Viable Pregnancy Research Articles

P-778 Exploration of maternal proteome over pregnancy based on corpus luteum number at conception

Abstract Study question Does the maternal plasma proteome profile differ depending on corpus luteum (CL) number at conception? Summary answer The proteome profiles show differences depending on the number of CL at conception and some differentially regulated proteins may be linked to preeclampsia. What is known already Frozen embryo transfer (FET) in a programmed cycle is associated with a higher risk for preeclampsia. These women also experience impaired maternal vascular health in early pregnancy and differences in the endocrine environment, such as a lack of relaxin. These changes may be related to the absence of products from the CL. Study design, size, duration Prospective cohort study (N = 878) between June 2015 and December 2018 in an academic setting. Participants/materials, setting, methods Women with viable pregnancies were recruited at 6-8 weeks and compared by number of CL: no CL (programmed cycle FET), 1 CL (spontaneous pregnancy after infertility, modified natural cycle FET), and multiple CL (fresh IVF). Peripheral blood was collected, and plasma frozen at -80 °C. MS-based proteomics was used to determine proteome profiles of 4 participants in each group at 11-14 and 35-37 weeks’ gestation and 6-12 weeks postpartum. Main results and the role of chance Over 1000 protein groups were identified and 650 could be quantified in all samples. We found significant differences based on number of CL. Many of these proteins have been reportedly linked to preeclampsia. The results in the first trimester indicate the importance of aminopeptidases involved in the breakdown of angiotensin III. In addition, extracellular matrix proteins were found to be differentially regulated. Also, at the end of the third trimester certain proteins were differentially regulated among the groups. Limitations, reasons for caution This was a pilot study and unable to determine if differences are related to selection bias or could exist already pre-pregnancy independent of CL number at conception. Wider implications of the findings The findings warrant confirmation in a larger patient cohort. The detected differences in the proteome might shed light upon phenomena observed in women during pregnancy that lack a CL and as well as molecular mechanisms underlying preeclampsia. Trial registration number not applicable

O-176 Hoping for the best, expecting the worst: pregnancy after loss

Abstract Recurrent pregnancy loss (RPL) is an extremely distressing condition and can be both physically and emotionally traumatising. The condition is compounded by the fact that even after diagnostic procedures, the majority of cases, remain unexplained. The early waiting period of a new pregnancy, when confirmation by ultrasound scan of an ongoing and viable pregnancy is awaited, represent a particularly challenging time for those affected by this condition. This waiting period is associated with high levels of distress due to the anxiety of possibly experiencing a further miscarriage. However, there is a lack of understanding amongst some health professionals of the emotional burden of this difficult waiting period, furthermore, limited support and counselling is available, and many women are left to manage their distressing emotions without coping support. While some seek frequent confirmation of viability by ultrasound scans, this approach is not feasible in most clinical settings and, in any case, appears to be of limited efficacy in reducing anxiety. An alternative approach was to provide the woman with tools that could bolster their ability to cope with this challenging period. Our programme of research has investigated the use of the Positive Reappraisal Coping Intervention (PRCI), a self- administered coping technique, based on the principles of positive reappraisal, as a method of providing much needed emotional support. Qualitative research findings have provided deep insight into the lived experience of RPL during the early waiting stages of a new pregnancy, establishing that for those with a history of RPL, this is a traumatic time of great uncertainty, emotional turmoil and immense personal significance, where those affected ‘hope for the best, but expect the worst.’ Whilst our programme of research is still ongoing, studies to date, have demonstrated that study participants were receptive to the use of the PRCI and that it appeared to convey benefits, with no apparent downside. It was a ‘go to’ resource in times of strong emotional need and one that stimulated positive coping, providing respite from the stressor of uncertainty. There is a compelling need to provide those experiencing RPL with increased emotional support to help them manage the stressful early waiting period of a new pregnancy. Findings suggest that PRCI could provide a useful adjunct to care pathways and has the potential to be made more widely available as an effective, safe, convenient, and low-cost intervention to provide emotional support in RPL clinics.

