Dr Alexandra Kermack

Purpose: To explore the teaching that foundation doctors at the University Hospital of North Midlands undertake and what training they believe is necessary to develop as clinical educators.

Methods: A mixed methods approach consisting of questionnaires and focus group discussions (FGDs), following an explanatory sequential design. FGD data was thematically analysed.

Results: Thirty-four responses to the questionnaire were analysed. 97% respondents felt that teaching was an important part of their job role. The amount of time spent teaching each week varied from no time to more than two hours, and on average 25% of this teaching occurred outside of clinical hours. Foundation doctors enjoy teaching and want to help others. Challenges described were lack of time, shortage of opportunities and others’ perceptions of their ability to teach. Foundation doctors requested tailored training and formalised feedback to facilitate their development as teachers.

Conclusion: This study has shown that foundation doctors undertake a significant amount of teaching and there is a clear desire for additional training. These doctors utilise different teaching methods to their seniors and therefore any training should focus on ad hoc sessions, ward supervision and bedside teaching. Local trusts, medical schools and the UK foundation programme could do more to support foundation doctors’ development as educators by giving them protected time and formalised feedback opportunities. Foundation doctors could be an untapped resource to support the medical school expansion plan in educating the increased numbers of medical students over the coming years.

Background: The Medical Certificate of Stillbirth (MCS) records data about a baby’s death after 24 weeks of gestation but before birth. Major errors that could alter interpretation of the MCS were widespread in two UK-based regional studies.

Methods: A multicentre evaluation was conducted, examining MCS issued 1 January 2018 to 31 December 2018 in 76 UK obstetric units. A systematic case-note review of stillbirths was conducted by Obstetric and Gynaecology trainees, generating individual ‘ideal MCSs’ and comparing these to the actual MCS issued. Anonymized central data analysis described rates and types of error, agreement and factors associated with major errors.

Results: There were 1120 MCSs suitable for assessment, with 126 additional submitted data sets unsuitable for accuracy analysis (total 1246 cases). Gestational age demonstrated ‘substantial’ agreement [K = 0.73 (95% CI 0.70–0.76)]. Primary cause of death (COD) showed ‘fair’ agreement [K = 0.26 (95% CI 0.24–0.29)]. Major errors [696/1120; 62.1% (95% CI 59.3–64.9%)] included certificates issued for fetal demise at <24 weeks’ gestation [23/696; 3.3% (95% CI 2.2–4.9%)] or neonatal death [2/696; 0.3% (95% CI 0.1–1.1%)] or incorrect primary COD [667/696; 95.8% (95% CI 94.1–97.1%)]. Of 540/1246 [43.3% (95% CI 40.6–46.1%)] ‘unexplained’ stillbirths, only 119/540 [22.0% (95% CI 18.8–25.7%)] remained unexplained; the majority were redesignated as either fetal growth restriction [FGR: 195/540; 36.1% (95% CI 32.2–40.3%)] or placental insufficiency [184/540; 34.1% (95% CI 30.2–38.2)]. Overall, FGR [306/1246; 24.6% (95% CI 22.3–27.0%)] was the leading primary COD after review, yet only 53/306 [17.3% (95% CI 13.5–22.1%)] FGR cases were originally attributed correctly.

Conclusion: This study demonstrates widespread major errors in MCS completion across the UK. MCS should only be completed following structured case-note review, with particular attention on the fetal growth trajectory.

Background: Observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery have reported inconsistent results. We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth, delivery mode and post-partum haemorrhage (PPH).

Methods: MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks' gestation until delivery. Gestational age, mode of delivery [categorized as spontaneous vaginal delivery (SVD), instrumental (including forceps and vacuum extraction) or Caesarean section] and PPH (>500 ml estimated blood loss) were determined from medical records.

