Society for Maternal-Fetal Medicine Consult Series #60: Management of pregnancies resulting from in vitro fertilization.

The use of assisted reproductive technology has increased in the United States in the past several decades. Although most of these pregnancies are uncomplicated, in vitro fertilization is associated with an increased risk for adverse perinatal outcomes primarily caused by the increased risks of prematurity and low birthweight associated with in vitro fertilization pregnancies. This Consult discusses the management of pregnancies achieved with in vitro fertilization and provides recommendations based on the available evidence. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that genetic counseling be offered to all patients undergoing or who have undergone in vitro fertilization with or without intracytoplasmic sperm injection (GRADE 2C); (2) regardless of whether preimplantation genetic testing has been performed, we recommend that all patients who have achieved pregnancy with in vitro fertilization be offered the options of prenatal genetic screening and diagnostic testing via chorionic villus sampling or amniocentesis (GRADE 1C); (3) we recommend that the accuracy of first-trimester screening tests, including cell-free DNA for aneuploidy, be discussed with patients undergoing or who have undergone in vitro fertilization (GRADE 1A); (4) when multifetal pregnancies do occur, we recommend that counseling be offered regarding the option of multifetal pregnancy reduction (GRADE 1C); (5) we recommend that a detailed obstetrical ultrasound examination (CPT 76811) be performed for pregnancies achieved with in vitro fertilization and intracytoplasmic sperm injection (GRADE 1B); (6) we suggest that fetal echocardiography be offered to patients with pregnancies achieved with in vitro fertilization and intracytoplasmic sperm injection (GRADE 2C); (7) we recommend that a careful examination of the placental location, placental shape, and cord insertion site be performed at the time of the detailed fetal anatomy ultrasound, including evaluation for vasa previa (GRADE 1B); (8) although visualization of the cervix at the 18 0/7 to 22 6/7 weeks of gestation anatomy assessment with either a transabdominal or endovaginal approach is recommended, we do not recommend serial cervical length assessment as a routine practice for pregnancies achieved with in vitro fertilization (GRADE 1C); (9) we suggest that an assessment of fetal growth be performed in the third trimester for pregnancies achieved with in vitro fertilization; however, serial growth ultrasounds are not recommended for the sole indication of in vitro fertilization (GRADE 2B); (10) we do not recommend low-dose aspirin for patients with pregnancies achieved with IVF as the sole indication for preeclampsia prophylaxis; however, if 1 or more additional risk factors are present, low-dose aspirin is recommended (GRADE 1B); (11) given the increased risk for stillbirth, we suggest weekly antenatal fetal surveillance beginning by 36 0/7 weeks of gestation for pregnancies achieved with in vitro fertilization (GRADE 2C); (12) in the absence of studies focused specifically on timing of delivery for pregnancies achieved with IVF, we recommend shared decision-making between patients and healthcare providers when considering induction of labor at 39 weeks of gestation (GRADE 1C).

Neonatal complications in vacuum-assisted vaginal delivery: are they associated with number of pulls, cup detachments, and duration of vacuum application?

PURPOSE: To explore whether the characteristics of vacuum delivery are associated with the occurrence of head injury and neonatal complications. METHODS: Retrospectively cohort study of vacuum-assisted attempted vaginal deliveries of singletons. We studied the association of total duration of vacuum application and number of pulls and cup dislodgement with (1) primary outcome: the occurrence of major (subgaleal hemorrhage, skull fracture, and intracranial hemorrhage) or minor (cephalohematoma, scalp laceration more extensive than simple abrasions) neonatal head injuries and (2) secondary outcome: the occurrence of neonatal complications, including 5-min Apgar score <7, umbilical artery pH < 7.10, shoulder dystocia, or need for neonatal intensive care unit admission. Logistic regression analysis was used to control for confounders. RESULTS: Vacuum-assisted delivery was attempted in 555 women. It was successful in 515 cases, and it failed in 40 (7.2 %). Head injury occurred in 32 (6.2 %) of vaginally delivered neonates, and it was related to duration of vacuum application (P = 0.004) and birth weight (P = 0.048). However, the associations lost a statistical significance at the multivariate analysis. Neonatal complications occurred in 25 cases (5 %), and they were associated with meconium-stained amniotic fluid (P < 0.001) and duration of vacuum application (P = 0.03) at the multivariate analysis. However, most of the complications were actually associated with the need for vacuum delivery rather than the procedure itself. CONCLUSION: Neonatal head injury after vacuum application is not independently related to total duration of vacuum application, number of pulls, or cup dislodgements.

Outcome of pregnancies after pelvic artery embolization for postpartum hemorrhage: retrospective cohort study.

