Live Birth Group Research Articles

O-236 The clinical and morphokinetic factors indicating a risk of pregnancy loss after a euploid embryo transfer

Abstract Study question Are there any clinical and morphokinetic factors which may affect the pregnancy outcome after a euploid embryo transfer? Summary answer Body mass index (BMI), endometriosis, the history of recurrent pregnancy losses and the number of previous frozen-thawed unsuccessful embryo transfer (FET) cycles impact pregnancy outcomes. What is known already Preimplantation genetic testing for aneuploidy (PGT-A) is largely used for various indications to detect chromosomal abnormalities in assisted reproductive technologies (ART). The most common reason for the first trimester pregnancy losses is chromosomal abnormalities. However, the factors that cause pregnancy loss after a euploid embryo transfer are not fully understood. Study design, size, duration The pregnancy results of all single euploid embryos tested with next generation sequencing (NGS) in Istanbul Memorial Hospital between January 2017 and March 2020 were evaluated in this single center retrospective cohort study. The cases that resulted in pregnancy below the age of 43 were analyzed according to outcomes; biochemical pregnancy loss (Group 1), clinical pregnancy loss (Group 2) and live birth (Group 3). Participants/materials, setting, methods The transfer of 2041 single euploid embryos resulted in 1492 pregnancies. The clinical and morphokinetic parameters observed using time lapse imaging (TLI) were compared among the three groups. Main results and the role of chance The overall pregnancy rate was 73.1%, the rates of biochemical pregnancy losses and clinical losses were 9.7% and 11.4% respectively. The live birth rate was 58.5%. The indications for PGT-A were as follows; recurrent pregnancy losses (RPL) (14.9%), recurrent implantation failure (RIF) (11.7%), advanced maternal age (AMA) (28.6%), a history of abnormal fetal karyotype or single gene defects (12.1%). In 32.6% cases PGT-A was performed to reduce time to pregnancy. There were no differences in terms of female age, AMH, the diagnosis or the duration of infertility, the mean numbers of oocytes retrieved, mature and fertilized oocytes. However, BMI values, the presence of severe endometriosis, including adenomyosis, the history of recurrent pregnancy losses and the number of previous unsuccessful FET cycles were significantly higher in Groups 1 and 2. When pregnancy losses were evaluated according to PGT indications, patients with a history of RPL had a significantly higher pregnancy loss rate (27.8%) compared to the other groups: AMA (19.6%), RIF (19.4%), genetic factors (21.6%) and cases where PGT was performed to reduce time to pregnancy (16.4%) (p < 0.05). When morphokinetic parameters were evaluated, they were found to be not significantly different in the three groups (p > 0.05). Limitations, reasons for caution The retrospective nature of the data is the major limitation of the study. On the other hand, the strength of the study is the large number of PGT-A tested embryos from a single center which used the same laboratory conditions. Wider implications of the findings PGT-A is widely used to avoid pregnancy losses. However, BMI values, the presence of severe endometriosis, including adenomyosis, the history of recurrent pregnancy losses and the number of previous unsuccessful FET cycles should be taken into consideration during counselling and/or treatment. Trial registration number not applicable

Analysis of related factors affecting cumulative live birth rates of the first ovarian hyperstimulation in vitro fertilization or intracytoplasmic sperm injection cycle: a population-based study from 17,978 women in China.

Background:More and more scholars have called for the cumulative live birth rate (CLBR) of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology. This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.Methods:Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles performed between January 2013 to December 2014. A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included. The study was followed up for 4 years to observe the CLBR. The multivariable logistic regression model was used to analyze the prognosis factor, P value of <0.05 was considered statistically significant.Results:The cumulative pregnancy rate was 58.14% (10,452/17,978), and the CLBR was 49.66% (8928/17,978). The female age was younger in the live birth group when compared with the non-live birth group (30.81 ± 4.05 vs. 33.09 ± 5.13, P < 0.001). The average duration of infertility was shorter than the non-live birth cohort (4.22 ± 3.11 vs. 5.06 ± 4.08, P < 0.001). The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group (both P < 0.001). Meanwhile, the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group (15.35 ± 7.98 vs. 11.35 ± 7.60, P < 0.001; 6.66 ± 5.19 vs. 3.62 ± 3.51, P < 0.001, respectively).Conclusions:The women's age, body mass index, duration of infertility years, infertility factors, controlled ovarian hyperstimulation protocol, the number of acquired oocytes, and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.

The unheard parental cry of a stillbirth: fathers and mothers.

