Subsequent Pregnancy Outcomes Research Articles

Karyotype of first clinical miscarriage and prognosis of subsequent pregnancy outcome

Research questionIs the karyotype of the first clinical miscarriage in an infertile patient predictive of the outcome of the subsequent pregnancy? DesignRetrospective cohort study of infertile patients undergoing manual vacuum aspiration with chromosome testing at the time of the first (index) clinical miscarriage with a genetic diagnosis and a subsequent pregnancy. Patients treated at two academic-affiliated fertility centres from 1999 to 2018 were included; those using preimplantation genetic testing for aneuploidy were excluded. Main outcome was live birth in the subsequent pregnancy. ResultsOne hundred patients with euploid clinical miscarriage and 151 patients with aneuploid clinical miscarriage in the index pregnancy were included. Patients with euploid clinical miscarriage in the index pregnancy had a live birth rate of 63% in the subsequent pregnancy compared with 68% among patients with aneuploid clinical miscarriage (adjusted odds ratio [aOR] 0.75, 95% CI 0.47–1.39, P = 0.45, logistic regression model adjusting for age, parity, body mass index and mode of conception). In a multinomial logistic regression model with three outcomes (live birth, clinical miscarriage or biochemical miscarriage), euploid clinical miscarriage for the index pregnancy was associated with similar odds of clinical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage for the index pregnancy (32% versus 24%, respectively, aOR 1.49, 95% CI 0.83–2.70, P = 0.19). Euploid clinical miscarriage for the index pregnancy was not associated with likelihood of biochemical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage (5% versus 8%, respectively, aOR 0.46, 95% CI 0.14–1.55, P = 0.21). ConclusionPrognosis after a first clinical miscarriage among infertile patients is equally favourable among patients with euploid and aneuploid karyotype, and independent of the karyotype of the pregnancy loss.

The association between prior cesarean delivery and subsequent in vitro fertilization outcomes in women undergoing autologous, frozen-thawed single euploid embryo transfer

The rates of cesarean deliveries continue to increase worldwide. Previous work suggests an association between a previous cesarean delivery and reduced fertility in natural conception and invitro fertilization treatment cycles. To our knowledge, there is no published research that explored the relationship between a previous cesarean delivery and the clinical outcomes after invitro fertilization and the subsequent transfer of a single frozen-thawed euploid embryo. This study aimed to investigate the relationship between the previous mode of delivery and subsequent pregnancy outcomes in patients undergoing a single frozen-thawed euploid embryo transfer after invitro fertilization. A retrospective cohort study was performed at a single academic fertility center from January 2012 to April 2020. All women with a history of a live birth undergoing autologous, frozen-thawed single euploid embryo transfers were identified. Cases included patients with a single previous cesarean delivery; controls included patients with a single previous vaginal delivery. Only the first embryo transfer cycle was included. The primary outcome was the implantation rate. Secondary outcomes included ongoing pregnancy and live birth rates, biochemical pregnancy rate, and clinical miscarriage rate. A total of 525 patients met the inclusion criteria and were included in the analysis. Patients with a previous cesarean delivery had a higher body mass index (24.5±4.5 vs 23.4±4.1; P=.004) than those in the vaginal delivery cohort; the rest of the demographic data were otherwise similar. In a univariate analysis, the implantation rate was significantly lower in patients with a previous cesarean delivery (111/200 [55.5%] vs 221/325 [68.0%]; P=.004). After adjusting for the relevant covariates, a previous cesarean delivery was associated with a 48% reduction in the odds of implantation (adjusted odds ratio, 0.52; 95% confidence interval, 0.34-0.78; P=.002). In addition, after adjusting for the same covariates, a previous cesarean delivery was significantly associated with a 39% reduction in the odds of an ongoing pregnancy and live birth (adjusted odds ratio, 0.61; 95% confidence interval, 0.41-0.90; P=.01). There were no differences in the biochemical pregnancy rates or clinical miscarriage rates. This study demonstrated a marked reduction in implantation and ongoing pregnancy and live birth associated with a previous cesarean delivery in patients undergoing a single euploid embryo transfer. Our work stresses the importance of reducing the primary cesarean delivery rates at a national level and elucidating the mechanisms behind the substantially lower implantation rates after a cesarean delivery.

