Use of anticoagulants to improve pregnancy outcomes in couples positive for M2 haplotype: A systematic review.

BACKGROUND: Placental mediated pregnancy complications (PMPC) are common, often recurring, and pose a significant health risk to mother and fetus. Evidence suggests that the hypercoagulable state associated with many PMPC, could reflect reduced expression of Annexin 5 (ANXA5), a naturally occurring anticoagulant protein in placental tissue. The ANXA5 M2 haplotype is a genetic variant, which results in reduced expression of ANXA5 protein. M2 haplotype carrier couples may therefore be at increased risk of PMPC. Evidence regarding the effectiveness of anticoagulation to prevent PMPC is inconsistent. Furthermore, studies have not selected or stratified for M2 haplotype carriers, in whom there is a predisposition to hypercoagulability, to assess the effectiveness of anticoagulation, which may vary from those without the M2 haplotype. OBJECTIVES AND RATIONALE: The aim of this study was to systematically review the current evidence to assess whether anticoagulant treatment improves pregnancy outcomes in couples positive for M2 haplotype. SEARCH METHODS: The review was registered on PROSPERO (CRD42022343943). A comprehensive literature search was performed using MEDLINE, Embase and Cochrane collaboration databases from inception to January 2023. Two reviewers assessed the articles for eligibility and extracted the data simultaneously. Primary outcome was successful pregnancy and live birth. Secondary outcomes included PMPC (implantation failure, miscarriage, pre-eclampsia, preterm birth and fetal growth restriction). OUTCOMES: From a pool of 410 references, 10 were selected for full text review, of which three studies (a post hoc analysis of a randomised controlled trial, cohort study and a case report) were included in this review. Included studies comprised of 223 individuals, 129 of whom who received anticoagulation treatment after testing positive for M2 haplotype. The studies collectively showed an improvement in pregnancy outcomes in M2 haplotype positive individuals however, given the heterogeneity of studies, it was not possible to conduct a meta-analysis and draw firm conclusions. WIDER IMPLICATIONS: Current evidence is limited, such that the value of screening couples for the M2 haplotype to select or stratify for treatment with prophylactic anticoagulation remains unknown. Thus, further studies including well designed, large, multi-centre randomised controlled trials are required to assess whether anticoagulation treatment will be effective in improving pregnancy outcomes in M2 haplotype couples.

Diagnosis and management of endometrial hyperplasia: A UK national audit of adherence to national guidance 2012-2020.

BACKGROUND: Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom-wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown. We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact. METHODS AND FINDINGS: In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression. Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] p < 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance. CONCLUSIONS: The care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer.

FIGO best practice guidance in surgical consent.

Obtaining medical consent preoperatively is one of the key steps in preparing for surgery, and is an important step in informed decision making with the patient. According to good medical practice guidelines, doctors are required to have the knowledge and skills to treat patients as well as inform them, respect their wishes, and establish trust between themselves and their patients. Valid consent includes elements of competence, disclosure, understanding, and voluntariness. Documentation of these elements is also very important. The International Federation of Gynecology and Obstetrics (FIGO) Education Communication and Advocacy Consortium (ECAC) has realized that the quality of consent varies considerably across the world and has developed simple guidelines regarding consent and procedure-specific checklists for the most common obstetric and gynecological procedures.

Postgraduate Training in Pediatric and Adolescent Gynecology: Trainees' Perspectives.

