Trimester Miscarriage Research Articles

Trisomy 16 mimicking hydatidiform mole.

The authors present a case of 1st trimester miscarriage where an early, complete hydatidiform mole was clinically suspected. Histopathological and immunohistochemical analyses excluded a complete mole, but the histomorphological profile was in concordance with a partial hydatidiform mole. Genetic analysis excluded a partial mole based on biparental genome composition, where further genetic analyses detected trisomy of chromosome 16. Trisomy of chromosome 16 is a frequent cause of 1st trimester abortions and may lead to highly abnormal placental histomorphology mimicking a partial mole. Genetic analyses are crucial for proper differential diagnosis and for the determination of adequate follow-up and prognosis for further pregnancies.

12386 Unilateral Spontaneous Adrenal Hemorrhage In Pregnancy

Abstract Disclosure: A. Gondhi: None. M. Campana: None. M. Riofrio: None. J. Fazendin: None. D. Vodopivec: None. Unilateral Spontaneous Adrenal Hemorrhage In Pregnancy Introduction: Spontaneous adrenal hemorrhage (SAH) in pregnancy is a rare and under recognized entity with an incidence of 0.14% - 1.1%, mostly unilateral. We present a case of unilateral SAH managed with adrenalectomy during pregnancy. Case presentation: A 24-year-old 14-weeks pregnant woman was referred for right flank pain and nausea due to right adrenal lesion. Medical history significant for 4 first trimester miscarriages and family history of Breast cancer and Uterine cancer in mother, Pancreatic cancer in multiple family members on paternal side. She was hemodynamically stable. Abdominal-US showed right adrenal lesion. Non-contrast MRI abdomen showed a large collection in the right adrenal gland measuring 9.6cm x 9cm. Ability to assess for underlying lesion challenging given the amount of blood products and lack of IV contrast. Laboratory analysis showed an appropriately suppressed cortisol with 1 mg overnight dexamethasone suppression test (cortisol 1.3 mcg/dl, N<1.8 mcg/d Dexamethasone level 332 ng/dl, N<180-550 ng/dl), normal DHEA-S (135 mcg/dl, N=18-391mcg/dl), non-suppressed ACTH (18 pg/ml, N 7.2-63 pg/ml), normal aldosterone (8.1 ng/dl, N=3-39.2 ng/dl) with a non-suppressed renin (17.8 pg/ml, N=4.2-52.2 pg/ml), normal fractionated plasma metanephrines (Free metanephrines <0.2 nMol/L, N<0.0.5nMol/L Free normetaphrines <0.2 nMol/L, N<0.9nMol/L), negative Antiphopholipid antibody testing (Beta 2 Glycoprotein I IgM <2 U/ml, N<20U/ml, Beta 2 Glycoprotein I IgG 2.2 U/ml, N<20U/ml). The patient underwent a laparoscopic converted to open right adrenalectomy. Pathology showed a 9.6cm adrenal gland with organizing hematoma, vascular congestion, and hemorrhage. It also showed periadrenal adipose tissue with atypia, MDM2 gene amplification by FISH negative – ruling out liposarcoma. Post-operatively, her symptoms resolved without complications to the pregnancy. Differentials for adrenal hemorrhage in this pregnant patient include: 1) underlying adrenal tumor (most commonly pheochromocytoma), 2) coagulopathy (e.g. antiphospholipid syndrome), and 3) pregnancy-related adrenal hemorrhage (rare, mostly unilateral due to increased vascular flow to the adrenal gland and the hypercoagulability). After evaluating the adrenal functionality, APLAS and assessing the malignant potential with imaging studies; conservative management is appropriate in stable patients. Our patient underwent surgery due to recurrent intractable pain, and uncertainty regarding malignant potential of the adrenal mass given history of multiple cancers in the family. Conclusion: Our case highlights that when indicated, adrenalectomy in the II trimester is a safe and effective option in pregnancy. Individualized treatment should be chosen for each patient following shared decision-making. Presentation: 6/1/2024

Third Trimester Stillbirth Associated With Hamartoma of Mature Cardiac Myocytes (HMCM).

Fetal primary cardiac tumors (FPCTs) are very rare. The majority of them correspond to cardiac rhabdomyomas, followed by other benign neoplasms or hamartomas. We describe the case of a third trimester female stillborn with an incidental autopsy finding of Hamartoma of Mature Cardiac Myocytes (HMCM), a rare benign cardiac tumor previously unreported in the fetal or neonatal period. The intrauterine demise occurred at 32 + 6 weeks gestation after an uneventful pregnancy. The fetal autopsy revealed a structurally normal heart with a small subendocardial nodule just below the membranous septum. Microscopically, the nodule was well-demarcated from the surrounding penetrating bundle of the conduction axis and the adjacent left ventricular myocardium and consisted of disorganized mature cardiac myocytes in a haphazard arrangement with patchy mild interstitial fibrosis, consistent with HMCM. Awareness that HMCM can occur in the fetus is important in order to consider it among the differential diagnosis of FPCTs.

