Subsequent Pregnancy Research Articles

Prevalence and association of placental lesions with obstetrical features and outcome: data from French prospective study

Since the Consensus Statement diffused by the Amsterdam Placental Workshop Group, knowledge of the meaning of placental vascular malperfusion has become essential in the unavoidable analysis of obstetrical history in a patient followed for autoimmune disease or any other maternal comorbidity. We aimed to analyse the prevalence of various placental lesions from a 6-months prospective observational study and to correlate the various placental profiles to obstetrical outcome, maternal diseases and pregnancy treatments. The frequency of foetal vascular malperfusion lesion could be estimated at 8.7%, in our population and to understand its neonatal associations. The study groups consisted of 208 consecutive women which ended the pregnancy and have placental analysis during the period of the study. From December 2015 to October 2017, from overall 4398 delivered pregnancies in university obstetrical department, 208 (4.7%) placental analysis have been done and included in the study. The placental analysis have been done for vascular obstetrical complications during the pregnancy (n = 106; 51%), unexplained abnormal foetal heart rate tracings (n = 59; 28,3%), suspicion of intra-amniotic infection (n = 12; 5,7%%), term new-borns Apgar score <7 or arterial cord blood pH ≤ 7 (n = 7; 3,5%), spontaneous preterm delivery (n = 19; 9,1%), intrahepatic cholestasis of pregnancy (n = 5; 2,4%). An adverse obstetrical event was noted in 87 cases (42%): preeclampsia or HELLP syndrome (n = 15; 7%), FGR (n = 59; 28%), gestational diabetes (n = 33; 16%) and gestational hypertension (n = 19; 9%). Placental histological analysis showed abnormal vascular features in 159 cases (76%), inflammatory features in 16 placentas (8%), vascular and inflammatory features in 10 cases (4%), chorioamnionitis in 38 cases (18%) and absence of any abnormality in 43 cases (21%). A cluster analysis of histological features allowed distinguishing three placental patterns: a normal pattern characterised by the absence of any placental lesions, an inflammatory pattern characterised by the presence of villitis and/or chronic intervillositis; a vascular pattern with the presence of thrombosis, maternal floor infarct with massive perivillous fibrin deposition, infarction and chronic villositis hypoxia. Women with inflammatory placental profile have significantly increased frequencies of tobacco use (50% vs. 9%; P = 0.03), pathological vascular Doppler (50% vs. 5%; P = 0.001), FGR (100% vs. 14%; P = 0.0001) and oligohydramnios (67% vs. 5%; P = 0.0001) than those with normal placentas. A higher rate of vascular or inflammatory lesion were observed in women with Hypertensive disorder of pregnancy, where as those with inflammatory pattern have significantly more frequent FGR (100% vs 34%; P = 0.02) and oligohydramnios (67% vs 5%; P = 0.0002). The placenta analysis is important to understand the origin of adverse obstetrical outcome and the risk for subsequent pregnancy.

Preconception Physical Exercise Is Associated with Phenotype-Specific Cardiovascular Alterations in Women at Risk for Gestational Hypertensive Disorders.

Background/Objectives: Gestational hypertensive disorders (GHD) pose significant maternal and fetal health risks during pregnancy. Preconception physical exercise has been associated with a lower incidence of GHD, but insights into the cardiovascular mechanisms remain limited. This study aimed to evaluate the effect of preconception physical exercise on the complete cardiovascular functions of women at risk for GHD in a subsequent pregnancy. Methods: A non-invasive hemodynamics assessment of arteries, veins, and the heart was performed on 40 non-pregnant women at risk for developing GHD in a subsequent pregnancy. Measurements of an electrocardiogram Doppler ultrasound, impedance cardiography and bio-impedance spectrum analysis were taken before and after they engaged in physical exercise (30-50 min, 3×/week, 4-6 months). Results: After a mean physical exercise period of 29.80 weeks, the total peripheral resistance (TPR), diastolic blood pressure and mean arterial pressure decreased in the total study population, without changing cardiac output (CO). However, in 42% (9/21) of women categorized with high or low baseline CO (>P75 or <P25 resp.), a shift in CO was observed towards the normal reference interquartile range (P25-P75). This was associated with improved hepatic venous and central arterial hemodynamic functions. Similar changes in TPR occurred in 38% (11/29) of women classified as having low or high baseline TPR. Conclusions: As in pregnancy, output- or resistance-dominant cardiovascular profiles already exist prior to conception. This study illustrates that preconception physical exercise shifts high or low CO and/or TPR towards the normal midrange, allowing women at risk for GHD to start a subsequent pregnancy with a more gestation-adaptable cardiovascular system.