Our objective was to compare the prevalence of depression, anxiety, stress, and domestic violence among parents after a stillbirth vs. livebirths and assessing of the need for psychological and pharmacological interventions for the affected individuals. This was a prospective cohort study conducted in a tertiary care public sector hospital Northern India. 150 consecutive couples with a recent stillbirth (group 1) and 150 couples with a recent live birth (group 2) were enrolled. They were screened for depression (EPDS scale), anxiety (GAD-7), stress (PSS). Apriori sample size was calculated. Screen positive mothers and fathers were compared for the presence of depression, anxiety and stress, domestic violence, and need for treatment interventions. Depression was higher in group 1 mothers (39.3 vs 14.0%, p < 0.001) as well as fathers (18.1 vs 6.7%, p value = 0.022). Anxiety and moderate to severe stress were also significantly higher in stillborn than liveborn groups respectively. Characteristics associated with higher risk are analyzed. Domestic violence was found in 6.7% in group 1 and 2.7% in group 2 mothers (p value 0.169). Pharmacotherapy and counselling were required by 11.3 and 18.0% in stillbirth versus 3.3 and 18.7% in livebirth group, respectively. Couples suffering stillbirths are at higher risk of depression, anxiety, and stress. We highlight this obstetrical public health issue, especially for the low middle income countries (LMIC) and advocate development of health policies for mental health screening of couples suffering stillbirths.

Neonatal and maternal outcomes among twin pregnancies stratified by mode of conception in the United States

To compare neonatal and maternal outcomes among twin pregnancies conceived as a result of different types of fertility treatments with those of spontaneously conceived twin pregnancies. Retrospective Cohort. Population-based analysis. Population-based analysis of twin pregnancies in the United States based on their mode of conception using the natality data from the National Center for Health Statistics from the Centers for Disease Control and Prevention (from January 2015 through December 2017). None. Adverse neonatal and maternal outcomes. The overall prevalence of early adverse maternal outcomes and medical complications and obstetric complications including the risk of unplanned hysterectomy, intensive care unit admission, maternal blood transfusion, and perineal laceration were significantly higher in the fertility treatment group (including both ovulation induction/intrauterine insemination and assisted reproductive technology groups) compared with those of the spontaneous conception group, even after adjusting for several potential confounders. The risk of adverse composite neonatal outcomes was slightly lower in the spontaneous conception live twin birth group even after adjustment for several potential confounders. The rate of maternal and neonatal morbidity in twins conceived via different fertility treatments was slightly increased compared with those of twins conceived spontaneously. Because the absolute risks of maternal and neonatal morbidity were low, overall reassurance regarding these outcomes can be provided to the patients undergoing all types of fertility treatments.

Which factors affect the likelihood of miscarriage after single euploid blastocyst transfer?

Research questionWhich parameters affect the likelihood of miscarriage after single euploid frozen–thawed blastocyst transfer (FBT)? DesignIn this retrospective study, clinical and laboratory data from 1051 single euploid FBTs were evaluated. Exclusion criteria were endocrine or systemic pathologies, uterine anomalies or pathologies, unilateral or bilateral hydrosalpinx, karyotypic abnormalities (either maternal or paternal) or thrombophilia. Patients were divided into two groups according to pregnancy outcome: live birth and miscarriage. ResultsBody mass index (BMI) (25.98 ± 0.5 versus 24.36 ± 0.21, P = 0.019), duration of infertility (6.62 ± 0.54 versus 4.92 ± 0.18, P = 0.006) and number of previous miscarriages (1.36 ± 0.13 versus 0.79 ± 0.05, P < 0.001) were significantly higher in the miscarriage group (n = 100) than in the live birth group (n = 589). Although the trophectoderm and inner cell mass (ICM) percentage scores were not statistically different among the miscarriage and live birth groups, the percentage of day-6 biopsied embryos was significantly higher in the miscarriage group. Binary logistic regression analysis revealed that BMI (OR 1.083, 95% CI 1.013 to 1.158, P = 0.02) and number of previous miscarriages (OR 1.279, 95% CI 1.013 to 1.158, P = 0.038) were independent factors for miscarriage. Patients with elevated BMI and a higher number of miscarriages were at increased risk of miscarriage. ConclusionAfter a single euploid FBT, BMI and number of previous miscarriages are predictors of miscarriage. Lifestyle interventions before FBT may decrease miscarriage rates.

Analysis of risk factors for obstetric outcomes after hysteroscopic adhesiolysis for Asherman syndrome: A retrospective cohort study.

