ESHRE Guidelines Research Articles

Meta-analysis of intrauterine hCG perfusion efficacy in recurrent implantation failure as defined by ESHRE guidelines

PurposeThis study evaluates the efficacy of intrauterine hCG perfusion for RIF, as defined by ESHRE 2023 guidelines, highlighting hCG as a cost-effective alternative to other immunotherapies, especially suitable for less developed regions. It aims to clarify treatment guidance amidst previous inconsistencies.MethodsThis meta-analysis, registered with PROSPERO (CRD42024443241) and adhering to PRISMA guidelines, assessed the efficacy and safety of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in RIF. Comprehensive literature searches were conducted through December 2023 in major databases including PubMed, Web of Science, Embase, the Cochrane Library, and key Chinese databases, without language restrictions. Inclusion and exclusion criteria were strictly aligned with the 2023 ESHRE recommendations, with exclusions for studies lacking robust control, clear outcomes, or adequate data integrity. The risk of bias was evaluated using the Newcastle-Ottawa Scale, ROBINS-I, and RoB2 tools. Data analysis was performed in R using the ‘meta’ package, employing both fixed and random effect models to account for study variability. Subgroup analyses by dosage, volume, hCG concentration, timing of administration, and type of embryo transfer were conducted to deepen insights, enhancing the reliability and depth of the meta-analysis in elucidating the role of hCG perfusion in RIF treatments.ResultsData from 13 studies, comprising six retrospective and six prospective studies from single centers, along with one multi-center RCT, totaling 2,157 participants, were synthesized to evaluate the effectiveness of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in patients with RIF. Significant improvements were observed in clinical pregnancy and embryo implantation rates across various dosages, timing of administration, and embryo developmental stages, without impacting miscarriage rates. Notably, the most significant efficacy within subgroups occurred with a 500 IU dosage and perfusion parameters of ≤ 500µL volume and ≥ 2 IU/µL concentration. Additionally, a limited number of studies showed no significant increases in ectopic pregnancy or multiple pregnancy rates, and a modest improvement in live birth rates, although the small number of these studies precludes definitive conclusions.ConclusionsThe analysis suggests that intrauterine hCG perfusion probably enhances embryo implantation, clinical pregnancy, and live birth rates slightly in RIF patients. Benefits are indicated with a dosage of 500 IU and a maximum volume of 500µL at concentrations of at least 2 IU/µL. However, substantial heterogeneity from varying study types and the limited number of studies necessitate cautious interpretation. These findings underscore the need for more rigorously designed RCTs to definitively assess the efficacy and safety.

O-316 Clinical application of PGT-A for recurrent pregnancy loss, what effects live birth after single euploid blastocyst transfer?

Abstract Study question Which factors effect the likelihood of live birth after euploid frozen embryo transfer (FET) in recurrent pregnancy loss (RPL)? Summary answer Female age and number of previous pregnancy loss do not effect the live birth rates after euploid blastocyst FET. What is known already PGT-A is helpful to discard the aneuploid embryos and has been proven to improve pregnancy outcomes and reduce miscarriage rate per embryo transfer. As approximately 50% of clinical miscarriages have chromosomal abnormalities, PGT-A has been suggested as a treatment option for RPL. However it is questionable on the cost effectiveness, effect on prognosis and labor-intensive. In addition, currently PGT-A use is not recommended by any society guidelines in RPL patients. ESHRE guideline on RPL stated ‘All couples with results of an abnormal fetal or parental karyotype may be informed about the possible treatment options available including their advantages and disadvantages.’ Study design, size, duration This retrospective cohort study from January 2018 to January 2023 was conducted at Bahçeci Health Group included patients underwent PGT-A/ICSI cycles. Patients with RPL (2 or more clinical pregnancy loss) had a complete RPL workup recommended by ASRM and reported no etiology for RPL was included in the study. Patients with uterine synechia, hydrosalpinx, endocrinological disorders and thin endometrium (endometrial thickness <6mm) were excluded Participants/materials, setting, methods A total of 366 single euploid blastocyst FETs employing hormone replacement therapy for endometrial preparation were evaluated. Patients were categorized into 2 group regarding female age (female age< 35 years and female age≥35 years. Demographic, embryological and endocrinological parameters were analyzed. Live birth rate (LBR) was the primary outcome. Clinical pregnancy rate (CPR) and miscarriage rate (MR) were the secondary outcome. Main results and the role of chance The mean female age of the study population was 33.9±4.6 years, the number of previous pregnancy loss was 3.2±1.6 and BMI was 23.8 ±7.9 kg/m2. Overall CPR, MR and LBR were 61.7% (226/366), 24.8% (56/226) and 46.5% (170/366) respectively. Comparison of clinical characteristics of the 195 women <35 years and 171 women ≥35 years revealed no significant deference in BMI, number of previous live birth, and number of previous pregnancy loss. CPR, MR and LBR were similar among two groups [ 63.6% (124/195) vs 59.6% (102/171), p = 0.44; 27.4% (34/124) vs 21.6% (22/102), p = 0.31; 46.2% (90/195) vs 46.8% (80/171), p = 0.9; respectively]. Binary logistic regression evaluating the independent factors that effect live birth revealed that female age and number of previous pregnancy loss were not found to be statistically significant factors. The only independent factor for live birth was day of embryo biopsy, transferring the day 6 biopsied embriyo significantly decreased the live birth [p = 0.003, OR: 0.47, 95% CI (0.29-0.77)]. Limitations, reasons for caution The maim limitation of the study is its retrospective nature. Wider implications of the findings PGT-A has been suggested to be a treatment for RPL. However there is insufficient data to call PGT-A as an efficient treatment for RPL. Investigating the factors that effect live birth after PGT-A may be the first step for selecting the most favorable group Trial registration number Not applicable