Maternal Malaria and the Risk of Subsequent Pregnancy Complications

Maternal malaria, primarily caused by Plasmodium falciparum, has well-documented immediate effects on pregnancy, including preterm birth, low birth weight, and placental dysfunction. However, its impact extends beyond the current pregnancy, potentially influencing outcomes in subsequent pregnancies. This review examines how maternal malaria affects future pregnancies, focusing on the mechanisms through which previous malaria infections contribute to subsequent complications. Key mechanisms include chronic placental damage, immune system alterations, and persistent inflammation, which can disrupt placental function and increase the risk of adverse outcomes such as preterm labor and placental abruption in future pregnancies. The review highlights evidence that women with a history of maternal malaria are at an elevated risk for complications in subsequent pregnancies, including an increased likelihood of preterm birth and low birth weight. Persistent placental damage and immune dysregulation resulting from past malaria infections contribute to these risks. Understanding these long-term effects is crucial for developing effective public health strategies and interventions aimed at mitigating the risks of adverse pregnancy outcomes in malaria-endemic regions. Keywords: Maternal malaria, Plasmodium falciparum, pregnancy complications, placental damage, immune dysregulation, chronic inflammation, preterm birth

Impact on Sexual Function and Wish for Subsequent Pregnancy after Uterus-Preserving Prolapse Surgery in Premenopausal Women.

(1) Background: Pelvic organ prolapse (POP) affects millions of women globally, impacting their quality of life and potentially influencing family planning decisions. This study aimed to assess the impact of uterus-preserving prolapse surgery on the sexual function, desire for children, and pregnancy outcomes in premenopausal women with symptomatic POP. (2) Methods: A survey study was conducted among patients who underwent sacrospinous hysteropexy at a tertiary hospital between 2001 and 2021. Telephone interviews were performed to gather data on sexual function, desire for children, and satisfaction with surgical outcomes. (3) Results: The study included 33 premenopausal women, revealing diverse factors influencing sexual activity and desire for children following surgery. While most of the participants expressed a desire for children after surgery, sexually inactive individuals were more likely to report an unfulfilled desire for children. Fear of incontinence during sexual activity emerged as a significant concern for the sexually inactive participants. (4) Conclusions: The study highlights the need for comprehensive counselling and tailored interventions to address the multifaceted needs of women with POP. Further research is warranted to highlight the long-term implications of uterus-preserving surgeries on women's health and well-being.

Comparison of ICSI and Spontaneous Pregnancy Outcomes in Women with Unexplained Infertility

Aim: This study aimed to investigate whether there is a difference between the results of intracytoplasmic sperm injection (ICSI) pregnancies and subsequent spontaneous pregnancies with a diagnosis of unexplained infertility. Material and Methods: In this retrospective study, a total of 48 women who first conceived with ICSI and then achieved spontaneous pregnancy were included. Duration and causes of infertility, time to spontaneous conception, pregnancy outcomes, and maternal and neonatal complications were evaluated. Results: Maternal age was older in the spontaneous pregnancy group compared to the ICSI group (p=0.029). The gestational age at delivery was found similar in both groups. Although birth weight was higher in the spontaneous pregnancy group, the difference between the groups was not statistically significant (p=0.382). The time to achieve pregnancy was shorter in the spontaneous pregnancy group (p=0.001). Gestational diabetes was significantly higher in the spontaneous pregnancy group (p=0.001), while amniotic fluid abnormality, gestational hypertension (p=0.001), and preterm delivery (p=0.001) were significantly higher in the ICSI group. While the number of babies with the 1st-minute low Apgar score was higher in the ICSI group (%4.16 vs 2.08%, p=0.001), the 5th-minute Apgar score was similar. Conclusion: Even if couples are evaluated as infertile, it should be taken into consideration that they can achieve spontaneous pregnancy. It may be rational to wait for spontaneous pregnancy in eligible couples with unexplained infertility and not to refer the patient for early assisted reproductive techniques.

Interpregnancy interval following missed abortion and the risk for preterm birth

ObjectiveShort inter-pregnancy interval (IPI) of <18 months following a live birth, has been associated with adverse pregnancy outcome. This study aimed to evaluate whether a short IPI following a medically treated missed abortion (MA) poses similar perinatal risks in a subsequent pregnancy. Study designThe retrospective analysis included patients with history of an MA at up to 10 weeks of gestation, treated with misoprostol (pgE1) only, and with a documented subsequent live pregnancy (2010–2022). 1110 Patients were allocated into two groups: IPI ≤18 months and IPI >18 months. The primary outcome was the risk for a spontaneous preterm birth (PTB) <37 weeks of gestation in the consecutive pregnancy. Secondary outcomes included maternal and neonatal adverse outcomes. Statistical analysis was performed using the Statistical Program for Social Sciences for Windows version 26 (SPSS Inc, Chicago, IL). ResultsThe cohort included 1,110 patients: 430 (38.74 %) patients with IPI <18 months and 680 (61.26 %) patients with IPI >18 months. The characteristics of the two groups were not significantly different. The rates of spontaneous PTB <37 and <34 weeks of gestation were significantly higher in the short vs. long IPI cohort (16.28 % vs. 7.06 % and 6.74 % vs. 5.0 %, respectively, p < 0.05). These patients also had a higher risk for Cesarean delivery (31.63 % vs. 23.34 %, p = 0.005) and postpartum hemorrhage (4.42 % vs. 2.06 %, p = 0.029) compared to patients with IPI >18 months. The observed differences remained statistically significant even after adjusting for potential confounding variables using multiple regression analysis. No other significant differences in neonatal or maternal outcomes were noted. ConclusionShort IPI (≤18 months) following a medical treatment MA may be associated with an increased risk of PTB, Cesarean delivery and PPH.