To investigate the factors influencing placenta accreta in pregnant women who previously underwent hysteroscopic adhesiolysis (HA). This retrospective study enrolled 265 women with intrauterine adhesions (IUAs) at the Sir Run Run Shaw Hospital from January 2014 to December 2018. We followed up their pregnancy outcomes and maternal complications. The menstrual pattern and gestational history before operation were significantly different between the live birth and pregnancy loss groups. The age, extent of cavity involved, type of adhesions, times of adhesiolysis performed, and time interval from surgery to pregnancy were not significantly different between these two groups. In the third trimester, 48 of 140 patients had 53 perinatal complications, including placenta accreta (27), gestational diabetes mellitus (10), pregnancy-induced hypertension (6), postpartum hemorrhage (4), intrahepatic cholestasis of pregnancy (2), placenta previa (1), oligohydramnios (1), and intrauterine growth restriction (1). Logistic regression analysis showed that extent of cavity involved and times of adhesiolysis performed were associated with placenta accreta. The extent of cavity involved and times of adhesive separation surgeries were risk factors for placenta accreta in patients. The menstrual model and gestational history may provide the main predictive factors for pregnancy loss.

The predictive value of endometrial thickness in 3117 fresh IVF/ICSI cycles for ectopic pregnancy

ObjectivesTo evaluate the predictive value of endometrial thickness (EMT) during in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles for ectopic pregnancy (EP). MethodsA total of 3068 patients with 3117 fresh IVF/ICSI cycles between January 2016 and February 2019 from the Reproductive Medicine Center of Sun Yat-Sen Memorial Hospital were included in this retrospective study. The patients were divided into an EP group (n = 92) and an intrauterine pregnancy (IUP) group (n = 3025). Multiple logistic regression analysis was conducted to evaluate the EP risk factors. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the risk factors for EP and calculate the cutoff value of EMT for EP prediction. ResultsThe incidence rate of EP was 2.95 % (92/3117). After adjustment for other factors in the logistic regression model, the incidence of EP decreased by 55 % with an EMT > 10 mm compared with an EMT ≤ 10 mm (odds ratio 0.450, 95 % confidence interval 0.296−0.684, P < 0.001). The EMT in the EP group was significantly thinner than that in the live birth (n = 2540) and spontaneous abortion (n = 485) groups (p < 0.017). The cutoff value of EMT for EP prediction was 10.65 mm, with a sensitivity of 59 % and a specificity of 63 %. ConclusionA decreased risk of EP was found among the patients with an EMT > 10 mm prior to embryo transfer. A certain EMT is needed to reduce the incidence of EP.

Consistency and timeliness of intrapartum care interventions as predictors of intrapartum stillbirth in public health facilities of Addis Ababa, Ethiopia: a case-control study.

Introductionapproximately one-third of the global stillbirth burden occurs during intrapartum period. Intrapartum stillbirths occurring in the health facilities imply that a foetus was alive on admission to labour and had greater chances of survival with optimum obstetric care. Active monitoring and follow-up by skilled birth attendants becomes critical to determine the progress of labour and to decide any emergency obstetrical care actions. Timely monitoring of labour progress indicators including fetal heart rate (FHR), uterine contraction maternal vital signs, vaginal examination (VE) are vital in reducing intrapartum stillbirth.Methodsa case-control study was conducted using primary data from chart review of medical records of women who experienced intrapartum stillbirth in 20 public health centres and 3 public hospitals of Addis Ababa between July 1st, 2010 to June 30th, 2015. Data were collected from charts of all cases of intrapartum stillbirths meeting the inclusion criteria and randomly selected charts of controls from each public health facility in 2: 1 control to case ratio.Resultsover 90% of both cases and controls received FHR monitoring care albeit the timing was substandard. More women in the live birth group than intrapartum stillbirth group received timely care related to uterine contraction (OR 2.42, 95% CI 1.77 - 3.30) and blood pressure monitoring (aOR 1.41, 95% CI 1.09 - 1.81). 1.2% and 0.3% of women in the intrapartum stillbirth and livebirth groups developed eclampsia respectively.Conclusionsubstandard timing and application of labour monitoring interventions including FHR, uterine contraction can predict intrapartum stillbirth in public health facilities.

Quantifying CD138+ cells in the endometrium to assess chronic endometritis in women at risk of recurrent pregnancy loss: A prospective cohort study and rapid review.