P-562 Molecular aspects of preimplantation genetic testing (PGT) for Neurofibromatosis type 1 (NF1) in three large European PGT centers: challenges and pitfalls

Abstract Study question What are the technical challenges and pitfalls of PGT for NF1 (n = 296 families) as experienced by three large European PGT centers? Summary answer The high (de novo) mutation rate and presence of germline mosaicism, especially in case of deletions, is challenging in PGT test development for NF1. What is known already NF1 is a neurocutaneous disorder with complete penetrance and extreme clinical variability. It is one of the most frequently requested autosomal dominant indications for PGT. The NF1 gene is large and has a high mutation rate. A high number of variants occur de novo, are mostly unique and more frequently associated with germline mosaicism in the index. These characteristics can pose difficulties in counseling, test development and PGT treatment. Large NF1 deletions are associated with a more severe phenotype and relative frequent mosaicism, but this has not been described in literature for intragenic deletions. Study design, size, duration Retrospective analysis of data on all test development procedures with the indication NF1 completed by August 2022 (n = 296). The data on test development were collected from medical files by the laboratories of the three participating PGT centers. The study was approved by the Medical and Ethical Review Committee of all three centers. The Medical Research Involving Human Subjects Act was not applicable. Participants/materials, setting, methods The three participating PGT centers were Maastricht University Medical Center (the Netherlands), University Hospital Brussels (Belgium) and Strasbourg University Hospital (France). Techniques applied were locus specific PCR-STR with or without the specific causative variant or genome wide haplotyping methods (NGS based OnePGT or karyomapping) or a combination of the above. Main results and the role of chance Test development was completed for 296 cases involving 228 different variants in the NF1 gene (125 truncating, 31 missense, 47 splice and 7 in-frame or synonymous variants, 8 larger deletions, 1 translocation, 9 awaiting further classification). We observed 36 recurring variants for 104 couples, of which 55 were sporadic cases, The majority of the 296 cases were sporadic (60%), signs of mosaicism were observed in 14 of these cases (8%). In our cohort, 6 sporadic cases involved a complete gene deletion (n = 1) or a deletion of ≥ 1 exons in the NF1 gene (n = 5). Mosaicism was detected in 4 of these cases (67%). In one case, the mutation was not detected in sperm cells during test set-up. PGT treatment was started for 10 couples with signs of mosaicism, in 6 no affected embryos were detected in 1-2 cycles and 1 resulted in a misdiagnosis because of phasing based on unaffected offspring. Two cases had NF1 caused by a different variant in the NF1 gene than their affected family members. A successful PGT test was developed in 289 cases (98%), 5 couples opted out during test development and in only 2 cases, development of a test was not possible for technical reasons. Limitations, reasons for caution The observed challenges and pitfalls depend on the techniques used and local procedures, so results may not be applicable to all PGT laboratories. However, due to the large sample size with exhaustive data and the fact that ESHRE guidelines were followed, there is probably little reason for caution. Wider implications of the findings Our findings could improve broader reproductive counseling of NF1 patients. Also, this large cohort contains previously unpublished variants in the NF1 gene, which is relevant for genetic diagnosis in NF1 patients in general. Our findings could possibly aid in test development for other autosomal dominant PGT indications with similar characteristics. Trial registration number Not applicable.