P-728 Age limits in medically assisted reproduction: Assessing clinical and pregnancy outcomes in women over 50 years of age undergoing donor oocyte in vitro fertilization

Abstract Study question Is pregnancy in women over 50 years of age undergoing donor oocyte IVF associated with adverse clinical and pregnancy outcomes? Summary answer In vitro fertilization treatment in women over 50 years of age using donor oocytes is not associated with adverse clinical and pregnancy outcomes. What is known already In vitro fertilization with donor oocytes (d-IVF) has become a common strategy for managing cases of very advanced maternal age. However, there is ongoing scientific debate entailing legal and societal implications regarding the age limit beyond which d-IVF should no longer be considered safe. Different age limits and guidelines have been proposed, with no globally accepted consensus. The most commonly reported age limit is 50 years, representing the median age of menopause. However, there is a lack of robust data to support that d-IVF beyond the age of 50 is associated with adverse clinical and pregnancy outcomes. Study design, size, duration A retrospective single-centre study was conducted to evaluate medical records of d-IVF cycles between July 2021-January 2023. A total of 575 medical records of women undergoing d-IVF were analyzed. The study population was divided into two groups based on maternal age: women aged 45-49 years (group A, n = 318) and women aged 50-54 years (group B, n = 257). The outcome measures were positive-hCG, clinical pregnancy, viable pregnancy at 12 weeks of gestation, pregnancy loss and live birth. Participants/materials, setting, methods For oocyte recipients advanced maternal age was the sole infertility etiology and endometrial preparation was performed employing conventional protocols. Oocyte donors were up to 35 years of age and oocyte donation cycles were performed according to national guidelines. Single or double embryo transfers (ETs) were performed at the cleavage or blastocyst stage. Embryo quality assessment was performed according to Veeck and Gardner grading systems. Statistical analysis was performed employing R Programming Language for Statistical Purposes. Main results and the role of chance The mean age of group A was 47.02 ± 1.35 while the mean age of group B was 51.84 ± 1.59. No statistically significant difference was observed regarding the age of oocyte donors (25.17 ± 4.18 vs 26.09 ± 4.13; p-value=0.26). Considering embryo transfer, 90 cleavage stage and 228 blastocyst stage transfers were performed in group A, and 75 cleavage stage and 182 blastocyst stage transfers were performed in group B (p-value=0.23). No statistically significant difference was observed between the two groups with regards to the number of transferred embryos (1.89 ± 0.35 vs 1.90 ± 0.36; p-value=0.69) and embryo quality (Group A: Good 157, Fair 143, Poor: 18; Group B: Good 121, Fair 117; Poor 19; p-value=0.66). Considering clinical and pregnancy outcomes no statistically significant difference was observed between the two groups regarding positive hCG rate (147/318 vs 109/257, respectively; RR: 0.91; 95%CI: 0.76-1.10; p-value=0.36), clinical pregnancy rate (129/318 vs 98/257, respectively; RR: 0.94; 95%CI: 0.77-1.15; p-value=0.55), viable pregnancy rate at 12 weeks of gestation (96/318 vs 70/257, respectively; RR: 0.90; 95%CI: 0.70-1.17; p-value=0.44), pregnancy loss rate (39/129 vs 33/98, respectively; RR: 1.13; 95%CI: 0.76-1.63; p-value=0.58) and live-birth rate (90/318 vs 65/257, respectively; RR: 0.91; 95%CI: 0.68-1.17; p-value=0.42). Limitations, reasons for caution The retrospective and the single-centre nature of the study are important reasons for caution. In addition, the relatively small sample size may serve as another limitation. The lack of neonatal outcomes may also be considered an additional limitation when interpreting data on the safety of d-IVF in the over-50s. Wider implications of the findings Women over 50 who undergo d-IVF are not at increased risk of complications. This highlights the need to reconsider age limits and provide robust evidence ascertaining both safety and reproductive autonomy. Studies are needed to assess neonatal outcomes and maternal age impact on long-term infant health from an epigenetic standpoint. Trial registration number Not applicable

P-774 Conventional-IVF versus NC-IVF: unravelling the origins of fetal cardiac programming in ART