To determine the value of uterine CD138+ cells, as a marker of chronic endometritis, in predicting subsequent reproductive outcome in women with history of recurrent pregnancy loss. A prospective longitudinal study. Tertiary specialized clinic. Women with history of recurrent pregnancy loss or implantation failure over a 12-months follow-up period. We quantified the CD138+ cells/high powered field (hpf) using immunohistochemistry and image analysis of endometrial biopsies obtained during the secretory stage post ovulation. Live birth and subsequent pregnancy loss. We calculated the receiver operator curve for predicting subsequent pregnancy loss and reported using relative risk (RR) and 95% confidence intervals (CI). We enrolled 344 women of whom 88 became pregnant (88/344, 25.5%). Half of them had a subsequent live birth (47/88, 53%) and the rest lost their pregnancy (41/88, 46%). The median CD138+ score was significantly lower in the live birth group (P < 0.005) and women with a CD138+ score ≥ 16/hpf had a higher risk of subsequent miscarriage (RR 10.0, 95% CI 2.78-36.02). CD138+ cells count showed a good prediction for subsequent pregnancy loss in high-risk women with an area under the curve of 0.75 (95% CI 0.59-0.82, P = 0.01). A cut-off value of 4-6 cells/hpf offered the best predictive accuracy with higher scores predicting worse reproductive outcome. Our findings are limited by the small event rate and the sample size of our cohort. Quantifying CD138+ cells by immunohistochemistry in women with a history of recurrent pregnancy loss is helpful to diagnose chronic endometritis and predict subsequent reproductive outcome.

Change of serum B-cell activating factor level in patients with positive antiphospholipid antibodies and previous adverse pregnancy outcomes and its significance.

Background:B-cell activating factor (BAFF) is vital for B cell survival. Serum BAFF levels are elevated in thrombotic antiphospholipid syndrome, but little is known about levels in patients with positive antiphospholipid antibodies (aPLs) and previous adverse pregnancy outcomes (APOs). We aimed to analyze serum BAFF concentrations of these patients in early pregnancy along with different pregnancy outcomes.Methods:Thirty-six pregnant patients positive for aPLs and previous APOs (patient group), 25 healthy pregnant females (HP group) and 35 healthy non-pregnant females (HNP group) from the Peking University Third Hospital, between October 2018 and March 2019, were enrolled in this study. Serum of HNP and serum of patients as well as HP in the first gestational trimester were collected. Enzyme-linked immunosorbent assay kits were used to measure serum BAFF and interferon-alpha (IFN-α) concentrations. Cytometric bead array analysis was used to measure serum concentrations of cytokines. The patient group was further divided into APOs and non-APOs (NAPOs) group, fetal loss and live birth group according to pregnancy outcomes. The Mann-Whitney U-test was used to assess significance between and within groups. Spearman rank-order was used to evaluate correlation coefficients between BAFF and related cytokines.Results:The serum BAFF level in HP group was significantly lower than HNP group (245.24 [218.80, 265.90] vs. 326.94 [267.31, 414.80] pg/mL, Z = −3.966, P < 0.001). The BAFF level was obviously elevated in patient group compared to that in HP group (307.77 [219.86, 415.65] vs. 245.24 [218.80, 265.90] pg/mL, Z = −2.464, P = 0.013). BAFF levels in APOs group tended to be higher than that in NAPOs group (416.52 [307.07, 511.12] vs. 259.37 [203.59, 375.81] pg/mL, Z = −2.718, P = 0.006). Compared to HP group, concentrations of IFN-α, interleukin (IL-6) and tumor necrosis factor were higher in patient group (33.37 [18.85, 48.12] vs. 13.10 [6.85, 25.47] pg/mL, Z = −2.023, P = 0.043; 39.16 [4.41, 195.87] vs. 3.37 [2.92, 3.90] pg/mL, Z = −3.650, P < 0.001; 8.23 [2.27, 64.46] vs. 1.53 [1.25, 2.31] pg/mL, Z = −3.604, P < 0.001, respectively). Serum BAFF levels had a positive correlation with the concentrations of both IL-6 and IL-10 (IL-6: r = 0.525, P = 0.002; IL-10: r = 0.438, P = 0.012).Conclusions:Serum BAFF levels are increased in patients with positive aPLs and previous APOs as compared to healthy pregnant females and tend to be higher in individuals with current APOs. The BAFF levels have a positive correlation with serum IL-6 and IL-10.

Malignant Ovarian Tumors During Pregnancy: A Multicenter Retrospective Analysis.