Results: A total of 965 women participated in the study until delivery. Gestation at birth and incidence of preterm birth (cholecalciferol 5.7%, placebo 4.5%, P = 0.43) were similar between the two treatment groups. SVD (versus instrumental or Caesarean delivery) was more likely in women randomized to cholecalciferol [Relative Risk (RR) 1.13, 95% confidence interval (CI) 1.02,1.25] due to lower instrumental (RR 0.68, 95%CI 0.51,0.91) but similar risk of Caesarean delivery (RR 0.94, 95%CI 0.74,1.19). PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P = 0.054) overall], but similar when stratified by delivery mode.

Conclusions: Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD.

Study question: Does the type of incubator used to culture human preimplantation embryos affect development to the blastocyst stage and alter amino acid utilization of embryos in assisted reproduction?

Summary answer: Culturing embryos in a time lapse system (TLS) was associated with a higher Day 5 blastocyst formation rate and altered amino acid utilization when measured from Day 3 to Day 5 compared to the standard benchtop incubator.

What is known already: Culture environment is known to be important for the developing preimplantation embryo. TLSs provide a stable milieu allowing embryos to be monitored in situ, whereas embryos cultured in standard benchtop incubators experience environmental fluctuations when removed for morphological assessment.

Study design, size, duration: A prospective clinical trial randomizing 585 sibling embryos to either the TLS (289 embryos) or the standard benchtop incubator (296 embryos) over a 23-month period in a UK University Hospital Fertility Clinic.

Participants/materials, setting, methods: Participants were aged 42 years or under, had an antral follicle count of ≥12 and ≥6 2 pronucleate zygotes. Zygotes were cultured individually in 25 µl of medium. Randomized embryos were graded and selected for transfer or cryopreservation on Day 5. For those embryos produced by women who underwent stimulation with recombinant FSH injections and were triggered with hCG, spent medium was collected on Day 5 for amino acid analysis by high pressure liquid chromatography. Clinical pregnancy was defined as the presence of a foetal heart beat on ultrasound scan at 7 weeks.

Main results and the role of chance: Overall, blastocyst formation rate on Day 5 was significantly higher in embryos cultured in the TLS (55%) compared to the standard incubator (45%; P = 0.013). Similarly, there was an increase in the number of blastocysts suitable for cryopreservation in the TLS (31%) compared to the standard incubator (23%; P = 0.032). There was a significant difference in the utilization of 12 amino acids by blastocysts cultured from Day 3 to Day 5 in the TLS compared to the standard incubator. Embryos cultured in the TLS displayed an increased total amino acid utilization (P < 0.001) and reduced amino acid production (P < 0.001) compared to those in the standard incubator. Irrespective of incubator used, embryos fertilized by ICSI depleted significantly more amino acids from the medium compared to those fertilized by conventional IVF. There was no difference in the mean score of blastocysts transferred, or the clinical pregnancy rate after transfer of embryos from either of the incubators.

Limitations, reasons for caution: The study was not powered to discern significant effects on clinical outcomes.

Wider implications of the findings: The metabolism and development of preimplantation embryos is impacted by the type of incubator used for culture. Further research is required to investigate the long-term implications of these findings.

Study funding/competing interest(s): NIHR Southampton Biomedical Research Centre Commercial and Enterprise Incubator Fund funded this study. The TLS was provided on loan for the study by Vitrolife. The authors declare no conflict of interests.

Trial registration number: ISRCTN73037149.

Objective: To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection.

Methods: Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant.

Results: Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3-1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2.

Conclusions: Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians' threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection. The proportion affected by pre-eclampsia amongst participants was not higher than would be expected, although we report a higher than expected proportion affected by eclampsia. There appears to be no effect on birthweight or congenital malformations in women affected by SARS-CoV-2 infection in pregnancy and neonatal infection is uncommon. This study reflects a population with a range of infection severity for SARS-COV-2 in pregnancy, generalisable to whole obstetric populations.

Objective: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID‐19 (PAN‐COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal–Perinatal Medicine (SONPM) National Perinatal COVID‐19 Registry.