Value of Serum Estradiol, Progesterone and Beta-Human Chorionic Gonadotropin in Prediction of 1st Trimester Miscarriage within 9 weeks of Gestation

Value of Serum Estradiol, Progesterone and Beta-Human Chorionic Gonadotropin in Prediction of 1st Trimester Miscarriage within 9 weeks of Gestation

Biochemical analysis of catecholamine and cortisol for the evaluation of the fetal distress in third trimester stillbirths

BackgroundStress hormones like catecholamine and cortisol are thought to reflect the magnitude of physical stress in adults and were studied in relationship to the cause of death and agony time. Intrauterine distress, intrapartum events, and modes of delivery can affect the fetal endocrine stress response, as reflected by biochemical analyses. The aim of the present study was to evaluate the role of catecholamines and cortisol as markers of ante-mortem fetal distress. The role of cortisol as a marker of circadian timing of delivery was also assessed.MethodsA 2-year prospective cohort-comparison inclusion of stillbirths and newborns took place with collection of antemortem data, labor parameters, neonatal outcome, post-mortem data and blood samples. Stillbirths were classified as acute or chronic on the basis of a multidisciplinary evaluation. Heart blood of stillbirths and cord blood of newborns were analyzed by high pressure liquid chromatography (HPLC) for adrenaline and noradrenaline and by immunoassay for cortisol determination.ResultsFifteen stillbirths and 46 newborns, as a comparison group, delivered by spontaneous vaginal birth, elective, and emergency cesarean sections were included. Stillbirths’ main cause of death was cord thrombosis. Levels of adrenaline and noradrenaline (median: 14,188 pg/ml and 230.5 pg/ml, respectively) were significantly higher (p < 0.001) in stillbirths than in newborns and were also higher in acute compared to chronic distress. Cortisol levels were significantly higher (p < 0.05) in spontaneous vaginal delivery (median: 18.2 μg/dl) compared to elective cesarean sections (median: 3.8 μg/dl). No difference in cortisol concentrations was detected between newborns delivered at morning and at afternoon/evening.ConclusionOur results suggest that the biochemical measurement of adrenaline and noradrenaline levels might reflect a marked physical stress response during the process of death in stillbirths. On the contrary, the elevation of cortisol levels could mirror the elevation in maternal cortisol level during vaginal delivery. For the post-mortem evaluation of stillbirths, the analysis of CA levels could provide additional data on the duration of distress, useful to integrate the forensic diagnosis.

P-439 Analysis of Products of Conception (POC) using Whole Genome Next Generation Sequencing (NGS) in pregnancy loss after euploid or mosaic embryo transfer