Abstract Study question Do fetuses from natural cycle IVF (NC-IVF) present signs of cardiac remodeling and suboptimal function similar to those observed in fetuses from conventional IVF (cIVF)? Summary answer Fetuses from both NC-IVF and cIVF present signs of fetal cardiac remodeling and suboptimal function as compared to spontaneously conceived fetuses (SC) from fertile couples. What is known already Previous publications have demonstrated that fetuses conceived by IVF present cardiac remodeling and suboptimal function. These fetuses show dilated atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation. However, the pregnancies included in these studies were obtained following cIVF. In IVF cycles, ovarian stimulation has an impact on the oocyte quality and the endometrial milieu that may potentially affect perinatal results and fetal cardiovascular programming. Our aim was to compare cardiac morphometry and myocardial function in fetuses conceived by cIVF with those obtained after NC-IVF, without ovarian stimulation. Study design, size, duration This is a nested case-control study of 120 singleton pregnancies within a prospective cohort recruited from 2017 to 2021, including 40 SC from fertile couples, 40 following NC-IVF and 40 after cIVF with fresh embryo transfer, matched by maternal age, ethnicity, and gestational age at scan. IVF pregnancies were recruited from a single assisted reproduction center, ensuring homogeneity in ovarian stimulation protocols, laboratory procedures, and embryo culture conditions. Participants/materials, setting, methods The study protocol included prospective collection of parental demographics, reproductive and ART data, a fetal ultrasound scan at 28-34 weeks assessing biometry, feto-placental Doppler and morphological and functional echocardiography, and perinatal outcomes. Comparisons between groups were adjusted by gestational age and fetal weight at scan, and birthweight centile. Oocyte donation and PGT cycles were exclusion criteria. All the laboratory procedures including gamete manipulation, fertilization methods and embryo culture conditions were identical for NC-IVF and cIVF. Main results and the role of chance There were no significant differences in demographic data, perinatal outcomes, biometry and feto-placental Doppler parameters between the study groups. Reproductive data and IVF indications were also similar among the IVF groups. As compared to the SC, both IVF groups showed significant signs of fetal cardiac remodeling (higher cardio-thoracic ratio: cIVF mean 0.31 [SD 0.04]* versus NC-IVF 0.31 [0.03]* versus SC 0.28 [0.04], adjusted P-value <0.001; larger right atria-to-heart ratio: cIVF 19.1% [3.0]*† versus NC-IVF 18.8% [3.3]* versus SC 17.4% [2.9], adjusted P-value <0.001; increased relative wall thickness: c IVF 0.80 [0.2]* versus NC-IVF 0.85 [0.3]* versus SC 0.72 [0.3], adjusted P-value <0.001) and suboptimal function (tricuspid ring displacement (mm): cIVF 7.1 [0.8]* versus NC-IVF 7.3 [0.9]* versus SC 7.5 [1.4], adjusted P-value 0.003; left myocardial performance index: cIVF 0.50 [0.06]* versus NC-IVF 0.49 [0.06]* versus SC 0.48 [0.08], adjusted P-value <0.001). * Adjusted P value <0.05 as compared with SC. † Adjusted P value <0.05 as compared to NC- IVF. Limitations, reasons for caution The sample size was limited by the difficulty in recruiting viable pregnancies obtained by NC-IVF from a single center. The reported cardiac changes are subclinical and, although they are recognized as potential cardiovascular risk factors, their association with the long-term cardiovascular disease in these subjects remains to be proven. Wider implications of the findings Our findings contribute to assess the safety of different ART procedures in terms of cardiac performance in fetal life, before the influence of postnatal factors, in order to unravel the origins of fetal cardiac remodeling in ART. Studies evaluating the long-term health in this population are needed. Trial registration number Not applicable

P-730 A feasibility study of the impact of the level of exposure to ambient air pollutants on outcomes of assisted reproductive technologies

Abstract Study question What is the impact of air pollution exposure on outcomes for couples having IVF treatment? Summary answer Environmental exposure to high levels of air pollutants may negatively influence IVF outcomes with potential implications for fertility treatment. What is known already Air pollutants are harmful substances in the atmosphere that have adverse effects on human health. Increased levels of air pollutants have been associated with respiratory disorders, cardiovascular disease, and increased morbidity in humans across all age groups. Existing evidence suggests that increased exposure to air pollutants may adversely affect fertility. The relationship between air pollutants and IVF outcomes remains poorly understood. Study design, size, duration This was an ethically approved prospective observational feasibility study conducted over a two-year period. Ten couples due to undergo an IVF cycle were recruited from a fertility centre in the UK. Environmental exposure to ambient air pollutant for particulate matter (PM) 2.5 and 10 micron size was measured using portable AirBeam monitors over the course of two weeks from commencement of the ovarian stimulation regime. Participants/materials, setting, methods Eligible participants were those aged 18-35 years old, undergoing fresh IVF, with a good ovarian reserve and ability to provide informed consent. Data of interest included: BMI, age, parity, ethnicity, smoking status. IVF data included: number of oocytes retrieved, embryo quality and cycle outcomes. AirBeam device data was extracted, analysed and correlated with IVF outcomes. Participants feedback was sought for qualitative input for future studies. Main results and the role of chance Total of 28,269 data points of ambient air pollutant data for PM 2.5 and 10 micron size were recorded amongst the ten participants. One participant was exposed to significantly high air pollutant levels during ovarian stimulation on certain days (PM2.5 - 81.06 µg/m³ and PM10 - 154.48 µg/m³) compared to standard annual air pollution level for the UK of 25 µg/m³ for PM2.5 and 40 µg/m³ for PM10. Two women did not have embryo transfer due to embryo arrest. Of those who had transfer, 50% (n = 4) had positive pregnancy tests however three experienced early pregnancy losses. At the time of writing there was one ongoing single viable pregnancy. On correlation of air quality data with clinical outcomes, the one participant who exhibited fluctuant very high exposure levels to the measured air pollutants, had unexpected low fertilization rate (20%) with IVF and no transfer due to embryo arrest. Of the nine participants returning the questionnaire feedback, all but one rated it acceptable to most acceptable to carry the device around. The main barrier was the size of device and battery life. All respondents were willing to recommend others to participate in a future similar study confirming feasibility to recruit. Limitations, reasons for caution As a feasibility study, with a limited sample size, our findings should be interpreted cautiously. The small cohort limits the generalisability of our results. Further research with larger sample sizes is required to validate our findings. Wider implications of the findings Understanding the impact of air pollutants on IVF outcomes is important for developing evidence-based guidance and interventions to optimise fertility treatment efficacy. Our study demonstrates the feasibility of personal air quality monitoring and emphasises the necessity for larger scale research and the practicality of pollutant exposure measurements in fertility treatments. Trial registration number REC reference: 21/NE/0233 IRAS project ID: 294240. Theramex BIRTH Grant

