Comprehensive appraisal of pregnancy and neonatal outcomes in singleton pregnancies conceived via in vitro fertilization in the USA (2016-2021).

OBJECTIVES: We set out to compare adverse pregnancy and neonatal outcomes in singleton gestations conceived via in vitro fertilization (IVF) to those conceived spontaneously. METHODS: Retrospective, population-based cohort using the CDC Natality Live Birth database (2016-2021). All singleton births were stratified into two groups: those conceived via IVF, and those conceived spontaneously. The incidence of several adverse pregnancy and neonatal outcomes was compared between the two groups using Pearson's chi-square test with Bonferroni adjustments. Multivariate logistic regression was used to adjust outcomes for potential confounders. RESULTS: Singleton live births conceived by IVF comprised 0.86 % of the cohort (179,987 of 20,930,668). Baseline characteristics varied significantly between the groups. After adjusting for confounding variables, pregnancies conceived via IVF were associated with an increased risk of several adverse pregnancy and neonatal outcomes compared to those conceived spontaneously. The maternal adverse outcomes with the highest risk in IVF pregnancies included maternal transfusion, unplanned hysterectomy, and maternal intensive care unit admission. Increased rates of hypertensive disorder of pregnancy, preterm birth (delivery <37 weeks of gestation), and cesarean delivery were also noted. The highest risk neonatal adverse outcomes associated with IVF included immediate and prolonged ventilation, neonatal seizures, and neonatal intensive care unit admissions, among others. CONCLUSIONS: Based on this large contemporary United States cohort, the risk of several adverse pregnancy and neonatal outcomes is increased in singleton pregnancies conceived via IVF compared to those conceived spontaneously. Obstetricians should be conscious of these associations while caring for and counseling pregnancies conceived via IVF.

Risk factors associated with third- and fourth-degree perineal lacerations in singleton vaginal deliveries: a comprehensive United States population analysis 2016-2020.

OBJECTIVES: Perineal lacerations are a common complication of vaginal birth, affecting approximately 85 % of patients. Third-and fourth-degree perineal lacerations (3/4PL) remain a significant cause of physical and emotional distress. We aimed to perform an extensive assessment of potential risk factors for 3/4PL based on a comprehensive and current US population database. METHODS: Retrospective population-based cohort analysis based on the US Centers for Disease Control and Prevention Natality Live Birth online database between 2016-2020. Baseline characteristics were compared between women with 3/4PL and without 3/4PL by using Pearson's Chi-squared test with statistical significance set at p<0.05. Bonferroni correction was used to account for multiple comparisons. Multivariable logistic regression was performed to evaluate the association between a variety of potential risk factors and the risk of 3/4P. RESULTS: Asians/Pacific Islanders had the highest risk of 3/4PL (2.6 %, aOR 1.74). Gestational hypertension and preeclampsia were associated with increased risk of 3/4PL (aOR 1.28 and 1.34, respectively), as were both pre-gestational and gestational diabetes (aOR 1.28 and 1.46, respectively). Chorioamnionitis was associated almost double the risk (aOR 1.86). Birth weight was a major risk factor (aOR 7.42 for greater than 4,000 g), as was nulliparity (aOR 9.89). CONCLUSIONS: We identified several maternal, fetal, and pregnancy conditions that are associated with an increased risk for 3/4PL. As expected, nulliparity and increased birth weight were associated with the highest risk. Moreover, pregestational and gestational diabetes, hypertensive disorders of pregnancy, Asian/Pacific Islander race, and chorioamnionitis were identified as novel risk factors.

Clinical potential of human amniotic fluid stem cells.

