy and caring for the index child. Three out of four respondents reported medium-term psychological problems, mostly anxiety for the health of the index child, fear for recurrence in subsequent pregnancies and feelings of guilt. Open maternal-fetal surgery for spina bifida did not appear to affect fertility in our cohort. Half of the attempts to conceive took place within 2 years. One uterine rupture and one placenta accreta occurred in 16 subsequent pregnancies. Most respondents reported psychological problems linked to the index pregnancy, which reinforces the need for long-term psychological support.

'You're never pregnant in the same way again': prior early pregnancy loss influences need for health care and support in subsequent pregnancy.

'You're never pregnant in the same way again': prior early pregnancy loss influences need for health care and support in subsequent pregnancy.

Childhood family stress modifies the association between perinatal stressful life events and depressive symptoms.

The childhood family environment can influence long-term well-being in part by modifying how individuals' respond to and cope with stress across the life span. Theoretical models propose that childhood stress will either exacerbate (stress sensitization) or attenuate (steeling effect) the effects of adult stress on mental health. This study tests whether childhood family stress modifies the association between stressful life events and depressive symptoms in pregnancy and consecutive postpartum periods. A sample of 127 women reported on depressive symptoms after one birth, during a subsequent pregnancy, and postpartum following that birth. Childhood family stress was assessed with the Risky Families Questionnaire. Stressful life events were measured at all three timepoints to capture the number of life events during both pregnancies and between pregnancies. Associations between stressful life events and depressive symptoms varied as a function of childhood family stress. At the between-persons level, more stressful life events were associated with greater depressive symptoms among women who reported infrequent exposure to childhood family stress in this sample, but not among women who reported more frequent exposure to childhood family stress. Results provide novel evidence that moderate exposure to childhood family stress may attenuate the association between stressful life events and depressive symptoms in the perinatal period, consistent with a steeling effect. That is, some degree of childhood family stress may promote resilience to perinatal stress. Findings underscore the utility of examining the interaction of risk factors across the life span in predicting perinatal mental health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A peptide-based human papillomavirus therapeutic vaccine, PepCan, or Candida adjuvant alone in treatment of cervical intraepithelial neoplasia 2/3 (CIN2/3).

5538 Background: A non-surgical alternative for treating CIN2/3 would be desirable for women of childbearing age due to a risk of cervical incompetency in subsequent pregnancies following surgical treatments. PepCan consists of four current good manufacturing-grade HPV 16 E6 peptides and a Candida skin testing reagent (Candin, Nielsen Biosciences), because of Candida’s ability to regress common warts in humans, and to promote T cell proliferation and interleukin-12 secretion in vitro. Methods: In this single-center, randomized, double-blind Phase II study (NCT02481414), women with biopsy-confirmed CIN2/3 were treated with PepCan or Candida (1:1). Four intradermal injections were given 3 weeks apart which were followed with two visits 6 months apart. Histological responses (primary endpoint) were assessed using quadrant biopsies, and those whose lesions regressed to no CIN were considered to be responders. Regression rate of each treatment group was compared to that of a historical placebo group following the same treatment schedule. A sample size of 35 per arm had 93% power to test the null hypothesis that π = 0.29 (historical control placebo rate) and detect a difference of 0.31 with a two-sided type I error of 5%. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events Version 4. Results: Of 99 subjects screened, 81 (81.8%) qualified for vaccination, and 80 received at least one vaccination. No dose-limiting toxicity was observed. With the intention-to-treat analysis, PepCan showed 30.8% efficacy (12 of 39, p=0.16) while Candida demonstrated 47.6% efficacy (20 of 42, p=0.0004). Likewise, with the per-protocol analysis, PepCan showed 45.8% efficacy (11 of 24, p=0.06) and Candida showed 62.1% efficacy (18 of 29, p=0.0002). There was no difference between efficacy of PepCan and Candida. Conclusions: PepCan and Candida treatments are safe. Only Candida was effective in inducing histological regression in the intention-to-treat and per-protocol analyses. Candida could become a new treatment for CIN2/3 by eliciting general immune stimulation similar to checkpoint inhibitors. Clinical trial information: NCT02481414 . [Table: see text]