Innovative Medical Treatments for Endometriosis

This presentation will focus on the following innovative areas in medical treatments for endometriosis. Where were we, say, a decade ago compared to where we are now? What diagnostic techniques should we employ to define the population we should treat? Does gold standard surgical treatment help patients avoid unwanted medical treatment - or should it now be the other way round? Do we still believe that medical treatment is not indicated for infertility related to endometriosis? What are the genuinely evidence-based innovative medical treatments for endometriosis? Consensus statements and guidelines represent a clear line in the sand of what may be considered gold standard practice of the time – the World Endometriosis Society’s consensus on current management of endometriosis (2013) 1 provides a good perspective on where we were around a decade ago; the ESHRE Guideline (2022) 2 reflects best practice today. There is growing consensus that a laparoscopic (+/- histological) diagnosis is no longer practical, or indeed needed, in most cases to implement the whole gamut of medical treatment, even though the entire evidence base for treating endometriosis hinges on laparoscopic diagnosis. Hence, “in 2023, there is a strong case for treatment of endometriosis to be based on a clinical diagnosis of ‘likely endometriosis’ supported by imaging findings, when appropriate, in lieu of a traditional diagnosis by laparoscopy +/- histology”. Following laparoscopic surgery, those not intending to conceive should consider the levonorgestrel intrauterine system or combined oral contraceptive pill for at least 18-24 months to reduce the recurrence of endometriosis-related pain symptoms; 2 following surgery for either endometriomas or deep endometriosis, long term hormone therapy should be considered to reduce the chance of recurrence.2 Given the respective evidence bases, progestin hormone therapy may be preferable to the combined oral contraceptive pill to turn the tide of increasing prevalence of endometriosis. 3 While medical treatment has not been recommended to improve fertility, indeed a delaying effect on fertility through medical treatment has traditionally been highlighted, innovative analysis methods, including network meta-analysis, have raised the question whether some medical treatments (dydrogesterone and GnRH agonists) might benefit fertility – and this is merit-worthy of further investigation. GnRH antagonists and aromatase inhibitors are the innovative medical treatments that have shifted from ‘showing potential’ to ‘recommended’, so we will delve into the data supporting this to discover that, for aromatase inhibitors, this remains far from convincing, but for GnRH antagonists, these present a genuine innovative medical treatment option for those suffering from endometriosis.

O-303 Contribution of targeted sequencing for genetic diagnosis of premature ovarian insufficiency in clinical practice

Abstract Study question What is the diagnostic yield of custom designed gene panel for patients with premature ovarian insufficiency (POI)? Summary answer The diagnostic yield of our POI gene panel (POIGP) is 7.3% What is known already POI is a specific female syndrome with a high clinical and genetic heterogeneity. It is characterized by a premature exhaustion of the ovarian function and infertility and affects approximately 1% of women. POI can be related to genetic factors which include chromosomal abnormalities, FMR1 premutation and rare variants in numerous genes. The advent of high throughput sequencing methods has led to the identification of an increasing number of variants implicated in the development of POI over the last decades. However, POI etiologies still remain undetermined in the majority of cases. Study design, size, duration An observational analytic cohort study of 150 patients presenting idiopathic POI (normal karyotype, absence of FMR1 premutation, absence of adrenal and/or ovarian antibodies) recruited prospectively at three Belgian academic and university hospitals between 2016 and 2021. Participants/materials, setting, methods Patients were included if they experienced POI, as defined by ESHRE guidelines on POI (2016). POI genes included in the panel were selected from PubMed using different key words mainly premature ovarian insufficiency, gonadal dysgenesis, hypergonadotropic hypogonadism, ovarian failure and genetics. The panel included 156 genes, variants were filtered based on allele frequency (≤1%) in latest available population databases and classified according to ACMG/AMP (American College of Medical Genetics/Association for Molecular Pathology) guidelines 2015. Main results and the role of chance Our analysis revealed a potential causative variant for 11 patients in the following genes: MEIOB, BMP4, CFTR, FANCA, FSHR, FANCG, MLH1, MRPS22 and STARD9. This means that the diagnostic yield of our POI gene panel (POIGP) is 7.3%. Patients were mainly Caucasian (63%), North African (17%) and sub-Saharan African (13%). They presented primary amenorrhea in 14.7% of cases. Consanguinity and/or a family history of POI or early menopause in 28% of cases. Mean patient’s age (years) at POI diagnosis was 28.9± 8.5 (mean ± SD). The overall mean coverage was 229X, and more than 95% of the target exome was represented with more than 30-fold coverage. Limitations, reasons for caution The present study was limited to monogenic etiologies of POI, potential oligogenic causes have not been searched. Functional studies and/or family segregation were not performed for the identified variants. Wider implications of the findings Our findings show the importance of targeted next generation sequencing in clinical practice and highlight the limit of our current genetic knowledge in the field of POI. A regular update of genes included in POIGP will improve its diagnostic yield. Trial registration number P2016/196/CCB B406201628264

