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Smith ER, Oakley E, Grandner GW, et al., 2023, Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: A sequential, prospective meta-analysis, American Journal of Obstetrics and Gynecology, Vol: 228, Pages: 161-177, ISSN: 0002-9378
OBJECTIVE: This sequential, prospective meta-analysis (sPMA) sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to: disease severity, maternal morbidities, neonatal mortality and morbidity, adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sPMA via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. STUDY APPRAISAL AND SYNTHESIS METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a two-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (pre-existing diabetes, hypertension, cardiovascular disease) versus those without were at higher risk for COVID-19 severity and pregnancy health outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% CI: 1.12, 2.71) more likely to be admitted to the ICU. Pregnant women who were underweight before pregnancy were at higher risk of ICU admission (RR 5.53, 95% CI: 2.27, 13.44), ventilation (RR 9.36, 95% CI: 3.87, 22.63), and pregnancy-related death (RR 14.10, 95% CI: 2.83, 70.36). Pre-pregnancy obesity was also a risk factor for severe COVID-19 outcomes including ICU admission (RR 1.81, 95% CI: 1.26,2.60), ventilation (RR 2.05, 95% CI: 1.20,3.51), any critical care (RR 1.89, 95% CI: 1.28,2.77), and pneumonia (RR 1.66, 95% CI: 1.18,2.33). Anemic pregnant women with COVID-19 also had in
Mullins E, McCabe R, Bird SM, et al., 2022, Tracking the incidence and risk factors for SARS-CoV-2 infection using historical maternal booking serum samples, PLoS One, Vol: 17, Pages: e0273966-e0273966, ISSN: 1932-6203
The early transmission dynamics of SARS-CoV-2 in the UK are unknown but their investigation is critical to aid future pandemic planning. We tested over 11,000 anonymised, stored historic antenatal serum samples, given at two north-west London NHS trusts in 2019 and 2020, for total antibody to SARS-CoV-2 receptor binding domain (anti-RBD). Estimated prevalence of seroreactivity increased from 1% prior to mid-February 2020 to 17% in September 2020. Our results show higher prevalence of seroreactivity to SARS-CoV-2 in younger, non-white ethnicity, and more deprived groups. We found no significant interaction between the effects of ethnicity and deprivation. Derived from prevalence, the estimated incidence of seroreactivity reflects the trends observed in daily hospitalisations and deaths in London that followed 10 and 13 days later, respectively. We quantified community transmission of SARS-CoV-2 in London, which peaked in late March / early April 2020 with no evidence of community transmission until after January 2020. Our study was not able to determine the date of introduction of the SARS-CoV-2 virus but demonstrates the value of stored antenatal serum samples as a resource for serosurveillance during future outbreaks.
Farahani L, Mowla S, Tharakan T, et al., 2022, Next generation sequencing analysis of the seminal microbiome in male partners of women with idiopathic recurrent pregnancy loss: results of a prospective cohort study, Publisher: OXFORD UNIV PRESS, Pages: I149-I149, ISSN: 0268-1161
Smith ER, Oakley E, He S, et al., 2022, Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods, PLoS One, Vol: 17, ISSN: 1932-6203
We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.
Salem V, Hirani D, Lloyd C, et al., 2022, Why are women still leaving academic medicine? A qualitative study within a London Medical School, BMJ Open, Vol: 12, ISSN: 2044-6055
Objectives: To identify factors that influenced women who chose to leave academic medicine.Design and main outcome measures: Independent consultants led a focus group of women in medicine who had left academia after completion of their postgraduate research degree at Imperial College London Faculty of Medicine. Thematic analysis was performed on the transcribed conversations.Participants and setting: Nine women physicians who completed a postgraduate degree (MD or PhD) at a large London Medical School and Academic Health Sciences Centre, Imperial College London, but did not go on to pursue a career in academic medicine.Results: Influences to leave clinical academia were summarised under eight themes—career intentions, supervisor support, institutional human resources support, inclusivity, work–life balance, expectations, mentors and role models, and pregnancy and maternity leave.Conclusion: The women in our focus group reported several factors contributing to their decision to leave clinical academia, which included lack of mentoring tailored to specific needs, low levels of acceptance for flexible working to help meet parental responsibilities and perceived explicit gender biases. We summarise the multiple targeted strategies that Imperial College London has implemented to promote retention of women in academic medicine, although more research needs to be done to ascertain the most effective interventions.