ASSESSMENT OF THE RECEPTIVITY OF THE ENDOMETRIUM TO STEROID HORMONES IN WOMEN WITH CHRONIC ENDOMETRITIS

Chronic endometritis (CE) is one of the main pathologies that lead to female infertility. Although research on the molecular and biological features of the endometrium in this disease has been conducted for a long time, the problem of studying the morphotype of CE remains relevant. Today, there is no universally accepted panel of immunohistochemical markers that would allow to fully evaluate the status of the endometrium before and after treatment, as well as to evaluate the effectiveness of the therapy. The purpose of our study was to study the features of the expression of markers of estrogen (ER) and progesterone (PR) receptors in order to make a prognosis for the recovery of patients with a possible subsequent pregnancy. For this, 2 research groups were formed using Peipel biopsies of female patients. Group I included cases before treatment, group II – after treatment. During the study, it was found that the criterion for the success of the treatment is a relative decrease of ER- and PR-positive cells both in the stroma (p<0.0001) and in the epithelium of the endometrium (p<0.0001). It was also found, that the expression of PR by the epithelium of the glands shouldn`t exceed 50% (p<0.0001), while for ER the critical level hasn`t been established (p=0.77) and it is possible to judge only the relative decrease in the expression of the marker.

Placental gene expression reveals reduced angiogenesis in primiparous mares

Primiparous mares produce smaller and lighter foals than in subsequent pregnancies. In most studies, their placenta is also smaller, more efficient and presents structural alterations, but maternal age is a confounding factor. This study aimed to characterize the effects of maternal parity using the mare's first two pregnancies or by comparing young mares with different parities over the same gestation year. The same young mares (4–6-year-old over the study) foaled for the first time in 2018 (primiparous in 2018, P18, n=10) and for the second time in 2020 (multiparous in 2020, M20, n=10). In 2020, another group of young mares foaled for the first time (primiparous in 2020, P20, n=18). All mares were inseminated with the semen of the same stallion and were fed identically over the study. To assess the effect of primiparity, M20 were compared to P18 (effect on the same mare), or P20 (effect in the same year). Placentas were recovered at foaling, measured, weighed and sampled close to the umbilical cord. Stereology was performed using MercartorPro software on HES-stained paraffin-embedded samples and analyzed using a linear model for paired samples or not and permutations with R software. Paired-end RNA-sequencing was performed (Illumina, NextSeq500) on 6 randomly chosen snap-frozen placentas/group. Differential expression was analyzed (DESeq2) using a false discovery rate (FDR) <0.05 cutoff. Gene Set Enrichment Analysis was performed on differential expressed genes using PANTHER overrepresentation test with GOBP database. Placental weight and surface were reduced and the efficiency (foal weight/placental surface, in kg/m2) was increased in primiparous mares in both comparisons (p<0.05). Volume was not modified by parity between the consecutives gestations but reduced in P20 vs M20 (p<0.05). Only the volume of allantoic stroma was significantly reduced in P18 vs M20 (p<0.05), whereas hemotrophic trophoblast and microcotyledonary vessels’ volume tended to be reduced in P20 vs M20 placentas (p<0.1). In consecutive gestations, 118 genes were differentially expressed in placenta while in the same year, only 2 genes (IL4R and FFAR, interleukin-4 and free fatty acid receptors) were differentially expressed (FDR <0.05). Among the 118 genes differentially expressed between consecutive pregnancies, apelin signaling, angiogenesis and catalytic activity were overrepresented. All genes involved in these pathways were under-expressed in P18 mares. Both the apelin (normalized enrichment score, NES=-2.16, FDR <0.05) and its receptor (NES=-2.48, FDR <0.05) were less expressed in the placenta of P18 vs M20. This is also observed in intrauterine growth retardation in humans. Although placental morphology was lightly affected in both analyses, the inter-individual variability seemed to hide parity effects for transcriptomic analysis. Consecutive gestations, however, demonstrate that the smaller placental and foal size in primiparous mares seems to originate from reduced vascularization.