O-258 Nuclear magnetic resonance profiling of the vaginal metabolome in adverse early pregnancy outcomes

Abstract Study question Is the vaginal metabolome predictive of early pregnancy outcomes? Summary answer The vaginal metabolome is moderately predictive of live normally-sited pregnancies when compared to a pregnancy with an adverse outcome. What is known already Approximately 15% of all pregnancies are lost in the first trimester and a further 1-2% are ectopic. To date, no non-invasive and clinically useful tests have been developed to differentiate live normally-sited pregnancies from non-viable and ectopic pregnancies. Metabolomics is the comprehensive analysis of small molecules in biological samples used to identify disease biomarkers. The vaginal metabolome has previously been shown to be predictive of later adverse pregnancy outcomes including preterm birth. In this study, we aimed to identify biomarkers of live normally-sited pregnancies when compared to non-viable intrauterine and ectopic pregnancies using NMR metabolomic profiling of vaginal swabs (LVS). Study design, size, duration This was a prospective cohort study (EXPEDITE). 222 pregnant women <10 weeks’ gestation with pain and/or bleeding were recruited over a period of 36 months at the Liverpool Women’s Hospital, a tertiary referral centre. Pregnancy outcomes were categorised according to ESHRE guidelines as live normally-sited pregnancy, miscarriage, tubal ectopic pregnancy or pregnancy of unknown location (PUL). Participants/materials, setting, methods Participants consented to self-collecting a LVS, which was extracted in acetonitrile and analysis by NMR spectroscopy; 1D 1H and 2D 1H-13C. Spectra were acquired at 25 °C on a 700 MHz spectrometer. Relative metabolite abundances underwent univariate and multivariate statistical analysis using MetaboAnalyst 5.0 and custom-built R scripts (p-value false discovery rate adjusted). Area under receiver operating characteristic curve (AUC) values were used to evaluate predictive models. Main results and the role of chance Our cohort of 222 women were categorised in to 100 (45 %) live normally-sited pregnancies, 29 (13 %) tubal ectopic pregnancies, 52 (23 %) miscarriages and 31 (14%) pregnancies of unknown location (PUL). Ten spectra from rare or uncertain pregnancy outcomes (e.g. molar pregnancy) were excluded. Univariate statistical analysis of all four groups identified isoleucine levels as significantly higher (p < 0.05) in live normally-sited pregnancies compared with all groups with adverse pregnancy outcome groups. Multivariate partial least squares discriminant analysis (PLS-DA) models of all groups failed to accurately predict pregnancy outcomes. To enhance the predictive models, miscarriage, tubal ectopic pregnancy and PUL groups were combined and compared to live normally-sited pregnancies. Univariate analysis revealed levels of several metabolites (including isoleucine, tyrosine and maltose) as significantly altered in live normally-sited pregnancies compared with all other outcomes. PLS-DA models demonstrated modest discrimination between live normally-sited pregnancies versus other outcomes (AUC = 0.75). In summary, this study has identified a vaginal metabolite profile and potential biomarkers associated with live normally-sited pregnancy in the first trimester. Limitations, reasons for caution The number of tubal ectopic pregnancies and PULs were relatively low compared to other outcomes. Additionally, several factors that may influence the vaginal metabolome, including infection and the vaginal microbiome, were not characterised in this study. Wider implications of the findings These findings may be useful in the development of diagnostic tests to confirm an intrauterine pregnancy and exclude potential life-threatening pregnancies. It is well established that the microbiome contributes to the vaginal metabolome. As such, our findings will inform future correlative studies of vaginal microbiome and metabolome in early pregnancy. Trial registration number NA