Methods: This was an analysis of data from the PAN‐COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS‐CoV‐2 infection at any stage in pregnancy, and the AAP‐SONPM National Perinatal COVID‐19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS‐CoV‐2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN‐COVID results are presented overall for pregnancies with suspected or confirmed SARS‐CoV‐2 infection and separately in those with confirmed infection.

Results: We report on 4005 pregnant women with suspected or confirmed SARS‐CoV‐2 infection (1606 from PAN‐COVID and 2399 from AAP‐SONPM). For obstetric outcomes, in PAN‐COVID overall and in those with confirmed infection in PAN‐COVID and AAP‐SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN‐COVID, in 16.1% of those women with confirmed infection in PAN‐COVID and in 15.7% of women in AAP‐SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN‐COVID and 0.3% in AAP‐SONPM. Neonatal SARS‐CoV‐2 infection was reported in 0.9% of all deliveries in PAN‐COVID overall, in 2.0% in those with confirmed infection in PAN‐COVID and in 1.8% in AAP‐SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small‐for‐gestational‐age (SGA) neonate were 8.2% in PAN‐COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP‐SONPM. Mean gestational‐age‐adjusted birth‐weight Z‐scores were −0.03 in PAN‐COVID and −0.18 in AAP‐SONPM.

Conclusions: The findings from the UK and USA registries of pregnancies with SARS‐CoV‐2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN‐COVID study, although not in the AAP‐SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS‐CoV‐2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy.

The fatty acid composition of human follicular fluid is important for oocyte development and for pregnancy following in vitro fertilization (IVF). This study investigated whether a dietary intervention that included an increase in marine omega-3 fatty acids, olive oil and vitamin D alters the fatty acid composition of human follicular fluid. The association of lifestyle factors with follicular fluid fatty acid composition was also investigated. Fifty-five couples awaiting IVF were randomized to receive the 6-week treatment intervention of olive oil for cooking, an olive oil-based spread, and a daily supplement drink enriched with vitamin D and the marine omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and 56 couples were randomized to receive placebo equivalents. Dietary questionnaires were completed, and samples of blood were taken before and after the intervention. Follicular fluid was collected at oocyte retrieval and the fatty acid profile assessed using gas chromatography. In the control group, individual fatty acids in red blood cells and follicular fluid were significantly correlated. Furthermore, a healthier diet was associated with a lower percentage of follicular fluid arachidonic acid. The follicular fluid of women in the treatment group contained significantly higher amounts of EPA and DHA compared to the control group, while the omega-6 fatty acids linoleic, γ-linolenic, dihomo-γ-linolenic, and arachidonic were lower. This is the first report of a dietary intervention altering the fatty acid composition of follicular fluid in humans. Further research is required to determine whether this intervention improves oocyte quality.

It is known that lifestyle factors affect sporadic miscarriage, but the extent of this on RPL (recurrent pregnancy loss) is less well known. A systematic review and meta-analysis was performed to assess the associations between lifestyle factors and RPL. Studies that analysed RPL in the context of BMI, smoking, alcohol and caffeine intake were included. The primary and secondary outcomes were odds of having RPL in the general population and odds of further miscarriage, respectively. Underweight and women with BMI > 25 are at higher odds of RPL in the general population (OR 1.2, 95% CI 1.12-1.28 and OR 1.21, 95% CI 1.06-1.38, respectively). In women with RPL, having BMI > 30 and BMI > 25 has increased odds of further miscarriages (OR 1.77, 95% CI 1.25-2.50 and OR 1.35, 95% CI 1.07-1.72, respectively). The quality of the evidence for our findings was low or very low. Being underweight and BMI > 25 contributes significantly to increased risk of RPL (general population). BMI > 25 or BMI > 30 increases the risk of further miscarriages (RPL population). Larger studies addressing the effects of alcohol, cigarette smoking and caffeine on the risk of RPL with optimisation of BMI in this cohort of women are now needed.