Effects of sub-physiological plasma progesterone concentration in the early luteal phase on embryonic and fetal development, pregnancy outcome and foal characteristics

High progesterone concentration in the early luteal phase supports pregnancy and postovulatory progestin treatment stimulates conceptus growth (Willmann et al., Theriogenology 2011;75,421) whereas reduced progesterone concentration changes histotroph composition (Beyer et al., Theriogenology 2019;125:236). Embryos obtained on day 34 from mares with reduced progesterone concentration were less developed than embryos from control pregnancies (Okada et al., Reprod Fert Develop 2020;32:1156). Sub-physiological progesterone concentrations in early pregnancy thus delay embryonic development at least until placentation. In this study, subsequent fetal growth, pregnancy loss and foal characteristics were investigated in pregnancies with reduced progesterone concentrations in the early luteal phase (PGF; n=7) and control pregnancies (CON; n=7) in the same mares. Estrous mares were inseminated every 48h until ovulation (day 0). Group PGF received 62.5µg of the prostaglandin F2α analogue cloprostenol daily on days 0-3 to induce sub-physiological progesterone concentrations whereas CON pregnancies remained untreated. Mares were assigned to PGF and CON treatments in alternating order and received the opposite treatment in the following year. Blood was obtained and conceptus size determined by transrectal (≤day 100) and transabdominal (>day 100) ultrasonography at regular intervals. IgG concentration was determined in colostrum at foaling and in foal plasma at 18-22 hrs after birth. Foals were weighed,measured, submitted to a clinical examination and the neutrophil / lymphocyte (N / L) ratio was determined as an indicator of maturity. Time from birth to first standing and first suckling was recorded. Data were analyzed with the SPSS statistics software, using two-way repeated measures ANOVA and χ2 analysis. Progesterone concentration was reduced in the first two weeks of PGF pregnancies (p<0.001; day 7 CON 35±3, PGF 11±2 ng/ml). All foals from CON pregnancies were healthy and mature, whereas 3/7 PGF pregnancies were lost (one embryonic death, one abortion, one non-viable foal, p=0.05). Size of the conceptus (day 49: PGF 6.6±07, CON 7.7±07 cm, p=0.006), embryo proper (day 54; PGF 4.4±0.8, CON 5.8±0.6 cm, p=0.015) and fetal orbita diameter (day 73 PGF 0.7±0.1, CON 1.0±0.1 cm, p=0.007) were smaller in PGF than in CON pregnancies. Size differences between PGF and CON pregnancies decreased over time and were no longer present at foaling. The viable PGF foals also did not differ in N / L ratio and time to standing and first suckling from CON foals In conclusion, reduced plasma progesterone concentration in the early luteal phase delays fetal growth beyond placentation and increases pregnancy loss. When viable foals are born, however, they are not compromised. Results indicate that pregnancies with sub-physiological progesterone concentrations will benefit from early progestogen substitution.

