Evaluation of the maternal systemic immune system during frozen euploid embryo transfer according to cycle outcome.

Infertility affects 15 % of couples in the US, and many turn to assisted reproductive technologies, including in vitro fertilization and subsequent frozen embryo transfer (FET) to become pregnant. This study aimed to perform a broad assessment of the maternal immune system to determine if there are systemic differences on the day of FET in cycles that result in a live birth compared to those that do not. Women undergoing FET of euploid embryos were recruited and blood was collected on the day of FET as well as at early timepoints in pregnancy. Sixty immune and angiogenic proteins were measured in plasma, and gene expression of 92 immune-response related genes were evaluated in peripheral blood mononuclear cells (PBMCs). We found plasma concentrations of interleukin-13 (IL-13) and macrophage derived chemokine (MDC) were significantly lower on the day of FET in cycles that resulted in a live birth. We also found genes encoding C-C chemokine receptor type 5 (CCR5), CD8 subunit alpha (CD8A) and SMAD family member 3 (SMAD3) were upregulated in PBMCs on the day of FET in cycles that resulted in live birth. Measurements of immune mediators from maternal blood could serve as prognostic markers during FET to guide clinical decision making and further our understanding of implantation failure.

Interactive video module and simulated model for uterine manipulation during laparoscopic hysterectomy.

BACKGROUND: Hysterectomy is one of the most common gynecologic surgeries, with an increasing proportion of hysterectomies performed by a laparoscopic approach. Uterine manipulation is critical for patient safety and surgical efficiency; however, the most junior member of the surgical team assumes the responsibility of uterine manipulation, commonly without preparation. The objective of our study was to determine whether kinesthetic learning using a low-cost simulated pelvic model while learning the uterine manipulation maneuvers of a laparoscopic hysterectomy improves learning efficacy and application efficiency compared to an interactive video module alone. METHODS: Our randomized control trial at an academic medical center included forty first-year and second-year medical students. Participants were randomized to the intervention group that used a low-cost simulated pelvic model for kinesthetic learning during the video module or the control group who only had the interactive video module to learn the uterine manipulation maneuvers of a laparoscopic hysterectomy. RESULTS: Participants in the intervention group were less likely to make unnecessary movements with demonstration of both pelvic side walls (right wall: control 78.9%, intervention 42.9%, p < 0.027; left wall: control 94.7%, intervention 66.7%, p < 0.046), and this was more pronounced in novice first-year participants (p < 0.009). Additionally, participants in the intervention group reported higher perceived preparedness (100% versus 71.4% in control group, p < 0.037). However, there was no difference in verbal or physical cues required, time per task, or force used between the groups. CONCLUSION: Kinesthetic practice may not be required for learning the uterine manipulation maneuvers of a laparoscopic hysterectomy, but it may be beneficial for more novice learners and to increase learners' perceived preparedness. Our novel interactive video module alone may be sufficient to prepare learners to perform uterine manipulation maneuvers prior to the operating room.

Association of an Obstetric Surgical Closing Protocol With Infection After Cesarean Delivery.

OBJECTIVE: To examine surgical site infection rates before and after the addition of a closing protocol to an existing surgical site infection risk-reduction bundle used during cesarean delivery. METHODS: We conducted a single-center retrospective cohort study to review the association of a closing protocol with rates of surgical site infection after cesarean delivery. The closing protocol included fresh surgical instruments and physician and scrub nurse glove change before fascia closure. Surgical site infections were defined using Centers for Disease Control and Prevention criteria. Eligible patients underwent cesarean delivery at our institution from July 1, 2013, through December 31, 2015 (n=1,708; preimplementation group), or from June 1, 2016, through April 30, 2018 (n=1,228; postimplementation group). RESULTS: The surgical site infection rate was 2.3% preimplementation and 2.7% postimplementation (difference 0.4%, 95% CI -1.6 to 0.7%]. The mean [SD] duration of the surgical procedure was longer postimplementation (59.6 [23.7] vs 55.6 [21.5] minutes; P<.001). CONCLUSION: Addition of a closing tray and glove change to our existing surgical site infection risk-reduction bundle was not associated with a reduction in the frequency of postcesarean surgical site infection but was associated with longer operating times.

Evaluating Markers of Immune Tolerance and Angiogenesis in Maternal Blood for an Association with Risk of Pregnancy Loss.

