Biopsy-free profiling of the uterine immune system in patients with recurrent pregnancy loss and unexplained infertility.

RESEARCH QUESTION: What are the differences in menstrual blood lymphocytes between controls, patients with recurrent pregnancy loss (RPL) and patients with unexplained infertility (uINF)? DESIGN: Prospective study including 46 healthy controls, 28 RPL and 11 uINF patients. A feasibility study compared lymphocyte compositions of endometrial biopsies and menstrual blood collected during the first 48 h of menstruation in seven controls. In all patients, peripheral and menstrual blood from the first and subsequent 24 h were analysed separately by flow cytometry, focusing on the main lymphocyte populations and natural killer (NK) cell subsets. RESULTS: The first 24 h of menstrual blood resembles the uterine immune milieu as tested by endometrial biopsy. RPL patients showed significantly higher menstrual blood CD56+ NK cell numbers than controls (mean ± SD: 31.13 ± 7.52% versus 36.73 ± 5.4%, P = 0.002). Menstrual blood CD56dimCD16bright NK cells within the CD56+ NK cell population were decreased in RPL (16.34 ± 14.65%, P = 0.011) and uINF (15.7 ± 5.91%, P = 0.02) patients versus control (20.42 ± 11.53%). uINF patients had the lowest menstrual blood CD3+ T cell counts (38.81 ± 5.04%, control versus uINF: P = 0.01) and cytotoxicity receptors NKp46 and NKG2D on CD56brightCD16dim cells were higher in uINF (68.12 ± 11.84%, P = 0.006; 45.99 ± 13.83%, P = 0.01, respectively) and RPL (NKp46: 66.21 ± 15.36%, P = 0.009) patients versus controls. RPL and uINF patients had higher peripheral CD56+ NK cell counts versus controls (11.42 ± 4.05%, P = 0.021; 12.86 ± 4.29%, P = 0.009 versus 8.4 ± 3.5%). CONCLUSIONS: Compared with controls, RPL and uINF patients had a different menstrual blood-NK-subtype profile, indicating an altered cytotoxicity. In future studies, this non-invasive analysis might enable identification and monitoring of patients receiving immunomodulatory medications.

Endometriosis is associated with pregnancy loss: a nationwide historical cohort study.

OBJECTIVE: To study whether endometriosis is associated with pregnancy loss and recurrent pregnancy loss (RPL). DESIGN: Nationwide historical cohort study with a nested case-control analysis. SETTING: National health registers. PATIENT(S): A total of 29,563 women born between 1957 and 1997 were identified in the national health registers, diagnosed with endometriosis between 1977 and 2017, and age-matched 1:10 with 295,630 women without endometriosis. The number of pregnancy losses was assessed, and data were analyzed with conditional logistic regression. INTERVENTION(S): Endometriosis (International Classification of Diseases, 8th Revision, 62530-62539, and International Classification of Diseases, 10th Revision, DN80.0-9). MAIN OUTCOME MEASURE(S): The primary outcomes of interest were the numbers of pregnancy losses categorized as 0, 1, 2, and ≥ 3 losses, unadjusted and adjusted for gravidity, and RPL. The secondary outcome measures were the predefined types of pregnancy losses. Pregnancy loss was defined as the spontaneous demise of a pregnancy until 22 weeks of gestation. Primary RPL was defined as 3 or more consecutive pregnancy losses with no prior live birth or stillbirth, and secondary RPL was defined as 1 or more births followed by 3 or more consecutive losses. RESULT(S): A total of 18.9%, 3.9%, and 2.1% of ever-pregnant women with endometriosis had 1, 2, and ≥ 3 pregnancy losses compared with 17.3%, 3.5%, and 1.5% of the women without endometriosis, corresponding to the odds ratios of 1.13 (95% confidence interval, 1.09-1.17), 1.18 (1.10-1.26), and 1.44 (1.31-1.59), respectively. When adjusted also for gravidity, the corresponding results were 1.37 (95% confidence interval, 1.32-1.42), 1.75 (1.62-1.89), and 2.57 (2.31-2.85), respectively. The following predefined subgroups of RPL were positively associated with endometriosis: primary; secondary; secondary after giving birth to a boy; after a complicated delivery; and ≥ 3 pregnancy losses before the age of 30 years. Six endometriosis subgroup analyses found an association between endometriosis and pregnancy loss. These analyses were women diagnosed in the 4 decades between 1977 and 2017, women with adenomyosis, and women with adenomyosis only. CONCLUSION(S): This nationwide cohort study found endometriosis to be associated with pregnancy loss and RPL, and the association strengthened with an increasing number of losses.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies at Delivery in Women, Partners, and Newborns.

OBJECTIVE: To investigate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in parturient women, their partners, and their newborns and the association of such antibodies with obstetric and neonatal outcomes. METHODS: From April 4 to July 3, 2020, in a single university hospital in Denmark, all parturient women and their partners were invited to participate in the study, along with their newborns. Participating women and partners had a pharyngeal swab and a blood sample taken at admission; immediately after delivery, a blood sample was drawn from the umbilical cord. The swabs were analyzed for SARS-CoV-2 RNA by polymerase chain reaction, and the blood samples were analyzed for SARS-CoV-2 antibodies. Full medical history and obstetric and neonatal information were available. RESULTS: A total of 1,313 parturient women (72.5.% of all women admitted for delivery at the hospital in the study period), 1,188 partners, and 1,206 newborns participated in the study. The adjusted serologic prevalence was 2.6% in women and 3.5% in partners. Seventeen newborns had SARS-CoV-2 immunoglobulin G (IgG) antibodies, and none had immunoglobulin M antibodies. No associations between SARS-CoV-2 antibodies and obstetric or neonatal complications were found (eg, preterm birth, preeclampsia, cesarean delivery, Apgar score, low birth weight, umbilical arterial pH, need for continuous positive airway pressure, or neonatal admission), but statistical power to detect such differences was low. Full serologic data from 1,051 families showed an absolute risk of maternal infection of 39% if the partner had antibodies. CONCLUSION: We found no association between SARS-CoV-2 infection and obstetric or neonatal complications. Sixty-seven percent of newborns delivered by mothers with antibodies had SARS-CoV-2 IgG antibodies. A limitation of our study is that we lacked statistical power to detect small but potentially meaningful differences between those with and without evidence of infection.

[The glucagon-like peptide-1 receptor-agonist semaglutide].

Semaglutide is a glucagon-like peptide-1 receptor-agonist (GLP-1 RA), which is injected subcutaneously once a week for treatment of Type 2 diabetes. In this review, the present results of semaglutide treatment are presented. Semaglutide has been evaluated in more than 8,000 patients across the spectrum of Type 2 diabetes. Trials with semaglutide have demonstrated superiority with sustained improved glycaemic control and weight loss compared to oral antidiabetic agents, other GLP-1 RAs and basalinsulin. In addition, semaglutide significantly decreased the occurrence of cardiovascular events compared with standard pharmacological diabetic treatment combined with placebo.