SOCIAL DEPRIVATION AND PRE-ECLAMPSIA RECURRENCE: THE NATIONWIDE CONCEPTION STUDY

Objective: The recurrence rate of pre-eclampsia in a subsequent pregnancy ranges between 10 and 20% in the literature. We aimed to study the association between social deprivation and the prevention and recurrence of preeclampsia. Design and method: All women of the nationwide Conception study (elaborated from French National Health Insurance Information System) who gave birth for the first time in France in 2010-2018, and who subsequently gave birth in the same period were included. Pre-eclampsia was identified through hospital diagnoses. Aspirin deliveries during the second pregnancy were collected to assess the rate and timing of initiation, and the treatment adherence. All medical consultations in the year before the beginning of their second pregnancy and until 20 weeks of gestation were identified. Women who benefitted from Universal Medical Coverage providing free access to health care for people with an annual income less than 60% of the poverty threshold were defined as living in social deprivation. The adjusted incidence rate ratios (aIRR) of preeclampsia during the second pregnancy were estimated using Poisson models adjusted for confounding Results: Of the 2,829,274 women included, 31,956 (1.9%) were diagnosed with a pre-eclampsia during their first pregnancy. From those, 4,697 (14.7%) had recurrent pre-eclampsia during the second pregnancy. Women living in social deprivation had more cardiovascular risk factors, were less likely to consult a physician in the year before and until 20 weeks of gestation (90.3% vs 97.5%), to receive prescribed aspirin at least once during their second pregnancy (33.7 vs 45.7%), to begin the treatment before 16 week of gestation (81.4 vs 90.7% among those receiving at least one delivery of aspirin during pregnancy), and to be adherent to therapy throughout the pregnancy (44.6 vs 55.9%). In multivariate analyses, women living in social deprivation were less likely to initiate aspirin during the second pregnancy (aIRR = 0.74 [0.70-0.78] and had a higher risk of pre-eclampsia recurrence (aIRR = 1.31 [1.28-1.33]). Conclusions: Greater efforts should be made to improve the medical monitoring and prevention strategies of socially deprived women with pre-eclampsia because of their high risk of recurrence.

The amenorrhea as a protective factor for healing of hysterotomy - a retrospective analysis one year postpartum.

The good healing of the hysterotomy after cesarean section is important for subsequent pregnancies. However, the factors which improve this healing have not been completely described, yet. In this study, we focused on factors which may affect healing of hysterotomy within one year after delivery, such as menstruation, breastfeeding, and the use of the contraception. Following delivery, total of 540 women were invited for three consecutive visits at six weeks, six months, and 12 months postpartum. The presence of menstruation, frequency of breastfeeding and contraception use were recorded. The scar was evaluated by vaginal ultrasound as already described. The impact of menstruation, breastfeeding, and contraception method on presence of niche was evaluated. The presence of menstruation increased odds to have niche by 45% (CI 1.046-2.018, p = 0.026). Secondarily, our results demonstrated a statistically significant protective effect of breastfeeding on the incidence of niche with OR 0.703 (CI 0.517-0.955, p = 0.024). Breastfeeding decreases odds to have niche by 30%. Also, the use of gestagen contraception lowered the odds by 40% and intrauterine device (IUD) or combine oral contraceptive (COC) by 46.5%. The other possibly intervening factors were statistically controlled. Amenorrhea, breast-feeding and progesterone-contraceptive decreases the risk of uterine niche within one year follow up.