Abstract Study question What is the outcome of genetic assessment for fetal chromosomal aberrations in miscarriages after euploid/mosaic embryo transfers (ET)? Summary answer POC testing should be recommended in patients with E/M-ET to screen for chromosomal aberrations occurring post-implantation or beyond the detection limit of PGT-A testing What is known already Spontaneous abortion is the most common complication of pregnancy, affecting approximately 15% of clinically recognized pregnancies. Although the etiology is diverse, fetal chromosomal aberrations account for 50-70% of first trimester miscarriages. Assessment of the fetal chromosomal composition is recommended by ACOG guidelines and aids in counselling and management of patients’ reproductive options. The value of this assessment in patients with miscarriage after euploid/mosaic ET has not evaluated. At the same time there is generally a lack of follow-up studies to examine the accuracy of PGT-A testing and investigate the rates of post-implantation errors causing miscarriage. Study design, size, duration This retrospective study had REB approval. This study was performed at the CReATe Fertility Centre and its Reproductive Genetics Laboratory in Toronto, Canada, between January 2019-December 2023.We evaluated the molecular karyotype of POC samples from first trimester &amp;lt;12GW miscarriages after ART: IVF-PGT-group euploid (E) and mosaic (M) embryo transfers (ET) and IVF-group; IUI and natural conception-NC groups; while controlling for maternal cell contamination (MCC) by high-resolution whole genome NGS. Participants/materials, setting, methods 549 POC samples from early miscarriages after fertility treatment were obtained by suction-dilatation-and curettage. Selection of fetal tissue/chorionic villi (4 representative samples for each case) was performed under a dissecting microscope. Maternal and paternal DNA was obtained to test for MCC. MCC was determined by testing maternal/gestational carrier and fetal DNA (fDNA) with highly informative STRs (AmpFLSTR Identifiler kit). Whole genome low-pass NGS (0.1xcoverage) was performed using the Illumina platform and analyzed with NxClinical Software. Main results and the role of chance Fetal tissue was obtained from 90.7% (498/549) of tested samples and the rest had MCC (9.3%, 51/549): IVF-PGT-A(n = 183), IVF(n = 92), IUI(n = 46) and NC(n = 173). The overall mean maternal age was 37±3.2years. The average gestational age at D&amp;C was 8w4d (range 5w-12w6d). Overall, NGS analysis of fDNA showed 44.6% male and 55.3% female fetuses, 57.6% (287/498) were euploid, 39.5% (197/498) were aneuploid and 1.8% (9/498) were mosaic. In IVF-PGT-A group there were 169 POC from euploid ET and 14 from mosaic ET. 98.2% (n = 166/169) of POCs from IVF-PGT-A euploid-ETs were confirmed as euploid, and 3 had confined placental mosaicism (CPM) (trisomy-11, trisomy-4, monosomy-X). POC from mosaic-ET (n = 14), showed CPM in 3/14(21.4%): TE mosaicism was confirmed in 1/14(7.1%), 2/14(14.3%) had CPM differing from the PGT-A result, 11/14(78.6%) were euploid. POC euploidy rate in IVF (no PGT-A) group was 59.8%(55/92), in IUI 34.8%(16/46) and in NC 24.3%(42/173). In NC group CPM was detected in 1.7%(3/173). The frequency of aberrations detected in POC(n = 197) were: T22, 16.5%; T16,12.9%; T15, 11.3%; T20, 5.2%; T8, 3.6%; T7, T9 and T13, 3.1%; T10 and T14, 2.6%; T18 and T21, 2.1%; T12, 1.5%; 1% of each T2, T4 and T11; monosomy-X,6.7% and 11.3% triploid (69,XXY or 69,XXX). Limitations, reasons for caution MCC is relatively high in POC samples from early pregnancies (9.3%) and controlling for it is warranted. Although 4 representative samples of placental tissue were tested, the true extent and existence of CPM may not be captured correctly. Wider implications of the findings NGS analysis of POC from first trimester miscarriages after fertility treatment would improve diagnostic accuracy, and could aid in patient counselling and management. We observed high PGT-A accuracy (100% for gender) and 98.2% for fetal ploidy with CPM rate of 1.8% (which is lower than observed after CVS (4%)). Trial registration number not applicable

P-573 Reframing reproductive odds: live birth rate in women with undetectable or negligible anti-mullerian hormone (AMH) levels

Abstract Study question what is the Live birth rate in women with undetectable or negligible AMH levels ? Summary answer Based on our findings, we suggest considering IVF for twith undetectable or negligible AMH levels. What is known already The reproductive outcomes of women with undetectable or negligible AMH levels have not been well studied. Nevertheless, it is widely believed that females with extremely low AMH levels may have difficulty conceiving and may experience early menopause. An undetectable AMH value is indicative of an ovarian reserve similar to that of a 44-year-old woman. It is important to note that fertility is not solely determined by AMH levels and that other variables, such as age, can also have an impact. Study design, size, duration This study was a retrospective cohort design. Data were collected from October 2009 to April 2022, and included 81 consecutive female participants aged 24 to 43 years with undetectable or negligible levels of AMH who had previously experienced a failed in vitro fertilization (IVF) cycle due to poor ovarian response. The participants were given DHEA after at least one failed IVF cycle, The primary outcome measure was live birth rate (LBR). Participants/materials, setting, methods The study participants were divided into two groups based on AMH levels. Group A had undetectable AMH equivalent to &amp;lt; 0.14 ng/ml (For SI units &amp;lt;1 pmol/L), and group B had negligible AMH levels between 0.14 ng/ml and 0.5 ng/ml (For SI units; 1 pmol/L to 3.6 pmol/L) as defined by Tocci et al. (2009). Both groups underwent IVF, and if the cycle failed, women received DHEA before next IVF cycle. The Primary outcome was LBR. Main results and the role of chance The study, which was conducted from October 2009 to April 2022, analysed a total of 81 cycles, with 41 in Group A and 40 in Group B. There were no significant differences in patient characteristics between the two groups. The overall spontaneous pregnancy rate was 17% (7/41) for women in Group A and 7.5% (3/40) for women in Group B, who received DHEA while waiting to start their next IVF cycle. All pregnancies resulted in live births. Additionally, one case in Group A converted from IVF to IUI and also resulted in a live birth. The overall LBR per woman and per embryo transfer (ET) were 53% (43/81) and 62.3% (43/69) respectively. The LBR per started cycle for Group A and Group B was 51.2% (21/41) and 55% (22/40) (p = 0.12), respectively. The LBR per ET for Groups A and B were 60% (21/35) and 64.7% (22/34) (p = 0.16), respectively. The rate of first trimester miscarriages was similar in both groups. The sub-analysis of patient age showed that the overall LBR for women under 37 years old was 44.4% (36/81) and 55.5% (45/81) for women aged 37 years old and above. The cycle cancellation rate was 14.81% (12/81). Limitations, reasons for caution The small sample size and the study’s retrospective design may introduce bias. Additionally, during the 12 years of the study period, AMH measurement techniques have changed. These limitations should be taken into account when interpreting the results. Further research is needed to establish the cost-effectiveness of these findings. Wider implications of the findings The presence of undetectable or negligible AMH levels should not automatically exclude the use of assisted reproductive technology. Supplementation with DHEA and a tailored ovarian stimulation protocol may improve reproductive outcomes in these cases and should be considered before resorting to oocyte donation. Trial registration number Not Applicable