Outcome of Patients with Pregnancy-Associated Breast Cancer Who Have Subsequent Pregnancies

BackgroundAfter treatment of pregnancy-associated breast cancer (PABC), some women desire future pregnancy. While safety of pregnancy after breast cancer has been demonstrated, the same cannot be said about women with PABC.ObjectiveThe aim of this study was to describe the incidence and outcomes of patients with PABC with subsequent pregnancies compared with those without another pregnancy.MethodsA retrospective chart review identified patients diagnosed with breast cancer during pregnancy or within 5 years postpartum between 2011 and 2023. Patients were then screened for further pregnancy. Clinicopathologic variables, oncologic outcomes, and pregnancy outcomes were recorded. The Chi-square test and t-test were used to compare patients with subsequent pregnancy with those without. Kaplan–Meier method and log-rank test were used to estimate 5-year disease-free survival (DFS).ResultsOverall, 75 patients with PABC were identified, 58 of whom had PABC and no further pregnancies (NSP-PABC) and 17 with subsequent pregnancy (SP-PABC). Compared with patients with NSP-PABC, patients with SP-PABC were significantly younger (p = 0.015) and less likely to have prior pregnancies (p < 0.001). Overall median follow-up was 4.3 years. Calculated 5-year DFS rates were 86.2% and 89.0% for the SP-PABC and NSP-PABC groups, respectively (p = 0.76). Calculated 5-year overall survival was 100% and 90.7% for the SP-PABC and NSP-PABC groups, respectively (p = 0.22). Within the SP-PABC group, 14/17 patients had successful deliveries.ConclusionsThis study provides the first descriptions of patients with PABC and subsequent pregnancy. Additional investigation, likely with pooled analysis from multiple institutions, is necessary to determine the oncologic and obstetric safety of pregnancy following PABC.

Impact of previous gestational diabetes management on perinatal outcomes in subsequent pregnancies affected by gestational diabetes mellitus.

To determine the impact of prior gestational diabetes mellitus (GDM) on perinatal outcomes in a subsequent GDM pregnancy. This retrospective cohort study included 544 multiparous patients with two consecutive pregnancies between 2012-2019, where the second (index) pregnancy was affected by GDM. The primary exposure was prior GDM diagnosis, categorized into medical and dietary management. The primary outcome was a composite including need for pharmacotherapy, large-for-gestational age, or neonatal hypoglycemia. Adjusted odds ratios (aOR) were calculated using multivariable logistic regressioncontrolling for maternal age, pre-pregnancy body mass index, and gestational age at GDM diagnosis in the index pregnancy. Of the 544 patients, 164 (30.1%) had prior GDM. Prior GDM significantly increased the likelihood ofcomposite outcome compared to no prior GDM (74.4% vs. 57.4%; P < 0.001). After adjusting for confounders, prior GDM remained significantly associated with the composite outcome (aOR 2.03, 95% confidence interval [CI] 1.31-3.15). Stratifying by prior GDM treatment modality, a significant association was found for prior pharmacotherapy-controlledGDM (aOR 3.29, 95% CI 1.64-6.59), but not for prior diet-controlled GDM (aOR = 1.54, 95% CI 0.92-2.60). A history of pharmacotherapy-controlled GDM in a previous pregnancy increases odds of adverse perinatal outcomes in a subsequent GDM pregnancy.

P-427 Do endometrial leucocytes and angiogenesis in the peri-implantation period predict hypertensive disorders in the subsequent pregnancy?

Abstract Study question Do endometrial leucocytes and angiogenesis in the peri-implantation period from women with a history of recurrent reproductive failure predict hypertensive disorders in the subsequent pregnancy? Summary answer uNK cells, T cells, B cells and macrophages in the peri-implantation endometrium did not correlate with hypertensive disease of pregnancy in the subsequent pregnancy. What is known already Women with a history of recurrent reproductive failure are thought to have a higher risk of hypertensive disorders of pregnancy (HDP) subsequently. Immunological interactions and vascular factors in the placental bed are considered to be two important pathways for the initiation and development of HDP. However, the prognostic value of endometrial leucocytes and angiogenesis around the time of implantation in a cycle prior to conception and HDP in the subsequent pregnancy is still unclear. Study design, size, duration This is a prospective cohort study. A total of 694 women were included in this study from Jan 2019 to Jun 2023. Participants/materials, setting, methods Immunohistochemistry for vWF and multiplex immunofluorescence for endometrial leukocytes, including CD56+ uNK cells, CD3+ T cells, CD20+ B cells and CD68+ macrophages, were performed in the precisely timed LH + 7 endometrium. The subsequent pregnancy outcomes of the subjects were followed up as well. Main results and the role of chance Endometrial leukocytes including CD56+ uNK cells, CD3+ T cells, CD20+ B cells and CD68+ macrophages were found in the peri-implantation endometrium. There was no significant difference in the CD56+ uNK cells, CD3+ T cells, CD20+ B cells and CD68+ macrophages numbers percentage between women with and without gestational hypertension in the subsequent pregnancy. The median micro vessel density in women who developed gestational hypertension in the subsequent pregnancy (9.4 ± 3.1 /mm2 ) was significantly (P=0.038) lower than the MVD in those who did not (13.5 ± 4.9/mm2 ). Limitations, reasons for caution 1. It is not clear whether the uNK cell number during the peri-implantation period is reflective of those in the first trimester when spiral artery remodelling occurs. 2. This study was carried out in women with reproductive failure and the results may not apply to the general populations. Wider implications of the findings Vascularization features in the endometrium may provide prognostic value of subsequent hypertensive disease of pregnancy. Trial registration number not applicable