OBJECTIVE: The effects of pelvic artery embolization (PAE) for postpartum hemorrhage (PPH) on subsequent pregnancies have been explored in small case series and one case-control study by mailed questionnaire with uncomplicated pregnancies as controls. We conducted a single-center retrospective cohort study using women with PPH without PAE for comparison. STUDY DESIGN: From a cohort of 103 women undergoing PAE for primary PPH between January 1999 and December 2012 (exposed) and 189 pregnancies with PPH not requiring PAE between January 2008 and December 2012 (unexposed), we queried the electronic medical records for readmissions to labor and delivery in subsequent years. Outcomes of subsequent pregnancies continuing past 20 weeks were obtained by chart review. RESULTS: Repeat pregnancies were documented in 17 of 103 exposed women (16.5%) and 18 of 189 unexposed women (9.5%). At delivery complicated by PPH, the groups did not differ in demographics, gestational age, units of blood transfused, or PPH cause. At the time of subsequent deliveries, there was a greater interdelivery interval in women exposed to PAE than those unexposed (1710 ± 938 days vs 904 ± 358 days; P = .002), and the 2 groups were similar in terms of gestational age and birthweight. However, there was a significantly higher rate of placenta accreta in exposed than unexposed women (23.5 % vs 0%; P = .04), with 3 of 17 sustaining total abdominal hysterectomy and 1 requiring repeat PAE for severe PPH. CONCLUSION: Pregnancies following PAE for PPH were more likely than those not receiving PAE for treatment to be complicated by placenta accreta. Pregnancies following PAE should be followed up for imaging evidence of placenta accreta.

Overview of low molecular weight heparin for preventative treatment of adverse obstetric outcomes related to abnormal placentation.

Different proportions of cases of preterm and severe preeclampsia, placental abruption, fetal growth restriction, and fetal death share a common causal pathway of abnormal placental implantation. Documentation of an association between the risk of such adverse pregnancy outcomes (APOs) and inherited thrombophilias prompted initial studies to evaluate the benefit of anticoagulants for the prevention of recurrences both in patients with and without inherited thrombophilias. Prenatal administration of low molecular weight heparin (LMWH) has been evaluated in case control, cohort and randomized clinical trials. The evidence suggests a benefit of LMWH in the reduction of recurrences of APOs, with a number needed to treat of 6 (95% confidence interval: 4-10) to prevent one case of recurrent APOs. Such benefit is independent of the presence of inherited thrombophilias or the administration of low dose aspirin. Further studies are needed to establish the optimal duration for the prophylaxis, to better delineate the mechanism of action of LMWH and to explore the role, if any, of maternal serum markers and uterine artery Doppler findings in the modulation of the LMWH prophylaxis.

Role of the second-trimester 'genetic sonogram' for Down syndrome screen in the era of first-trimester screening and noninvasive prenatal testing.

Ultrasonography for the screening of Down syndrome was first introduced about 25 years ago. Different combinations of markers detectable at second-trimester ultrasonography have been proposed under the banner of 'genetic sonogram'. In recent years, several developments in first-trimester screening and the recent introduction of noninvasive prenatal testing for aneuploidy screening have had important implications for the prevalence of these conditions in the second-trimester and the screening performance of a genetic sonogram. Several second-trimester sonographic markers for Down syndrome have been reported; meta-analysis has shown that the most powerful predictors are mild ventriculomegaly, increased nuchal fold, hyperechoic bowel, and absent or hypoplastic nasal bone. Whereas use of individual markers should be discouraged and scoring systems of multiple markers are now obsolete, use of combined likelihood ratio and logistic regression analysis formulae provides better accuracy. However, there is significant heterogeneity in results among studies. Despite such limitations, the genetic sonogram will continue to have a place in prenatal screening, particularly in twin and higher-order multiple pregnancies, in countries with limited access to the most recent genetic screening tests, in cases with borderline results at maternal serum screening tests, and as noninvasive supplementary test for high-risk women reluctant to undergo invasive diagnostic testing.

Fetal hydronephrosis: natural history and risk factors for postnatal surgery.

BACKGROUND: The objective of this study was to assess the ability of prenatal ultrasound to predict an unfavorable outcome and the need for postnatal surgery in cases of fetal hydronephrosis (HY). METHODS: Antenatal HY was classified according to the renal pelvis anteroposterior (AP) diameter in the third trimester. Postnatal outcome was considered favorable in the presence of spontaneous resolution or postnatal diagnosis of HY <20 mm, and unfavorable in the presence of postnatal diagnosis of >20 mm HY or urinary tract pathologies. RESULTS: Prenatal diagnosis of HY was made in 120 fetuses (for a total of 161 abnormal renal units). The rates of postnatal urinary tract pathology were 14, 27 and 53% for antenatal HY of ≤7, 8-15 and >15 mm, respectively. An AP diameter ≥7 mm in the third trimester had a sensitivity of 100% and a specificity of 23% to predict unfavorable outcome. A formula inclusive of AP diameter and presence or absence of urinary tract anomalies can predict the need for postnatal surgery. CONCLUSIONS: The majority of infants with congenital HY have a favorable postnatal outcome. Risk of unfavorable outcome increases with the degree of dilatation of the renal pelvis and the presence of urinary tract anomalies. An AP diameter ≥7 mm in the third trimester warrants postnatal follow-up.