OBJECTIVE: The purpose of this study was to evaluate resident trainees' perspectives on the pediatric and adolescent gynecology (PAG) training in obstetrics and gynecology training programs in Europe. STUDY DESIGN: This study was a cross-sectional survey using an online questionnaire, on the basis of the PAG training in obstetrics and gynecology section of the European Board & College of Obstetrics and Gynaecology Project of Achieving Consensus in Training curriculum. We aimed to survey the national programs in 35 European Network of Trainees in Obstetrics and Gynaecology (ENTOG) member countries. Taking part in the survey was voluntary. The questionnaire was shared on the ENTOG online platforms. RESULTS: Ninety obstetrics and gynecology trainees in 33 of 35 countries responded to our questionnaire. Of the 35 ENTOG member countries, 33 participated in the survey, and a total of 90 responses were collected, giving a response rate of 9% of all European trainees and representing 94% of the member countries. Only 27% of trainees reported having a PAG rotation during their training program, and a PAG elective was only available to 34% of the trainees. Forty-one percent reported that PAG training was not included in their curriculum (no official rotations or lectures planned). Despite the lack of formal training, 72% of trainees felt able to diagnose and manage prepubertal vaginal bleeding and adnexal masses in children and adolescents by the end of their training. Most (58%) also confirmed that they could determine indications for treatment of vulval, vaginal, perineal, and rectal conditions. However, despite scoring positively for the management and counseling of subjects that often overlap with adult patients, such as "contraception in adolescents with health problems," "acute abdominal pain," "menstrual abnormalities," and "vaginal discharge," the study revealed poorer scores when the trainees were asked about more specific PAG topics such as "premature puberty" and "developmental disorders of the genital tract." CONCLUSION: Most core training programs across Europe do not include formal PAG training, and trainees reported a need to improve the provision of core PAG training in Europe.

Chromosomal polymorphisms in assisted reproduction: a systematic review and meta-analysis.

This systematic review and meta-analysis investigated the effects of chromosomal polymorphisms in reproductive outcomes following IVF or ICSI. Literature in CENTRAL, CINAHL, EMBASE and MEDLINE were searched from 1974 to March 2020 with no language restrictions. Ten published cohort studies were chosen for analysis. Studies included females, males and couples undergoing assisted reproductive treatments with the presence or absence of chromosomal polymorphisms. Reproductive outcomes were reported and their quality assessed using the Newcastle-Ottawa Quality Assessment Scale. Meta-analysis of five cohort studies (9,659 participants) indicated that female carriers with chromosomal polymorphisms had a higher miscarriage rate compared to non-carriers (risk ratio (RR) 1.54 (95% CI 1.19-1.98), whereas no significant association was found for males (RR 0.96, 95% CI 0.64-1.43) and couples (RR 1.93, 95% CI 0.32-11.83) indicating that this effect appeared to be gender-dependent. There was no association between chromosomal polymorphisms and a higher rate of biochemical, clinical, ongoing pregnancy, and preterm and live birth.

EBCOG position statement inequalities in antenatal care provision in Europe: In the wake of an EBCOG survey.

Health inequalities adversely affect the health outcomes generally but more so for those who are socially deprived, immigrants of unknown status and low socioeconomic status. The inequitable access to care during pregnancy can lead to long term adverse inter-generational effects. Current economic crisis within Europe will have deepening effect on the health of the vulnerable families. The European Board and College of Obstetrics and Gynaecology calls for action by the European Union.

Folic acid fortification of flour to prevent neural tube defects in Europe - A position statement by the European Board and college of obstetrics and gynaecology (EBCOG).

Neural tube defects are disabling birth defects developing during the very early stages of conception. Children born with spina bifida face significant physical, psychological and social consequences. They may have bowel and urinary dysfunction, and no lower limb muscle control, resulting in lifelong wheelchair use. There is robust evidence that periconceptual folic acid supplementation prevents neural tube defects, when compared with no intervention. However, approximately 40% pregnancies in Europe are unplanned, and women may therefore not be taking prophylactic folic acid at the time of conception. There is evidence that low dose folic acid consumption via flour fortification provides further benefits in prevention of neural tube defects.

The implementation of the European Working Time Directive in Europe and its impact on training in obstetrics and gynaecology: A ten year follow-up.