PurposeThe aim of this study was to investigate the clinical characteristics and management of malignant ovarian tumors during pregnancy, as well as the feto-maternal outcomes and analyze the influential factors on the pregnancy outcomes.Patients and MethodsEighty-five patients with ovarian malignancies during pregnancy treated at 12 tertiary hospitals between 2009 and 2019 were analyzed in this study. The clinical features, histopathological characteristics, clinical management, and maternal and perinatal outcomes were retrospectively analyzed. The clinical features and managements were compared between abortion group and live birth group.ResultsThe following diagnoses were made: 41 (48.24%) patients with borderline ovarian tumors, 18 (21.18%) patients with epithelial ovarian cancers, 17 (20.00%) patients with non-epithelial ovarian malignancies and 9 (10.59%) patients with metastatic ovarian tumors. Thirty-six (42.45%) patients underwent conservative surgical treatment. Thirty-four (40.00%) patients opted for fertility-sparing surgery, and fifteen (17.56%) patients received radical surgery. Chemotherapy was administered to 32.94% of the patients. The proportion of ovarian malignancies diagnosed in the first trimester in the abortion group was higher than that in the live birth group (P<0.05). However, tumor diameter, reproductive history, stage and surgical indications showed no significant differences between groups. A total of 67 live babies were recorded in this study, including 19 premature babies and 1 full-term newborn who died of respiratory distress. All of the BOTs were diagnosed with stage I, among whom 38 (92.68%) patients exhibited disease-free survival. Twenty-eight ovarian cancers were in stage I–II and 26 of them had disease-free survival with the longest follow-up time of 10 years. Five of the sixteen patients in advanced stage (stage III–IV) died, four of whom had metastatic tumors.ConclusionPregnant women with early-stage malignant ovarian tumors appear to have favorable outcomes. Conservative surgery is acceptable for early-stage borderline ovarian tumors during pregnancy. The gestational age of ovarian malignancy detection is key for pregnancy outcomes.

Obstetrical and perinatal outcomes in fetuses with early versus late sonographic diagnosis of short femur length: A single-center, prospective, cohort study

ObjectivesThe aim of this study was to evaluate obstetrical and perinatal outcomes in fetuses with short femur length diagnosed before or after 24 weeks of gestation. Study DesignThis was a prospective cohort study on singleton pregnancies with a diagnosis of fetal femur < 5 centile. Included patients were divided into two groups: patients with a first diagnosis of femur length < 5th percentile at 14-24 weeks (group A) and those with the first diagnosis made at > 24 weeks (group B). Results147 patients were included for the analysis. Group A and group B included 66 (44.9%) and 81 (55.1%) cases. Abnormal fetal karyotype and skeletal dysplasia rates were significantly higher (27.3% vs 3.7%,P < 0.001 and 19.7% vs 3.7%, P = 0.002) in group A. Women in group B had a higher incidence of small for gestational age and intrauterine growth restriction (7.6% vs 24.7%, P = 0.007 and 19.7% vs 44.4%, P = 0.002). There was a significant higher incidence of live births in group B (34.9% vs 97.5%, P < 0.001), while the rate of termination of pregnancy was increased in group A (56.1% vs 1.2%, P < 0.001). No significant difference was found in perinatal outcomes of live births, when comparing group A and B. ConclusionsThe incidence of abnormal karyotype and skeletal dysplasia is higher when short femur length diagnosed earlier in gestation, while the incidence of small for gestational age, intrauterine growth restriction and the rate of live births are significantly increased when short femur length is diagnosed later during pregnancy.

Labour admission assessment results of index pregnancy as predictors of intrapartum stillbirth in public health facilities of Addis Ababa: A case-control study.