Mowla S, Tharakan T, Farahani L, et al., 2022, Associations between seminal microbiota composition and ROS in men with fertility disorders, Publisher: ELSEVIER, Pages: S1187-S1187, ISSN: 0302-2838
Hawkins J, Glasier A, Hall S, et al., 2021, Early medical abortion by telemedicine in the United Kingdom: A costing analysis, BJOG: an International Journal of Obstetrics and Gynaecology, Vol: 129, ISSN: 1470-0328
Objective:To determine the potential cost savings resulting from the introduction of routine early medical abortion at home by telemedicine in the United Kingdom.Design:A costing studySetting:United KingdomPopulation:Women in 2020 undergoing early medical abortion provided by three independent abortion providers and two NHS abortion clinics.Methods:Computation of the costs of each abortion procedure and of managing failed or incomplete abortion and haemorrhage requiring blood transfusion.Outcome measures:Cost savingsResults:Overall estimated cost savings are £15.80 per abortion undertaken by independent abortion providers representing a saving to the NHS of over £3 million per year. Limited data from NHS services resulted in an estimated average saving of £188.84 per abortion.ConclusionsWere telemedicine EMA to become routine, an increase in the number of women eligible for medical rather than surgical abortion, and a reduction in adverse events resulting from earlier abortion could result in significant cost-savings.
Suntharalingham J, Ishida M, Buonocore F, et al., 2021, Analysis of Placental Steroidogenesis as a Cause of Recurrent Miscarriage, ESPE, Publisher: KARGER, Pages: 296-297, ISSN: 1663-2818
Summerfield J, Regan L, 2021, How can we achieve sustainable development Goal-5: gender equality for all by 2030?, Clinical Obstetrics and Gynecology, Vol: 64, Pages: 415-421, ISSN: 0009-9201
The Sustainable Development Goals (SDGs) were launched in 2016 to expand the 2000 Millennium Development Goals. SDG-5 calls on governments to achieve gender equality and empowerment of all girls, highlighting the importance of sexual and reproductive health (SRH). There are large variations across the globe in maternity safety and there is clear evidence that a significant percentage of maternity mortality is preventable through the provision of reliable contraception and safe abortion services for women. If SDG-5 is to be achieved by 2030, it is essential that women have access to appropriate life-saving healthcare and support services.
Glasier A, Regan L, 2021, Induced abortion via telemedicine should become the norm: a commentary, BJOG: an International Journal of Obstetrics and Gynaecology, Vol: 128, Pages: 1475-1476, ISSN: 1470-0328
Mullins E, Regan L, Radice H, et al., 2021, Post-delivery contraception: a business case for a new, sustainable regional service, RCOG Congress 2021, Publisher: WILEY, Pages: 253-254, ISSN: 1470-0328
Mulji Y, Cousins C, Kapur S, et al., 2021, Initiation of a Post-Delivery Contraception Service (PDCS) in North West London, RCOG Congress 2021, Publisher: WILEY, Pages: 254-254, ISSN: 1470-0328
Coomarasamy A, Dhillon-Smith RK, Papadopoulou A, et al., 2021, Recurrent miscarriage: evidence to accelerate action, The Lancet, Vol: 397, Pages: 1675-1682, ISSN: 0140-6736
Women who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs.