O-065 PGT-A reveals triploid embryos among normally fertilized oocytes: Frequency and blastocyst features

Abstract Study question Is there any embryo parameter that could differentiate 2 pronucleus (PN) triploid from 2 PN euploid embryos? Summary answer Accuracy in the fertilization check is still necessary as 2 PN but triploid embryos are due mostly to retention of the second polar body (PB). What is known already Since blastocyst culture has evolved and the development of genetic technologies enables to know the karyotipe of the embryos, the concept of normal fertilization is being revised. Commonly, correct fertilization is denoted by the appearance of 2 PN 16-18h after insemination. Deviation from 2PN is considered evidence of abnormal fertilization and ploidy anomalies. However, not all oocytes exhibiting 2 PN are euploids. After performing NGS in trophectoderm biopsies for preimplantation genetic testing for aneuploidy (PGT-A), a percentage of embryos are categorized as triploids. Study design, size, duration Retrospective study including 1862 cycles from 1605 patients aged 18-45 years old who underwent PGT-A with NGS of trophectoderm biopsies in our IVF center from 2019 to 2023. From 6526 analyzed blastocysts in an independent Genetics laboratory, 59 were categorized as triploids. These 59 blastocysts were obtained from 57 PGT-A cycles and belonged to 54 women. In total, these patients had 266 biopsied blastocysts. From the remaining 207 embryos, 42 were called as euploids. Participants/materials, setting, methods In embryos cultured in time-lapse, fertilization was re-evaluated to check the appearance of 2PN and the second PB extrusion. Genetic triploid embryos were analysed in relation to the day of biopsy (day 5 vs day 6), the trophectoderm quality and the timing of the first cell divisions (time of cleavage from 2 to 6 cells: t2, t3, t4, t5, t6). Categorical variables are shown as rate. T-student tests were performed. P-value&amp;lt;0.05 was considered statistically significant. Main results and the role of chance The re-evaluation of the fertilization of the 59 triploids categorized as 2 PN revealed 50 oocytes 2 PN, 8 embryos 3 PN and 1 embryo 2 PN + 1 micronuclei configuration. Therefore, the prevalence of real triploidy in 2PN embryos was 0,8% (n = 50/6526; CI95%:0,6-1,0%). These data showed that 2PN zygotes may give rise to embryos with altered ploidy. From 27 triploid 2PN embryos was possible to access to the whole development time-lapse images. Just 33,3% of triploid embryos exhibited the extrusion of the second PB, while 100% of euploid sibling embryos showed this extrusion (N = 9/27 vs N = 24/24,;p&amp;lt;0,005). Comparing 2 PN triploid and the rest of the embryos from the same cohorts, there were no differences regarding the day of biopsy (N = 31/176 day 5 biopsy, 17.6% vs N = 19/81 day 6 biopsy, 23.5%; p &amp;gt; 0.05). On the contrary, a worse blastocyst quality showed a significant relation with triploidy (N = 23/161,14,2% of good quality embryos are triploid vs N = 27/96, 38,6% of fair quality embryos are triploids; p:0.006).Embryos cleavage time points up to 6-cell stage did not show any significative difference between triploid and euploid embryos (t2: 27.36h vs 25.8h; t3: 38.5h vs 35.6h; t4 39.4h vs 37.2h; t5 52.8h vs 47.0h; t6 56.2h vs 52.1h; all comparisons p &amp;gt; 0.05). Limitations, reasons for caution The incidence of triplody from 2PN zygotes may vary among IVF laboratory settings. The small sample size may be responsible of no difference in morphokinetics. Wider implications of the findings Fertilization check should persist in IVF procedures. Special consideration should be given to the second PB extrusion as triploidy is the most common form of aneuploidy observed in the first trimester miscarriages. The role of diploid spermatozoa, the size of the pronucleus and location should be explored in further studies. Trial registration number NOT APPLICABLE