Pregnancy loss affects approximately 20% of couples. The lack of a clear cause complicates half of all miscarriages. Early evidence indicates the maternal immune system and angiogenesis regulation are both key players in implantation success or failure. Therefore, this prospective study recruited women in the first trimester with known viable intrauterine pregnancy and measured blood levels of immune tolerance proteins galectin-9 (Gal-9) and interleukin (IL)-4, and angiogenesis proteins (vascular endothelial growth factors (VEGF) A, C, and D) between 5 and 9 weeks gestation. Plasma concentrations were compared between groups defined based on (a) pregnancy outcome and (b) maternal history of miscarriage, respectively. In total, 56 women were recruited with 10 experiencing a miscarriage or pregnancy loss in the 2nd or 3rd trimester and 11 having a maternal history or miscarriage. VEGF-C was significantly lower among women with a miscarriage or pregnancy loss. Gal-9 and VEGF-A concentrations were decreased in women with a prior miscarriage. Identification of early changes in maternal immune and angiogenic factors during pregnancy may be a tool to improve patient counseling on pregnancy loss risk and future interventions to reduce miscarriage in a subset of women.

Timing of delivery with coronavirus disease 2019 pneumonia requiring intensive care unit admission.

Approximately 4% of pregnant patients with coronavirus disease 2019 require intensive care unit admission. Given the practical implications of advanced ventilatory and circulatory support techniques, urgent or emergent delivery for nonreassuring fetal status frequently presents a logistical impossibility. This article proposes a protocol for obstetrical management of patients in these situations, emphasizing coordinated preparation among obstetrical, anesthesiology, and intensivist teams for planned preterm delivery at gestational ages when neonatal outcomes are likely to be favorable.

Sequential Minimally Invasive Fetal Interventions for Two Life-Threatening Conditions: A Novel Approach.

INTRODUCTION: In utero interventions are performed in fetuses with "isolated" major congenital anomalies to improve neonatal outcomes and quality of life. Sequential in utero interventions to treat 2 anomalies in 1 fetus have not yet been described. CASE PRESENTATION: Here, we report a fetus with a large left-sided intralobar bronchopulmonary sequestration (BPS) causing mediastinal shift, a small extralobar BPS, and concomitant severe left-sided congenital diaphragmatic hernia (CDH). At 26-week gestation, the BPS was noted to be increasing in size with a significant reduction in right lung volume and progression to fetal hydrops. The fetus underwent ultrasound-guided ablation of the BPS feeding vessel leading to complete tumor regression. However, lung development remained poor (O/E-LHR: 0.22) due to the left-sided CDH, prompting fetal endoscopic tracheal occlusion therapy at 28-week gestation to allow increased lung growth. After vaginal delivery, the newborn underwent diaphragmatic repair with resection of the extralobar sequestration. He was discharged home with tracheostomy on room air at 9 months. DISCUSSION/CONCLUSION: Sequential in utero interventions to treat 2 severe major anomalies in the same fetus have not been previously described. This approach may be a useful alternative in select cases with otherwise high morbidity/mortality. Further studies are required to confirm our hypothesis.

Fetal Surgery in the Era of SARS-CoV-2 Pandemic: A Single-Institution Review.

OBJECTIVE: To cope with the changing health care services in the era of SARS-CoV-2 pandemic. We share the institutional framework for the management of anomalous fetuses requiring fetal intervention at Mayo Clinic, Rochester, Minnesota. To assess the success of our program during this time, we compare intraoperative outcomes of fetal interventions performed during the pandemic with the previous year. PATIENTS: We implemented our testing protocol on patients undergoing fetal intervention at our institution between March 1, and May 15, 2020, and we compared it with same period a year before. A total of 17 pregnant patients with anomalous fetuses who met criteria for fetal intervention were included: 8 from 2019 and 9 from 2020. METHODS: Our testing protocol was designed based on our institutional perinatal guidelines, surgical requirements from the infection prevention and control (IPAC) committee, and input from our fetal surgery team, with focus on urgency of procedure and maternal SARS-CoV-2 screening status. We compared the indications, types of procedures, maternal age, gestational age at procedure, type of anesthesia used, and duration of procedure for cases performed at our institution between March 1, 2020, and May 15, 2020, and for the same period in 2019. RESULTS: There were no statistically significant differences among the number of cases, indications, types of procedures, maternal age, gestational age, types of anesthesia, and duration of procedures (P values were all >.05) between the pre-SARS-CoV-2 pandemic in 2019 and the SARS-CoV-2 pandemic in 2020. CONCLUSIONS: Adoption of new institutional protocols during SARS-CoV-2 pandemic, with appropriate screening and case selection, allows provision of necessary fetal intervention with maximal benefit to mother, fetus, and health care provider.

Fresh versus frozen embryo transfer has no effect on childhood weight.