Relugolix combination therapy for endometriosis pain

The treatment of endometriosis-associated pain continues to be a major problem for women and their clinicians. 1 Dunselman GA Vermeulen N Becker C et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014; 29: 400-412 Crossref PubMed Scopus (1352) Google Scholar , 2 Nnoaham KE Hummelshoj L Webster P et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011; 96 (e8): 366-373 Summary Full Text Full Text PDF PubMed Scopus (732) Google Scholar Laparoscopy, required to confirm the diagnosis, is usually combined with surgical ablation or excision of endometriotic lesions to alleviate pain and hormonal contraceptives are used to control symptoms before and after the operation. 1 Dunselman GA Vermeulen N Becker C et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014; 29: 400-412 Crossref PubMed Scopus (1352) Google Scholar , 3 National Institute of Health and Care ExcellenceEndometriosis: diagnosis and management. https://www.nice.org.uk/guidance/ng73Date: Sept 6, 2017 Date accessed: March 31, 2022 Google Scholar Recurrence of pain is common, with 40–50% of women with endometriosis reporting recurrence within 5 years of treatment 4 Guo SW Recurrence of endometriosis and its control. Hum Reprod Update. 2009; 15: 441-461 Crossref PubMed Scopus (417) Google Scholar and nearly two-thirds of women requiring repeat surgery. 5 Saraswat L Ayansina D Cooper KG Bhattacharya S Horne AW Bhattacharya S Impact of endometriosis on risk of further gynaecological surgery and cancer: a national cohort study. BJOG. 2018; 125: 64-72 Crossref PubMed Scopus (37) Google Scholar Gonadotrophin releasing hormone (GnRH) analogues (agonists and antagonists), which cause profound suppression of ovarian oestrogen production, are often used as second-line agents to control pain and reduce the need for further surgery, 6 Brown J Pan A Hart RJ Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 2010; 8CD008475 Crossref Google Scholar but they can lead to hypoestrogenic side-effects including hot flushes, night sweats, and loss of bone mineral density; these side effects can be addressed with the addition of hormone replacement therapy (HRT) without compromising treatment efficacy. 7 Barbieri RL Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol. 1992; 166: 740-745 Summary Full Text PDF PubMed Scopus (276) Google Scholar , 8 Sagsveen M Farmer JE Prentice A Breeze A Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral density. Cochrane Database Syst Rev. 2003; 4CD001297 Google Scholar Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2)Once-daily relugolix combination therapy significantly improved endometriosis-associated pain and was well tolerated. This oral therapy has the potential to address the unmet clinical need for long-term medical treatment for endometriosis, reducing the need for opioid use or repeated surgical treatment. Full-Text PDF Open Access

P–425 Recurrent pregnancy loss: what can we learn from different international guidelines?