Association of Working Status with Clinical Pregnancy and Miscarriage among Women undergoing In Vitro Fertilization: Single-Centre Cross-Sectional Study.

Middle-aged working women represent most patients attending fertility clinics for in vitro fertilization (IVF) treatment. In this study, we aimed to identify the association of women's working status with clinical pregnancy and miscarriage in the first trimester after IVF treatment. In this single-centre cross-sectional study at a private clinic in Kazakhstan, we reviewed electronic medical records of all IVF with intracytoplasmic sperm injection (ICSI) and fresh embryo transfer (ET) cycles from January 2018 to December 2019 (n=654). 300 cycles in patients with normal ovarian reserve and registered working status of a female partner in the medical records were selected for the analysis. The study's primary outcome measures were clinical pregnancy rates and clinical miscarriage in the first trimester. 204 women were employed, while 96 were not employed before the start of treatment. The mean age of all patients was 32.2 ± 4.8 years, ranging from 23 to 46 years. Two-thirds of working women had office-based occupations employed as doctors, school and university teachers, accountants, clerks, and managers. One-third of the study participants had manual labor jobs, including service positions and plant workers. There was no association between women's working status and clinical pregnancy rate adjusted for age, antral follicle count, history of pelvic adhesiolysis, and embryo development stage at embryo transfer. However, working women had almost five times the risk of the first trimester miscarriage compared to non-working women [adjusted odds ratio (aOR) 4.56, 95% confidence interval (CI): 0.52 to 4.96] adjusted for age and number of retrieved oocytes. Women who work before commencing IVF treatment can be reassured of having equal chances of conception following the treatment compared to non-working women. The observed risk of first trimester miscarriage in working women necessitates further research before drawing any conclusions from medical and public health points.

Association of Placental Umbilical Cord Insertion Site with Maternal and Fetal Outcomes: A Prospective Study

Abstract Introduction Adequate fetal growth during pregnancy depends upon the normal development and insertion of the umbilical cord. Central/paracentral placental cord insertion is considered normal, while marginal/velamentous cord insertion is considered abnormal. Although the location of placental umbilical cord insertion can be determined by ultrasound (US), it is not included in the routine protocol of a targeted anomaly scan. Through this study, we determined different placental umbilical cord insertion sites by US and categorized them as normal and abnormal, identified the risk factors involved, and evaluated the outcome of pregnancies using standard protocols. The rationale of this study was to identify pregnancies that require frequent monitoring and surveillance for an optimal perinatal outcome. Methods A prospective cohort study was conducted in a tertiary care hospital for 18 months. A total of 345 pregnant women who attended the antenatal outpatient department between 18 and 22 weeks for targeted imaging for fetal anomalies scan were included in the study after informed consent. Detailed history followed by US documentation of the cord insertion site on the placenta was done and women were followed up throughout pregnancy to look for development of complications including hypertensive disorders, antepartum hemorrhage (APH), and fetal growth restriction (FGR). Intrapartum adverse events like fetal distress and intrapartum hemorrhage were assessed. Confirmation of US findings was done by macroscopic examination of the placenta and measuring the distance between the placental cord insertion and the edge of the placenta. The weight of the placenta was also documented. Newborns were evaluated for adverse outcomes like preterm birth, low birth weight, need for resuscitation, and neonatal intensive care unit (NICU) admission. Follow up of neonates and mothers was done till discharge. Results Placental cord insertion was accurately determined at the anomaly scan with 100% sensitivity and specificity. The study showed 44 abnormal placental cord insertions (ACIs)—42 had marginal and 2 had velamentous cord insertions. There was a high incidence of ACI noted in women aged more than 28 years, with body mass index of more than 26.38, multiparity, previous history of myomectomy, first trimester miscarriage, and conceived by assisted reproductive technology. Women with ACI had an increased risk of small for gestational age/FGR and APH and had an average baby weight of 2.7 kg, which was 200 g less than babies with normal cord insertion. They also had lower mean Apgar scores at 5 minutes and required resuscitation and NICU admission. Conclusion Our study concluded that it will be a good practice to document the placental cord insertion during the mid trimester anomaly scan so that we can identify the subset of pregnant women who are prone to develop complications, thereby providing adequate surveillance for an optimal perinatal outcome.