OBJECTIVE: To evaluate the effect of frozen, compared with fresh, embryo transfer on neonatal and pediatric weight and weight gain trajectory. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Women who underwent fresh or frozen embryo transfer at the Mayo Clinic from 2010 to 2014. All included embryo transfers resulted in a singleton live birth. Children were followed from birth to at least 18 months. When possible, growth was evaluated to 5 years of age. INTERVENTIONS(S): Fresh versus frozen embryo transfer. MAIN OUTCOME MEASURE(S): Propensity score methodology was used to balance the two groups by maternal characteristics and gestational age before evaluating outcomes. Each infant and childhood growth measurement was compared between the two groups. RESULT(S): Of the 136 women, 87 underwent a fresh embryo transfer and 49 underwent a frozen embryo transfer. Birth length and head circumference were significantly different in infants delivered after fresh versus frozen embryo transfer. There was a statistically significant difference in birth weight between infants born after fresh versus frozen embryo transfer. However, this difference did not persist when adjusted for gestational age, sex, and maternal factors. Childhood growth measurements including age- and sex-specific weight, and body mass index percentiles were not significantly different between groups. CONCLUSION(S): This study confirmed an association of frozen embryo transfer and increased birth weight, but the association did not persist when controlling for confounding maternal factors. We found no effect of fresh versus frozen embryo transfer on neonatal weight and childhood weight gain trajectory.

Implementation of the "Pregnancy Reasonably Excluded Guide" for Pregnancy Assessment: A Quality Initiative in Outpatient Gynecologic Surgery.

OBJECTIVE: Preoperative evaluation for pregnancy at our institution lacked standardization among individual health care providers and surgical services. This pilot project aimed to improve assessment for pregnancy before scheduled outpatient gynecologic surgical procedures. The Pregnancy Reasonably Excluded Guide incorporates historic, evidence-based criteria to facilitate identification of patients with a higher chance of pregnancy. METHODS: We retrospectively reviewed documentation for women undergoing gynecologic surgery at an outpatient surgical center from March through September 2016, before and after implementation of the pregnancy assessment protocol. After implementation, all eligible women (aged 18-50 years, not undergoing an emergent or pregnancy-related procedure) were assessed using the Pregnancy Reasonably Excluded Guide on arrival to the preoperative area. The Pregnancy Reasonably Excluded Guide checklist uses traditional and World Health Organization criteria for reasonable exclusion of pregnancy. Nursing staff reviewed responses with patients and pregnancy tests were completed as indicated by patient responses. Women who were unable to read, understand, or freely respond to the checklist received pregnancy testing. Pregnancy assessment, testing, results, and delays were recorded. This project was deemed exempt by the institutional review board. RESULTS: Two hundred thirteen eligible patients underwent outpatient gynecologic procedures during the study period (excluding a 2-week washout period at implementation). In the preimplementation period, 93 of 136 patients (68%) had pregnancy risk documented; 73 of 77 (95%) had documentation in the postimplementation period (P≤.01). Pregnancy tests were completed in 45 preimplementation patients (33%) and 16 postimplementation patients (21%) (P=.06). No pregnancy test results were positive. No procedural delays were associated with pregnancy assessment. CONCLUSION: Patient-centered assessment using the Pregnancy Reasonably Excluded Guide at presentation for outpatient gynecologic surgery significantly improved evaluation and documentation of pregnancy status before scheduled procedures without increasing the number of pregnancy tests or causing procedural delays.

Standardizing Second-Trimester Medical Termination: Effects on Clinical Outcomes.

OBJECTIVE: The objective of this study was to evaluate length of induction and postdelivery complications before and after implementation of a standardized approach to second-trimester medical termination of pregnancy. STUDY DESIGN: This was a retrospective cohort study of all women undergoing medical termination of pregnancy between 130/7 and 266/7 weeks of gestation at a single, academic institution from July 1, 2012, through June 30, 2015. The primary outcome was the time from the start of induction of labor to delivery of the fetus. Postdelivery complications including the need for dilation and curettage (D&C), blood transfusion, and readmission to the hospital were secondary outcomes of interest. RESULTS: A total of 62 women met inclusion criteria; 38 before and 24 after the intervention. There were no differences in measured baseline characteristics (p > 0.05). There was a significant decrease in induction time after the intervention (12.3 compared with 8.6 hours, p = 0.031). There was no significant difference in rates of D&C or other measured complications (p > 0.05). CONCLUSION: Implementation of a standardized clinical guideline for second-trimester medical termination was associated with a decrease in length of induction. There was no significant difference in need for D&C or postdelivery complications; however, we were underpowered for these secondary outcomes.