Predicting the Outcomes of In Vitro Fertilization Using Baseline Maternal Serum Inflammatory Markers: A Retrospective Cohort Study.

Achieving pregnancy through in vitro fertilization (IVF) remains a challenge, with less than one-third of women succeeding. There is a pressing need for reliable predictive tools to assess the likelihood of post-IVF pregnancy. While some serum inflammatory biomarkers have been investigated for their predictive potential, substantial knowledge gaps persist. This study examined the utility of different inflammatory markers in predicting IVF outcomes. Inflammatory markers including the white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet count, mean platelet volume, platelet distribution width, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate, and vitamin D3 were assessed. Study outcomes were chemical pregnancy (positive serum beta-human chorionic gonadotropin 2 weeks post-embryo transfer), clinical pregnancy (detection of pregnancy sac via transvaginal ultrasonography), and viable pregnancy (detection of fetal heart rate). Univariate and multivariate logistic regression analyses were conducted, with multivariate analysis incorporating age, body mass index, infertility duration, type, and etiology, as well as all studied serum inflammatory markers, embryo count, stage, quality, and endometrial thickness. Lower NLR (p<0.001, odds ratio [OR]=0.372 [0.247-0.559]) and CRP (p=0.035, odds ratio=0.956 [0.916-0.997]) predicted chemical pregnancy in univariate analysis, with NLR maintaining significance in multivariate analysis (p=0.022, OR=0.319 [0.120-0.848]). Lower NLR (p<0.001, OR=0.309 [0.198-0.482]) and PLR (p=0.013, OR =0.994 [0.990-0.999]) predicted clinical pregnancy, with NLR surviving multivariate analysis (p=0.005, OR = 0.217 [0.075-0.626]). Lower NLR (p<0.001, OR = 0.320 [0.198-0.516]) also predicted viable pregnancy, maintaining statistical significance in multivariate analysis (p = 0.002, OR = 0.177 [0.058-0.541]). Other studied inflammatory markers did not predict IVF outcomes. NLR emerged as a robust independent predictor of pregnancy attainment after IVF.

Single day 14 serum hCG values allow prediction of viable pregnancy and are significantly higher in frozen as compared to fresh single blastocyst transfer

PurposeTo evaluate if single serum human chorionic gonadotropin (hCG) level measurements are sufficient for pregnancy monitoring after single embryo transfer (sET) and to compare the hCG levels between fresh (FRET) and frozen embryo transfers (FET) in medically assisted reproduction.MethodsThis was a retrospective exploratory cohort study including all patients who met the inclusion criteria, who received a single FRET (n = 249) or FET (n = 410) of a day five blastocyst at the IVF clinic at the Johannes Kepler University Linz between 2011 and 2020. hCG levels were measured on day 14 after embryo transfer. Threshold values for the viability of pregnancies were determined using receiver operating characteristic (ROC) curves.ResultsSignificantly higher hCG levels were found in those who received FET than in those who received FRET (1222.8 ± 946.7 mU/ml vs. 862.7 ± 572.9 mU/ml; p < 0.001). Optimal threshold values predicting a viable pregnancy were 368.5 mU/ml and 523 mU/ml in the FRET and FET groups, respectively.ConclusionsAfter FET, higher hCG values after 14 days of embryo transfer must be considered in pregnancy monitoring. Additionally, a single threshold hCG value seems to be sufficient for determining pregnancy viability. To exclude ectopic pregnancies, subsequent ultrasound examination is a mandatory requirement.

Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Endometrial compaction to predict pregnancy outcomes in patients undergoing assisted reproductive technologies: a systematic review and meta-analysis.

Does endometrial compaction (EC) help predict pregnancy outcomes in those undergoing ART? EC is associated with a significantly higher clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR), but this does not translate to live birth rate (LBR). EC describes the progesterone-induced decrease in endometrial thickness, which may be observed following the end of the proliferative phase, prior to embryo transfer. EC is proposed as a non-invasive tool to help predict pregnancy outcome in those undergoing ART, however, published data is conflicting. A literature search was carried out by two independent authors using PubMed, Cochrane Library, MEDLINE, Embase, Science Direct, Scopus, and Web of Science from inception of databases to May 2023. All peer-reviewed studies reporting EC and pregnancy outcomes in patients undergoing IVF/ICSI treatment were included. The primary outcome is LBR. Secondary outcomes included other pregnancy metrics (positive pregnancy test (PPT), CPR, OPR, miscarriage rate (MR)) and rate of EC. Comparative meta-analyses comparing EC and no EC were conducted for each outcome using a random-effects model if I 2 > 50%. The Mantel-Haenszel method was applied for pooling dichotomous data. Results are presented as odds ratios (OR) with 95% CI. Out of 4030 screened articles, 21 cohort studies were included in the final analysis (n = 27 857). No significant difference was found between LBR in the EC versus the no EC group (OR 0.95; 95% CI 0.87-1.04). OPR was significantly higher within the EC group (OR 1.61; 95% CI 1.09-2.38), particularly when EC ≥ 15% compared to no EC (OR 3.52; 95% CI 2.36-5.23). CPR was inconsistently defined across the studies, affecting the findings. When defined as a viable intrauterine pregnancy <12 weeks, the EC group had significantly higher CPR than no EC (OR 1.83; 95% CI 1.15-2.92). No significant differences were found between EC and no EC for PPT (OR 1.54; 95% CI 0.97-2.45) or MR (OR 1.06; 95% CI 0.92-1.56). The pooled weighted incidence of EC across all studies was 32% (95% CI 26-38%). Heterogeneity due to differences between reported pregnancy outcomes, definition of EC, method of ultrasound, and cycle protocol may account for the lack of translation between CPR/OPR and LBR findings; thus, all pooled data should be viewed with an element of caution. In this dataset, the significantly higher CPR/OPR with EC does not translate to LBR. Although stratification of women according to EC cannot currently be recommended in clinical practice, a large and well-designed clinical trial to rigorously assess EC as a non-invasive predictor of a successful pregnancy is warranted. We urge for consistent outcome reporting to be mandated for ART trials so that data can be pooled, compared, and concluded on. H.A. was supported by the Hewitt Fertility Centre. S.G.P. and J.W. were supported by the Liverpool University Hospital NHS Foundation Trust. D.K.H. was supported by a Wellbeing of Women project grant (RG2137) and MRC clinical research training fellowship (MR/V007238/1). N.T. was supported by the National Institute for Health and Care Research. D.K.H. had received honoraria for consultancy for Theramex and has received payment for presentations from Theramex and Gideon Richter. The remaining authors have no conflicts of interest to report. PROSPERO CRD42022378464.

Viable cesarean scar pregnancy from primary care perspective: A case report

Ectopic pregnancies within previous cesarean section scars are rare but potentially life-threatening complications. Diagnosis can be challenging, particularly in primary care settings, where the focus is often on routine primary care services. We present a case report of a patient who initially presented to a primary care clinic with non-specific symptoms of ectopic pregnancy and was referred to a tertiary center for incomplete miscarriage. It was found to be a viable ectopic pregnancy within a cesarean scar. This case highlights the importance of keeping an open mind in patients with a history of cesarean section and uterine manipulation procedures such as manually evacuating a retained placenta. It emphasizes prompt diagnosis and referral to a specialized healthcare facility.

Diagnostic utility of clinicodemographic, biochemical and metabolite variables to identify viable pregnancies in a symptomatic cohort during early gestation

A significant number of pregnancies are lost in the first trimester and 1–2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin β (β-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of β-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations.

Clinical factors associated with subsequent surgical intervention in women undergoing early medical termination of viable or non-viable pregnancies.