Obstetric Anal Sphincter Injury: Interpregnancy Interval and Route of Subsequent Delivery.

Knowledge on the interpregnancy interval (IPI) among women with an obstetric anal sphincter injury (OASI) is both limited and not well understood. The objectives of this study were to describe the IPI among women with OASI and to compare women with OASI based on the route of subsequent obstetric delivery and OASI recurrence. This was a retrospective single-cohort study of women who had an OASI between 2013 and 2015 at a tertiary academic medical center. Demographics, obstetric delivery data, postpartum sequelae, and subsequent pregnancy delivery data from 2013 to 2021 were collected. The IPI was defined as the time from date of first vaginal delivery to date of conception of the subsequent pregnancy. Women without a subsequent pregnancy were censored at the date of last contact. The IPI was evaluated using a survival analysis (Kaplan-Meier estimator). A total of 287 women experienced an OASI, and subsequent pregnancy occurred for 178 (62.0%) women. The median IPI was 26.4 months (95% confidence interval: 23.7-29.9) for women with a prior OASI. Of the 97 women who did not have a subsequent pregnancy documented during the study, the median follow-up was 64.0 months (interquartile range: 5.7-80.0). Subsequent delivery route data were available for 171 women; of those, 127 (74.3%) experienced a subsequent vaginal delivery and 44 (25.7%) experienced a cesarean delivery. Of the 127 women who experienced a subsequent vaginal delivery, 3 (2.4%) experienced a recurrent OASI. The IPI among women with OASI is similar to the IPI for all women in Ohio and in the United States.

P-431 Perinatal outcomes after recurrent pregnancy loss: a systematic review and meta-analysis

Abstract Study question Are women with recurrent pregnancy loss (RPL) at higher risk of adverse perinatal outcomes in a subsequent pregnancy? Summary answer Women with a history of RPL have significant higher odds of adverse perinatal outcomes in a subsequent pregnancy. What is known already Studies have suggested that RPL women may have higher risks for obstetrical and perinatal complications such as hypertensive disorders, placental abruption, placenta accreta spectrum disorders, preterm delivery, and perinatal death in a subsequent pregnancy compared to those without an RPL history. However, the existing body of research presents a conflicting narrative, thus highlighting the need for a comprehensive understanding of the implications of RPL on pregnancy outcomes. Study design, size, duration A systematic review and meta-analysis was conducted. MEDLINE, EMBASE, Google Scholar and Cochrane databases were searched from inception until July 2023 for studies on RPL and adverse perinatal outcomes. Data was extracted by two independent reviewers. Participants/materials, setting, methods DerSimonian and Laird random effect meta-analyses were performed to pool effect estimates. Results were presented as odd ratios with their respective 95% confidence intervals. Subgroup analyses were conducted for those with unexplained RPL and by number of pregnancy losses. Sensitivity analysis using only high-quality studies and influence analysis were performed. The Newcastle-Ottawa Scale was used to assess for risk of bias. Main results and the role of chance The systematic search yielded 8,915 records, of which 42 studies (n = 5,619,124) were included in our meta-analysis. Women with RPL had higher odds of pre-eclampsia (OR 1.19; 95% CI, 1.03-1.37), pregnancy-induced hypertension (OR 1.24; 95% CI, 1.03-1.48), gestational diabetes (OR 1.76; 95% CI, 1.28-2.44), cesarean delivery (OR 1.65, 95% CI, 1.47-1.85), placental abruption (OR 1.57; 95% CI, 1.37-1.81), placenta previa (OR 1.93; 95% CI, 1.59-2.35; 7 studies), placenta accreta (OR 4.42; 95% CI, 3.09-6.33), preterm birth (OR 1.79; 95% CI, 1.65-1.93), very preterm birth (OR 2.58; 95% CI, 2.08-3.18), small for gestational age (OR 1.31; 95% CI, 1.15-1.78), congenital anomalies (OR 1.25; 95% CI, 1.02-1.53), stillbirth (OR 1.25; 95% CI, 1.04-1.51) and perinatal death (OR 2.04; 95% CI, 1.58-2.71) compared to women without a history of RPL. There was no association with aneuploidy. Limitations, reasons for caution Significant inter-study heterogeneity and inconsistent adjustment for confounders was noted across included studies. Wider implications of the findings RPL patients are at higher odds of adverse perinatal outcomes in a subsequent pregnancy, and therefore require additional counselling and monitoring in said pregnancy. There is an urgent need for further prospective research clarifying the relationship between RPL and perinatal outcomes. Trial registration number N/A

