Risk of Preterm Delivery in Very Advanced Maternal Age Parturients Utilizing In Vitro Fertilization.

OBJECTIVE: Among patients ≥45 years, the birth rate in the United States continues to increase. As fertility declines with age, this cohort often utilizes assisted reproductive technology, specifically in vitro fertilization (IVF). While both advancing maternal age and IVF are independently associated with adverse maternal outcomes, data regarding their additive effect are scant. This article aims to determine if patients who conceive via IVF are at increased risk for preterm birth (PTB) compared to patients with non-IVF pregnancies in a very advanced maternal age (vAMA) cohort (≥45 years). STUDY DESIGN: Retrospective cohort study of all pregnant patients ≥45 years old who delivered at a single institution (2014-2021). Those with incomplete delivery/neonatal records or multiples beyond twins were excluded. We compared individuals who conceived via IVF to those who conceived without IVF. The primary outcome was preterm delivery <37 weeks gestation. Secondary outcomes included other adverse perinatal outcomes. Using multivariable logistic regression, we adjusted for multiple gestation as well as confounders found to be significantly different in the univariable analysis and other known risk factors for PTB. RESULTS: In our study cohort of 420 vAMA patients, individuals who underwent IVF were more likely to be older, privately insured, nulliparous, and with a twin gestation. The PTB rate in vAMA patients who underwent IVF was 24.4 compared to 8.4% in patients who did not use IVF (p < 0.001). After adjusting for confounders, IVF was an independent risk factor for PTB <37 weeks in vAMA patients (adjusted odds ratio {aOR] = 4.3, 95% confidence interval [CI]: 1.7-10.4, p = 0.001). In vitro fertilization was also associated with a composite of adverse maternal outcomes (hypertensive disorder of pregnancy, postpartum hemorrhage, blood transfusion, and unplanned hysterectomy) (aOR 1.7, 95% CI [1.1-2.9], p = 0.03). CONCLUSION: In the vAMA population, conception via IVF is associated with an increased risk of PTB <37 weeks. KEY POINTS: · This study examines IVF as an independent risk factor for PTB in patients ≥45 years at delivery, which has not been specifically addressed in prior studies.. · In vAMA patients, use of IVF is associated with an increased risk of PTB <37 weeks. These patients also have higher rates of cesarean delivery. Neonates from IVF pregnancies are more likely to be very low birth weight or low birth weight.. · Bodies of research exist for both advanced maternal age and assisted reproductive technology, there is a paucity of data specifically in parturients of vAMA who conceive via IVF..

Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series.

PROBLEM: We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals. METHOD OF STUDY: Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab for treatment of severe COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had severe COVID-19 with bilateral pulmonary infiltrates and oxygen requirement. Eculizumab was administered on day 1 (1200 mg IV) with additional doses if still hospitalized (1200 mg IV on Days 4 and 8; 900 mg IV on Days 15 and 22; optional doses on Days 12 and 18). The primary outcome was survival at Day 15. Secondary outcomes included survival at Day 29, need for mechanical ventilation, and duration of hospital stay. We evaluated pharmacokinetic and pharmacodynamic data, safety, and adverse outcomes. RESULTS: Eight participants were enrolled at the Cedars-Sinai Medical Center, six during pregnancy (mean 30 ± 4.0 weeks) and two in the postpartum period. Baseline oxygen requirement ranged from 2 L/min nasal cannula to 12 L/min by non-rebreather mask. The median number of doses of eculizumab was 2 (range 1-3); the median time to hospital discharge was 5.5 days (range 3-12). All participants met the primary outcome of survival at Day 15, and all were alive and free of mechanical ventilation at Day 29. In three participants we demonstrated that free C5 and soluble C5b-9 levels decreased following treatment. There were no serious adverse maternal or neonatal events attributed to eculizumab at 3 months. CONCLUSION: We describe use of eculizumab to treat severe COVID-19 in a small series of pregnant and postpartum adults. A larger, controlled study in pregnancy is indicated.

Pregnancy outcomes in very advanced maternal age women.

BACKGROUND: Advanced maternal age is associated with adverse pregnancy and delivery outcomes. Few studies have directly compared outcomes between women of advanced maternal age (35-44 years old) and women of very advanced maternal age (≥45 years old). OBJECTIVE: We aimed to determine the differences in outcomes between women of advanced maternal age and women of very advanced maternal age. STUDY DESIGN: This was a retrospective cohort study conducted at a large urban US medical center. Demographic and obstetrical data were collected in all patients who delivered within the study window (2012-2018). Characteristics and outcomes were compared between women of advanced maternal age and women of very advanced maternal age. Chi-square analyses were used to compare categorical variables. The Student t test or Wilcoxon tests were used, depending on the distribution, to compare continuous variables. RESULTS: A total of 45,435 women had delivery data for analysis. Of these women, 26,700 (59%) were not of advanced maternal age, 18,286 (40%) were of advanced maternal age, and 449 (1%) were of very advanced maternal age. Race and ethnicity varied significantly by age group. Nulliparity and postpartum hemorrhage were statistically higher in the very advanced maternal age group. Of note, cesarean delivery rates were 69.5% in the very advanced maternal age group and 39.5% in the advanced maternal age group (P<.001). Chronic hypertension, gestational hypertension, preeclampsia with and without severe features, superimposed preeclampsia, and eclampsia were all statistically significantly higher (at least 2-fold) in the very advanced maternal age group than the advanced maternal age group (P<.001). There was no significant difference in the rates of hemolysis, elevated liver enzymes, and low platelet count between the 2 groups. Rates of neonatal intensive care unit admission, Apgar score of <7 at 5 minutes, and neonatal length of stay of >5 days after cesarean delivery were higher in neonates from mothers of very advanced maternal age. Birthweights of neonates were significantly lower in mothers of very advanced maternal age. CONCLUSION: There were several important significant differences in the outcomes between women of very advanced maternal age women and women of advanced maternal age, especially concerning hypertensive disorders and cesarean delivery rates. These findings may influence patient counseling and strategies for antepartum surveillance.

