Global Transcriptomic Analysis of Placentas from Women with Gestational SARS-CoV-2 Infection during the Third Trimester of Pregnancy.

The COVID-19 pandemic has had a significant and enduring influence on global health, including maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above gap, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women immediately after term delivery, seven of which had SARS-CoV-2 infection confirmed by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We separately extracted total RNA from placental tissues from maternal and fetal compartments, constructed cDNA libraries, and sequenced them to assess mRNA. Our analysis revealed 635 differentially expressed genes when a false discovery rate (FDR ≤ 0.05) was applied in the maternal placental tissue, with 518 upregulated and 117 downregulated genes in the SARS-CoV-2-positive women (n = 6) compared with the healthy SARS-CoV-2-negative women (n = 8). In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. We observed a significant downregulation of nine genes belonging to the pregnancy-specific glycoprotein related to the immunoglobulin superfamily in the maternal compartment with active SARS-CoV-2 infection (fold change range from -13.70 to -5.28; FDR ≤ 0.01). Additionally, comparing symptomatic women with healthy women, we identified 1788 DEGs. Furthermore, a signaling pathway enrichment analysis revealed that pathways related to oxidative phosphorylation, insulin secretion, cortisol synthesis, estrogen signaling, oxytocin signaling, antigen processing, and presentation were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risks of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta's anti-viral effects in maternal SARS-CoV-2 infection.

Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial.

STUDY QUESTION: Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? SUMMARY ANSWER: A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. WHAT IS ALREADY KNOWN: The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. STUDY DESIGN SIZE, DURATION: This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. MAIN RESULTS AND THE ROLE OF CHANCE: Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the ±5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. LIMITATIONS, REASONS FOR CAUTION: For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. WIDER IMPLICATIONS OF THE FINDINGS: Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials number NCT01920022. TRIAL REGISTRATION DATE: 06 August 2013. DATE OF FIRST PATIENT'S ENROLMENT: 13 October 2013.

Knowledge, Practices, and Restrictions Related to Menstruation among Young Women from Low Socioeconomic Community in Mumbai, India.

The main objective was to assess knowledge, practices, and restrictions faced by young women regarding their menstrual hygiene. The views of adult women having young daughters were also included and both views were compared. In addition, the factors influencing the menstrual hygiene practices were also studied. The study was carried out during 2008 in Mumbai, India. The mixed methods approach was followed for the data collection. Both qualitative and quantitative methods were used to collect the data. For quantitative survey, totally 192 respondents (96 adult and 96 younger women) were selected. While young women were asked about questions related to their menstruation, adult women were asked questions to find out how much they know about menstrual history of their daughters. The qualitative data helped to supplement the findings from the quantitative survey and to study the factors affecting menstrual practices in young women. The mean age at menarche reported was 13.4 years and 30-40% of young girls did not receive any information about menstruation before menarche. It is thus seen that very few young girls between the age group 15 and 24 years did receive any information before the onset of menstruation. Among those who received some information, it was not adequate enough. The source of information was also not authentic. Both young and adult women agreed on this. Due to the inadequate knowledge, there were certain unhygienic practices followed by the young girls resulting in poor menstrual hygiene. It also leads to many unnecessary restrictions on young girls and they faced many health problems and complaints, which were either ignored or managed inappropriately. The role of health sector was almost negligible from giving information to the management of health problems of these young girls. This paper reemphasizes the important, urgent, and neglected need of providing correct knowledge to the community including adolescent girls.

Studies on uterine contractility following mifepristone and various routes of misoprostol.

During pregnancy, uterine contractility is suppressed by progesterone. The progesterone receptor inhibitor, mifepristone, increases uterine contractility and sensitizes the myometrium to prostaglandin. The maximum effect is achieved when prostaglandins are administered 36 to 48 h after mifepristone. The recommended prostaglandin analogue used with mifepristone for medical abortion is misoprostol. It is licensed for oral use but other routes are used to improve efficacy. The difference in the effect of various routes of administration can be explained by pharmacokinetics and the effect on uterine contractility. Oral misoprostol leads to an increased uterine tonus without regular contractions. In contrast, vaginal and sublingual administration leads to a longer-lasting effect on the myometrium and subsequent development of regular contractions. Recently, a new oral slow-release preparation of misoprostol has been studied. Future studies will show whether prostaglandin analogues with a prolonged effect on the myometrium may further improve the regimens for medical abortion.

The effect of orally and vaginally administered misoprostol on inflammatory mediators and cervical ripening during early pregnancy.

OBJECTIVES: The objective of the present study was to investigate the effect of vaginally and orally administered misoprostol on the local cervical inflammatory response. METHODS: Healthy women with a normal intrauterine pregnancy between 8 and 12 weeks of gestation presenting for an elective termination of pregnancy by vacuum aspiration were recruited into a cohort study with a control and a treatment group. In the treatment group, the women were randomized to misoprostol, 400 mug, given either orally or vaginally 3 h before surgery. Immunohistochemistry staining of CD45, CD68, MMP 8, MMP 9, TIMP 1 and TIMP 2 were assessed in cervical biopsies obtained directly prior to mechanical cervical dilatation and vacuum aspiration. RESULTS: In the treatment group, there was a greater amount of CD45-positive cells in the subepithelium region of the cervix compared to the control group. The staining of CD68 was similar in both groups. The immunostaining of MMP 8 and MMP 9 was greater in the treatment group, while the expression of TIMP 1 and TIMP 2 did not differ between control and treatment groups. CONCLUSIONS: Compared to untreated controls, treatment with misoprostol was associated with a greater expression of inflammatory cells. It could be hypothesized that administration of misoprostol mimics the cervical ripening at term pregnancy by a possible influx and activation of inflammatory cells, which increases MMP 8 and MMP 9 and thereby leads to the degradation of collagen and cervical softening.