O-201 Antinuclear antibodies in women with recurrent early pregnancy loss: prevalence and impact on subsequent pregnancy outcome

Abstract Study question What is the prevalence of antinuclear antibodies (ANAs) in women with recurrent early pregnancy loss (REPL) and do they affect subsequent pregnancy outcome? Summary answer The prevalence of ANAs in women with REPL was 13.0%, and their presence did not negatively impact subsequent pregnancy outcomes, including EPL and livebirth rates. What is known already An etiological factor cannot be identified in more than half of the couples experiencing REPL. Immunologic mechanisms could be involved, with the presence of autoimmune disease (AD) associated to lower reproductive outcomes. For the mere presence of ANAs, in the absence of AD, the evidence on the association with REPL is controversial, with most studies having a small sample size with important clinical and methodological heterogeneity. Study design, size, duration This is a single-centre, retrospective cohort study from a tertiary referral hospital including 960 women referred for REPL between January 2014 and December 2019. During the entire study period, maternal serum ANA detection was part of the routine diagnostic REPL work-up, defined as two or more pregnancy losses before the 10th week of gestation, including previous spontaneous conceptions and pregnancies following autologous IVF/ICSI treatment. Participants/materials, setting, methods Women under the age of 40 at ANA analysis were eligible for inclusion. Confirmed AD, uterine anomalies, parental chromosomal abnormalities and uncontrolled endocrine disorders were exclusion criteria. The prevalence of positive ANA titers and the impact of ANA positivity on the outcome of a subsequent pregnancy were investigated with EPL rate as the main outcome parameter and biochemical pregnancy rate, clinical miscarriage rate and live birth rate as secondary outcome measures. Main results and the role of chance Positive ANA screening at a titer of ≥ 1/80 was observed in 125/940 women (13.0%), a prevalence in line with previously published data in the general population not experiencing REPL. There were no statistically significant differences in maternal age, body mass index, ethnicity, or conception method between ANA-positive and -negative women. No higher number of previous EPLs was observed in ANA-positive compared to ANA-negative women (respectively 2.7 versus 2.8, p = 0.06). Women with ANAs had significantly more thyroid antibodies (21.6% versus 10.2%, p &amp;lt; 0.001). For a subsequent pregnancy, no association was observed between ANA positivity and reproductive outcome with an unadjusted EPL rate of 30/86 (34.9%, ANA-positive) versus 206/509 (40.5%, ANA-negative, p = 0.32). Logistic regression analysis did not identify ANAs as an independent predictive risk factor for additional EPL (OR 0.73, 95%CI 0.45-1.20, p = 0.22). Similarly, there was no significant difference in live birth rates between both groups (p = 0.5), with 54/86 (62.8%) in ANA-positive and 300/509 (58.9%) in ANA-negative patients. Limitations, reasons for caution The current data are limited by the absence of a formal control group without REPL, the retrospective nature of the study and potential bias due to unmeasured confounders. Wider implications of the findings These findings further questions systematic ANA measurement in the diagnostic work-up of REPL without AD. Furthermore, when ANAs are detected, patient counselling and treatment adaptations should be considered with caution, given our inability to eventually detect any significant differences in the pregnancy outcomes between ANA-positive and -negative REPL patients. Trial registration number not applicable