Abstract Study question To which extent do the current international guidelines and recommendations concerning recurrent pregnancy loss (RPL) differ? Summary answer All guidelines apply definitions for RPL, however few diagnostic and therapeutic options are described. Diagnostics should be based on best evidence and current scientific knowledge. What is known already Established risk factors for RPL include anatomical, genetic, endocrine, hemostatic and immune alterations. The European Society of Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine (ASRM), German/Austrian/Swiss Society of Obstetrics and Gynecology (DGGG/OEGGG/SGGG) and the Royal College of Obstetricians and Gynecologists (RCOG) published guidelines concerning diagnostic and therapeutic options in RPL. Due to the different guideline processes and date of publication actuality as well as complexity differ widely. Study design, size, duration We compared the guidelines of the ESHRE, ASRM, DGGG/OEGGG/SGGG and RCOG with regard to definition, diagnostic and therapeutic aspects. The guidelines were published between 2011 and 2018. Structured guideline processes with regular (complete) updates are only provided by the DGGG/OEGGG/SGGG. Participants/materials, setting, methods After thorough literature research (Pubmed, Embase) all existing guidelines and recommendations were analysed and compared considering the current state of knowledge. The RCOG recommendations from 2011 were updated in 2014 and 2017, the ARSM expert letter was last updated in 2012. The ESHRE guideline was published in 2017. The first version of the DGGG/OEGGG/SGGG guideline was published 2006, updated in 2013 and upgraded to a higher evidence-level in 2018 and is currently under review. Main results and the role of chance All guidelines agree that a diagnostic work-up is indicated after at least two clinical pregnancies and should exclude anatomical malformations, an antiphospholipid syndrome and thyroid dysfunction. Furthermore, lifestyle modifications are recommended by all. The general evaluation of an inherited thrombophilia is not recommended by any guideline. Exclusion of other risk factors like parental chromosomal disorders, a polycystic ovary syndrome or insulin resistance are only included in some guidelines, partly due to a lack of diagnostic criteria (luteal phase insufficiency) or due to the different year of publication of the recommendations (e.g. chronic endometritis). All guidelines recommend treating APLS by administering low-dose aspirin (75–100mg daily) in combination with unfractionated/low-molecular-weight heparin. With regard to uterine malformations whether or not a septum should be dissected is still a matter of debate: ESHRE and RCOG consider evidence insufficient, while DGGG/OEGGG/SGGG and ASRM recommend a surgical intervention. In case of chronic endometritis, the DGGG/OEGGG/SGGG recommends antibiotic therapy e.g. with doxycycline (200 mg daily for 14 days). Limitations, reasons for caution Different health economic as well as consensus aspects in the process of guideline development have a significant influence on the individual guidelines and recommendations. Wider implications of the findings: Since personalized diagnostic and therapeutic strategies in RPL patients are required, physicians have to decide when to follow the guideline and when to expand diagnostics and therapy. Therefore, the knowledge of the weaknesses of each guideline and its developmental process is helpful for treating RPL couples. Trial registration number -

P–749 Knowledge of women undergoing surgery for endometrioma regarding the impact of the disease and its treatment on ovarian reserve and fertility

Abstract Study question Do women undergoing surgery for endometrioma due to pain, a cyst and/or subfertility understand the impact of the disease and its treatment on ovarian reserve and fertility. Summary answer The majority of women treated in a fertility setting are well informed compared to those in a general medical setting. What is known already: Infertility affects 30% to 50% of women with endometriosis. Ovarian endometriomas are reported in 17–44% of infertile women with endometriosis and are typically associated with more severe disease. Endometriomas are associated with diminished ovarian reserve, due to the endometrioma per se or due to surgical interventions required to treat and excise the disease. ESHRE guidelines recommend that women should be informed pre-operatively of the potential reduction in ovarian reserve associated with surgery and that ovarian reserve tests should be performed when future fertility is a concern. Study design, size, duration In conjunction with our histopathology colleagues we identified a cohort of women with a histological diagnosis of one or more ovarian endometriomas who underwent surgery in our unit between 2010 and 2019. We developed a scoping questionnaire, targeted at women currently over the age of 40, who had previously undergone surgery for endometrioma under the age of 35. Patients were contacted by telephone and consent obtained to send an email with a survey link. Participants/materials, setting, methods We identified 47 women who had a histological diagnosis of endometrioma. Of these, 30 were contactable by telephone, of whom 29 consented to being sent information regarding the study and a link to the questionnaire. 21 women completed the survey. Respondents were divided into 2 groups for analysis. Group 1 cited ‘fertility’ or ‘both pain and fertility’ as an indication for their surgery while group 2 had ‘pain’ or ‘ovarian cysts’ but no fertility concerns. Main results and the role of chance: The majority (62%) of patients were diagnosed with endometriosis while aged 25–34. The indication for surgery was evenly divided between pain (32%), fertility (37%) and ovarian cysts (37%). 60% of women reported having endometriomas diagnosed preoperatively. Striking differences were noted between groups 1 and 2. Of the women who cited ‘fertility’ or ‘both pain and fertility’ (n = 9) as an indication for their surgery, 78% (n = 7) reported being aware of any possible negative impact of endometriosis on their fertility, with 78% also being aware of the possible negative impact of surgery for endometriosis on their fertility. This compared to only 36% (n = 4) and 27% (n = 3) respectively in Group 2. In group 1, 56% (n = 5) remembered having an AMH level checked pre operatively while 78% (n = 7) also had an ultrasound pre-operatively. In contrast, only 33% (n = 3) of Group 2 remember having an AMH level checked pre operatively though 64% (n = 7) had an ultrasound pre-operatively. Of those whose surgery was performed by a fertility specialist, 75% (n = 6) reported being aware of the impact of endometriosis and also the impact of surgery on ovarian reserve, compared to 44% (n = 4) of those who surgery was performed by a non-fertility specialist. Limitations, reasons for caution This is a retrospective study and the numbers are small. We were only able to identify women with an endometrioma via pathology records, so those with no excision of disease (eg those who had ablation of an endometrioma) were excluded from this analysis. Wider implications of the findings: This suggests the majority of patients treated in a fertility setting are counselled regarding the benefit of surgery but also the risk to ovarian reserve. This is not the case in other settings. It is time to disseminate guidelines such as those produced by ESHRE to our general gynaecology colleagues. Trial registration number Not applicable