Quenby S, Gallos I, Dhillon-Smith R, et al., 2021, Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss, The Lancet, Vol: 397, Pages: 1658-1667, ISSN: 0140-6736
Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5–18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3–11·4%), two miscarriages is 1·9% (1·8–2·1%), and three or more miscarriages is 0·7% (0·5–0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need
Coomarasamy A, Gallos ID, Papadopoulou A, et al., 2021, Sporadic miscarriage: evidence to provide effective care, The Lancet, Vol: 397, Pages: 1668-1674, ISSN: 0140-6736
The physical and psychological effect of miscarriage is commonly underappreciated. The journey from diagnosis of miscarriage, through clinical management, to supportive aftercare can be challenging for women, their partners, and caregivers. Diagnostic challenges can lead to delayed or ineffective care and increased anxiety. Inaccurate diagnosis of a miscarriage can result in the unintended termination of a wanted pregnancy. Uncertainty about the therapeutic effects of interventions can lead to suboptimal care, with variations across facilities and countries. For this Series paper, we have developed recommendations for practice from a literature review, appraisal of guidelines, and expert group discussions. The recommendations are grouped into three categories: (1) diagnosis of miscarriage, (2) prevention of miscarriage in women with early pregnancy bleeding, and (3) management of miscarriage. We recommend that every country reports annual aggregate miscarriage data, similarly to the reporting of stillbirth. Early pregnancy services need to focus on providing an effective ultrasound service, as it is central to the diagnosis of miscarriage, and be able to provide expectant management of miscarriage, medical management with mifepristone and misoprostol, and surgical management with manual vacuum aspiration. Women with the dual risk factors of early pregnancy bleeding and a history of previous miscarriage can be recommended vaginal micronised progesterone to improve the prospects of livebirth. We urge health-care funders and providers to invest in early pregnancy care, with specific focus on training for clinical nurse specialists and doctors to provide comprehensive miscarriage care within the setting of dedicated early pregnancy units.
Coomarasamy A, Devall AJ, Brosens JJ, et al., 2020, Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence, Obstetrical and Gynecological Survey, Vol: 75, Pages: 743-744, ISSN: 0029-7828
Historically, a lack of methodologically strong and generalizable studies has limited policy makers from recommending the use of progesterone supplementation to improve outcomes in women at high risk of miscarriage. The PROMISE and PRISM trials were carried out to rectify this and generate robust evidence on the role of progesterone supplementation to prevent miscarriage.
Coomarasamy A, Devall AJ, Brosens JJ, et al., 2020, Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence, American Journal of Obstetrics and Gynecology, Vol: 223, Pages: 167-176, ISSN: 0002-9378
Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progest
Devall AJ, Gallos ID, Khalaf Y, et al., 2020, Re: Effect of progestogen for women with threatened miscarriage: a systematic review and meta-analysis, BJOG: an International Journal of Obstetrics and Gynaecology, Vol: 127, Pages: 1303-1304, ISSN: 1470-0328
Makins A, Arulkumaran S, 2020, The negative impact of COVID-19 on contraception and sexual and reproductive health: Could immediate postpartum LARCs be the solution?, International Journal of Gynecology and Obstetrics, Vol: 150, Pages: 141-143, ISSN: 0020-6695
Bourne T, Shah H, Falconieri N, et al., 2019, Burnout, well-being and defensive medical practice among obstetricians and gynaecologists in the UK: cross-sectional survey study, BMJ Open, Vol: 9, ISSN: 2044-6055
Objectives: To determine the prevalence of burnout in doctors practising obstetrics and gynaecology, and assess the association with defensive medical practice and self-reported wellbeing.Design: Nationwide online cross-sectional survey study; December 2017-March 2018. Setting: Hospitals in the United KingdomParticipants: 5661 practising Obstetrics and Gynaecology consultants, specialty and associate specialist doctors and trainees registered with the Royal College of Obstetricians and Gynaecologists Primary and Secondary Outcome Measures: Prevalence of burnout using the Maslach Burnout Inventory and defensive medical practice (avoiding cases or procedures, overprescribing, over-referral) using a 12-item questionnaire. The odds ratios of burnout with defensive medical practice and self-reported wellbeing.Results: 3102/5661 doctors (55%) completed the survey. 