Women with Recurrent Pregnancy Loss More Often Have an Older Brother and a Previous Birth of a Boy:Is Male Microchimerism a Risk Factor?

Known etiologic factors can only be found in about 50% of patients with recurrent pregnancy loss (RPL). We hypothesized that male microchimerism is a risk factor for RPL and aimed to explore whether information on family tree and reproductive history, obtained from 383 patients with unexplained RPL, was supportive of this hypothesis. The male:female sex ratio of older siblings was 1.49 (97:65) in all RPL patients and 1.79 (52:29) in secondary RPL (sRPL) patients, which differed significantly from the expected 1.04 ratio (p = 0.027 and p = 0.019, respectively). In contrast, the sex ratio of younger siblings was close to the expected ratio. Sex ratio of the firstborn child before sRPL was 1.51 (p = 0.026). When combined, 79.1% of sRPL patients had at least one older brother, a firstborn boy, or both. This differed significantly from what we expected based on the distribution of younger siblings and a general 1.04 sex ratio of newborns (p = 0.040). We speculate whether (s)RPL patients possibly acquired male microchimerism from older brother(s) and/or previous birth of boy(s) by transplacental cell trafficking. This could potentially have a detrimental impact on their immune system, causing a harmful response against the fetus or trophoblast, resulting in RPL

Sex Differences in Early Cognitive Development After Prenatal Exposure to Opioids

Abstract Objective Prenatal opioid exposure has been linked with impaired cognitive development, with boys potentially at elevated risk. In the present study, we examined cognitive and language development of children prenatally exposed to opioids, with an additional focus on sex differences. Methods A sample of 378 children (n = 194 girls and n = 184 boys) aged 1.2–42.8 months was drawn from the Danish Family Outpatient Clinic database. Developmental outcomes were assessed using the Bayley-III cognitive and language scales, and substance exposure was determined with urine screening and/or verbal report. Children exposed to opioids (n = 94) were compared to children with no prenatal substance exposure (n = 38), and children exposed to alcohol (n = 131) or tobacco (n = 115). Group and sex differences were investigated with separate linear mixed models for each Bayley scale, controlling for concurrent cannabis exposure. Results There were significantly reduced scores in opioid-exposed boys compared to boys with no prenatal substance exposure, but no difference between opioid-exposed and nonexposed girls. Additionally, alcohol-exposed boys had lower cognitive scores than nonexposed boys, and alcohol-exposed girls had lower scores on both scales compared to opioid-exposed girls. There were otherwise no significant differences according to group, sex, or scale. Conclusions The present findings indicate poorer cognitive and language development in boys after prenatal opioid exposure. As academic performance is rooted in cognitive functioning, long-term follow-up might be necessary for exposed children

Relationship between a uterine fibroid diagnosis and the risk of adverse obstetrical outcomes:a cohort study

ObjectiveThe aim was to investigate the association between clinically significant uterine fibroids and preterm birth, caesarean section (CS), postpartum haemorrhage (PPH), placental abruption, intrauterine growth restriction (IUGR) and uterine rupture.Methods, participants and settingA historical cohort study based on data from the Danish National Birth Cohort, the Danish National Patient Registry and the Danish National Birth Registry (DNBR). The final study population consisted of 92 696 pregnancies and was divided into four groups for comparison. Group 1: pregnancies of women without a fibroid diagnosis code or fibroid operation code; group 2: pregnancies of women with a fibroid diagnosis code before pregnancy, during pregnancy or up to 1 year after delivery, and no fibroid operation code before pregnancy; group 3: pregnancies of women with a fibroid diagnosis code given more than 1 year after delivery; and group 4: pregnancies of women with a fibroid operation code given before pregnancy.ResultsA diagnosis of fibroids before pregnancy yielded an increased risk of preterm birth (gestational age (GA) ≤37 weeks) (OR 2.27 (1.30─3.96)) and extreme preterm birth (GA 22+0─27+6 weeks, OR 20.09 (8.04─50.22)). The risk of CS was increased (OR 1.83 (1.23─2.72)) for women with a fibroid diagnosis code given before pregnancy; significantly increased risk of elective CS (OR 1.92 (1.11─3.32)), but not acute CS (OR 1.54 (0.94─2.52)). The risks of PPH, placental abruption or IUGR were not increased in any of the groups.ConclusionWe found a strong association between clinically significant uterine fibroids and preterm birth, and an association between clinically significant uterine fibroids and CS. In contrast, no association between clinically significant uterine fibroids and PPH, placental abruption or IUGR was seen

EFFORT study:Comparing impact of operation and assisted reproductive technologies on fertility for women with deep infiltrating endometriosis - study protocol for a multicentre randomised trial

INTRODUCTION: Deep infiltrating endometriosis (DIE) affecting the rectum or sigmoid colon is associated with infertility, severe pain and decreased quality of life. As most women with DIE are young, many have a pregnancy intention. Treatment possibilities of endometriosis-associated infertility are surgery or assisted reproductive technologies (ART). However, no studies have compared the two interventions directly. Therefore, this study aims to determine the cumulative pregnancy rate (CPR) and the live birth rate (LBR) after first-line surgery compared with first-line ART for women with rectosigmoid DIE and a pregnancy intention. METHODS AND ANALYSIS: Multicentre, parallel-group, randomised trial of women with rectosigmoid DIE and a pregnancy intention for at least 6 months in Aarhus, Denmark and Bordeaux, France. 352 women aged 18–38 years are randomised 1:1 to either surgical management (shaving, disc excision or segmental resection) or ART management (at least two in vitro fertilisation or intracytoplasmic sperm injection procedures if not pregnant after the first cycle). Women in the surgical intervention group will attempt to get pregnant by either spontaneous conception or ART, depending on the endometriosis fertility index score. Primary outcome measures are CPR and LBR at 18 months’ follow-up. Secondary outcomes are: Non-viable pregnancies, time to pregnancy, pain score, quality of life, complication rate, bowel and bladder function, endocrine and inflammatory profile, number of oocytes, blastocysts, frozen embryos and blastocyst morphology score within 18 months after either intervention. ETHICS AND DISSEMINATION: Conduct of this study is approved by the Danish National Committee on Health Research Ethics and Comité de Protection des Personnes Ile de France VIII. Study participants must sign an informed consent form. The results will be presented at national and international conferences and published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: This trial is registered at ClinicalTrials.gov (no. NCT04610710). PROTOCOL VERSION: The Danish National Committee on Health Research Ethics: Fifth protocol version approved 7 September 2020 (no. 1-10-72-96-20). Comité de Protection des Personnes Ile de France VIII: Version 1.1 22JAN2021 the 9 March 2021