The transcriptomic profile of endometrial receptivity in recurrent miscarriage

ObjectiveTo characterise the endometrial transcriptomic profiles of women who suffered recurrent miscarriage and to set the foundation for the development of an endometrial receptivity test that could predict the fate of subsequent pregnancies. Study designThis was a prospective multicentre cohort study performed at the Tommy's National Centre for Miscarriage Research in Birmingham, Saint Mary’s Hospital in Manchester and Royal Devon & Exeter Hospital, United Kingdom. The study was conducted between December 2017 and December 2019. Endometrial biopsies were obtained during the window of implantation from 24 women aged 18–35 years, who were not pregnant and regularly menstruating, diagnosed with unexplained recurrent miscarriage by standard investigations as per the ESHRE guidelines. Exclusion criteria included risk factors such as smoking, obesity or hyperprolactinemia. The RNA transcripts abundances were quantified using Kallisto. R packages tximport and DESeq2 were used to summarize count estimates at the gene level and to analyse the differential gene expression. ResultsWomen who suffered four or more miscarriages had 19 differently expressed genes after adjustment for multiple comparisons. They were related to biological processes such as immunity (HLA-DMA, CCR8, ALOX5), energy production (ATP12A), hormone secretion (CGA), adhesion (CHAD, ADGRF2, AQP5, TBCD, CTNND1, NKD2) and cell proliferation (NCCRP1). Based on 421 differently expressed genes, women who achieved a subsequent live birth displayed an enrichment of processes related to the regulation of cell structure and proliferation, and a depletion of processes related to immunity, trans-membrane transport and coagulation. ConclusionsWomen in the extreme miscarriage cohort had a distinctive endometrial transcriptomic signature compared to women with low order miscarriages. There was a partial overlap with the transcriptome of asynchronous endometrium suggesting the endometrial factor to be a different entity in the context of recurrent miscarriage. Women who achieved a live birth in their subsequent pregnancy displayed an enrichment of genes related to the regulation of cell structure and proliferation, while women who suffered a subsequent miscarriage displayed an enrichment of genes related to immunity, trans-membrane transport and coagulation.

Endometriosis-associated pain in women undergoing hysterectomy.

Pain is a cardinal symptom of endometriosis and its management can be challenging. Analgesics are commonly used as first line treatment for endometriosis-associated pain, despite there being a paucity of evidence regarding their use for this indication. Clinicians are advised to consider NSAIDs or other analgesics to reduced endometriosis-associated pain due to the known benefit of NSAIDs in primary dysmenorrhea (ESHRE guideline "Management of women with endometriosis." Dunselman et al., Hum Reprod. 2014; 29(3):400-12). Women who fail to respond to conservative treatments and who have completed their family may be offered hysterectomy with removal of the ovaries and all visible endometriosis lesions, alongside advice that hysterectomy will not necessarily cure the symptoms or the disease.

Author

The Cochrane database was searched for systematic reviews about endometriosis. The ESHRE guidelines were also included. A search of the British Journal of Obstetrics and Gynaecology “BJOG”, and the Journal of Minimal Invasive Gynaecology “JMIG” individual database for articles about surgical management of endometriosis was done.

The role of lymphocytes in fetal development and recurrent pregnancy loss.