BackgroundApproximately one-third of the global stillbirth burden occurs during intrapartum period. The ability to assess obstetric parameters including effacement, dilatation, uterine contraction, decent, rupture of the uterus, and moulding of the foetal head are among the essential competencies required by obstetric service providers admitting women for labour in health facilities. Misdiagnosis of these conditions could result in unnecessary obstetric interventions and unfavourable obstetric outcomes including intrapartum stillbirth. This study aimed to assess associations between missed diagnosis plus complication of labour on admission and intrapartum stillbirth.MethodsA case-control study using primary data from chart review of medical records of women who experienced intrapartum stillbirth in 20 public health centres and three public hospitals of Addis Ababa between 01 July 2010 and 30 June 2015 was conducted. Data were collected from charts of all cases meeting the inclusion criteria. Medical records of women with livebirths were randomly selected and reviewed from each public health facilities in two to one (2:1) control to case ratio. Accordingly, 728 cases of stillbirth out of 1,056 charts met the inclusion criteria whereas 1,551 controls out of 1,705 were also considered in the study.ResultsProportionally, more women in the stillbirth group (39.4%) than in the livebirth group (30.2%) experienced ruptured membrane on admission, with the difference being statistically significant (OR 1.7, 95% CI 1.37–2.03). Significantly higher proportion of women in the intrapartum stillbirth group experienced FRH lower than 110/min, a result suggestive of foetal distress on admission. Proportionally, more women in the intrapartum stillbirth group (14.5%) than in the livebirth group (4.5%) had breech foetal presentation on admission for labour, the difference being statistically significant (aOR 3.26 95% CI 1.93–5.50). Intrapartum stillbirth was slightly higher among women with cervical dilatation 4cm or more on admission (OR 1.2, 95% CI 1.00–1.45). This could be owing to delay in seeking obstetric care or misdiagnosis of the condition, a situation that seeks more rigorous study to determine the underlying causal links. Diagnosis of foetal member was missed among more cases than controls where the difference was statistically significant (aOR 1.51, CI 1.03–2.19).ConclusionLow FHR, non-vertex foetal presentations and ruptured cervical membrane were predictors of intrapartum stillbirth. Health facilities could avert unnecessary foetal loss by undertaking timely actions to manage obstetric emergencies on admission to labour.

Placental Morphology and Cellular Characteristics in Stillbirths in Women With Diabetes and Unexplained Stillbirths.

Women with diabetes have increased stillbirth risk. Although the underlying pathophysiological processes are poorly understood, stillbirth is frequently related to abnormal placental structure and function. To investigate placental morphology and cellular characteristics in the placentas of women with diabetes who had stillbirths and stillbirths of unexplained cause. Placentas from women with uncomplicated live births, live births in women with diabetes, unexplained stillbirths, and stillbirths related to diabetes (n = 10/group) underwent clinical histopathologic assessment and were also investigated using immunohistochemical staining to quantify syncytial nuclear aggregates, proliferation, trophoblast area, vascularization, T cells, placental macrophages (Hofbauer cells), and the receptor for advanced glycation end products. Ki67+ cells were decreased in unexplained stillbirths compared with live births in women with diabetes. Both stillbirth groups had increased cytokeratin 7+/nuclear area compared with controls. Blood vessels/villi were decreased in unexplained stillbirth compared with live births from women with diabetes. Compared with uncomplicated controls, CD163+ macrophages were increased in live births in women with diabetes and unexplained stillbirths, and further increased in stillbirths related to diabetes. There was no change in CD3+ T cells or syncytial nuclear aggregates. Receptor for advanced glycation end products-positive cells were decreased in both stillbirth groups compared with diabetes-related live births. Co-localization of receptor for advanced glycation end products in macrophages was increased in both stillbirth groups compared with live birth groups. Stillbirths related to diabetes exhibit placental phenotypic differences compared with live births. Further investigation of these parameters may provide understanding of the pathologic mechanisms of stillbirth and aid the development of stillbirth prevention strategies.

Pregnancy outcomes and risk factors in pregnant women with systemic lupus erythematosus

Objective: To analyze the pregnancy outcomes and risk factors in pregnant women with systemic lupus erythematosus (SLE), for providing a reference for the clinical diagnosis and treatment of the SLE. Materials and Methods: Seventy-eight SLE patients with 82 pregnancies were enrolled in this study. The general information of patients, maternal history data, clinical symptoms, and laboratory examination data one to three months before pregnancy, during pregnancy, at delivery and after childbirth, drug treatment, and pregnancy outcomes were collected. The single factor and logistic regression analyses of the risk factors related to SLE with deterioration and fetal loss were performed. Results: The single-factor analysis showed that there was significant difference in complement 3, 24-hour urinary protein, anti-dsDNA antibody, anti-CL antibody, pre-pregnancy prednisone dose, and SLE disease activity index (SLEDAI) between SLE with deterioration group and SLE without deterioration group, respectively (p &lt; 0.05 or p &lt; 0.01), with significant difference in complement 3, combined antiphospholipid syndrome (APS), SLEDAI, and SLE deterioration during pregnancy between fetal loss group and live birth group, respectively (p &lt; 0.01). The multi-factor regression analysis showed that, the complement 3 and SLEDAI were the main risk factors of SLE with deterioration during pregnancy, and the combined APS and SLEDAI were the main risk factors of fetal loss. Conclusion: The pregnancy has a high risk in women with SLE. The complement 3 and SLEDAI are the main risk factors of SLE with deterioration during pregnancy, and the combined APS and SLEDAI are the main risk factors of fetal loss. The reasonable and effective strategies should be formulated based on these factors, in order to reduce the risk of adverse pregnancy outcomes.