3073/3102 (99%) met the inclusion criteria (1462 consultants, 1357 trainees and 254 specialty and associate specialist doctors). 1116/3073 (36%) doctors met the burnout criteria, with levels highest amongst trainees (580/1357 [43%]). 258/1116 (23%) doctors with burnout reported increased defensive practice compared to 142/1957 (7%) without (adjusted odds ratio 4.35, 95% CI 3.46 to 5.49). Odds ratios of burnout with wellbeing items varied between 1.38 and 6.37, and were highest for anxiety (3.59, 95% CI 3.07 to 4.21), depression (4.05, 95% CI 3.26 to 5.04), and suicidal thoughts (6.37, 95% CI 95% CI 3.95 to 10.7). In multivariable logistic regression, being of younger age, white or ‘other’ ethnicity, and graduating with a medical degree from the UK or Ireland had the strongest associations with burnout.Conclusions: High levels of burnout were observed in obstetricians and gynaecologists and particularly amongst trainees. Burnout was associated with both increased defensive medical practice and worse doctor wellbeing. These findings have implications for the wellbeing and retention of doctors as well a
Demetriou C, Chanudet E, GOSgene, et al., 2019, Exome sequencing identifies variants in FKBP4 that are associated with recurrent fetal loss in humans, Human Molecular Genetics, Vol: 28, Pages: 3466-3474, ISSN: 0964-6906
Recurrent pregnancy loss (RPL) is defined as two or more consecutive miscarriages and affects an estimated 1.5% of couples trying to conceive. RPL has been attributed to genetic, endocrine, immune and thrombophilic disorders, But many cases remain unexplained. We investigated a Bangladeshi family where the proband experienced 29 consecutive pregnancy losses with no successful pregnancies from three different marriages. Whole exome sequencing identified rare genetic variants in several candidate genes. These were further investigated in Asian and White European RPL cohorts, and in Bangladeshi controls. FKBP4, encoding the immunophilin FK506 binding protein 4, was identified as a plausible candidate, with three further novel variants identified in Asian patients. None were found in European patients or controls. In silico structural studies predicted damaging effects of the variants in the structure-function properties of the FKBP52 protein. These were located domains reported to be involved in Hsp90 binding and peptidyl-prolyl cic-trans isomerase (PPIase) activity. Profound effects on PPIase activity were demonstrated in transiently transfected HEK293 cells comparing wildtype and mutant FKBP4 constructs. Mice lacking Fkbp4 have been previously reported as infertile through implantation failure. This study therefore strongly implicates FKBP4 as associated with fetal losses in humans, particularly in the Asian population.
Asfour V, Gibbs K, Franklin L, et al., 2019, Ultrasound technique for the assessment of urethral descent assessment technique (UDAT) in healthy volunteers, Journal of Obstetrics and Gynaecology, ISSN: 0144-3615
Bladder neck descent (BND) has been implicated in the pathophysiology of stress incontinence and prolapse. The aim of this study was to evaluate a novel 2D technique for the evaluation of BND, the Urethral Descent Assessment Technique (UDAT). UDAT involves measuring BND during dynamic manoeuvres in live 2D ultrasound, by using the geometrical properties of parallel lines. The internal urethral meatus and distal end of the urethra are used as reference points. Y1 is the urethral height at rest (also the urethral length when the urethra is straight). Y2 is the urethral height on Valsalva. Y1 and Y2 are parallel lines. Y1–Y2 = BND. A horizontal line (X) connecting Y1 and Y2 is the forward movement of the bladder neck.Y1 mean 30.4 mm (95% CI ± 1.36 mm). Y2 mean 24.2 mm (95% CI ± 2.58 mm). X mean 12.1 mm (95% CI ± 1.66 mm). BND mean 6.2 mm (95% CI ± 1.47 mm). Bland–Altman plots and linear regression showed that UDAT is repeatable and reliable.
Bourne T, Shah H, Falconieri N, et al., 2019, Investigating burnout, wellbeing and defensive medical practice among obstetricians and gynaecologists in the United Kingdom, RCOG World Congress 2019, Publisher: WILEY, Pages: 121-122, ISSN: 1470-0328
Regan L, 2019, Abortion law in the British Isles: progress needs to become the rule not the exception, BJOG: An International Journal of Obstetrics & Gynaecology, Vol: 126, Pages: 840-840, ISSN: 1470-0328
Regan L, Simpson JL, 2019, Your Pregnancy Week by Week What to Expect from Conception to Birth, Publisher: Dorling Kindersley, ISBN: 9780241333396
In this fully updated edition of Your pregnancy week by week, Regan gives you all the information and advice you need to make the right choices for you and your baby.