Fetal survival and development is supported by the maternal immune system. Questions regarding those mechanisms have risen from development of transplantation medicine and observation of graft rejection. Initial theories of anatomic division, fetal immune immaturity and maternal immune system inertia were found incorrect. Rejection of fetal "semi-allograft" by maternal immune system could result in pregnancy loss. Two pregnancy losses of any etiology are considered recurrent and effort should be made to name the probable cause. Immune causes of pregnancy loss are probably multifactorial, thus difficult to research and implement findings in clinical practice. Although a full understating of pregnancy loss is not established, new therapies are being developed. This review summarizes the role of lymphocytes in pregnancy develop- ment, presents data from studies on recurrent pregnancy loss patients, evidence of new therapies and ESHRE guidelines regarding immunologic investigations.

Selection of key recommendations for the management of women with endometriosis by an international panel of patients and professionals.

Can the differences in patients' and professionals' perspective regarding essential endometriosis care be accommodated in one set of key recommendations? Consensus between patients and professions on a key set of recommendations for essential endometriosis care was achieved. Guideline development alone will not lead to healthcare improvement. Quality indicators are needed to monitor actual care and guideline adherence. These can help with better implementation of the ESHRE guidelines in European hospitals and thereby improve the quality of endometriosis care. The first step in the development of quality indicators is to select a compact set of key recommendations. Using a RAND modified Delphi method, this study reports the systematic selection of key recommendations based on the ESHRE guideline 'Management of Women with Endometriosis' by an international expert panel of both patients and professionals during the study period of September 2015 and December 2015. An international panel of patients (n = 10) and medical professionals (n = 11) rated and prioritized the 83 recommendations extracted from the ESHRE guideline for relevance in three rounds. A strict consensus methodology was used to select key recommendations. The main outcome measure was one set of key recommendations for endometriosis care. A representative set of 17 key recommendations was selected from the preliminary set of 83 recommendations. This selection covers all dimensions of endometriosis care, including diagnosis, treatment of endometriosis-associated pain, treatment of endometriosis-associated infertility and miscellaneous topics such as prevention, menopause and relationship with cancer. Of the 21 experts, 17 participated in at least one round while 16 (76.2%) participated in all 3 rounds. The feasibility of the selected key recommendations was not assessed in this study. As not all panel members took part in all three rounds, some response bias may have occurred. This set of key recommendations is the first step in the development of quality indicators for monitoring and improving endometriosis care. The set is generic and can be used in hospitals internationally. A practice test should be conducted to assess the feasibility of our key recommendations in clinical practice. No funding was received for the conduct of this study. Members of the EndoKey study group did not receive payment. The authors and members of the EndoKey study group have no conflict of interest.

ESHRE Guideline on Management of Women with Endometriosis: Is There Evidence Supporting Surgery in Endometriosis?

The ESHRE guideline on the management of women with endometriosis containing 83 recommendations in 8 chapters, was recently published. Among other topics, the guideline development group collected the best available evidence on surgery for pain and for fertility problems in endometriosis and made recommendations.

Session 56: From experimental to established: ESHRE guidelines and position papers

Session 56: From experimental to established: ESHRE guidelines and position papers

The Diagnosis and Treatment of Deep Infiltrating Endometriosis

Endometriosis and adenomyosis uteri are the most common benign disorders affecting girls and women after uterine myomas (fibroids), with a prevalence of roughly 5% to 15%. There have been many advances in diagnostic assessment and in our understanding of the disease over the past decade. Steady improvements in treatment have been accompanied by heightened consciousness of the diagnosis among the affected women and the doctors who care for them. A selective literature search was carried out in the Cochrane and PubMed databases using the key words "endometriosis," "deep infiltrating endometriosis," "endometriosis AND diagnostics," "endometriosis AND surgical therapy," "endometriosis AND endocrine treatment," and others. The AWMF and ESHRE guidelines were also taken in account. The main manifestations are primary or secondary dysmenorrhea, bleeding disturbances, infertility, dysuria, pain on defecation (dyschezia), cycle-dependent or (later) cycle-independent pelvic pain, nonspecific cycle-associated gastrointestinal or urogenital symptoms. Cycle-associated problems of urination and/or defecation that are due to endometriosis are most common in young, premenopausal women. Whenever such manifestations are present, endometriosis should be considered in the differential diagnosis, and evidence for it should be sought in the clinical history, physical examination, and ultrasound findings. If endometriosis is histologically confirmed and is of the deeply infiltrating kind, the recommended management today is to refer the patient to an endometriosis center.

ESHRE guidelines for good clinical and laboratory practice for investigation and treatment of infertile couples

ESHRE guidelines for good clinical and laboratory practice for investigation and treatment of infertile couples