Management strategies of heterotopic pregnancy following in vitro fertilization-embryo transfer

ObjectiveThe purpose of this study was to evaluate the efficiency and safety of different treatment modalities for heterotopic pregnancy (HP) in vitro fertilization-embryo transfer (IVF-ET) cycles to avoid influence on intrauterine pregnancy (IUP). Materials and methodsCases of HP (n = 90) were from the IVF/ICSI registry database at the Reproductive Hospital Affiliated to Shandong University. An additional 360 women were randomly selected as controls. The primary outcome to examine the risk factors, diagnostic modalities and the impact of different treatment modalities for HP. ResultsOur results showed that surgical treatment had a certain effect on improving the live-birth rate, although the effect was not statistically significant (87.9% vs. 70.8%, P = 0.055). The risk factors for HP included previous tubal surgery and hydrosalpinx. Fourteen days after embryo transfer, the serum levels of β-human chorionic gonadotropin (β-hCG) and estradiol (E2) were lower in the HP group than in the IUP group (P < 0.05). Furthermore, age and endometrial thickness showed a significant difference between the early abortion and the live-birth groups of HP. ConclusionsIn our retrospective study, we supported early surgical laparoscopic intervention to minimize the incidence of abortion of IUP, which resulted in a better live-birth rate. A history of ectopic pregnancy and previous tubal surgery may increase the risk of HP. Low levels of serum β-hCG and E2 on the 14th day after embryo transfer could indicate the incidence of HP.

Is hysteroscopic metroplasty using the incision method for septate uterus a risk factor for adverse obstetric outcomes?

This study aimed to assess whether hysteroscopic metroplasty using the incision method for septate uterus is a risk factor for adverse obstetric outcomes during pregnancy or delivery. This retrospective, single-center cohort study of obstetric complications included 41 patients with recurrent pregnancy loss or unexplained infertility who underwent hysteroscopic metroplasty using the incision method for septate uterus. As controls, we recruited 1139 women who delivered at our hospital during the same period. The primary outcomes were mean weeks of delivery, mean birthweight, rate of cesarean section, rate of breech presentation, rate of post-partum hemorrhage, rate of preterm delivery, rate of placental abruption, rate of placenta previa, rate of placenta accreta and uterine rupture during pregnancy and delivery. The two groups did not differ in terms of age, mean weeks of delivery, mean birthweight, rate of post-partum hemorrhage, rate of preterm delivery, rate of placental abruption, rate of placenta previa or rate of placenta accreta. The rates of cesarean section and breech presentation were significantly higher in the study group than in the control group (56.1 vs 27.7%; P = 0.0002 and 19.5 vs 6.8%; P = 0.007, respectively). There were no cases of uterine rupture during pregnancy or delivery following hysteroscopic metroplasty. Hysteroscopic metroplasty using the incision method for septate uterus is not a risk factor for adverse obstetric outcomes. No severe complications, such as placenta abruption, placenta previa, placenta accreta, uterine rupture or heavy hemorrhage, were observed in the postoperative live birth group.

Endogenous progesterone levels could predict reproductive outcome in frozen embryo replacement cycles supplemented with synthetic progestogens: A retrospective cohort study.

PurposeA retrospective, cohort study was conducted between 2009 and 2017 in a private infertility center to determine the predictive value of endogenous estrogen (E2) and progesterone (P4) levels in hormone‐replacement frozen embryo replacement (FER) treatment cycles.MethodsA total of 120 consecutive, infertile patients who became pregnant after FER cycles were analyzed (age: 37.4 ± 4.4 years). Electively vitrified blastocysts were created during natural cycle IVF or mild ovarian stimulation treatments and subsequently transferred through delayed vitrified‐thawed blastocyst transfer cycles supplemented with estrogens and a combination of synthetic progestogens. Serum E2 and progesterone P4 levels were intensively monitored every five days (from the day after embryo transfer until 9w1d of pregnancy) and compared among patients with a subsequent live birth (n = 76) or first‐trimester pregnancy loss (n = 44).ResultsEndogenous placental activity started as early as 5‐6th pregnancy week differing significantly according to pregnancy outcome. For P4, the exponential rise from 6w2d onwards allowed distinguishing between failing and successful conceptions. For P4, lower quartiles of the live birth group did not intersect with upper quartiles of the miscarriage group.ConclusionsInnovative FER protocols incorporating synthetic progestogens allow the correct measurement of endogenous placental activity and could help to monitor early first‐trimester ART pregnancies.