OBJECTIVE: To reassess the compliance with the European Working Time Directive (EWTD) in the member countries of the European Network of Trainees in Obstetrics and Gynaecology (ENTOG) and to investigate the impact of the EWTD on training. STUDY DESIGN: In this observational, cross-sectional study, an online questionnaire, containing multiple-choice questions and open questions, was distributed among Obstetrics and Gynaecology trainees in 33 ENTOG member countries. The questionnaire was designed as a follow-up of a similar survey conducted by ENTOG in 2009 and assessed the overall compliance with the EWTD, the adaptations needed to achieve this compliance, the impact of the EWTD on the quality of training and the well-being of trainees. The answers were analysed using descriptive statistics in Microsoft Excel. RESULTS: 59 responses from 28/33 (84.8%) ENTOG member countries were collected. Only 5 out of 28 (17.9%) countries were found to be nationally compliant with EWTD. There were no clear differences in the compliance between different types of the hospitals (university/teaching/district), but a trend was observed towards higher rate of implementation in smaller hospitals (<1500 deliveries per year). Regarding the changes needed to become EWTD-compliant and yet maintain high-quality training, the most common suggestions were: hiring extra junior doctors, restructuring training, having less doctors on duty simultaneously, consultants performing more hands on work, dedicated training sessions, reduction of administrative tasks and simulation training for surgical skills. The majority of trainees, 7 out of 12, (58.3%) in the EWTD-compliant hospitals experienced a positive effect on their training, whereas the majority of trainees in non-compliant hospitals, 31 out of 47, (66%) were uncertain about the impact of the EWTD on the quality of training. Among the positive changes, better work-life balance and more consultants available out of the daily working hours were listed. CONCLUSIONS: Despite the introduction and implementation of the EWTD over two decades ago, the compliance rates across Europe remain low and seem not to have altered in the last ten years. In order to ensure the quality of training and, most importantly patient safety, we suggest that European nations keep striving to implement the EWTD for doctors in training. We also suggest for nations that have yet to implement this directive to use the strategies as an exemplar in countries that follow EWTD.

Experiences of young girls and women undergoing ovarian tissue cryopreservation: a systematic review and thematic synthesis.

The aim of this study was to explore the experiences of young girls and women who underwent or considered ovarian tissue cryopreservation (OTC) using a systematic review of qualitative studies with thematic synthesis framework. Major electronic databases: MEDLINE, EMBASE, the Cochrane Library, CINAHL and PsycINFO were searched from 1946 to May 2020 and reference lists of relevant articles were hand searched. Any studies that described a qualitative inquiry and highlighted the experiences of women with regards to OTC were included. Two independent reviewers screened the title and abstracts and made a selection against inclusion criteria. Main outcomes measures were experiences of women who have considered and/or undergone OTC, decision making in women who underwent or considered OTC and patient education. Nineteen studies were assessed for full text eligibility and four were included in analysis. 144 verbatim quotations from 85 participants in high income countries (UK, USA and Denmark) were included. Two studies adopted grounded theory approach, one phenomenology and one inductive content analysis. Four themes were generated; participants described their experiences as emotional, involving complex decision-making, helping them prepare for the long-term consequences of potentially losing their fertility and hormonal function, as well as their experience being educational. Additionally, the more practical aspects of the procedure such as OTC being invasive as well as costs implications were highlighted. Women and young girls are often involved in making time-sensitive decisions whether or not to undergo OTC. Healthcare professionals involved in the care of young girls and women undergoing this method need to also take into consideration the emotional wellbeing of the patients as well as the time and expertise it requires to help them make an informed decision.

Care of pregnant women with epilepsy in the United Kingdom: A national survey of healthcare professionals.

OBJECTIVES: To map the care provided to pregnant women with epilepsy in UK maternity units and identify future research priorities by conducting a nationwide survey of healthcare professionals. STUDY DESIGN: A prospective cross-sectional electronic survey was conducted between 29 April and 30 October 2021. The survey included 23 questions developed and refined with relevant stakeholders, including a woman with lived experience of epilepsy and pregnancy. We used descriptive analyses to summarise responses and estimated proportions with medians and interquartile ranges. RESULTS: 144 individual healthcare professionals from 94 hospitals, representing 77 NHS Trusts, participated in the survey. Obstetricians were the most common responders (45%, 65/144) and almost half (47%, 7/15) of regions had a survey response rate per NHS Trust greater than 50%. Six pregnant women with epilepsy, on average, were booked into antenatal care per hospital per month, and 49% (46/94) of hospitals saw women for specialist antenatal care in the first trimester. The care provided across healthcare systems varied, with multiple pathways for referral to specialist care within regions. Midwife referral was the most used care pathway (80%, 75/94). Less than a third of hospitals (31%, 29/94) ran joint obstetric/neurology clinics for pregnant women with epilepsy. Most survey respondents (81%, 117/144) were confident talking to pregnant women about their risk of seizures but only a minority (20%, 29/144) used validated calculators to assess this risk. There was broad agreement across healthcare professionals that the priorities for research should focus on how to improve communication and address pregnant women's concerns regarding epilepsy and pregnancy, and to develop further understanding on the optimal use and long-term effects of anti-seizure medication. CONCLUSION: Our UK nationwide survey of hospital-based maternity services for pregnant women with epilepsy identified wide variation in when, how and by whom these women are seen, with differences between and within the UK regions. This survey highlights areas for improvement in the care of pregnant women with epilepsy.