OBJECTIVES: To determine whether amniotic fluid derived stem cells maintain their stem cell characteristics (a) after processing by a licensed cell therapy center and (b) after the cells undergo simulated clinical application. METHODS: Amniotic fluid was collected by laparotomy - a small uterine incision was made at proposed site for delivery and a sterile catheter inserted to collect fluid into a sterile bag. After flow stopped the catheter was withdrawn, the cesarean completed and the collected fluid delivered to the cell therapy center for processing and cryostorage. A clinical setting was simulated where amniotic fluid cells received from cell therapy center were thawed at room temperature for a maximum of 3 h and passed through a clinical cell delivery device to monitor cell viability. The cells were examined for viability, stability, growth, differentiation, and markers of stemness. RESULTS: Amniotic fluid stem cells processed from a clinical cell therapy center behave similarly to amniotic fluid stem cells processed in a research laboratory with respects to viability, stability, growth, differentiation and maintain markers of stemness. There were differences due to heterogeneity of samples which were not methodological. Growth in cell culture and differentiation were satisfactory. Simulation of treating the cells in a clinical environment show a general stability in viability of amniotic fluid cells at room temperature for 3 h minimum and when passed through a clinically approved delivery device. CONCLUSIONS: The data indicate human amniotic fluid processed in a clinical facility could be used therapeutically if proven to be safe.

Maternal education and racial/ethnic disparities in nulliparous, term, singleton, vertex cesarean deliveries in the United States.

BACKGROUND: Racial and ethnic disparities in obstetrical and neonatal outcomes are prevalent in the United States. Such racial or ethnic disparities have also been documented in the prevalence of cesarean deliveries. OBJECTIVE: We aimed to evaluate the impact of maternal education on racial or ethnic disparities in the prevalence of low-risk nulliparous, term, singleton, vertex cesarean deliveries in the United States. STUDY DESIGN: This is a retrospective analysis of the Centers for Disease Control and Prevention live births database (2016-2019). Nulliparous, term, singleton, vertex births from the following racial/ethnic groups were included: non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic. Pregnancies complicated by gestational or pregestational diabetes mellitus and hypertensive disorders were excluded. Data were analyzed on the basis of the level of maternal education (less than high school graduate, high school graduate, college graduate, and advanced degree). We compared the prevalence of cesarean deliveries among the different racial or ethnic groups within each education level using Pearson chi-square test with Bonferroni adjustment. Multivariate logistic regression was performed to assess the association between cesarean deliveries and maternal race/ethnicity, maternal education, and the interaction between maternal race or ethnicity and education level, while controlling for potential confounders. To demonstrate the effect of the interaction, separate logistic regression models with similar covariates were performed for each education level and for each race/ethnicity group. Statistical significance was determined as P<.05, and results were displayed as adjusted odds ratios with 95% confidence intervals. RESULTS: The overall prevalence of cesarean deliveries during the study period was 23.4% (695,214 of 2,969,207 births). All racial or ethnic minority groups had higher rates of cesarean deliveries than non-Hispanic White women (non-Hispanic Black, 27.4%; non-Hispanic Asian, 25.6%; Hispanic, 23.0%; and non-Hispanic White, 22.4%; [P<.001 for all comparisons]). Similar racial or ethnic differences in cesarean delivery rates were detected among all education levels. Higher levels of education were associated with a lower likelihood of cesarean delivery (adjusted odds ratio, 0.88; [95% confidence interval, 0.87-0.89]) in women with advanced degrees than in women who did not graduate from high school. However, although maternal education was associated with a protective effect in non-Hispanic White and non-Hispanic Asian women (adjusted odds ratio, 0.83 [95% confidence interval, 0.81-0.85] and adjusted odds ratio, 0.81 [95% confidence interval, 0.77-0.86], respectively, for women with advanced degrees), it had a smaller protective effect in non-Hispanic Black women (adjusted odds ratio, 0.93 [95% confidence interval, 0.89-0.97]) and no protective effect in Hispanic women (adjusted odds ratio, 0.98 [95% confidence interval, 0.96-1.01]). CONCLUSION: We document a significant racial/ethnic disparity in the prevalence of low-risk nulliparous, term, singleton, vertex cesarean deliveries in the United States. Furthermore, our findings suggest that although a higher level of maternal education is associated with a lower likelihood of cesarean delivery, this protective effect varies among racial or ethnic groups. Further research is needed to investigate the underlying causes for this racial/ethnic disparity.

Adverse outcomes associated with twin pregnancies conceived via in vitro fertilization.