No abstract available.

No abstract available.

Objective: To study the impact of increased dietary intake of omega-3 fatty acids, vitamin D, and olive oil for 6 weeks before in vitro fertilization (IVF) or IVF-intracytoplasmic sperm injection (ICSI) on morphokinetic markers of early embryo development.

Design: A double-blinded randomized controlled trial.

Setting: Academic IVF unit.

Patient(s): A total of 111 couples undergoing IVF or IVF-ICSI were recruited.

Interventions(s): Fifty-five couples received the 6-week study intervention of a daily supplement drink enriched with omega-3 fatty acids and vitamin D plus additional olive oil and olive oil-based spread, and 56 couples received the control intervention.

Main outcome measure(s): The primary end point for the study was the time taken for completion of the second cell cycle after fertilization (CC2). Secondary end points included time to complete the third and fourth cell cycles (CC3 and CC4), the synchrony of the second and third cell cycles (S2 and S3), and the day 3 and day 5 Known Implantation Data Scores (KIDScores).

Result(s): There was no difference in CC2 between the two groups. However, CC4 was accelerated in the study group compared with the control group, and a significantly shortened S3 as well as an increase in KIDScore on day 3 were observed, indicating improved embryo quality in the study group.

Conclusion(s): This study demonstrates that a short period of dietary supplementation alters the rate of embryo cleavage. Further research is required to investigate the mechanisms that regulate this effect, and whether the impact on embryo development translates into improved clinical outcomes.

Clinical trial registration number: ISRCTN50956936.

The recognition of 'fetal origins of adult disease' has placed new responsibilities on the obstetrician, as antenatal care is no longer simply about ensuring good perinatal outcomes, but also needs to plan for optimal long-term health for mother and baby. Recently, it has become clear that the intrauterine environment has a broad and long-lasting impact, influencing fetal and childhood growth and development as well as future cardiovascular health, non-communicable disease risk and fertility. This article looks specifically at the importance of the developmental origins of ovarian reserve and ageing, the role of the placenta and maternal nutrition before and during pregnancy. It also reviews recent insights in developmental medicine of relevance to the obstetrician, and outlines emerging evidence supporting a proactive clinical approach to optimizing periconceptional as well as antenatal care aimed to protect newborns against long-term disease susceptibility.

Approximately one in six couples suffer from subfertility, and many seek treatment with artificial reproductive technologies (ART). Despite improvements in laboratory techniques and ovarian stimulation, ongoing pregnancy rates per cycle remain at ~25%. Couples wanting to improve their chances may turn to adjuvant therapies, such as nutritional supplements. There is growing evidence that periconceptional nutritional status is a key determinant of fertility and long-term health of the offspring, and a lucrative market has developed to meet the demand based on these benefits. However, the practice of routine dietary supplementation before and during IVF treatment has not been subject to well-powered prospective randomised trials. In this article, the potential roles of specific nutritional supplements in the context of improving IVF outcomes are reviewed and an assessment is made of the evidence base supporting their clinical use in this context. Finally, current research needs in the field are outlined.

Study question: Do the amino acid levels of human uterine fluid vary with age, BMI, phase of menstrual cycle, benign pathology or diet?

Summary answer: The levels of 18 amino acids in human uterine fluid were shown to be affected only by maternal diet.

What is known already: Murine, bovine and ovine uterine amino acid content has been reported, but no reliable data on the human exist. Murine studies have demonstrated that the intrauterine periconceptional nutritional environment is affected by maternal diet.

Study design, size, duration: Uterine secretions were aspirated from 56 women aged 18-45 years. The women were recruited preoperatively from gynaecological theatre operating schedules or hysterosalpingo-contrast-sonography (HyCoSy) lists. A proportion of these women had proven fertility; however, the majority were being investigated for subfertility. The BMI, gynaecological history and dietary pattern of these women were also assessed.