Why are women considering ovarian tissue cryopreservation to preserve reproductive and hormonal ovarian function? A qualitative study protocol.

INTRODUCTION: Current fertility preservation options available to women are oocyte cryopreservation (egg freezing) or embryo cryopreservation. A newer procedure, ovarian tissue cryopreservation (OTC), has become available in some centres, which offers another option for women and girls considering fertility preservation. These procedures are commonly offered to women about to undergo treatments for cancer. OTC involves removing sections of ovarian tissue and cryopreserving it for future reimplantation, often several years later. OTC offers girls and women who may become infertile with optionality and the possibility of pregnancy. OTC has potential for other applications, including restoring ovarian endocrine function beyond biological menopause. This is not without controversy but has led to some women considering undergoing the procedure for purposes of ovarian hormonal preservation (conservation of ovarian endocrine function). OTC is invasive, involves two surgical procedures with concomitant risks and can be costly. Understanding why women may consider and ultimately undergo OTC is timely, so that evidence-based and women-centred care can be provided. METHODS: A pragmatic narrative qualitative design will be used. A purposive sample of women aged 18-45 who are considering, or have sought, OTC will be recruited over 1-year period. Potential participants will be approached via a clinic that offers OTC on a private basis or via social media. ANALYSIS: Participant interviews will be audio and, if consented, video recorded. These will be conducted face-to-face or virtually. The recordings will be transcribed verbatim and analysed using a thematic analysis approach supported by NVivo software. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Institutional Ethical Review ERN_19-1578A. We expect to disseminate the findings of this study through journal articles, conference presentations and multimedia to public.

Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis.

BACKGROUND: Ovarian tissue cryopreservation involves freezing and storing of surgically retrieved ovarian tissue in liquid or vapour nitrogen below -190°C. The tissue can be thawed and transplanted back with the aim of restoring fertility or ovarian endocrine function. The techniques for human ovarian tissue freezing and transplantation have evolved over the last 20 years, particularly in the context of fertility preservation in pre-pubertal cancer patients. Fresh ovarian tissue transplantation, using an autograft or donor tissue, is a more recent development; it has the potential to preserve fertility and hormonal function in women who have their ovaries removed for benign gynaecological conditions. The techniques of ovarian tissue cryopreservation and transplantation have progressed rapidly since inception; however, the evidence on the success of this intervention is largely based on case reports and case series. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the current evidence by incorporating study-level and individual patient-level meta-analyses of women who received ovarian transplants, including frozen-thawed transplant, fresh or donor graft. SEARCH METHODS: The review protocol was registered with PROSPERO (CRD42018115233). A comprehensive literature search was performed using MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials from database inception to October 2020. Authors were also contacted for individual patient data if relevant outcomes were not reported in the published manuscripts. Meta-analysis was performed using inverse-variance weighting to calculate summary estimates using a fixed-effects model. OUTCOMES: The review included 87 studies (735 women). Twenty studies reported on ≥5 cases of ovarian transplants and were included in the meta-analysis (568 women). Fertility outcomes included pregnancy, live birth and miscarriage rates, and endocrine outcomes included oestrogen, FSH and LH levels. The pooled rates were 37% (95% CI: 32-43%) for pregnancy, 28% (95% CI: 24-34%) for live birth and 37% (95% CI: 30-46%) for miscarriage following frozen ovarian tissue transplantation. Pooled mean for pre-transplant oestrogen was 101.6 pmol/l (95% CI: 47.9-155.3), which increased post-transplant to 522.4 pmol/l (95% CI: 315.4-729; mean difference: 228.24; 95% CI: 180.5-276). Pooled mean of pre-transplant FSH was 66.4 IU/l (95% CI: 52.8-84), which decreased post-transplant to 14.1 IU/l (95% CI: 10.9-17.3; mean difference 61.8; 95% CI: 57-66.6). The median time to return of FSH to a value <25 IU/l was 19 weeks (interquartile range: 15-26 weeks; range: 0.4-208 weeks). The median duration of graft function was 2.5 years (interquartile range: 1.4-3.4 years; range: 0.7-5 years). The analysis demonstrated that ovarian tissue cryopreservation and transplantation could restore reproductive and hormonal functions in women. Further studies with larger samples of well-characterized populations are required to define the optimal retrieval, cryopreservation and transplantation processes. WIDER IMPLICATIONS: Ovarian tissue cryopreservation and transplantation may not only be effective in restoring fertility but also the return of reproductive endocrine function. Although this technology was developed as a fertility preservation option, it may have the scope to be considered for endocrine function preservation.