OBJECTIVE: To compare adverse pregnancy and neonatal outcomes in twin pregnancies conceived by in vitro fertilization (IVF) to those conceived spontaneously. METHODS: Retrospective analysis of the Centers for Disease Control and Prevention, Natality Live Birth database for the years 2016-2019. All twin live births were included and stratified into two groups: those from pregnancies conceived via IVF and those from pregnancies conceived spontaneously. The incidence of several adverse pregnancy and neonatal outcomes were compared between the two groups. Statistical analysis included multivariable logistic regression to adjust for the following potential confounders: maternal age, race/ethnicity, body mass index, education level, type of medical insurance, chronic hypertension, pregestational diabetes, and prior preterm birth. Data were presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Twin live births from pregnancies conceived via IVF comprised 9.5% of the study cohort (39,356 of 415,560). Baseline characteristics varied significantly between IVF and spontaneously conceived twins. After adjusting for these variables, IVF in twins was associated with an increased risk of multiple adverse outcomes including gestational diabetes (aOR = 1.35, 95% CI = 1.30-1.39), hypertensive disorders of pregnancy (aOR = 1.70, 95% CI = 1.65-1.75), preterm birth prior to 28 weeks (aOR = 1.53, 95% CI = 1.43-1.63), maternal intensive care unit admission (aOR = 2.03, 95% CI = 1.79-2.31), maternal blood transfusion (aOR = 2.97, 95% CI = 2.75-3.20), unplanned hysterectomy (aOR = 3.37, 95% CI = 2.73-4.16), and prolonged ventilation in newborns (aOR = 1.76, 95% CI = 1.69-1.82), compared to spontaneously conceived twin pregnancies. CONCLUSIONS: Based on this large United States population-based cohort, twin pregnancies conceived via IVF represent a subgroup of twins that have an increased risk for several adverse pregnancy and neonatal outcomes, compared to those conceived spontaneously. With increased contemporary utilization of IVF, obstetricians should consider these risks while caring for patients with twin pregnancies conceived via IVF.

Employer-based insurance coverage increases utilization of planned oocyte cryopreservation.

PURPOSE: To determine the utilization of planned oocyte cryopreservation (OC) in the year immediately prior to, and the year of, insurance coverage commencement for employees at our institution. METHODS: Patient demographics and cycle outcomes were retrospectively compared between the first OC cycles occurring in 2017 vs. 2018 according to insurance coverage and type, age, and the number of oocytes retrieved and cryopreserved. Continuous demographic variables including age, BMI, day 3 FSH and E2, AMH, gravidity, and parity were compared using student T-tests. Cycle outcomes, including the number of oocytes retrieved and cryopreserved were compared using linear regression models, adjusting for potential confounders including age, BMI, and ovarian reserve parameters. RESULTS: Between January 2017 and December 2018, 123 patients underwent planned OC at our institution. Patient age ranged from 23 to 44 years and did not significantly differ from 2017 to 2018 (mean 34.9 vs. 35.2). There was a 12% increase in planned OC utilization from 2017 (N = 58) to 2018 (N = 65). Significantly, more patients had any insurance coverage in 2018 vs. 2017 (71.9% vs. 40.4%, p = 0.001), a 78% increase. From 2017 to 2018, the number of patients with hospital-based insurance coverage undergoing planned OC increased by a factor of 8 (5 to 41.5%, p < 0.001), while the number of self-pay patients significantly decreased (p = 0.001). No differences were found regarding cycle outcomes. CONCLUSION: A greater proportion of women at our institution had insurance coverage for planned OC in 2018 vs. 2017. Employer-based insurance coverage for planned OC was associated with a significant increase in utilization by hospital employees.

Isthmocele endometriosis: the relationship between cesarean section and endometriosis.