Side effects from epidural analgesia in laboring women and risk of cesarean delivery.

BACKGROUND: Epidural analgesia may cause maternal hypotension and changes in the fetal heart rate. The implications of such side effects on the course of labor and delivery are incompletely understood. OBJECTIVE: This study aimed to assess whether the occurrence of maternal or fetal side effects associated with labor epidural analgesia increased the risk for cesarean delivery. STUDY DESIGN: This was a cohort study of all women who underwent epidural analgesia during labor for the period October 1, 2020 to December 31, 2020. Excluded were cases of multiples, fetal death, noncephalic presentation, and gestational age at birth <37.0 weeks. Maternal vital signs and fetal heart rate tracings for the 1 hour before and 1 hour after epidural analgesia was administered were reviewed. The occurrence of maternal hypotension, defined as a continuous variable and dichotomized into a decrease in maternal systolic blood pressure to <90 mm Hg or a drop in systolic blood pressure by >20% below the last value before epidural analgesia was administered, was related to changes in the fetal heart rate category. The principal outcome was cesarean delivery rate; binary logistic regression analysis was used to control for confounders, and mediation model analysis was used to quantify the extent to which significant variables participated in the causation pathway to cesarean delivery (SPSS version 28 was used for the analyses). RESULTS: A total of 439 women met the study criteria. Significant adverse reactions owing to epidural occurred in 184 of 439 women (41.9%) and included severe maternal hypotension in 159 of 439 participants (36.2%) and worsening fetal heart rate category in 50 of 439 participants (11.4%). The logistic regression analysis revealed that cervical dilation at epidural (P=.03), the duration of labor after epidural (P<.001), and worsening fetal heart rate category within 60 minutes of epidural administration (P=.01) were independently associated with recourse to cesarean delivery. The mediation analysis showed that both cervical dilatation at epidural administration and worsening fetal heart rate category had significant direct and indirect effects in the pathway to cesarean delivery. CONCLUSION: Worsening fetal heart rate category related to labor epidural independently increased the risk for cesarean delivery.

Efficacy of antepartum fetal surveillance for stillbirth prevention.

OBJECTIVE: In 2019 the American College of Obstetricians and Gynecologists (ACOG) issued specific recommendations for performance of antepartum fetal surveillance (AFS) based on individual risk factors. As similar recommendations were already in place at our institution, we have evaluated the impact of AFS on stillbirth (SB) occurrence in a 5-year cohort. METHODS: Retrospective cohort study of all deliveries between 7/1/2013 and 6/30/2018. Excluded were multiples, anomalous fetuses or newborns, and deliveries before 32 0/7 weeks' gestation. AFS was conducted from 32 weeks with a modified biophysical profile, with a complete biophysical profile as back-up for non-reactive non-stress tests. All cases of SB were prospectively identified and individually reviewed to verify the presence of risk factors, the results of fetal testing if done, and calculate the interval between last fetal test and delivery. The electronic medical records during the study period were queried to identify women who underwent AFS and those who did not. Chi-square was used to compare the rates of SB between the two groups. RESULTS: 16,827 women fulfilled the study inclusion and exclusion criteria, 5711 (34%) had risk factors which prompted AFS; 37% had 2 or more risk factors. SB occurred in 1.8‰ of them (10/5711) (3 had 1 risk factor, 5 had 2, and 2 had 3 risk factors). Rates of SB at ≥32.0 weeks were similar between women who had AFS and those who did not (1.8 vs. 2.3‰, p = 0.51, OR = 0.75, 95%CI 0.36-1.55). The false-negative rate at <7 days of a reassuring AFS among compliant women was 1.4‰ (8/5711). Rates of preterm delivery were similar in the tested vs untested population (6.5 vs. 6.0%, p = 0.22). CONCLUSION: Implementation of AFS in women with risk factors similar to those recommended by the ACOG may lower the risk of SB from 32 weeks to that of low-risk pregnancies.

Effect of access to antenatal care on risk of preterm birth among migrant women in Italy: A population-based cohort study.