Effects of interpregnancy interval on pregnancy outcomes of subsequent pregnancy: a multicenter retrospective study

Objective: To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy. Methods: A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO's recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics. Results: A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant (P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% (OR=1.42, 95%CI: 1.07-1.88, P=0.015), 46% (OR=1.46, 95%CI: 1.13-1.88, P=0.004), and 64% (OR=1.64, 95%CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study (P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age (OR=2.87, 95%CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 (OR=1.59, 95%CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes (OR=1.58, 95%CI: 1.18-2.13, P=0.002) and premature delivery (OR=1.52, 95%CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM (OR=5.34, 95%CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM (OR=1.44, 95%CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia (OR=4.11, 95%CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia (OR=1.46, 95%CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery (OR=1.47, 95%CI: 1.13-1.92, P=0.004). Conclusions: Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Timing of early resynchronization protocols affects subsequent pregnancy outcome in dairy cows

The aim of this study was to evaluate the outcomes of an early resynchronization protocol (Resynch) initiated at different timepoints after timed artificial insemination (TAI) and with unknown pregnancy status. Holstein cows (n = 164) were submitted to the following TAI protocol: D0, insertion of an intravaginal progesterone (P4) device and 2 mg im estradiol benzoate (EB); D8, removal of P4 device and treatment with 0.5 mg im sodium cloprostenol (PGF); D9, 0.1 mg im Lecirelin (LEC); and D10, TAI1. Cows were then randomly assigned to Resynch protocols starting either on day 20 (Resynch20D, n = 82) or 25 after TAI1 (Resynch25D, n = 82) with the insertion of a new P4 device and EB treatment. In both groups, P4 device was removed on day 8 after the beginning of Resynch, the same day of pregnancy diagnosis by ultrasonography. In pregnant cows there was no further action. Non-pregnant cows were treated with 0.5 mg im PGF, had a blood sample collected for serum P4 analysis and we measured and recorded the size of the largest follicle and the presence or absence of a corpus luteum (CL). One day later, cows were treated with 0.1 mg im LEC and TAI2 occurred 12–14 h later. The diameter of the largest follicle and serum P4 were compared between groups by ANOVA for the main effects of treatment, presence of a CL, and their interaction, whereas pregnancy per artificial insemination (P/AI) and the percentage of cows with a CL on the day of ultrasonography were analyzed using the Chi-square test. Follicle diameter on day 8 of Resynch was greater for cows in the Resynch20D group compared with Resynch25D (15.9 ± 3.9 vs 12.2 ± 2.5 mm, respectively; P = 0.046). The Resynch25D group had a greater percentage of cows with a CL (51.9 vs 18.9%, respectively; P = 0.0008) and higher serum P4 (2.8 ± 1.1 vs 1.7 ± 0.8 ng/mL; P = 0.041) at the end of the protocol compared with Resynch20D. P/AI at TAI1 was 35.4 and 36.6% (P > 0.10) for cows enrolled in Resynch20D and Resynch25D groups, respectively. P/AI to TAI2, after Resynch protocols, was greater in Resynch25D than Resynch20D (44.2 vs 22.6%, respectively; P < 0.05). In conclusion, starting an early resynchronization protocol 25 days after TAI increases P/AI compared with starting 20 days after TAI, and this was associated with a presumed greater proportion of cows with a functional CL at the moment of P4 device removal.

Red blood cell alloimmunization in pregnancy: A 10-year single-center study

Background/Aim. Pregnancy-induced red blood cell (RBC) alloimmunization is important not only because of the possible negative effects on subsequent pregnancy outcomes in case the fetus carries the antigen but also because of the optimal trans-fusion management in cases of obstetric hemorrhage. Timely detection of RBC antibodies is part of testing, prevention, and treatment strategy, aimed at achieving better outcomes for alloimmunized mothers with an affected fetus. The aim of the study was to determine the frequency and specificity of alloantibodies among pregnant women from the South Backa District, Serbia, with special attention to the incidence of anti-D alloantibodies. Methods. A retrospective study was conducted in the Blood Transfusion Institute of Vojvodina and covered the period from January 1, 2010, to December 31, 2019. Screening and antibody identification were performed by an indirect antiglobulin test in gel-microcards (ID-Card Liss/Coombs) with two test RBC (ID-DiaCell I-II screening cells, Bio-Rad, Cressier, Switzerland) on an automated system (IH-500, Bio-Rad). Results. Among 25,694 tested pregnant women, 1.38% were actively immunized, while 1.12% of women acquired antibodies in the current pregnancy. Among 3,622 (14.09%) RhD-negative women, 1.77% produced anti-D antibodies during the ongoing pregnancy. Distribution of anti-body specificity was: anti-D 23.34%, anti-M 11.85%, anti-E 9.41%, anti-K 9.41%, anti-C 5.92%, anti-Fyb 5.92%, anti-c 3.13%, anti-S 3.13%, anti-Lea 3.13%, anti-Leb 3.13%, anti-Cw 1.75%, anti-Jka 1.40%, anti-P 1.05%, anti-Lub 0.70%, anti-Fya 0.35%, autoantibody of undetermined specificity 0.70%, and irregular antibodies of undetermined specificity 15.68%. Conclusion. Immunoglobulin prophylaxis has led to a significant reduction in the frequency of D-alloimmunization among pregnant women in the South Backa District over the last ten years. However, the incidence of anti-D antibodies is still significantly higher than in published data for developed countries. We also identified the other, less commonly present, clinically significant antibodies. There is a need to introduce uniform recommendations for immunohematological testing in pregnancy on the territory of the Republic of Serbia in accordance with modern requirements.