OBJECTIVE: To present a case of endometriosis within an isthmocele membrane and concomitant diffuse peritoneal endometriosis after cesarean sections. In addition, we describe a unique, color-contrasted surgical repair technique and propose a possible correlation between isthmocele formation and endometriosis. DESIGN: Narrated video article featuring the diagnosis, unique surgical management, and pathological findings of a case of isthmocele endometriosis. Informed consent was obtained from the patient, and all identifiers were removed. SETTING: University-affiliated hospital. PATIENT(S): A 44-year-old patient with three prior cesarean sections and a laparoscopic appendectomy, in none of which endometriosis was visualized. She presented with progressive pelvic pain, dysmenorrhea, dyspareunia, and secondary infertility with recurrent embryo transfer failures. The progressively debilitating symptoms started 14 years ago, shortly after her last cesarean section. Magnetic resonance imaging and ultrasound demonstrated a retroverted uterus and a prominent, thin, fluid-filled cesarean scar defect with a residual myometrial thickness of 1.1 mm. INTERVENTION(S): A combined hysteroscopic and laparoscopic approach was performed to allow for complete resection of the defect and reconstruction of the myometrium. The bladder was backfilled with indocyanine green dye to help identify its borders. Methylene blue was added to the hysteroscopy irrigation solution to create contrast and assist with the isthmocele identification. Wide excision of the isthmocele was performed, followed by a three-layer closure and excision of all apparent peritoneal lesions using the Aqua Blue Contrast Technique. MAIN OUTCOME MEASURE(S): Restoration of normal anatomy, resection of isthmocele, and resolution of the symptoms. RESULT(S): In the pathological assessment, multiple foci of endometriosis were identified within the isthmocele membrane, clearly differentiated from intrauterine endometrial tissue. Additionally, all seven excised peritoneal specimens contained peritoneal endometriosis. Two weeks after the procedure, a transvaginal sonographic scan confirmed a thick anterior uterine wall with a myometrial thickness of 9.2 mm, and the patient reported almost complete resolution of her symptoms. CONCLUSION(S): This case demonstrates endometriosis within the isthmocele membrane, with concomitant symptomatic peritoneal endometriosis. We propose a laparoscopic isthmocele excision technique and a three-layer reconstruction, followed by peritoneal endometriosis excision using methylene blue contrast. We suggest a possible link between isthmocele and endometriosis and emphasize the need for wide excision of the isthmocele margins and maintaining clean borders, given the possibility of endometriosis within the isthmocele, which may be a cause or a contributor to the tissue weakness and isthmocele formation.

Adverse perinatal outcomes of chlamydia infections: an ongoing challenge.

OBJECTIVES: Chlamydia trachomatis is one of the most common sexually transmitted diseases in the world, but there are limited data on its impact on perinatal outcomes. Our objective was to investigate the association between chlamydia infections and adverse perinatal outcomes. METHODS: This is a retrospective analysis of the United States Centers for Disease Control and Prevention natality live birth database for the years 2016-2019. The rates of adverse perinatal outcomes were compared between patients with a chlamydia infection during pregnancy and patients without such infection, using Pearson's chi-square test with the Bonferroni adjustment. A multivariate logistic regression was then used to adjust outcomes for potential confounders. RESULTS: Chlamydia infections were associated with small, but statistically significant, increased odds of preterm birth (<37 weeks), early preterm birth (<32 weeks), low birthweight (<2,500 g), congenital anomalies, low 5-min Apgar score (<7), neonatal intensive care unit admission, immediate neonatal ventilation, prolonged (>6 h) neonatal ventilation, and neonatal antibiotic treatment for suspected sepsis. CONCLUSIONS: Chlamydia infections during pregnancy are associated with adverse perinatal outcomes. These results call for increased education regarding the potential risks of pregnancies with a chlamydia infection, as well as for increased antenatal surveillance and post-natal pediatric assessment in these pregnancies.

Race and ethnicity are among the predisposing factors for fetal malpresentation at term.