Effect of mid-diestrus oxytocin treatment on early pregnancy in the mare

Progesterone supplementation in early pregnancy is commonplace in equine reproduction. Recently, there has been some controversy questioning the beneficial effects of routine progesterone administration and rising concerns of medication exposure as an occupational hazard for humans. Although premature luteal regression and resulting low plasma progesterone concentrations are rare in the mare, select cases benefit from luteal support. Duration of luteal function can be prolonged following oxytocin administration during mid-diestrus in the non-pregnant mare (Vanderwall.et.al. Journal of Equine Veterinary Science. 2012; 32:536-541). The aim of this field study was to investigate the effects of oxytocin administration on early pregnancy in the mare. Thoroughbred mares (n = 39; age 5 to 19 years) were enlisted and bred over 55 estrous cycles. Prior to natural breeding, uterine cultures were obtained, and mares were assigned to 1 of 2 groups: Oxytocin treatment (OT); oxytocin 60 units, intramuscularly, once daily, days 7-14 post-ovulation; or Control (CT); no treatment. Mare reproductive cycles were monitored by transrectal palpation and ultrasonography. Ovulation was documented and defined as day 0. Pregnancy diagnosis was performed by transrectal ultrasonography day 14 post-ovulation. If pregnancy was confirmed, a blood sample was collected and assayed for plasma progesterone concentration. Mares that did not conceive were administered prostaglandin F2αanalogue (cloprostenol; 250mcg once intramuscularly) at day 16 post-ovulation. These mares were rebred and treatment was determined by the stage in the study; therefore, some mares underwent the same treatment more than once. Subsequent pregnancy examinations were performed on days 28 and 45 of pregnancy. Data were analyzed using two-tailed Fisher's Exact tests for small counts, with significance defined at p < 0.05. First and per-cycle pregnancy rates for OT and CT were 90.9 and 91.3% and 68.2 and 55.1%, respectively. Median progesterone concentrations for OT were 6.9 and 7.0 ng/ml for CT. There were no differences between OT and CT groups for first (p = 0.165) or per cycle (p = 0.289) pregnancy rates, days 28 and 45 pregnancy rates (p = 1.0), or progesterone concentrations (p = 1.0). In this population of mares, oxytocin administration during mid-diestrus in early pregnancy did not induce a negative effect on pregnancy rate nor a positive effect on progesterone concentration. Whilst the study design did not assess the effect of OT on the inter-ovulatory interval (IOI), the authors’ hypothesize that the IOI would be increased, due to prolonged luteal function, in the non-pregnant OT mare if prostaglandin F2α analogue was not administered. Further investigation in this area may reveal potential beneficial effects of oxytocin administration in early pregnancy.

Factors associated with successful vaginal birth after one lower uterine transverse cesarean section delivery

A Trial of labor after cesarean section is an attempt to deliver vaginally by a woman who had a previous cesarean delivery and when achieved by a vaginal delivery it is called successful vaginal birth after cesarean section. Vaginal birth after a caesarian section is a preferred method to decrease complications associated with repeated caesarian section delivery for both mother and fetus. It has a higher success rate when the right women are selected for a trial of labor. This study aimed to assess factors associated with successful vaginal birth after one lower uterine transverse cesarean section and to validate the Flamm and Geiger score at the public hospitals of Bahir Dar City, Northwest, Ethiopia, 2021. A health facility-based retrospective cross-sectional study was conducted from March 1 to 15/2021. A medical record review of 408 women charts with a trial of labor after one lower uterine transverse cesarean section from January 1/2020 to December 31/2020 was done and 345 women charts with complete maternal and fetal information were included in the study with a response rate of 84.6%. The data were collected using a structured checklist, entered into Epi data 3.1, and analyzed using SPSS 25.0 version. Logistic regression analyses were done to estimate the crude and adjusted odds ratio with a confidence interval of 95% and a P-value of less than 0.05 considered statistically significant. This study identified that the trial of labor after cesarean section rate was 69.5%, and the success rate of vaginal birth after one lower uterine transverse cesarean section was 35.07%. Of the failed trial of labor, fetal distress (38.9%) and failed progress of labor (32.1%) were the main indications for an emergency cesarean section. The maternal age group of 21–30 years, prior vaginal birth after or before cesarean section, non-recurring indication (fetal distress and malpresentation), ruptured membrane, cervical dilatation ≥ 4 cm, cervical effacement ≥ 50%, and low station (≥ 0) at admission were associated with successful vaginal birth after one lower uterine transverse cesarean section. For the Flamm and Geiger score at a cut point of 5, the sensitivity and specificity were 73.6% and 86.6% respectively. In this study area, the trial of labor after cesarean section rate is encouraging, however, the success rate of vaginal birth after one lower uterine transverse caesarian section was lower. The maternal socio-demographic and obstetric-related factors were significantly associated with successful vaginal birth after one lower transverse caesarian section delivery. This study indicated that when the Flamm and Geiger score increases, the chance of successful vaginal birth after one lower uterine transverse caesarian section also increases. We suggest emphasizing counselling and encouraging the women, as their chance of successful vaginal delivery will be high in the subsequent pregnancy, especially if the indications of primary caesarian section delivery were non-recurring.