Can information regarding the index stillbirth determine risk of adverse outcome in a subsequent pregnancy? Findings from a single-center cohort study.

Women with a history of stillbirth have an almost five-fold increased risk of stillbirth in a subsequent pregnancy, as well as increased risk of other adverse maternal and neonatal outcomes. The reasons for this association are not well understood but could relate to recurrent causes. We aimed to determine whether information from the time of index stillbirth, including cause, is associated with outcome of a subsequent pregnancy. A retrospective cohort study was conducted at a UK tertiary maternity center. Cases were included if stillbirth was investigated, subsequent pregnancy care was provided, and the birth occurred in the same unit. Data on maternal characteristics, findings of investigations, and classification of death using the ReCoDe system were extracted, and logistic regression was performed to determine whether these factors were associated with adverse outcome in the subsequent pregnancy. In this cohort (n=266), there were 69 adverse outcomes, including three perinatal deaths. Preterm delivery (16.2%) and birthweight <10th centile (12.4%) were the most common adverse outcomes. Of the preterm births, 69.8% were iatrogenic and 47% of these were due to abnormalities of fetal growth. On multivariate analysis women with a preexisting medical condition (adjusted odds ratio [aOR] 2.12, 95% CI 1.10-4.12) and those who smoked in their subsequent pregnancy (aOR 6.80, 95% CI 1.99-23.30) were at increased risk of adverse outcome. Neither ReCoDe classification of stillbirth (P=.61) nor gestation of stillbirth (P=.36) were associated with subsequent pregnancy outcome. Placental histopathological findings of maternal vascular malperfusion (aOR 11.34, 95% CI 2.20-58.62), fetal vascular malperfusion (aOR 9.27, 95% CI 1.09-78.82), and chorioamnionitis (aOR 6.35, 95% CI 1.16-34.78) in the index stillbirth were associated with adverse outcome in subsequent pregnancy. These associations were independent of maternal characteristics. Placental examination at time of stillbirth is important, as certain placental disorders inform the risk of adverse outcome in subsequent pregnancy. In this cohort, information regarding maternal characteristics and classification of cause of stillbirth do not provide significant prognostic information about the risk of adverse outcome in subsequent pregnancies. Optimal management of maternal medical disorders and access to smoking cessation are essential.

455 Abdominal versus laparoscopic myomectomy: does it affect subsequent pregnancy outcome?

To determine whether the abdominal (open) versus laparoscopic methods of myomectomy affect the obstetrical outcomes of subsequent pregnancies. A retrospective cohort study was conducted at a tertiary university medical center. The study population included women who had a documented birth following a myomectomy at our institution between the years 1997 and 2018. The obstetrical characteristics and immediate perinatal outcomes of the subsequent pregnancy following myomectomy were collected and compared between those who had open versus laparoscopic myomectomy. Data were retrieved from patients’ medical records via the institutional computerized database. Cases that lacked detailed surgery and delivery reports were excluded. Data was analyzed using a chi-square test for categorical variables and one-way ANOVA for continuous variables. A P-value < 0.05 was considered statistically significant. During the study period, 57 women met the inclusion criteria, of whom 66.6% (38/57) had open and 33.3% (19/57) had laparoscopic myomectomies. Women who underwent an open myomectomy had a higher rate of cesarean section than those in the laparoscopic group (89.5% vs. 42.1%, p<0.001). No cases of severe maternal or perinatal complications, uterine ruptures or placental abruptions were identified. No other significant differences were noted between the two types of myomectomy Open myomectomy is associated with a higher rate of cesarean delivery than laparoscopic. No adverse maternal or neonatal outcomes were detected in either study group.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