Mifepristone-misoprostol treatment for medical abortion and miscarriage are safe and effective. This study aimed to assess clinical factors associated with subsequent surgical intervention after medical termination of early viable or non-viable pregnancy. This retrospective, single-center study included women who underwent medical abortion at Taipei Medical University between January 2010 and December 2019. A total of 1,561 subjects, with 1,080 viable and 481 non-viable pregnancies, who were treated with oral mifepristone 600 mg followed by misoprostol 600 mg 48 h later were included. Data of all pregnancies and medical termination of pregnancy were evaluated using regression analysis. The main outcome was successful termination of pregnancy. The success rate of medical abortion was comparable in women with viable and non-viable (92.13% vs. 92.93%) pregnancies. Besides retained tissue, more existing pregnancies with ultrasonographic findings were found in the non-viable pregnancy group than in the viable pregnancy group (29.4% vs. 14.1%, p = 0.011). Multivariate analysis showed that previous delivery was an independent risk factor for failed medical abortion among all included cases. In women with viable pregnancy, longer gestational age [adjusted odds ratio (aOR): 1.483, 95% confidence interval (CI): 1.224-1.797, p < 0.001] and previous Cesarean delivery (aOR: 2.177, 95% CI: 1.167-40.62, p = 0.014) were independent risk factors for failed medical abortion. Number of Cesarean deliveries (aOR: 1.448, 95% CI: 1.029-2.039, p = 0.034) was an independent risk factor for failed medication abortion in women with non-viable pregnancies. This is the first cohort study to identify risk factors for subsequent surgical intervention in women with viable or non-viable pregnancies who had undergone early medically induced abortions. The success rate of medical abortion is comparable in women with viable and non-viable pregnancies. Previous delivery is an independent risk factor for failed medical abortion. Clinical follow-up may be necessary for women who are at risk of subsequent surgical intervention.

Venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in metastatic choriocarcinoma during systemic chemotherapy: Case report

Rationale: Gestational trophoblastic neoplasms are rare and include multiple different types of tumors such as hydatidiform moles, placental site trophoblastic tumors, and choriocarcinoma. Metastatic choriocarcinoma is well described with an excellent prognosis when treated appropriately with chemotherapy. The most common location for metastatic disease is the lungs which can unfortunately lead to severe acute respiratory distress syndrome (ARDS) in the most severe cases. Patient concerns: Metastatic cancer has historically been a contraindication for the use of extracorporeal life support (including extracorporeal membrane oxygenation or extracorporeal membrane oxygenation [ECMO]). With advancing technology and medicine, this contraindication has been called into question. Prior case reports describe the use of ECMO in complicated cases of metastatic cancer and even choriocarcinoma with lung metastasis and refractory ARDS. Diagnoses: We describe a case in which a patient with choriocarcinoma in viable pregnancy developed lung metastasis and ARDS. Interventions: The patient was managed with venovenous ECMO successfully. Outcomes: The patient was cannulated for VV-ECMO for 14 days with subsequent full pulmonary recovery. Lessons: The purpose of this work is to help providers understand the broad utility of ECMO and the need to assess candidacy for this therapy on a case by case basis, even in the setting of metastatic cancer.

Clomiphene Citrate Administered in Periconception Phase Causes Fetal Loss and Developmental Impairment in Mice.

Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this study investigated the consequences in mice for fetal development and pregnancy outcome of periconception clomiphene citrate administration at doses approximating human exposures. A dose-dependent adverse effect of clomiphene citrate given twice in the 36 hours after mating was seen, with a moderate dose of 0.75 mg/kg sufficient to cause altered reproductive outcomes in 3 independent cohorts. Viable pregnancy was reduced by 30%, late gestation fetal weight was reduced by 16%, and ∼30% of fetuses exhibited delayed development and/or congenital abnormalities not seen in control dams, including defects of the lung, kidney, liver, eye, skin, limbs, and umbilicus. Clomiphene citrate also caused a 30-hour average delay in time of birth, and elevated rate of pup death in the early postnatal phase. In surviving offspring, growth trajectory tracking and body morphometry analysis at 20 weeks of age showed postweaning growth and development similar to controls. A dysregulated inflammatory response in the endometrium was observed and may contribute to the underlying pathophysiological mechanism. These results demonstrate that in utero exposure to clomiphene citrate during early pregnancy can compromise implantation and impact fetal growth and development, causing adverse perinatal outcomes. The findings raise the prospect of similar iatrogenic effects in women where clomiphene citrate may be present in the periconception phase unless its use is well-supervised.