“We are competing with culture” the chasm between healthcare professionals and Australian Samoan women in the prevention and management of gestational diabetes mellitus

Objective: The Samoan community has a disproportionately higher incidence of gestational diabetes mellitus (GDM). We explored consumer and healthcare providers’ insight into perceptions of risk, attitudes to lifestyle behaviour change and experiences of GDM among Australian Samoan women in South Western Sydney. Methods: Semi-structured interviews and a focus group with Samoan women recruited through three churches, a diabetes and pregnancy clinic in South Western Sydney and via social media were conducted. Semi-structured interviews with healthcare providers’ were also conducted. Main themes were thematically analysed to identify recurring patterns using Quirkos software. Identified themes were framed against the constructs of the Health Belief Model. Results: One focus group (n=4) and 12 one-to one interviews were conducted among Samoan women. Eighteen semi-structured interviews with healthcare providers’ were also conducted. There was a high concordance between Samoan women and healthcare providers’ regarding perception of risk and barriers to maintaining a healthy lifestyle. However, Samoan women reported negative interactions with healthcare providers’ that hindered their behaviour change, while healthcare providers’ reported that normalisation of diabetes, confusion of GDM with type 2 diabetes and spiritual health beliefs were deterrents to behaviour change among Samoan women. Conclusion: Cross-cultural factors can influence the uptake of a healthy lifestyle. Future research should consider use of culturally tailored strategies when developing educational resources targeting Samoan women. Implications for research, policy and practice: The participants’ viewpoints expressed in this study suggest a critical need for the development of culturally-tailored health promotion strategies for Samoan women and cultural training for healthcare providers’, to improve GDM care and subsequent pregnancy outcomes.

Subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate.

An ectopic pregnancy occurs when an embryo implants outside of the uterus, usually in a fallopian tube. When detected early, treatment is often with a medication called methotrexate. When methotrexate does not work, surgery is required. A recent clinical trial of ectopic pregnancy treatment (called GEM3) found that adding a drug called gefitinib to methotrexate did not reduce the need for surgery. We have used data from the GEM3 trial, combined with data collected 12 months after the trial finished, to investigate post-methotrexate pregnancy outcomes. We found no difference in pregnancy rates, pregnancy loss rates and recurrent ectopic pregnancy rates between those treated medically only and those who subsequently also needed surgery. The surgical technique used also did not affect pregnancy rates. This research provides reassurance that women with ectopic pregnancies treated medically who need surgery have similar post-treatment pregnancy outcomes to those treated successfully medically.

Identifying and predicting the pathogenic effects of a novel variant inducing severe early onset MMA: a bioinformatics approach

BackgroundMethylmalonic acidemia (MMA) is a rare metabolic disorder resulting from functional defects in methylmalonyl-CoA mutase. Mutations in the MMAB gene are responsible for the cblB type of vitamin B12-responsive MMA.ResultsThis study used Whole-exome sequencing (WES), Sanger sequencing, linkage analysis, and in-silico evaluation of the variants’ effect on protein structure and function to confirm their pathogenicity in a 2-day-old neonate presenting an early-onset metabolic crisis and death. WES revealed a homozygous missense variant on chromosome 12, the NM_052845.4 (MMAB):c.557G > A, p.Arg186Gln, in exon 7, a highly conserved and hot spot region for pathogenic variants. After being confirmed by Sanger sequencing, the wild-type and mutant proteins’ structure and function were modeled and examined using in-silico bioinformatics tools and compared to the variant NM_052845.4 (MMAB):c.556C > T, p.Arg186Trp, a known pathogenic variant at the same position. Comprehensive bioinformatics analysis showed a significant reduction in the stability of variants and changes in protein–protein and ligand–protein interactions. Interestingly, the variant c.557G > A, p.Arg186Gln depicted more variations in the secondary structure and less binding to the ATP and B12 ligands compared to the c.556C > T, p.Arg186Trp, the known pathogenic variant.ConclusionThis study succeeded in expanding the variant spectra of the MMAB, forasmuch as the variant c.557G > A, p.Arg186Gln is suggested as a pathogenic variant and the cause of severe MMA and neonatal death. These results benefit the prenatal diagnosis of MMA in the subsequent pregnancies and carrier screening of the family members. Furthermore, as an auxiliary technique, homology modeling and protein structure and function evaluations could provide geneticists with a more accurate interpretation of variants’ pathogenicity.Graphical