Suntharalingham JP, Ishida M, Buonocore F, et al., 2019, Analysis of CDKN1C in fetal growth restriction and pregnancy loss, F1000Research, Vol: 8, Pages: 90-90, ISSN: 2046-1402
Background: Cyclin-dependent kinase inhibitor 1C (CDKN1C) is a key negative regulator of cell growth encoded by a paternally imprinted/maternally expressed gene in humans. Loss-of-function variants in CDKN1C are associated with an overgrowth condition (Beckwith-Wiedemann Syndrome) whereas "gain-of-function" variants in CDKN1C that increase protein stability cause growth restriction as part of IMAGe syndrome ( Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia and Genital anomalies). As two families have been reported with CDKN1C mutations who have fetal growth restriction (FGR)/Silver-Russell syndrome (SRS) without adrenal insufficiency, we investigated whether pathogenic variants in CDKN1C could be associated with isolated growth restriction or recurrent loss of pregnancy. Methods: Analysis of published literature was undertaken to review the localisation of variants in CDKN1C associated with IMAGe syndrome or fetal growth restriction. CDKN1C expression in different tissues was analysed in available RNA-Seq data (Human Protein Atlas). Targeted sequencing was used to investigate the critical region of CDKN1C for potential pathogenic variants in SRS (n=58), FGR (n=26), DNA from spontaneous loss of pregnancy (n= 21) and women with recurrent miscarriages (n=71) (total n=176). Results: All published single nucleotide variants associated with IMAGe syndrome are located in a highly-conserved "hot-spot" within the PCNA-binding domain of CDKN1C between codons 272-279. Variants associated with familial growth restriction but normal adrenal function currently affect codons 279 and 281. CDKN1C is highly expressed in the placenta compared to adult tissues, which may contribute to the FGR phenotype and supports a role in pregnancy maintenance. In the patient cohorts studied no pathogenic variants were identified in the PCNA-binding domain of CDKN1C. Conclusion: CDKN1C is a key negative regulator of growth. Variants in a very localised
Jayasena CN, Radia UK, Figueiredo M, et al., 2019, Reduced testicular steroidogenesis and increased semen oxidative stress in male partners as novel markers of recurrent miscarriage, Clinical Chemistry, Vol: 65, Pages: 161-169, ISSN: 1530-8561
BACKGROUND: Recurrent pregnancy loss, (RPL) affecting 1%–2% of couples, is defined as ≥3 consecutive pregnancy losses before 20-week' gestation. Women with RPL are routinely screened for etiological factors, but routine screening of male partners is not currently recommended. Recently it has been suggested that sperm quality is reduced in male partners of women with RPL, but the reasons underlying this lower quality are unclear. We hypothesized that these men may have underlying impairments of reproductive endocrine and metabolic function that cause reductions in sperm quality.METHODS: After ethical approval, reproductive parameters were compared between healthy controls and male partners of women with RPL. Semen reactive oxygen species (ROS) were measured with a validated inhouse chemiluminescent assay. DNA fragmentation was measured with the validated Halosperm method.RESULTS: Total sperm motility, progressive sperm motility, and normal morphology were all reduced in the RPL group vs controls. Mean ±SE morning serum testosterone (nmol/L) was 15% lower in RPL than in controls (controls, 19.0 ± 1.0; RPL, 16.0 ± 0.8; P < 0.05). Mean ±SE serum estradiol (pmol/L) was 16% lower in RPL than in controls (controls, 103.1 ± 5.7; RPL, 86.5 ± 3.4; P < 0.01). Serum luteinizing hormone and follicle-stimulating hormone were similar between groups. Mean ±SE ROS (RLU/sec/106 sperm) were 4-fold higher in RPL than in controls (controls, 2.0 ± 0.6; RPL, 9.1 ± 4.1; P < 0.01). Mean ±SE sperm DNA fragmentation (%) was 2-fold higher in RPL than in controls (controls, 7.3 ± 1.0; RPL, 16.4 ± 1.5; P < 0.0001).CONCLUSIONS: Our data suggest that male partners of women with RPL have impaired reproductive endocrine function, increased levels of semen ROS, and sperm DNA fragmentation. Routine reproductive assessment of the male partners may be beneficial in RPL.
Finch E-L, Taheri M, Gedroyc W, et al., 2018, The treatment effect and re-intervention rate following MRI-guided focused ultrasound treatment of uterine fibroids since 2011 at St Mary's Hospital, RCOG National Trainee Conference, Publisher: Wiley, Pages: 13-14, ISSN: 1470-0328
Goddard A, Burn W, Regan L, et al., 2018, Open letter to Simon Stevens to ensure that tobacco dependence treatment is provided for every smoker cared for by the NHS, as part of the long term plan, BMJ, Vol: 363, ISSN: 0959-8138
Regan L, 2018, Abortion: View from Westminster, International Journal of Gynecology & Obstetrics, Vol: 143, Pages: 133-136, ISSN: 0020-7292
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