Ultrasound markers of adverse pregnancy outcomes in embryonal period: literature review and own clinical cases

A goal of the review was to search and describe all currently known prenatal ultrasound markers of adverse pregnancy outcomes. The review is instantiated by multiple ultrasound images of own clinical cases. Taking into account the authors wide experience, it is possible to use all of presented ultrasound signs as predictors (markers) of an adverse pregnancy outcome in the early stages. From our point of view, it is reasonable to divide the markers into two groups, “primary markers” and “dynamic markers”. In the case of “Primary markers” revealing on initial ultrasound, it is reasonable to perform control ultrasound in 7–10 days to confirm the viable pregnancy or missed miscarriage. The “Dynamic markers” can be used on control ultrasound, and some of them may be used in shorter dynamic period when there is a need to predict the outcome earlier than 7-10 days. Generally, the review describes 22 early pregnancy ultrasound markers of adverse pregnancy outcome. These are imaging features of the gestational sac, yolk sac, embryo size, embryo heartbeat, and amnion. Early pregnancy ultrasound is not mandatory, but in a real-case scenario, almost all women undergoes ultrasound on early stage of pregnancy in objective or subjective causes. Therefore, in the first days of pregnancy, women should receive a highly professional diagnostic by a physician, able to assess the risks and prognosis of pregnancy outcome. The authors of the review particularly notes that the assessment of ultrasound markers of adverse pregnancy outcomes must be carried out with the strictest adherence to the medical ethics, deontology, and medical privacy.

The impact of first-trimester subchorionic hematomas on pregnancy outcomes after euploid embryo transfer: a retrospective cohort study

BackgroundThe aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer.MethodsWe retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors.ResultsA total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio [aOR] 1.99, 95% confidence interval [CI] 1.25–3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39–0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups.ConclusionsThe presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.

Predictive effect of thiol/disulfide homeostasis dynamics on early pregnancy viability: A case-control study.

The main aim of this study was to investigate the differences in maternal serum thiol/disulfide homeostasis among women with abortion imminens (AI), missed abortion (MA), and healthy pregnancies during the first trimester. This was a prospective case-control study. This study was conducted on pregnant women who visited the Obstetrics Clinic at University of Health Sciences Turkey, Etlik Zübeyde Hanım Gynecology Training and Research Hospital and were diagnosed with either AI or MA during the 6th to 14th weeks of pregnancy. The participants had a normal pregnancy follow-up, no chronic illnesses, and did not take any multivitamin or antioxidant supplements except for folic acid. The study incorporated 33 pregnant women with AI, 36 with MA, and 40 with normal pregnancies. Age, and body mass index were matched across the three groups. This study used a recently developed automated spectrophotometric technique to quantify thiol/disulfide concentrations. The AI group had considerably elevated levels of total thiol and native thiol (SH) compared with the MA group. Nevertheless, there was no notable disparity observed between the group of healthy pregnancies and the other two groups. Serum disulfide (SS) levels did not exhibit any significant variations among the three groups. Similarly, the ratios of SS/SH, SS/total thiol, and SH/total thiol did not show any significant differences between the groups (p>0.05). Patients with MA had decreased levels of total thiol and SH, which possess antioxidant capabilities, compared to the AI group. A decrease in antioxidant levels in the body may contribute to the etiology of MA. When considering our findings alongside existing literature, it remains inconclusive whether the serum thiol-disulfide ratio can predict a healthy pregnancy or MA following AI. Therefore, it is not yet seen as a promising diagnostic tool for assessing pregnancy viability. Additional investigation is required to establish the influence of dynamic thiol/disulfide homeostasis on early pregnancy loss.

Serum Vitamin D3 level in spontaneous abortion cases in comparison to ongoing viable pregnancies: A case–control study in a tertiary medical college

Background: The immunoregulatory functions of Vitamin D3 play a vital role in the maintenance of normal pregnancy. Several studies have reported the association of low serum Vitamin D3 levels with spontaneous abortion. Aims and Objectives: The purpose of the study was to determine the association between serum Vitamin D3 level and spontaneous abortion cases in a tertiary medical college. Materials and Methods: The case–control study was conducted at the Department of Gynecology and Obstetrics, Medical College, Kolkata. The study population included 50 women with spontaneous abortion (cases) and 50 women with viable pregnancy beyond 20 weeks of gestation (controls). The cases and controls were matched with respect to age, socioeconomic status, and laboratory parameters. Investigations performed for both groups were ultrasonography for confirmation of abortion and viable pregnancy, serum Vitamin D3, and other biochemical markers. Data were compared between cases and controls using the Chi-square test and unpaired “t” test along with the calculation of odds ratios (OR). Results: About 24% of cases and 10% of controls belonged to Vitamin D3 deficient category. The difference was statistically significant (P=0.009, d.f.=2) (OR: 2.84, 95% confidence intervals [CI]: 0.92–8.80). Bleeding PV was present in 50% of cases and 4% of controls (P=0.0001, d.f.=1) (OR: 24.00, 95% CI: 5.25–109.65). Abdominal pain was complained by 46% of cases and 10% of controls (P=0.0001, d.f.=1) (OR: 7.67, 95% CI: 2.61–22.54). Conclusion: Vitamin D3 deficiency was present more in spontaneous abortion cases in comparison to viable pregnancies. Routine daily supplementation of vitamin D3 during the first trimester of pregnancy should be incorporated into the ongoing national program. Training of health workers to educate pregnant women and their family members regarding the importance of vitamin D3 is the need of the hour.