Risk factors for re-presentation for postpartum hypertension in patients without a history of hypertension or preeclampsia.

BACKGROUND: Re-presentation for evaluation of hypertension following discharge after delivery is common. However, a subset of patients who re-present for evaluation of postpartum hypertension do not have a history of hypertension. Identification of those at risk may help guide postpartum management and prevent re-presentations to the hospital. OBJECTIVE: This study aimed to establish risk factors for re-presentation for hypertension within 30 days of discharge after delivery in patients without a history of hypertension compared with women who did not re-present and to distinguish from risk factors for re-presentation for another reason. STUDY DESIGN: Subjects were identified through data extraction from a single institution between January 2012 and December 2018. We included subjects without an International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision code for (1) chronic hypertension or (2) a hypertensive disorder of pregnancy during their delivery encounter who re-presented to the hospital within 30 days. Thus, the re-presentation group was divided into the following 2 groups: those who re-presented for hypertension and those who re-presented for any other reason. Each re-presentation group was compared with the cohort of patients who delivered within the study window and did not re-present using the Student t test or Wilcoxon tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Multivariable regression was also performed on all potentially important risk factors. RESULTS: Factors that emerged as uniquely significant in the re-presentation group for hypertension were maternal age of ≥40 years and antenatal prescription of low-dose aspirin. Black race and body mass index of ≥30 kg/m2, although significant in both re-presentation groups, were more strongly predictive of re-presentation for hypertension. These factors remained independently significant when compared with each other in a multivariable analysis. CONCLUSION: There are identifiable risk factors for postpartum re-presentation for hypertension in patients without a history of hypertension. Upon discharge, providers may consider close blood pressure monitoring and follow-up in patients who have any of the following risk factors: age of ≥40 years, black race, body mass index of ≥30 kg/m2, or those who were prescribed low-dose aspirin in pregnancy.

Premenstrual dysphoric disorder in women with epilepsy: relationships to potential epileptic, antiepileptic drug, and reproductive endocrine factors.

The purpose of this prospective observational investigation was to determine whether the frequency of premenstrual dysphoric disorder (PMDD) and the severity of PMDD symptoms differ between women with epilepsy and controls without epilepsy and whether there exists a relationship between the severity of PMDD symptoms and some epileptic, antiepileptic drug, and reproductive endocrine features. The results suggest that epilepsy, antiepileptic drug levels, ovulatory status, and hormone levels and ratios may all influence PMDD in women with epilepsy. PMDD severity scores may be greater in people with right-sided than in those with left-sided epilepsy, and in people with temporal than in those with nontemporal epileptic foci. PMDD severity scores may be greater with anovulatory cycles, and scores may correlate negatively with midluteal serum progesterone levels and positively with midluteal estradiol/progesterone ratios. Mood score may vary with particular antiepileptic drugs, favoring carbamazepine and lamotrigine over levetiracetam. PMDD severity scores may correlate directly with carbamazepine levels, whereas they correlate inversely with lamotrigine levels.

A comparison of anastrozole and testosterone versus placebo and testosterone for treatment of sexual dysfunction in men with epilepsy and hypogonadism.

Hyposexuality is commonly associated with low bioavailable testosterone (BAT) and relative estradiol elevation in men with epilepsy. This prospective, randomized, double-blind trial compared the effects of depotestosterone+the aromatase inhibitor anastrozole (T-A) versus depotestosterone+placebo (T-P) on sexual function, hormone levels, mood, and seizure frequency in men with epilepsy. Forty men with focal epilepsy, hyposexuality, and hypogonadism were randomized 1:1 to two groups (T-A or T-P) for a 3-month treatment trial of depotestosterone+either anastrozole or matching placebo. Outcomes included both efficacy and safety measures. Normalization of sexual function (S-score) occurred with greater frequency in the T-A (72.2%) than in the T-P (47.4%) group, but the difference was not statistically significant. T-A resulted in significantly lower estradiol levels and S-scores correlated inversely with estradiol levels at baseline and during treatment. Beck Depression Inventory II (BDI-II) scores improved significantly in both groups and changes in S-score correlated inversely with changes in BDI-II score. Changes in seizure frequency correlated with changes in BDI-II score. Seizure frequency decreased with both treatments and showed significant correlations with estradiol levels. Triglyceride levels increased with T-P and decreased with T-A. The difference in triglyceride changes between the two treatments was significant and correlated with changes in estradiol levels. Significant correlations between estradiol levels and S-scores, as well as seizure outcomes and triglyceride levels, suggest further study regarding a potential role for anastrozole in the treatment of men with epilepsy who have hyposexuality and hypogonadism.