P061 A comparative analysis of Systemic Lupus Erythematosus, Rheumatoid arthritis and Juvenile Idiopathic Arthritis pregnancy outcomes: Results from a three-year prospective, case-controlled, single centre study of 183 patients

Abstract Background/Aims Patients with inflammatory rheumatic diseases (IRD) have an increased risk of adverse pregnancy outcomes (APO), although the comparative risk of APO in rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) pregnancies has not been directly compared. Therefore, this study examined pregnancy outcomes (PO) of subjects with RA, JIA, and SLE, who had all received pre-pregnancy counselling to ensure disease control, to identify whether there are any differences in APO between each individual IRD group. Pregnancy outcomes were compared with healthy pregnant subjects lacking IRD, to determine the comparative risk of APO in RA, JIA and SLE pregnancies. Methods A prospective case-controlled study was conducted at University College London Hospital from February 2018 to February 2021. A total of 183 patients were enrolled into the study, consisting of 120 pregnant patients including 60 patients with an IRD (n = 29 RA, n = 12 JIA and n = 19 SLE), 60 pregnant patients without any IRD and 63 non-pregnant patients with IRD (n = 30 RA, n = 12 JIA, n = 21 SLE). Pregnancy outcome data was obtained from all pregnant patients and the individual IRD groups’ outcomes were compared to each other and against outcomes from pregnancies without an IRD. Results Patients were predominantly Caucasian, ranging from 17-45 years of age. Of 111 reported PO, 99.09% (n = 110) resulted in a live birth (n = 27 (100.00%) RA, n = 11 (100.00%) JIA, n = 18 (94.74%) SLE versus n = 54 (100.00%) pregnancies without IRD). Overall, 5.56% (n = 1 SLE pregnancy) resulted in a spontaneous early trimester miscarriage, 6.36% (n = 7) were pre-term births (n = 3 (11.11%) RA, n = 1 (9.09%) JIA, n = 2 (11.11) SLE pregnancies versus n = 1 (1.85%) pregnancy without IRD). No stillbirths/foetal deaths were reported. Only two maternal complications were reported (n = 1 Group B strep infection, n = 1 gestational diabetes in RA pregnancies). In total six foetal complications were observed in four RA (n = 1 each for enlarged kidney, tongue tied, neonatal jaundice and Group B strep infection), n = 1 JIA (tongue tied) and n = 1 SLE (prolapsed cord) pregnancies. In relation to disease activity statuses in pregnancy, the majority of IRD pregnant patients were in remission (n = 42 (73.68%), n = 18 RA, n = 6 JIA and n = 18 SLE), 28 (49.12%) IRD patients had low disease activity (n = 8 RA, n = 2 JIA and n = 18 SLE) and nine (15.79%) had moderate/high disease activity (n = 6 RA, n = 2 JIA and n = 1 SLE). Only two (3.51%) RA patients reported disease flares during pregnancy, whereas no JIA/SLE patients experienced any flares. Conclusion This first prospective case-controlled study of RA, JIA, SLE and healthy pregnancies has identified favourable and comparable PO between IRD pregnancies with good disease control. This study highlights the importance and need for IRD pregnant women to undergo pre-pregnancy counselling and maintenance of disease control during pregnancy to enhance the chances of successful pregnancy outcomes. Disclosure H. Nguyen: None. D.A. Isenberg: Consultancies; AstraZeneca, Merck Serono, Eli Lilly, Servier, Genentech. D.J. Williams: Grants/research support; National Institute for Health Research University College London Hospitals Biomedical Research Centre. I. Giles: Grants/research support; UCB Pharma.

Severe Vitamin D deficiency is associated with increased risk of first trimester miscarriage in the Eastern Black Sea region of Turkiye

Objective: To measure 25-hydroxyvitamin D (25(OH)D) serum concentration among pregnant women in the first trimester and its association with first-trimester pregnancy loss in the Eastern Black Sea region of Turkiye. Methods: In this retrospective, cross-sectional study, we collected health records of pregnant women attending prenatal care at our department between March 2020 and December 2020. Serum 25 (OH)D levels were measured in the first trimester, and the patient's characteristics and the course of the pregnancy were analyzed. We investigated the association between maternal vitamin D deficiency and the risk of subsequent miscarriage. Results: The final analysis included 246 pregnant women, with 50 (20.3%) had a miscarriage in the first-timester. The prevalence of vitamin D deficiency was high in the group, with 78.5% of the study group having serum levels of 25(OH)D

Are early pregnancies implanted close to the tubal ostia at increased risk of miscarriage? A prospective observational study.