Post-warming degree of blastocoel re-expansion is the best prognosticator for live birth rates in vitrified-warmed single blastocyst transfer cycles

Recent studies have presented contradictory results regarding significance of Inner-cell-mass (ICM)/Trophectoderm (TE) gradation and degree of blastocoel expansion/re-expansion for increased live-birth rates. Also, few studies have reported combined results from fresh/frozen and single/double transfer cycles. This study aimed at individually assessing the relevance of grades of ICM, TE and degree of post-warm blastocoel re-expansion on live-birth rates exclusively in vitrified-warmed single-blastocyst transfer cycles. Retrospective study (n=216) vitrified-warmed elective single blastocyst transfer cycles. Oocyte donation, Embryo-donation, assisted hatching and preimplantation genetic diagnosis cycles were excluded. All blastocysts were graded as per Gardner and Schoolcraft method of classification as 1-6 for degree of expansion and grades A/B/C for ICM and TE. Natural-cycle endometrial preparation with hormone supplementation followed by luteal-phase support with micronized progesterone. Endometrial response was noted by ultrasound. Single blastocyst-transfer was done 3 hours after warming of vitrified blastocyst. Warmed blastocyst was compared with pre-vitrified blastocyst for degree of expansion, gradation of ICM/TE. β-hCG level measured on day8 of transfer indicated pregnancy. Live-birth was the primary outcome measure. Women were classified into Live-birth (LB; n=74) and non-pregnant (NP; n=142) groups. Age, BMI, infertility period, number of oocytes retrieved, rate of formation of good quality cleavage-stage and blastocyst-stage embryos and survival rates post-warming did not differ significantly between the two groups. Same brand of embryo-transfer catheter and same brand and volume of media was used for transfer. However, degree of re-expansion was significantly higher in LB group than in NP group (Mean ± SD: 3.6 ± 1.0 v 3.2 ± 0.94, P=0.0068). The Fisher-Exact test odds-ratio for achieving a live-birth with 3-4 degree of re-expansion was 2.78 (p=0.0016) whereas the odds ratio was much lower (0.36) with any other degree of re-expansion. Although ICM grade was higher/better in Live-birth group than in non-pregnant group, the difference remained statistically non-significant (Odds ratio 1.25, p=0.82). No significant difference was observed in TE grades between the two study groups (p=0.17). A notable difference was also observed in endometrial echopattern (p=0.03) although the endometrial thickness remained comparable between the groups. Thus, post-warming degree of re-expansion is the single most promising predictive factor for live birth rates in such cycles. Re-expansion of blastocoel to an expanded grade 3/4 is superior to ICM and TE cell gradation for better live-birth rates in vitrified-warmed single blastocyst transfer cycles. However, larger multicentric trials may be required to establish it as robust predictor of live-birth.

Elevated percentage of CD3+T cells and pregnancy outcome in women with recurrent pregnancy loss

BackgroundEven though the immune factor is not yet established as a cause of recurrent pregnancy loss (RPL), tons of other studies have shown that a significant proportion of immune abnormalities exist in RPL. MethodsWe conducted a retrospective cohort study with 850 women who were diagnosed with RPL. The percentages of CD3+, CD3+CD4+ and CD3+CD8+T cells of each participant, detected by flow cytometry, were obtained before pregnancy and at 6 weeks of gestation as part of their routine medical examination. ResultsPeripheral blood CD3+ T cells prior to pregnancy (at baseline), increased significantly in women who had a miscarriage compared with the subsequent live birth group. Moreover, the percentage of CD3+ and CD3+CD4+T cells during pregnancy increased significantly as compared with the baseline level. After adjusting for potential confounders, the multiple regression equation showed that the CD3+ T cells <67.84% was associated with the risk of miscarriage (OR 1.05, 95% CI, 1.01 to 1.11, p = .04). Additionally, a nonlinear relationship was observed between the percentage of CD3+T cells and the risk of miscarriage. ConclusionsThe risk of miscarriage increased as the percentage of population with CD3+ value below 67.84% has increased, nevertheless, the miscarriage risk did not increase further when the level of CD3+T cells was >67.84%.