P-432 The association of early pregnancy loss and thrombophilia

Abstract Study question Is there a correlation between thrombophilia and the occurrence of pregnancy loss? Summary answer No statistically significant association is observed between thrombophilia and the live births. What is known already The understanding of recurrent pregnancy loss is a subject of controversy, encompassing both its causes and potential treatments and there is currently no consensus regarding the criteria for examining patients experiencing pregnancy loss, the specific tests to be conducted, or the appropriate treatment approaches. The connection between hereditary thrombophilia and pregnancy loss remains unclear. Study design, size, duration Within the timeframe of 01/12/2020 to 01/06/2022, pregnancy loss clinic of a tertiary university hospital received a total of 296 patients who had experienced at least one pregnancy loss. Following examination, these patients were encouraged to return to clinic if they became pregnant again. Among them, 192 patients did become pregnant and sought further care. These patients received treatment based on pregnancy loss clinic’s management algorithm, and their subsequent pregnancies were closely monitored. Participants/materials, setting, methods This prospective study involved 192 patients who, after undergoing examination, experienced subsequent pregnancies. These patients were categorized into two groups based on their obstetric outcomes: live birth and pregnancy loss. The primary focus of the study was to compare hereditary and acquired thrombophilia between these two groups. Additionally, secondary outcomes included a comparison of obstetric history, genetics, uterine anomalies, and results from biochemical and hormonal examinations between the two groups. Main results and the role of chance 150 of 192 patients achieved live birth (78.13%). The prevalence of hereditary thrombophilia mutations showed no significant differences between the two groups. Specifically, in the pregnancy loss group, the FV Leiden mutation rate was 12.5%, compared to 13.7% in the live birth group (p = 0.836). The Prothrombin gene mutation was observed in 7.5% of the pregnancy loss group and 7.25% of the live birth group (p = 1.000). Additionally, the PAI 4G/5G polymorphism was present in 60% of the pregnancy loss group and 52% of the live birth group (p = 0.347), the MTHFR/C677T polymorphism was detected in 62.5% of the pregnancy loss group and 56.5% of the live birth group (p = 0.500), and the MTHFR/1298C polymorphism was identified in 62.5% of the pregnancy loss group and 60.1% of the live birth group (p = 0.788). While antithrombin III levels were comparable between the two groups (p = 0.53), a noteworthy decline in antithrombin III levels was observed with an increasing history of losses: 110.2 for one loss, 106.0 for two losses, and 100.2 for three or more losses (p = 0.033). The homocysteine level was found to be 10.85 μM (range: 6.60-24.80 μM) in the pregnancy loss group and 9.40 μM (range: 4.90-37.00 μM) in the live birth group (p = 0.023). Limitations, reasons for caution A limitation of our study is its single-center nature. Additionally, we did not include a healthy control group with no history of pregnancy loss, preventing a direct comparison between the pregnancy loss group and a group unaffected by such experiences. Wider implications of the findings Our study provides valuable insights into questioning the live birth expectations of women who have experienced pregnancy loss and underscores the significance of thrombophilia in the context of pregnancy loss. Trial registration number not applicable

O-291 Sonographic Symphony: a systematic review and network meta-analysis of the use of 2D, 3D, 4D ultrasound’s influence on embryo transfer outcomes

Abstract Study question To comprehensively evaluate and compare pregnancy and live birth rates following clinical touch, 2D, 3D or 4D ultrasound guided embryo transfer of a blastocyst. Summary answer The use of 3D and 4D ultrasound is not superior to 2D transabdominal ultrasound, but all forms of ultrasound are superior to clinical touch alone. What is known already While several factors contribute to the overall success of embryo transfer, the accurate placement of the embryo within the uterine cavity remains a critical determinant of implantation and subsequent pregnancy. While two-dimensional (2D) ultrasound provides basic imaging during embryo transfer, assisting with catheter placement, three-dimensional (3D) ultrasound adds volume and spatial information, aiding in assessing the endometrial cavity and embryo positioning. Meanwhile, four-dimensional (4D) ultrasound introduces real-time visualisation, offering dynamic insights into embryo movement and potential implantation. Although 2D remains a standard for most transfers, there is a growing interest in leveraging advanced imaging technologies to improve assisted reproductive outcomes. Study design, size, duration We searched bibliographical databases, including the Cochrane Central Register of Controlled Trials, EMBASE and Medline, from inception until August 2023. Randomised controlled trials that compared 2D transabdominal (2D TAUS), 2D transvaginal (2D TVUS), 3D and 4D ultrasound guided embryo transfer with one another or with clinical touch were included. The primary outcome was live birth rate (LBR), and the secondary outcome was clinical pregnancy rate (CPR) per transfer. Participants/materials, setting, methods Two reviewers independently screened selected studies and extracted the data. Pairwise and network meta-analyses (NMA) were conducted according to the technique used. Effect estimates were odds ratio (OR) with 95% confidence interval (CI) for each outcome respectively. Summary estimates were calculated using random-effects methods and quality assessment was performed using GRADE. Main results and the role of chance Twenty-eight trials, reporting data from 10,521 embryo transfer procedures, were included. Four different ultrasound modalities were evaluated: 2D transabdominal guided embryo transfer (2D TAUS) (21 trials), 2D transvaginal guided embryo transfer (2D TVUS) (four trials), 3D transabdominal guided embryo transfer (one trial) and 4D transabdominal guided embryo transfer (one trial). Compared to 2D TAUS, there was no difference in LBR in the network meta-analysis when using 2D TVUS (OR 1.14; 95% CI: 0.75-1.74), 3D ultrasound (OR 0.98; 95% CI: 0.49-1.97) or 4D ultrasound modality (OR 1.28; 95% CI: 0.56- 2.94). The use of clinical touch was associated with lower LBR (OR 0.71; 95% CI: 0.49-1.03). Compared to 2D TAUS, there was no difference in clinical pregnancy rate in the network meta-analysis when using 2D TVUS (OR 1.17; 95% CI: 0.86-1.58), 3D ultrasound (OR 0.97; 95% CI: 0.57-1.63) or 4D ultrasound modality (OR 1.30; 95% CI: 0.71- 2.38). The use of clinical touch was associated with lower CPR (OR 0.74; 95% CI: 0.64-0.85). Limitations, reasons for caution Variability in study designs, methodologies, and participant characteristics across primary studies can complicate the synthesis of results. There was only one study directly comparing 3D and 4D interventions which resulted in sparse data, affecting the precision and reliability of estimates. Wider implications of the findings Published evidence supports the continued use of 2D transabdominal ultrasound guided embryo transfer in routine clinical practice. There is insufficient evidence to support the introduction of 3D and 4D ultrasound when performing embryo transfers. Larger randomised controlled trials specifically assessing the superiority of these modalities are recommended. Trial registration number not applicable