Participants/materials, setting, methods: Reverse phase high performance liquid chromatography was used to analyse the concentrations of 18 amino acids within the uterine fluid and blood serum. The results were analysed against the women's stage of cycle, age, BMI and diet.

Main results and the role of chance: The profile of 18 amino acids in uterine fluid was described. In total, human uterine fluid was observed to contain an amino acid concentration of 3.54 mM (interquartile range: 2.27-6.24 mM). The relative concentrations of 18 amino acids were not significantly altered by age, BMI, cycle phase or the presence of specific benign gynaecological pathologies. However, a diet identified by a validated scoring system as being less healthy was associated with higher concentrations of asparagine (P = 0.018), histidine (P = 0.011), serine (P = 0.033), glutamine (P = 0.049), valine (P = 0.025), phenylalanine (P = 0.019), isoleucine (P = 0.025) and leucine (P = 0.043) in the uterine fluid compared with a healthier diet, defined as one with a higher intake of fresh vegetables, fruit, whole-grain products and fish and a low intake of red and processed meat and high fat dairy products. There were no significant correlations between serum amino acid concentrations and those in the uterine fluid.

Limitations, reasons for caution: Our results enabled us to detect the effect of diet on the concentrations of amino acids in human uterine fluid; however, the study may not have had sufficient numbers to detect mild effects of BMI or age.

Wider implications of the findings: These findings increase our understanding of the nutritional environment encountered by the preimplantation embryo, and indicate how periconceptional diet may alter this. Given the importance of early embryo environment for programming of development and future health, this information may aid in the development of nutritional interventions aimed at optimizing the preimplantation phase of human embryo development in vivo.

Study funding/competing interests: This work was funded by the NIHR, the Medical Research Council (G0701153) and the University of Southampton and was supported by the NIHR BRC in Nutrition and Southampton University NHS Foundation Trust. The authors declare no conflicts of interest.

Background: In vitro fertilisation (IVF) treatment provides an opportunity to study early developmental responses to periconceptional dietary interventions. Retrospective studies have suggested links between preconception diet and fertility, and more recently, a "Mediterranean" diet has been reported to increase pregnancy rates by up to 40%. In addition, a prospective study examining increased intake of omega-3 polyunsaturated fats demonstrated a quickened rate of embryo development after IVF. However, up to now, few prospective randomised controlled trials have investigated the impact of periconceptional dietary interventions on fertility outcomes.

Methods and design: The study is a randomised controlled trial of a dietary intervention consisting of olive oil for cooking, an olive oil based spread, and a daily supplement drink enriched with Vitamin D (10 microgram daily) and marine omega-3 fatty acids (2 g daily) for 6 weeks preconception versus a control diet of sunflower seed oil for cooking, a sunflower oil based spread, and a daily supplement drink without added Vitamin D or marine omega-3 fatty acids. Couples undergoing IVF will be randomised to either the intervention or control group (55 in each arm). The primary endpoint is embryo developmental competency in vitro, measured by validated morphokinetic markers. Secondary outcomes will include the effect of the dietary intervention on the nutritional content of the intrauterine environment.

Discussion: This approach will enable rigorous examination of the impact of the dietary intervention on early embryo development, together with the influence of the peri-implantation intra-uterine nutritional environment.

Trial registration: ISRCTN50956936.

Preconceptional health has been shown to be an important determinant of fertility, fecundity and perinatal outcomes. In recent years the impact of periconceptional factors on developmental programming, and the health of the resultant child have become increasingly clear. Since fertility specialists care for couples during this critical phase, they have a unique opportunity to collaborate with the couple to optimise preconceptional health and thus fertility and pregnancy outcomes. In this review article, the current evidence available for the importance of preconceptional health care is considered, specific lifestyle and dietary interventions are described and the care of the medically complicated patient prior to fertility treatment is discussed. Finally strategies for overcoming challenges in implementing preconceptional care into the fertility clinic are addressed.