The aim of this article is to assess any association between the risk of miscarriage and the distance of an early pregnancy from the closest tubal ostia. Early pregnancy was defined as a gestational sac ⩽ 15 mm mean diameter within the upper half of the endometrial cavity. The shortest distance from the gestational sac (chorionic membrane) to the closest tubal ostia and the interostial distance were measured. The outcomes for pregnancies at varying distances from a tubal ostia were compared using Fisher's exact test. The receiver operating characteristic curve assessed the distance from the sac to the ostia as a predictor of miscarriage. A Wilcoxon rank-sum test was used to assess any difference in the distance from the ostia between women who miscarried and those who did not. Outcome data were available for 212/230 patients. The relative risk of miscarriage was 5/6 (83%) in the group with gestational sacs ⩽ 4 mm from the ostium versus 70/206 (34%) > 4 mm (p = 0.02). The proportion of miscarriages was 11/20 (55%) if the distance from the tubal ostium was ⩽5 mm versus 64/192 (33%) if >5 mm (p = 0.08). There was a good neonatal outcome for those with live births. The risk of first trimester miscarriage was high with early pregnancies implanted close to the tubal ostia, but this finding did not reach statistical significance. A larger study is needed to establish whether 4 or 5 mm could be used as a clinically useful criterion for defining early pregnancies that are at increased risk of miscarriage.

Use of artificial intelligence embryo selection based on static images to predict first-trimester pregnancy loss

Research questionCan an artificial intelligence (AI) embryo selection assistant predict the incidence of first trimester spontaneous abortion (SA) using static images of IVF embryos? DesignIn a blind, retrospective study, a cohort of 172 blastocysts from IVF cases with single embryo transfer and a positive biochemical pregnancy test was retrospectively ranked by the AI morphometric algorithm ERICA™. Making use of static embryo images from a light microscope, each blastocyst was assigned one of four possible groups (Optimal, Good, Fair, Poor), and linear regression was used to correlate the results with the presence or absence of a normal fetal heart rate (FHR) as an indicator of ongoing pregnancy or SA, respectively. Additional analyses included modelling for recipient age and chromosomal status established by preimplantation genetic testing (PGT-A). ResultsEmbryos grouped as Optimal/Good had a lower incidence of SA (16.1%) compared to embryos classified as Fair/Poor (25%, P=0.005, Odds ratio (OR)=0.46). The incidence of SA in chromosomally normal embryos (determined by PGTA) was 13.3% for Optimal/Good embryos and 20.0% for Fair/Poor embryos, although this difference was not statistically significant (P=0.531). There was a significant association between embryo rank and recipient age (P=0.018) in that the incidence of SA was unexpectedly lower in older recipients (21.3% in ≤35, 17.9% in 36-38, 16.4% in ≥39, P=0.0181, OR=0.354). Overall, these results support a correlation between risk of SA and embryo rank as determined by AI; the classification accuracy was calculated to be 67.4%. ConclusionsThis preliminary study suggests that AI (ERICA™), which was designed as a ranking system to assist with embryo transfer decisions and ploidy prediction, might also be useful in providing information for couples on the risk of SA. Future work will include larger sample size and karyotyping of miscarried pregnancy tissue.

Impact of congenital uterine anomalies on obstetric and perinatal outcomes: systematic review and meta-analysis.

Congenital uterine anomalies (CUA) can be associated with impairments of early and late pregnancy events. To assess the impact of CUA on reproductive outcomes in pregnancies conceived spontaneously or after assisted reproduction. Systematic review and meta-analysis of cohort studies comparing patients with CUA versus women with normal uterus. A structured literature search was performed in leading scientific databases to identify prospective and retrospective studies. The Newcastle-Ottawa scale, adapted to AHRQ standards, was used to assess the risk of bias. Pooled odds ratios (OR) were calculated. Publication bias and statistical heterogeneity were assessed, and meta-regression was used to analyse the heterogeneity. Miscarriage, ectopic pregnancy, placental abruption, term, and premature rupture of membranes (PROM), malpresentation at delivery, preterm delivery prior to 37, 34 and 32 weeks, caesarean delivery, intrauterine growth restriction/small for gestational age, foetal mortality and perinatal mortality. 32 studies were included. CUAs increased significantly the risk of first/second trimester miscarriage (OR:1.54;95%CI:1.14-2.07), placental abruption (OR:5.04;3.60-7.04), PROM (OR:1.71;1.34-2.18), foetal malpresentation at delivery (OR:21.04;10.95-40.44), preterm birth (adjusted OR:4.34;3.59-5.21), a caesarean delivery (adjusted OR:7.69;4.17-14.29), intrauterine growth restriction/small for gestational age (adjusted OR:50;6.11-424), foetal mortality (OR:2.07;1.56-2.73) and perinatal mortality (OR:3.28;2.01-5.36). CUA increases the risk of complications during pregnancy, delivery, and postpartum. Complications most frequent in CUA patients were preterm delivery, foetal malpresentation, and caesarean delivery. Bicornuate uterus was associated with the highest number of adverse outcomes, followed by didelphys, subseptate and septate uterus.