P-386 The effect of intravenous immunoglobulin versus placebo in patients with recurrent pregnancy loss: a systematic review and meta-analysis of randomized trials

Abstract Study question In women with recurrent pregnancy loss (RPL), how does intravenous immunoglobulin (IVIg) compared with placebo affect live birth rate (LBR) in the first subsequent pregnancy? Summary answer IVIg significantly improved LBR in the per protocol (PP), but not the intention to treat (ITT) analysis. LBR increased significantly with number of pregnancy losses. What is known already RPL is defined as two or more pregnancy losses before 24 weeks of gestation, impacting 1-2% of fertile couples. It results from diverse causes, and immunological factors are increasingly implicated in unexplained RPL cases. IVIg has been studied as a treatment with various proposed mechanisms. Existing research on IVIg in RPL has shown conflicting results, but a recent Japanese randomized controlled trial (RCT) reported a significantly increased LBR when IVIg was administered early and in high-dose. Study design, size, duration We conducted a systematic review and meta-analysis of relevant (RCTs, incorporating individual patient data (IPD) to evaluate IVIg’s impact on LBR in RPL patients. Participants/materials, setting, methods This study adhered to PRISMA guidelines and was registered in PROSPERO (ID CRD42023375788). We searched PubMed, Embase, and Cochrane libraries for relevant RCTs up to March 20, 2023. We conducted a meta-analysis with predefined primary (live birth and clinical pregnancy rates) and secondary outcomes. Risk ratios with 95% confidence intervals were calculated for dichotomous outcomes, and mean and standard deviation for continuous variables. We contacted the original authors to perform subgroup analyses based on IPD. Main results and the role of chance A total of 10 RCTs comprising 594 women were included in the meta-analysis, and IPD were retrieved from six RCTs including 354 women. No statistically significant results in LBR between IVIg and placebo treated women were found in the ITT analysis (RR: 1.02 [95% CI 0.86-1.22] p = 0.78). In the PP analysis, LBR was increased in the IVIg group compared with placebo (RR: 1.23 [1.00-1-50]). A statistically significant increase in clinical pregnancy rate was found in the IVIg group compared with placebo among women receiving high dose (median ³ 77.5 g) IVIg (RR: 1.79, [95% CI 1.21-2.65], p = 0.004). Furthermore, a statistically significant decrease in pregnancy loss rate was found in patients receiving high doses of IVIg (RR: 0.76 [95% CI 0.60-0.96], p = 0.02) compared to placebo. In the IPD analysis, RRs for live birth in the IVIg group compared with placebo increased steadily with the number of previous pregnancy losses. RRs for live birth in patients receiving IVIg compared with placebo were 5.26 (1.58-17.53) and 7.50 [1.20-47.05) in patients with ≥6 and ≥7 consecutive pregnancy losses, respectively. In analyses of IPD data adjusted for maternal age, the RRs for live birth were almost similar. Limitations, reasons for caution Limitations in the systematic review include potential bias due to financial support from pharmaceutical companies in half of the studies; potential confounding in subgroup analysis, missing individual patient data; and clinical and methodological heterogeneity among the included RCTs, which all may impact the overall reliability of results. Wider implications of the findings The findings highlight the importance of patient selection and personalized treatment. The PP analysis favored IVIg, emphasizing importance of protocol adherence. Secondly, the effectiveness of IVIg seems to increase with number of previous consecutive pregnancy losses. Thirdly, the dose of IVIg seem to impact its effectiveness. Trial registration number CRD42023375788

O-200 Association between proton pump inhibitors use and the risk of maternal infections during pregnancy and postpartum: a Swedish population-based cohort study