Objective: To evaluate the association between maternal migration status and preterm birth, and whether a better adherence to antenatal care during pregnancy mitigates the risk of preterm birth. Design: Population-based cohort. Setting: Administrative databases of the Lombardy region, Italy. Population: First singleton births of women aged 15-55 years at 22-42 gestational weeks, between 2016 and 2021. Methods: Assessed the risk of preterm birth (<37 weeks). Main outcome measures: A multivariable logistic regression mediation model calculated the mediation effect of adherence to antenatal care in the association between maternal migrant status and preterm birth and the residual effect not mediated by it. Analyses were adjusted for the socio-demographic and pregnant characteristics of the women. Results: Of 349,753 births in the cohort, Italian nationality accounted for 71 %; 28.4 % were documented migrants and 0.4 % undocumented migrants. Among them, 5.3 %, 6.4 %, and 9.3 % had a preterm birth, respectively. Using deliveries of Italian citizens as referent, migrants had a significantly increased risk of preterm birth (adjusted relative risk: 1.22, 95 % confidence interval: 1.18-1.27). Adherence to antenatal care mediated the 62 % of such risk. We have calculated that adherence to antenatal pathways set to the highest level for the whole population could lead to a 37 % reduction in preterm birth risk. Conclusion: Part of the excess of preterm birth among documented and undocumented migrants in Italy can be explained by a lack of adherence to the antenatal care path despite equal access to National Health care. The adherence of all pregnant women to antenatal care would reduce the risk of preterm birth by about one-third.

Perinatal complications in twin pregnancies after 34 weeks: effects of gestational age at delivery and chorionicity.

OBJECTIVE: To evaluate the perinatal outcome of twins approaching term in relation to chorionicity and gestational age at delivery. STUDY DESIGN: We accessed data pertaining to a cohort of 471 twin pregnancies with certain chorionicity delivered at > 34.0 weeks' gestation. Twin gestation per se, estimated fetal weight below the 10th percentile, or any intertwin discordance was not an indication for delivery before 40.0 weeks. Predictors of adverse perinatal outcome were identified using logistic regression analysis. RESULTS: There were no stillbirths. Adverse neonatal outcome occurred in 27% of monochorionic versus 16% of dichorionic gestations. At multivariate analysis, lower gestational age at delivery (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.57 to 0.87), monochorionicity (OR 2.06, 95% CI 1.16-3.63), and either twin being growth-restricted (OR 2.35, 95% CI 1.22 to 4.54) were independent predictors of adverse neonatal outcome. Analysis of adverse neonatal outcome stratified by gestational age and chorionicity identified 36 to 37 weeks as optimal timing for delivery of monochorionic twins, and dichorionic twin pregnancies should be allowed to continue until term. CONCLUSION: Among twin gestations delivered after 34 weeks with appropriate fetal growth, reassuring fetal status at weekly assessment, and absence of obstetric complications, delivery after 36 weeks for monochorionic twins and at term for dichorionic twins minimizes the risk of stillbirths and neonatal morbidity.

Rate of decline of fetal base excess after neuraxial anesthesia for scheduled cesarean delivery.

BACKGROUND: In scheduled cesarean deliveries, the rate of decrease in the umbilical artery pH is related to the severity of maternal hypotension and the interval from spinal placement to delivery. Base excess values have greater use than umbilical artery pH values to time the duration of fetal acidemia because they demonstrate a linear rather than logarithmic correlation with the degree of acidosis. OBJECTIVE: This study aimed to evaluate the rate of decline in the fetal base excess in scheduled cesarean deliveries that were converted to emergency cesarean delivery owing to fetal bradycardia following spinal anesthesia. STUDY DESIGN: All cases of scheduled cesarean deliveries in gestations at >34 weeks' gestation under spinal anesthesia that were converted to emergency cesarean deliveries owing to fetal bradycardia in the period May 2019 to May 2021 were reviewed. Included were those with (1) a preoperative reactive nonstress test and (2) fetal acidemia (umbilical artery pH <7.20). Excluded were those with anesthesia other than spinal and a birthweight below the 10th percentile for gestational age. Time intervals between the completion of spinal anesthesia and delivery were calculated and related to umbilical cord gas analytes. RESULTS: From a cohort of 1064 scheduled cesarean deliveries, 7 fulfilled the study criteria yielding 8 neonates. Mean ± standard error of the mean interval of spinal anesthesia to delivery was 15.0±1.9 minutes, and the decrease in mean blood pressure after spinal anesthesia was 39.1±3.0 mm Hg. Umbilical artery base excess ranged from -5.2 to -16.6 mmol/L (median, -8.0). Based on published normative data of prelabor fetal umbilical artery base excess (-2±0.6 mmol/L), the mean rate of base excess decrease was 0.38±0.25 mmol/minute. CONCLUSION: The rate of decrease in base excess when scheduled cesarean deliveries are converted to emergency cesarean deliveries owing to fetal bradycardia related to spinal anesthesia (1 mmol/2.6 min) matches the estimated rate of loss of base excess (1 mmol/2-3 minutes) reported in cases of severe bradycardia or sentinel events during labor.