The influence of the COVID-19 outbreak on European trainees in obstetrics and gynaecology: A survey of the impact on training and trainee.

OBJECTIVE: The purpose of this study is to evaluate how the obstetrics and gynaecology residency program and trainees have been affected by the Corona Virus Disease-19 (COVID-19) pandemic in Europe. STUDY DESIGN: This study is a cross-sectional explorative survey using an online questionnaire. The questionnaire comprised of 40 questions that were subdivided into 4 subjects; workload, specialist training aspects in obstetrics and gynaecology, health and safety of the trainee and women's health and maternal health issues. Inclusion criteria consisted of being a trainee in Obstetrics and Gynaecology (ObGyn) at the time of the COVID-19 pandemic in Europe or trainees who had recently finished their training during the time of the outbreak. Taking part in the survey was voluntary. The questionnaire was shared on the website of the European Network for Trainees in Obstetrics and Gynaecology (ENTOG), ENTOG social media, in the ENTOG-newsletter and through the national representatives of ENTOG. RESULTS: 110 ObGyn trainees from 25 different countries responded to the questionnaire. Almost all trainees (95 %, N = 105) reported an effect on their training due to COVID-19 pandemic. Training was interrupted in 21 % of cases (n = 23). Trainees observed a decrease in educational activities or lectures and a decrease in number of patients. The possibility of training surgical skills decreased, because 67 % (N = 74) trainees reported that surgeries were cancelled. Trainees expressed concerns about reaching the goals of their ObGyn specialist training in 60 % (n = 66) of cases. A decrease in workload was experienced during the first COVID-19 wave in Europe by 60 % (n = 66) of trainees. On average these trainees worked 33 % less hours compared to a normal workweek. Although 22 % (n = 24) were expected to be available continuously for 24 h a day and 7 days a week for unscheduled duties, 15 % (n = 16) were deployed to work on special COVID-units. Concerning preparation, 45 % of the trainees (n = 50) had not received any training for treating COVID-positive patients. Trainees claimed to have enough personal protective equipment (PPE), although problems were reported. Any form of psychosocial support was arranged for 65 % of trainees (n = 71) by the hospital or department. The results of the survey suggest that obstetric care was not affected much (92 % (n = 102) of the respondents said at least necessary care continued) while patients in need for reproductive medicine were affected the most; out of the 110 departments 58 % (n = 60) were closed and 35 % (n = 36) reduced their activities. Access to family planning and benign gynaecology were also significantly reduced; 77 % and 87 % respectively of the departments were less accessible or only open to emergency cases. CONCLUSION: COVID-19 pandemic has had a tremendous effect on the ObGyn training in Europe. Exposure to learning opportunities, surgeries and teaching has been decreased during the outbreak and may result in a decrease in quality of care provided to women in the future if impairment of training is not recovered.