Misoprostol – effectiveness, safety and efficacious dose in first trimester miscarriages

Misoprostol – effectiveness, safety and efficacious dose in first trimester miscarriages

Differences of Fibronectin Levels in First Trimester Normal Pregnency and Miscarriage

Differences of Fibronectin Levels in First Trimester Normal Pregnency and Miscarriage

Raised First Trimester Thyroid Peroxidase Antibodies May Predict First Trimester Miscarriage: A Case Control Study.

Miscarriages constitute a significant aspect of failed pregnancies and a source of worry for the patient and caregiver. Some of the causes of miscarriages remain unknown. Immunological conditions such as thyroid autoimmunity could play significant roles. Our objective was to determine the relationship between raised thyroid peroxidase antibodies and first trimester miscarriages in a low resource setting. This was a case control study at the Gynaecological Clinic of the University of Calabar Teaching Hospital, Nigeria; from 14th February 2020 to 13th January 2021, involving 145 cases who had first trimester miscarriages, and their matched controls who had apparently normal pregnancies, at same gestational ages. Sera of venous blood from both participants and controls were analysed for thyroid peroxidase antibodies using enzyme-linked immunosorbent assay, and analysed using SPSS version 20, and GraphPad Prism 8.4.3 statistical software. Being a civil servant and low social status had significant odds for first trimester miscarriage. Raised thyroid peroxidase antibodies in the first trimester had 10-fold odds for miscarriage. Odds ratio 10.34, 95% CI: 3.22 to 32.98, P-value = 0.0001. The test had a sensitivity of 89.66% and specificity of 54.41%. The positive predictive value was 17.93%, while the negative predictive value was 97.93% and a likelihood ratio of 1.966. Rising thyroid peroxidase antibodies in early pregnancy could be a predictor for miscarriage. This is so because patients with raised thyroid peroxidase antibodies in the first trimester had a 10-fold risk of having a first trimester miscarriage.

Prevalence of Molar Pregnancy in Histopathological Examination of Products of Conception Following First Trimester Miscarriages

Prevalence of Molar Pregnancy in Histopathological Examination of Products of Conception Following First Trimester Miscarriages

Pattern‐Recognition Receptors and Cervical Microbiome in Patients with Early Miscarriages

Early miscarriages are one of the main causes of reproductive losses. The objective of this study was to estimate Toll‐ and NOD‐like receptors mRNA expression levels and their correlation with microbiome composition in the endocervix of patients with 1st trimester miscarriages (n = 15) compared to those with healthy ongoing pregnancies (n = 15). Samples of the cervical epithelium were collected using a cytobrush. The expression of Toll‐like receptors (TLR1, TLR2, TLR4, and TLR6) and NOD‐like receptors (NOD1, NOD2, NLRP1, and NLRC4) was estimated by quantitative reverse‐transcriptase PCR. Cervical microbiome composition was assessed by 16S rRNA next‐generation sequencing. We found no differences in community state types (CSTs) and alpha‐ and beta‐diversity between the groups. The dominant microorganisms in both groups were Lactobacillus iners. Bifidobacterium breve and Aeromonas popoffii, whose abundance was significantly higher in patients with miscarriages compared to those with ongoing pregnancies. Corynebacterium callunae and Turicibacter sanguinis, on the contrary, were significantly higher in women of the control group. Only decreased expression of TLR2 was observed in patients with miscarriages. The expression of other Toll‐ and NOD‐like receptors showed no significant differences between the groups. NOD1 mRNA expression had a strong positive correlation with the abundance of L. iners, L. delbrueckii, and Aerococcus christensenii; TLR6 mRNA expression had a strong positive correlation with L. iners. The findings suggest that variations in Toll‐ and NOD‐like receptors mRNA expression and specific shifts in the cervical microbiome might play a role in the immunological landscape, potentially contributing to the pathogenesis of early miscarriages.