Oral rehydration therapy versus intravenous rehydration therapy in the first 12 h following hospitalization for hyperemesis gravidarum: A randomized controlled trial.

To evaluate oral rehydration therapy (ORT) compared with intravenous rehydration therapy (IVT) in the early inpatient management of hyperemesis gravidarum (HG). A total of 124 women hospitalized for HG from February 10, 2021 till January 6, 2023 were randomized to ORT (n = 61) or IVT (n = 63) for an initial 12 h. Inclusion criteria includes women older than 18 years, with a viable intrauterine pregnancy less than 14 weeks at their first hospitalization for HG with ketonuria of at least 2+. Primary outcomes were (1) satisfaction score with allocated intervention, (2) weight change, and (3) ketonuria change at 12 h. Secondary outcomes included vomiting frequency, nausea score, serial vital signs, hematocrit and electrolyte levels at 12 h, deviation from treatment protocol (cross-over therapy), participant recommendation of allocated treatment to a friend, and length of hospital stay. Primary outcomes of (1) participant satisfaction score (on a 0-10 visual numerical rating scale) was 7 (interquartile range [IQR] 5-8) versus 9 (IQR 8-10), P < 0.001; (2) weight gain was 293 ± 780 g versus 948 ± 758 g, P < 0.001; and (3) ketonuria improvement was 50/61 (82.0%) versus 49/63 (77.8%) (relative risk [RR] 1.05, 95% confidence interval [CI] 0.88-1.26, P = 0.561) for ORT versus IVT, respectively. For secondary outcomes, vomiting frequency was 2.6 ± 2.7 versus 1.1 ± 1.4 episodes (P < 0.001), participant cross-over rate to opposing treatment 20/61 (32.8%) versus 0/63 (0%) (P < 0.001) (in the 12-h study period) and participant recommendation of allocated treatment to a friend rate 24/61 (39.3%) versus 61/63 (96.8%) (RR 0.41, 95% CI 0.30-0.56, P < 0.001) for ORT versus IVT, respectively. By hospital discharge, 31/61 (50.8%) of women allocated to ORT had required IVT. Other secondary outcomes of serial assessments of nausea score and vital signs, hematocrit and electrolyte levels, and length of hospital stay were not different. ORT was inferior to IVT in two primary outcomes and three secondary outcomes. Cross-over rate to intravenous therapy from oral therapy was 50.8% by hospital discharge. Intravenous rehydration therapy should remain as first-line rehydration therapy in the early inpatient treatment of HG. The present study was registered in ISRCTN registry on December 6, 2020 with trial identification number: ISRCTN 40152556 (https://doi.org/10.1186/ISRCTN40152556). The first participant was recruited on February 10, 2021.

Early preterm abdominal pregnancy: A case report

Background: Abdominal pregnancies, a rare form of ectopic pregnancy, pose significant risks to themother and fetus. The severity of complications depends on the gestational age at presentation,abdominal pregnancy location, and attachment to abdominal organs.Case presentation: A 38-year-old, para 3+0 gravida 4 presented with abdominal pain and moderatepallor at 30 weeks gestational age, extrapolated from obstetric ultrasound due to an unknown last normalmenstrual period. She was HIV-positive and on highly active antiretroviral therapy. She had a history oforal contraceptive use before conception. Ultrasound revealed a viable intraabdominal pregnancy at 30weeks with the placenta attached to the mesentery in the right upper quadrant with a nongravid uterus.She was transfused with four units of packed red blood cells before elective laparotomy. Intraoperatively,the gestational sac in the upper quadrants and membranes were ruptured. A live male infant wasdelivered, weighing 990g, Apgar scores of 8 at 1 and 9 at 5. The placenta, which was attached to the leftfallopian tube and the broad ligament was extracted. The infant was admitted to the newborn unitbecause of prematurity. The postoperative period was uneventful, and the mother and baby were doingwell at the writing of this abstract.Conclusion: Early preterm abdominal pregnancy should be managed by elective laparotomy to optimizeoutcomes for both the mother and fetus. Cases with limited attachment to the viscera tend to havefavorable outcomes. Neonatal outcome primarily depends on gestational age at delivery.