Association Between Previous Cesarean Section and Subsequent Ectopic Pregnancy: A Comparative Observational Study

Background: The rise in cesarean delivery rates across the world has raised concerns about its potential impact on the outcome of subsequent pregnancies. Among the concerns is the increased risk of ectopic pregnancy, particularly in the tubal or scar site. This study aimed to assess the connection between previous cesarean delivery and subsequent ectopic pregnancy. Methodology: This is a comparative observational study conducted over a period of 1.5 years at Lalla Ded Hospital in Srinagar. The study recruited 148 cases with clinical symptoms of ectopic pregnancy and confirmed diagnosis, along with 4852 matched controls with intrauterine pregnancies. The inclusion criteria comprised women with a previous history of normal vaginal delivery or cesarean section. Patients with a history of ectopic pregnancy, pelvic inflammatory disease, abortions, tubal pathology or surgery, ARTs, and use of intrauterine contraceptive devices were excluded. The data were analyzed using SPSS version 20.0. Results: Out of the 148 eligible cases, 106 (4.2%) had a previous cesarean section, and 42 (1.7%) had a normal vaginal delivery. The odds ratio for women with a previous cesarean section was 2.59 (95% confidence interval= 1.81 to 3.75), which means that they had a 2.59 times higher risk of having subsequent ectopic pregnancy than those with normal vaginal delivery. Conclusion: The study concludes that a previous cesarean section is linked to an increased risk of subsequent ectopic pregnancy. Women with a history of cesarean section should receive close monitoring during early pregnancy to detect and manage ectopic pregnancy promptly. Further research is necessary to identify the underlying mechanisms and develop strategies to reduce the risk of ectopic pregnancy in these women. Keywords: cesarean delivery, ectopic pregnancy, long-term morbidity, risk factors

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.

A Retrospective Cohort Study to Determine Whether the Previous Route of Delivery Affects the Uterine Artery Blood Flow.

In our study, we aimed to investigate the effect of the previous delivery route on uterine artery pulsatility index (PI) and obstetric outcome.We aim to assess the effects of previous cesarean delivery (CD) and placental location on first- and second-trimester uterine artery Doppler indices as well as first-trimester pregnancy-associated plasma protein-A (PAPP-A)multiples of the median (MoM) levels in the subsequent pregnancy. We designed a retrospective cohort study to collect the participants' clinical and uterine artery Doppler.Data regarding pregnant women's first- and second-trimester exams, who were referred to our maternal-fetal medicine unit, were collected from hospital records between June 2015 and December 2019. Uterine artery PI MoM values were not different between the cases with the anterior and non-anterior placental locations. No significant difference was found in the first- and second-trimester uterine artery PI MoMvalues by delivery route (p = 0.57). However, the intrauterine growth restriction rate was higher in the CD group (p < 0.001). In this study, we compared the uterine blood flow indices between the previous cesarean and vaginal delivery groups. We observed no significant difference between the patients with different delivery routes.

A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures.

NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th-7th week of gestation-w.g.) and 66 women in the 11th-13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.