823 African-American race and subsequent pregnancy outcomes after a prior preterm birth

Whether African American (AA) race is a true causal risk factor for recurrent preterm birth (PTB) versus reflective of socioeconomic factors is debated. We investigate if AA race is a risk factor for recurrent PTB and adverse outcomes in the subsequent pregnancy after the first PTB, accounting for select social factors. Retrospective cohort study of nulliparas whose first delivery was between 16-37 weeks gestational age (GA) and had a subsequent pregnancy between 2013-2018. Multiple gestations in the index PTB were excluded. Women were grouped by self-identified race/ethnicity: AA, non-AA. The primary outcome was any recurrent PTB. Secondary outcomes were early PTB <34 weeks, delivery GA, cesarean delivery (CD), and perinatal outcomes. Outcomes were compared between groups; multivariable logistic regression calculated adjusted odds ratios (95% CI) with non-AA women as reference. Of 1744 women with singleton PTBs 16-37 weeks, 257 (15%) had a subsequent delivery in our study period –140 (54%) were AA. AA women were younger, more likely unmarried, used government insurance, and delivered vaginally in the index PTB (all p<0.05). Index PTB GA was similar (30 weeks AA vs 31 non-AA, p=0.12); AA women had a shorter interpregnancy interval (IPI: 11 months [IQR 5-22] vs 15 [9-25], p=0.003). In the subsequent pregnancy, there were no significant differences (crude or adjusted) in PTB <37 weeks, delivery GA, early PTB, preeclampsia, or perinatal outcomes between groups (Table). In fact, there were no subsequent PTBs <28 weeks. Of note, AA women had significantly higher odds of blood transfusion, and lower neonatal birthweights. Outcomes were unchanged when stratifying non-AA women into individual racial/ethnic groups. AA race was not significantly associated with risk for recurrent PTB, even when accounting for select socioeconomic factors – suggesting a role for race perhaps in the index PTB. While AA women had shorter IPIs, IPI was within appropriate ranges. Larger studies of race, recurrent PTB, and availability of immediate long-acting postpartum contraception are needed.

964 Prior spontaneous preterm birth: subsequent pregnancy outcomes among women with PPROM vs spontaneous preterm labor

Women with a history of spontaneous preterm birth (sPTB) are at an increased risk for recurrent preterm birth. Preterm premature rupture of membranes (PPROM) and spontaneous preterm labor (sPTL) have potentially varying mechanisms and etiopathogenesis. The objective of our study was to evaluate the differential impact of history of PPROM vs sPTL on subsequent pregnancy management and perinatal outcomes. Retrospective review of women delivering at a single hospital from July 2018- November 2019 to identify women with a history of sPTB of singleton gestations. The cohort was divided into two groups based on a history of sPTL vs PPROM. Demographic data, pregnancy management, and perinatal outcomes were abstracted through a review of electronic medical records and compared across the 2 groups using student’s t test and chi squared/Fischer’s exact test for continuous and categorical data respectively. Out of 2,803 women, 168 women had a history of sPTB: 125 (74%) with a history of sPTL and 43 (23%) with a history of PPROM. Demographic characteristics were similar across groups. We found no significant differences in the pregnancy interventions (Table 1) and perinatal outcomes (Table 2) among study groups. Subgroup analyses were performed evaluating the impact of vaginal vs IM progesterone. While there were no significant differences noted in women with a history of PPROM, differences were noted among women with a history of sPTL. Women who received IM progesterone had longer cervical lengths (mean ± SD) [36.3mm ± 4.4; N=21 vs 20.5 ± 12.2; N=18 p<0.001] and delivered at a later gestational age (mean ± SD) (37.2 ± 1.6 weeks; N=28 vs 34.7 ± 5.6 weeks; N = 23) as compared to women receiving vaginal progesterone. In our cohort, similar outcomes were noted in subsequent pregnancies among women with history of PPROM and sPTL. However, subgroup analyses in women with a history of sPTL suggest a potential benefit of IM progesterone. Further research in a larger cohort is warranted to delineate the differential impact of the history of sPTB in the context of PPROM vs sPTL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

1018 Microscopic focus of accreta on placental pathology: clinical context impacts morbidity risks in subsequent pregnancy

To describe association of microscopic focus of placenta accreta (MFPA) with subsequent pregnancy outcomes, and to compare outcomes among women with incidentally identified MFPA and those with symptomatic MFPA. Retrospective cohort of all deliveries at Kaiser Permanente Northern California from 2008-2019. A search of placental pathology database identified all cases with an index finding of MFPA and subsequent delivery of a live singleton. Index pregnancies with MFPA were categorized as asymptomatic (aMFPA) or symptomatic (sMFPA) by absence or presence of hemorrhagic morbidity and/or clinically adherent placenta. Rates of hemorrhagic morbidity and clinically adherent placenta in the subsequent pregnancy were compared among aMFPA and sMFPA index pregnancies in bivariate analysis and multivariate models controlling for potential confounders. Of 140 patients with MFPA in the index pregnancy, 64% were asymptomatic and 36% were symptomatic. Of the entire cohort, 28% had hemorrhagic morbidity and/or adherent placenta in the subsequent pregnancy. sMFPA in the index pregnancy was associated with higher rate of subsequent hemorrhagic morbidity and/or adherent placenta compared to aMFPA (39% vs 8%, p < 0.0001; Table 1). After adjusting for age, race, parity, body mass index, in-vitro fertilization, prior uterine surgery, cesarean delivery, and placenta previa, sMFPA in the index pregnancy was highly associated with hemorrhagic morbidity and/or adherent placenta compared to aMFPA (aOR 11.5, 95% CI 2.9-45.8). Of 71 patients with placental pathology in the subsequent pregnancy, 32% had recurrent MFPA. Recurrent MFPA was associated with increased morbidity compared to those without recurrence or those with no placental pathology (61% vs 40% vs 9%, p<0.0001; Table 2). Symptomatic MFPA is highly associated with hemorrhagic morbidity and/or adherent placenta in the next pregnancy compared with incidentally identified MFPA, particularly if MFPA is recurrent. This data can inform counseling and management of women with MFPA planning subsequent pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Bayesian Hierarchical Approach to Modelling Risk of Miscarriage during First Trimester of Subsequent Intrauterine Pregnancy in Women

Background: Accuracy of pregnancy outcome predictions are essential for clinicians to be effective in handling pregnant women experiencing symptoms of miscarriage when presented in the Early Pregnancy Units (EPU). Therefore, the focus of this study is to improve accuracy in modeling risk of miscarriage during first trimester of subsequent intrauterine pregnancy. To achieve this, the study formulates and analyze a Bayesian two-level random intercept logistic model M2 that takes into consideration hierarchical structure in the subsequent pregnancy outcome. This research work is motivated by the recent epidemiological research works that indicated a two-level structure in the subsequent pregnancy outcome with respect to previous pregnancy outcome. Materials and Methods: The proposed Bayesian hierarchical logistic random intercept model M2 was formulated using the concept of multilevel and Bayesian modeling. Analysis of the proposed Bayesian hierarchical logistic random intercept modelM2 was implemented using the Markov Chain Monte Carlo simulation, in specific Gibbs sampling. Assessment and comparison of the proposed Bayesian hierarchical logistic random intercept model to other reviewed classical approaches using the DIC and AIC. Results: Assessment of model fitness using DIC and AIC indicates that the proposed Bayesian two-level random intercept logistic modelM2has the lowest value of DIC= 121.2 among both classical and Bayesian approaches M0, M1 and M2. This indicates that the proposed Bayesian model M2 is the most plausible approach in modeling risk of miscarriage during first trimester of subsequent intrauterine pregnancy. Assessment of the between cluster variation as a result of the two-level hierarchical structure in subsequent pregnancy outcome, and prior information which, according to this study, are revealed to be essential in modeling risk of miscarriage during first trimester of the subsequent intrauterine pregnancy in women. Relative biases for the model parameter estimates were all below maximum threshold of |0.2| thus indicating accurate model estimations. Conclusion: The proposed Bayesian two-level random intercept logistic model M2 is the most plausible approach in modeling risk of miscarriage during first trimester of subsequent pregnancy. Taking into account between previous pregnancy outcome cluster variations and updating observations with prior information is essential to improve accuracy in modeling the risk of miscarriage during first trimester of subsequent pregnancy.

Association Between Interpregnancy Interval and Adverse Neonatal and Maternal Outcomes Stratified by Gestational Age in Previous Pregnancy in China

Background: With the increasing need to explore the association between interpregnancy interval (IPI) and adverse maternal and neonatal outcome, numerous studies have been conducted worldwide. However, national reports of the IPI in China are lacking. Furthermore, except for age as a known factor for IPI and adverse maternal and neonatal outcomes, the effect of gestational age in previous pregnancy is unknown. The aim of this study was to determine the IPI distribution between 2010 and 2019 and identify the effect of IPI and gestational age in previous pregnancy on adverse maternal and neonatal outcomes in China. Methods: We used individual data from China's National Maternal Near Miss Surveillance System (NMNMSS) between 2010 and 2019. The surveillance system collected data prospectively on all pregnant and postpartum women admitted to the obstetric department. The analysis was restricted to women with records of at least two consecutive singleton births and without any complication that the NMNMSS collected during their previous pregnancy. Multivariable generalized linear models with the restricted cubic spline (RCS) were used to evaluate the effect of IPI on each adverse neonatal and maternal outcome on different categories of gestational age in previous pregnancy. Further analysis was performed in subgroups categorized by the gestational age of previous pregnancy. Results: Over the study period, 408,843 women with 420,810 pregnancies were enrolled in our study. The median and quartile range of IPI was 32 [22, 47] months. Few women (49,084, 11.67%) became pregnant again within an extremely short (≤6 months) or long (≥60 months) IPI, and over half (289,846, 68.88%) of the women became pregnant again after an IPI between 7 and 42 months. The risk of large for gestational age (LGA), Gestational Diabetes Mellitus (GDM) and gestational hypertension was increased with increased IPI, while the risk of spontaneous preterm and small for gestational age (SGA) was inversely decreased with increased IPI. The relationship between IPI and all the other adverse neonatal and maternal outcomes was in a “U” shape. The risk of adverse neonatal and maternal outcomes differs between subgroups stratified by gestational age in the previous pregnancy. The risk of spontaneous preterm and abortion at short IPI, iatrogenic preterm, GDM, preeclampsia or eclampsia and gestational hypertension at long IPI increased more when women were of a greater gestational age in the previous pregnancy. Conclusions: This was the first comprehensive exploration of the IPIs of Chinese women from a national database. In this research, both extreme short and long IPI were associated with a higher risk of adverse maternal and neonatal outcomes. The gestational age in the previous pregnancy was also a determinant factor for the adverse maternal and neonatal outcomes in subsequent pregnancies. Funding Statement: This study was supported by the National Key R&D Program of China (Grant No. 2019YFC1005100), the National Health Commission of the People’s Republic of China, the China Medical Board (Grant No. 11-065), the WHO (Grant No. CHN-12-MCN-004888), and UNICEF (Grant No. 2016EJH016). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committee of the West China Second University Hospital.

Amniotic fluid embolism- implementation of international diagnosis criteria and subsequent pregnancy recurrence risk.

An international diagnostic criterion for amniotic fluid embolism (AFE) diagnosis has recently been published. Data regarding subsequent pregnancies is scarce. We sought to implement recent diagnostic criteria and detail subsequent pregnancies in survivors. A case series of all suspected AFE cases at a tertiary medical center between 2003 and 2018 is presented. Cases meeting the diagnostic criteria for AFE were included. Clinical presentation, treatment, and outcomes described. Pregnancy outcomes in subsequent pregnancies in AFE survivors detailed. Between 2003 and 2018 14 women were clinically suspected with AFE and 12 of them (85.71%) met the diagnostic criteria for AFE. Three cases occurred during midtrimester dilation and evacuation procedures, and the remaining occurred in the antepartum period. Of the antepartum cases, mode of delivery was cesarean delivery or vacuum extraction for expedited delivery due to presentation of AFE in 8/9 cases (88.88%). Clinical presentation included cardiovascular collapse, respiratory distress and disseminated intravascular coagulopathy (DIC). Heart failure of varying severity was diagnosed in 75% (9/12) cases. Composite maternal morbidity was 5/12 (41.66%), without cases of maternal mortality. 11 subsequent pregnancies occurred in four AFE survivors. Pregnant women were followed by a high-risk pregnancy specialist and multidisciplinary team if pregnancy continued beyond the early second trimester. Six pregnancies resulted in a term delivery. No recurrences of AFE were documented. Use of a diagnostic criterion for diagnosis of AFE results in a more precise diagnosis of AFE. Nevertheless, the accuracy of clinical diagnosis is still high. Subsequent pregnancies were not associated with AFE recurrence.

Single-cell RNA Sequencing Deciphers Immune Landscape of Human Recurrent Miscarriage

Single-cell RNA Sequencing Deciphers Immune Landscape of Human Recurrent Miscarriage

Comparison of uterine artery embolization and myomectomy: A long-term analysis of 863 patients

Objectives: The objective of this study is to compare the rates of secondary intervention following uterine artery embolization (UAE) versus myomectomy for the treatment of symptomatic uterine fibroids. Material and Methods: This is a multicenter retrospective cohort study. Eight hundred and sixty-three patients are included in this analysis, 451 patients who underwent UAE and 412 patients who underwent myomectomy between January 1, 2008, and December 31, 2012. The UAE group was significantly older than the myomectomy group with a median age of 46 versus 38 (P &lt; 0.0001). Patient data were collected from electronic medical records between the time of their initial procedure and December 31, 2017. The primary endpoint was secondary intervention rate. Secondary endpoints included time to secondary intervention, post-procedural complications, differences in mean hemoglobin levels following the procedures, symptomatic improvement, and subsequent pregnancy outcomes. All statistical analyses were two sided and performed using SAS EG 7.13 (Cary, NC). Results: The median follow-up for the UAE and myomectomy groups was 7 and 7.3 years, respectively. Overall, the rates of secondary intervention were not statistically significant between the UAE and myomectomy groups, 8.9% and 11.2%, respectively (P = 0.26). However, stratified analysis in women aged 30–39 years old demonstrated an increased rate of secondary intervention in the UAE arm with a hazards ratio of 3.76 (P = 0.0099). In patients ≥40 years old, there was no significant difference in secondary intervention rate. Both groups demonstrated a significant increase in mean hemoglobin at 1 year following initial procedure with a mean difference (SD) of 1.8 (2.1) in the UAE group and 1.8 (2.5) in the myomectomy group (P &lt; 0.0001 for both groups). The myomectomy group had a higher rate of post-procedural blood transfusion than the UAE group, 2.9% versus 0.9%, respectively (P = 0.028). Both groups had comparable rates of post-procedural pelvic infection and rehospitalization. Patients with pre-procedural menorrhagia who received UAE reported a higher rate of symptomatic improvement when compared to the myomectomy group, 75.4% versus 49.5% (P &lt; 0.0001). Both groups reported similar rates of improvement in bulk symptoms, 46.1% and 43.2%, respectively (P = 1.0). Conclusion: Overall, UAE and myomectomy have comparable rates of secondary intervention during a median 7-year follow-up period. However, in women between 30 and 39 years of age, UAE resulted in higher rates of secondary intervention. UAE may be more effective in controlling patients’ menorrhagia and has lower rates of post-procedural blood transfusions.

Surgical outcomes of cesarean scar pregnancy: an 8-year experience at a single institution.

To summarize the outcomes of different surgical treatment modalities for cesarean scar pregnancy (CSP) at a single institution over 8 years. A case series of patients diagnosed with CSP who were admitted to Nanjing Drum Tower Hospital from January 2011 to December 2018 was retrospectively studied. Medical records of all the patients were carefully reviewed. Data on patient demographics, pregnancy characteristics, treatment modalities, response to therapy, and subsequent pregnancy outcomes were collected and analyzed. A total of 117 patients undergoing surgical treatments for CSP were included. Thirty-three patients (28.21%) underwent ultrasound-guided curettage; while, 74 (63.25%) and 10 (8.55%) patients received laparoscopy-monitored curettage and laparoscopic CSP resection, respectively. Most of the patients (21/33) who underwent ultrasound-guided surgery had type I CSP; while, 54 out of 84 patients who opted for laparoscopic surgeries had type II CSP. Eleven women underwent a uterine artery embolization procedure before the operation. There was no difference in the use of an intrauterine balloon for hemostasis among the three groups. Only 8 patients needed additional systemic methotrexate treatment. Twenty-four out of 57 women (42.11%) succeeded in conceiving again and gave birth to 21 healthy babies. Only 1 woman (1/24, 4.17%) experienced recurrence of CSP. These data indicated the safety and efficiency of ultrasound-guided curettage, laparoscopy-monitored curettage, and laparoscopic CSP resection for the treatment of CSP.

A case study of ruptured cornual ectopic with successful outcome in subsequent pregnancy

Cornual pregnancy is a fearful condition with dreadful complications. Due to rarity and late presentation, it poses diagnostic and therapeutic challenges. There is no consensus on treatment strategies till date and risk of rupture after repair in subsequent pregnancy always remains a major concern. We hereby discuss a case of 27 year female who presented with ruptured cornual ectopic pregnancy, underwent cornual wedge resection with repair and had subsequent pregnancy with a successful outcome.

Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial.

STUDY QUESTIONAre the long-term reproductive outcomes following recurrent dilatation and curettage (D&C) for miscarriage in women with identified and treated intrauterine adhesions (IUAs) comparable to women without IUAs.SUMMARY ANSWERReproductive outcomes in women with identified and treated IUAs following recurrent D&C for miscarriage are impaired compared to women without IUAs; fewer ongoing pregnancies and live births are achieved with a prolonged time to a live birth.WHAT IS KNOWN ALREADYThe Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in women undergoing recurrent D&C for miscarriage resulted in a lower rate of IUAs, 13% versus 31% (relative risk 0.43, 95% CI 0.22 to 0.83), lower mean adhesion score and significant less moderate to severe IUAs. It is unclear what the impact is of IUAs on long-term reproductive performance.STUDY DESIGN, SIZE, DURATIONThis was a follow-up of the PAPA study, a multicenter randomized controlled trial evaluating the application of ACP gel in women undergoing recurrent D&C for miscarriage. All included women received a diagnostic hysteroscopy 8–12 weeks after randomization to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Here, we present the reproductive outcomes in women with identified and treated IUAs versus women without IUAs, 46 months after randomization.PARTICIPANTS/MATERIALS, SETTING, METHODSBetween December 2011 and July 2015, 152 women with a first-trimester miscarriage with at least one previous D&C, were randomized for D&C alone or D&C with immediate intrauterine application of ACP gel. Participants were approached at least 30 months after randomization to evaluate reproductive performance, obstetric and neonatal outcomes and cycle characteristics. Additionally, the medical files of all participants were reviewed. Main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception and time to live birth were also recorded.MAIN RESULTS AND THE ROLE OF CHANCEIn women pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in women with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in women without IUAs odds ratio (OR) 0.18 (95% CI 0.06 to 0.50, P-value <0.001). Documented live birth was also lower in women with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs, OR 0.22 (95% CI: 0.08 to-0.59, P-value 0.004). The median time to conception was 7 months in women with identified and treated IUAs versus 5 months in women without IUAs (hazard ratio (HR) 0.84 (95% CI 0.54 to 1.33)) and time to conception leading to a live birth 15 months versus 5.0 months (HR 0.54 (95% CI: 0.30 to 0.97)). In women with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in women without IUAs, P-value 0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%), P-value 0.001. No differences were recorded in mean birth weight between the groups.LIMITATIONS, REASONS FOR CAUTIONIn the original PAPA study, randomization was applied for ACP gel application. Comparing women with and without IUAs is not in line with the randomization and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomization were removed as part of the study protocol; the influence of IUAs on reproductive outcome may therefore be underestimated. Women undergoing a recurrent D&C for miscarriage were included, a specific group likely to generate clinically significant adhesions. The findings should therefore not be generalized to all women undergoing D&C for miscarriage.WIDER IMPLICATIONS OF THE FINDINGSAs IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential. Expectative and medical management should therefore be considered as serious alternatives for D&C in women with a miscarriage. In case D&C is necessary, application of ACP gel should be considered.STUDY FUNDING/COMPETING INTEREST(S)The original PAPA study (NTR 3120) was an investigator initiated study that was funded by the Foundation for scientific investigation in Obstetrics and Gynaecology of the Saint Lucas Andreas Hospital (currently renamed OLVG Oost), SWOGA. The syringes containing ACP gel were received from Anika Therapeutics, the manufacturer of Hyalobarrier® Gel Endo. The current follow-up study was also an investigator-initiated study without funding. The funder and sponsor had no role in the design of this follow-up study, data collection, data analysis, data interpretation, trial design, patient recruitment, writing of the report or any aspect pertinent to the study. ABH, RAL, JAFH and JWRT have no conflict to declare. HAMB reports being a member of safety board research Womed.TRIAL REGISTRATION NUMBERNetherlands Trial Register NTR 3120.

A Comparison Between the Effect of Vaginal Sildenafil Versus Oral Estradiol Valerate on Ultrasound Parameters of Endometrial Receptivity and Follicular Growth in Iraqi Females Receiving Letrozole for Induction of Ovulation

Endometrial thickness (ET) is one of the best predictors of implantation rate and pregnancy success rate because endometrial growth depends on hormones. Estrogen regulates the proliferative phase, endometrial proliferation induced by estrogen after menstruation is largely dependent on blood flow to the basal endometrium that produces progesterone receptors which are required for progesterone-regulated endometrial growth in the secretory process. To compare the effect of estradiol valerate vs. sildenafil citrate on endometrial receptivity and subsequent pregnancy outcome in unexplained infertility patients receiving letrozole for ovulation induction. Herein, 21 patients with unexplained infertility underwent ovulation induction by letrozole (2.5 mg). Patients were divided into 2 groups; group A (10 patients) were given sildenafil tablets vaginally (25 mg) four times daily and group B (11 patients) were treated with estradiol valerate tablet 2 mg/12 hours. Patients were evaluated by transvaginal ultrasonography (TVS) to determine endometrial thickness, pattern, size, and the number of the dominant follicles, serum assessment of Vascular Endothelial Growth Factor (VEGF) level at trigger day, and chemical pregnancy outcome 14 days later. Results showed that the endometrial thickness, patterns of the endometrium, VEGF, size of the dominant follicle at the trigger day, and pregnancy rates were not significantly different between the two groups. However, the difference in the number of the dominant follicles at trigger day was statistically significant which is more in the sildenafil treated group. The present study confirmed the findings of both Sildenafil and E2 valerate to boost endometrial receptivity and pregnancy rate.

Evaluation and Management of Women who Have Experienced Stillbirth in Their Previous Pregnancies

Objective: To evaluate the subsequent pregnancy outcomes of women who have experienced unexplained stillbirth in their previous gestations.Study Design: This retrospective cohort consisted of 14 pregnancies who had stillbirth (without known risk factors) in their previous pregnancies. These patients had been included in a special preconceptional care program to be evaluated in terms of etiological risk factors for stillbirth. At least one of the risk factors, such as methylenetetrahydrofolate reductase (MTHFR) polymorphisms, hereditary thrombophilias and autoimmune problems, were defined in this study population. After detection of pregnancy, the patients were administered low-dose low-molecular-weight heparin (LMWH) (enoxaparin, 1×2000 Anti-XA IU/0.2 mL/day), low-dose salicylic acid (100 mg/day) and low-dose corticosteroid (methylprednisolone, 1×4 mg/day orally) in necessary cases.Results: Out of 14 pregnancies, 4 (28.5%) ended up with miscarriages at 9, 11, 11 and 15 gestational weeks, respectively. The remaining 10 pregnancies ended up with alive deliveries. The mean gestational week at birth was 36.4±0.51, while the mean birthweight was 2882±381.01 g. Out of 10 pregnancies, only one was diagnosed as IUGR. Only two newborn necessitated hospitalization in the neonatal intensive care unit (NICU) due to respiratory problems. Both newborns were discharged from the NICU without any further complication at the post-partum 5th day. Conclusion: Patients with a prior stillbirth should be screened for MTHFR polymorphisms, autoimmune problems and hereditary thrombophilias, especially in case of absence of any etiological factor. Management of these patients with low-dose aspirin, low-dose low molecular weight heparin and corticosteroids seemed to be beneficial for increasing live birth rates and avoiding obstetric complications.