OBJECTIVE: Fetal malpresentation complicates approximately 3% to 4% of all term births. It requires special considerations for delivery and exposes the mother and neonate to obstetrical interventions and potential adverse outcomes, such as umbilical cord prolapse, head entrapment and birth trauma, hypoxic ischemic encephalopathy, cesarean delivery, and cesarean delivery-related complications. We set out to explore the maternal and fetal factors associated with noncephalic malpresentation at term, with specific interest on the impact of maternal race and ethnicity on fetal malpresentation. STUDY DESIGN: This was a retrospective analysis of the Centers for Disease Control and Prevention Natality Live Birth database for the years from 2016 through 2018. All term, singleton deliveries for the following racial and ethnic groups were included: non-Hispanic White, non-Hispanic Black, Asian, and Hispanic. Race and ethnicity were assigned based on self-identification and individuals with >1 racial category were excluded from the analysis. Malpresentation was defined as a noncephalic presentation at term and included breech and transverse presentations. The malpresentation group included all noncephalic births and cephalic births that occurred following successful external cephalic version, whereas all other cephalic births served as controls. A multivariable logistic regression analysis was used to assess the rate of malpresentation, with adjustment for potential confounders including maternal age, race and ethnicity, parity, birthweight, fetal malformations, malformations of the central nervous system (CNS), and chromosomal anomalies. The results are displayed as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Statistical significance was set at a P value of <.05. Institutional review board approval was not required because the de-identified data are publicly available through a data use agreement. RESULTS: There were 9,692,203 term, singleton births during the study period. The malpresentation group included 354,689 births (3.66% of the total). The Table shows the rate of malpresentation for various maternal and fetal factors. We found a substantial racial and ethnic disparity in the malpresentation rates. Non-Hispanic White women had the highest malpresentation risk, whereas non-Hispanic Black women had the lowest risk (3.93% vs 2.81%; aOR, 1.38; 95% CI, 1.36-1.39). Hispanic and Asian women were also at increased risk for malpresentation when compared with non-Hispanic Black women (aOR, 1.30; 95% CI, 1.29-1.32 and aOR, 1.12; 95% CI, 1.10-1.14, respectively). In addition, several maternal and fetal conditions were noted to be associated with an increased risk for malpresentation at term, including older maternal age (aOR, 2.81; 95% CI, 2.74-2.88; for patients >40 years), nulliparity (aOR, 1.50; 95% CI, 1.48-1.51), low birthweight (aOR, 1.80; 95% CI, 1.77-1.83 for birthweight under 2500 g), and fetal malformations of the CNS and chromosomal anomalies (aOR, 3.53; 95% CI, 3.06-4.06 and aOR, 2.32; 95% CI, 2.05-2.63, respectively). CONCLUSION: Based on a large US population database, we identified several maternal, fetal, and racial and ethnic factors that are associated with an increased rate of noncephalic malpresentation at term. Specifically, fetal CNS malformations, congenital or chromosomal anomalies, advanced maternal age, low birthweight, and nulliparity are risk factors for noncephalic presentation. Interestingly, non-Hispanic White women have the highest risk for malpresentation, whereas non-Hispanic Black women have the lowest risk. Previous publications found that low birthweight, advanced maternal age, nulliparity, and congenital fetal malformations are risk factors for malpresentation.1-3 Nonetheless, the current data available on race and ethnicity are sporadic, with limited reports suggesting that sub-Saharan ethnicity is associated with a lower rate of malpresentation2 and that White race is associated with a higher rate.4 We present a large-scale, nationwide US-based study to confirm the racial and ethnic disparity regarding malpresentation in the United States. This may be explained by the known variation in the shape of the bony birth canal in different racial and ethnic groups and populations from different geographic locations.5 Further investigation is needed to explore the racial and ethnic disparity described.

Blastomere biopsy for PGD delays embryo compaction and blastulation: a time-lapse microscopic analysis.

PURPOSE: The purpose of the study was to explore the effect of blastomere biopsy for preimplantation genetic diagnosis (PGD) on the embryos' dynamics, further cleavage, development, and implantation. METHODS: The study group included 366 embryos from all PGD treatments (September 2012 to June 2014) cultured in the EmbryoScope™ time-lapse monitoring system. The control group included all intracytoplasmic sperm injection (ICSI) embryos cultured in EmbryoScope™ until day 5 during the same time period (385 embryos). Time points of key embryonic events were analyzed with an EmbryoViewer™. RESULTS: Most (88 %) of the embryos were biopsied at ≥8 cells. These results summarize the further dynamic development of the largest cohort of biopsied embryos and demonstrate that blastomere biopsy of cleavage-stage embryos significantly delayed compaction and blastulation compared to the control non-biopsied embryos. This delay in preimplanation developmental events also affected postimplantation development as observed when the dynamics of non-implanted embryos (known implantation data (KID) negative) were compared to those of implanted embryos (KID positive). CONCLUSION: Analysis of morphokinetic parameters enabled us to explore how blastomere biopsy interferes with the dynamic sequence of developmental events. Our results show that biopsy delays the compaction and the blastulation of the embryos, leading to a decrease in implantation.