Abstract Study question Is there an association between use of proton pump inhibitors (PPIs) and maternal infection during or after pregnancy and subsequent pregnancy complications? Summary answer Use of PPIs in the 3 months before pregnancy or during the first trimester was associated with an elevated risk of maternal infection. What is known already PPIs alter gastric acidity and the gut microbiome, which may increase infection risks in the general population, but their impact on pregnant women is unknown. Study design, size, duration We conducted a Nationwide population-based cohort study using data from Swedish healthcare registers. PPIs use was defined as ≥ 1 prescription fill of a PPI in the 90 days before the first day of the last menstrual period (LMP) to the end of the 1st trimester (LMP+97 days). Maternal infections were identified from the start of the 2nd trimester to 90 days postpartum and classified as mild, moderate/ severe infections, and infection-related pregnancy complications. Participants/materials, setting, methods All pregnancies resulting in live or stillbirths between 2006 to 2019 in Sweden, identified using the Medical Birth Register. Log-binomial regression was used to estimate associations (relative risk (RR) and 95% confidence intervals (CI)) between PPIs and maternal infection, adjusting for potential confounders including birth year, maternal age at delivery, early pregnancy BMI, comorbidities, smoking in early pregnancy, maternal country of birth, maternal education, and parity. Main results and the role of chance Among 1,510,560 pregnant women, 42,599 (2.8%) used PPIs, and use increased over the study period time from 1.5% in 2006 to 3.44% in 2019. Compared to pregnant women without PPI use, those with PPI use had higher rates and risks of any infection (49.7% vs 36.8%; adjusted RR 1.30, 95%CI 1.29-1.32), mild infection (20.9% vs 16.1%; adjusted RR 1.30, 95%CI 1.28-1.33), moderate to severe infection (23.4% vs 15%; adjusted RR 1.47, 95%CI 1.45-1.50), and infection-related pregnancy complications (11.2% vs 9.2; adjusted RR 1.12, 95%CI 1.09-1.15). Conclusion Our results show an association between PPI use and an elevated risk of infection in pregnant women. Next steps include the further investigation into the infection types. PPI therapy has benefits and drawbacks that should be carefully weighed, especially in patients who are prone to infections. While our study highlights potential concerns, it does not imply that all pregnant women are at increased risk. More research is needed to understand the underlying mechanisms and assess potential preventive measures. Prescribing PPIs during pregnancy should be determined on a case-by-case basis, considering the patient’s individual health state. We acknowledge the necessity for caution, particularly in vulnerable populations, and more research is needed to demonstrate clinical correlations. Limitations, reasons for caution Potential confounding by indication due to underlying morbidities cannot be fully accounted for. Further research is required to establish clinical connections. Wider implications of the findings Clinicians should carefully weigh the benefits of PPI therapy during pregnancy, particularly in patients prone to infections. Trial registration number not applicable

Predicting risk of the subsequent early pregnancy loss in women with recurrent pregnancy loss based on preconception data

BackgroundFor women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data.MethodsA prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features.ResultsIn the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer–Lemeshow test was 7.427, and P = 0.505.ConclusionsPredicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability.Trial registrationThis study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

Drug-induced Liver Injury from Intravenous Immunoglobulin for Prevention of Recurrent Gestational Alloimmune Liver Disease: A Clinical Catch-22

Gestational alloimmune liver disease (GALD) is a rare autoimmune syndrome in which maternal antibodies lead to in utero fetal hepatocyte destruction, often presenting as neonatal liver failure and hemochromatosis. Antenatal intravenous immunoglobulin (IVIG) is generally accepted to be safe in pregnancy with demonstrable benefits for reducing GALD recurrence risk in subsequent pregnancies. Here we present a case of a 33-year-old woman with a prior neonatal demise due to GALD who received multiple prophylactic IVIG infusions in a subsequent twin pregnancy complicated by maternal jaundice and acute hepatitis. A liver biopsy demonstrated hepatocellular injury with bridging necrosis and cholestatic features consistent with drug-induced liver injury. This case demonstrates the importance of close clinical monitoring during IVIG therapy and the need for further research into alternative prophylaxis options for GALD. Key Points

Healthcare professional perspectives on improving inter-pregnancy care after a baby loss for women with type 1 and type 2 diabetes.

Women with diabetes (WWD) (type 1 and type 2) are around four times more likely to experience baby loss: miscarriage, stillbirth, neonatal death or termination of pregnancy for medical reasons. Many WWD become pregnant again soon after loss. This study aimed to explore healthcare professional perspectives on improving inter-pregnancy care for WWD after baby loss, as they play a crucial role in facilitating access to support for WWD to prepare for subsequent pregnancy. Eighteen healthcare professionals recruited through social media and professional networks between November 2020 and July 2021 participated in a semi-structured remote interview. Data were analysed using thematic analysis. Three main themes were identified: (1) supporting WWD who want to become pregnant again after baby loss; (2) recognising multiple hidden burdens in the inter-pregnancy interval after loss; (3) discontinuities and constraints in inter-pregnancy care. Most participants tended to assume WWD wanted time and space before thinking about pregnancy after loss, so they did not routinely broach the subject. Participants reported receiving little or no training on managing sensitive conversations. Care provision varied across providers, and unclear referral pathways were challenging to navigate. Participants reported concerns that not all healthcare professionals knew how to mitigate pregnancy risks. It is unclear who is responsible for supporting WWDs preconception health between baby loss and subsequent pregnancy. Healthcare professionals may be reticent to initiate conversations about pregnancy for fear of causing upset or distress. Future research is required to scope out ways to raise awareness among healthcare professionals and practical tips on sensitively raising the topic of subsequent pregnancy.

Obstetric and perinatal outcomes of women with a history of recurrent pregnancy loss: a meta-analysis of cohort studies.

To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies(pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy.