Adenomyosis and Infertility: A Literature Review.

Background and Objectives: Adenomyosis (the presence of ectopic endometrial glands and stroma below the endometrial-myometrial junction) is a benign condition which is increasingly diagnosed in younger women suffering from infertility. The aim of this narrative review was to study the pathophysiology and prevalence of adenomyosis, the mechanisms causing infertility, treatment options, and reproductive outcomes in infertile women suffering from adenomyosis. Materials and Methods: A literature search for suitable articles published in the English language was performed using PubMed from January 1970 to July 2022. Results: The literature search retrieved 50 articles that met the purpose of this review and summarized the most recent findings regarding the accuracy of diagnostic methods, pathophysiology, and the prevalence of adenomyosis and optimal strategies for the treatment of infertile women with adenomyosis. Conclusions: Adenomyosis is a common gynecological disorder, affecting women of reproductive age. It negatively affects in vitro fertilization, pregnancy and the live birth rate, as well as increases the risk of miscarriage. With the advent of non-invasive diagnoses with MRI and TVUS, the role of adenomyosis in infertility has been better recognized. Overall, more randomized controlled trials (RCTs) are needed to provide strong data on the accuracy of diagnostic methods, the pathophysiology and the prevalence of adenomyosis, the fertility outcomes of patients and the optimal strategy for the treatment.

Exploring the challenges for a new classification of adenomyosis.

The availability of non-invasive diagnostic tests is an important factor in the renewed interest in adenomyosis, as the disease can now be more accurately mapped in the uterus without a need for hysterectomy. An agreed system for classifying and reporting the condition will enhance our understanding of the disease and is envisaged to enable comparison of research studies and treatment outcomes. In this review, we assess previous and more recent attempts at producing a taxonomy, especially in view of the latest proposal for subdivision of adenomyosis into an internal and an external variant. In this context, we also explore the uncertainties linked to classifying involvement of the uterovesical pouch, the pouch of Douglas and lesions in the outer myometrium. Two opposing hypotheses are forwarded to explain the pathogenesis of these variants, namely that disease localized in these areas originates from an invasion by uterine adenomyosis of peritoneal organs; alternatively, that lesions present in the outer myometrium originate from peritoneal endometriosis. At the root of debates around these opposing theories of pathogenesis is fragmentary evidence. Because of the limitations of currently available evidence, and until this issue is resolved, broad agreement on a hypothesis to underpin any proposed classification is unlikely.

Reproductive outcomes with donor sperm in couples with severe male-factor infertility after intracytoplasmic sperm injection failures.

PURPOSE: To evaluate reproductive outcomes of artificial insemination and IVF with donor sperm (AID or IVF-D) for male-factor couples with a history of unsuccessful ICSI attempt. METHODS: This retrospective cohort includes couples with severe male-factor infertility who failed ICSI treatment, and subsequently underwent semen donation treatment. We report the following outcomes: (1) live birth rates in AID and IVF-D treatment for couples with severe male infertility factors and prior ICSI failures; (2) paternal impact on embryo development of the same oocyte cohort; (3) prognostic factors in obtaining a live birth with donor semen. RESULTS: Of 92 women with failed ICSI cycles (26 with multiple attempts), 45 couples underwent AID treatment. Live birth rate per cycle of AID was 18.9%. Fifty-three patients underwent IVF-D including 6 couples who previously did not conceive with AID. Embryological outcomes including fertilization, viable cleavage embryos, and blastocyst formation rates were significantly lower in ICSI cycles with partner sperm compared with IVF-D (P < 0.01). Logistic regression analysis showed that female age and the severity of spermatogenetic disorder are prognostic factors in obtaining a live birth with donated sperm. CONCLUSION: Couples with severe male infertility factor (azoospermia or extreme oligoasthenospermia) and a history of unsuccessful ICSI cycles benefit from treating with donor sperm. ICSI fertilization, embryo viability, and progression of the embryo to the blastocyst stage are significantly deteriorated by semen parameters. The prognostic factors identified may help couples plan their treatment and prepare for their parenthood journey.

Progress in the diagnosis and management of adolescent endometriosis: an opinion.

Increasing evidence indicates that early onset endometriosis (EOE), starting around menarche or early adolescence, may have an origin different from the adult variant, originating from neonatal uterine bleeding (NUB). This implies seeding of naïve endometrial progenitor cells into the pelvic cavity with NUB; these can then activate around thelarche. It has its own pathophysiology, symptomatology and risk factors, warranting critical management re-evaluation. It can also be progressive, endangering future reproductive capacity. This variant seems to be characterized by the presence of ovarian endometrioma. Today, the diagnosis of endometriosis in young patients is often delayed for years; if rapidly progressive, it can severely affect pelvic organs, even in the absence of serious symptoms. Given the predicament, great attention must be paid to symptomatology that is often non-specific, justifying a search for new, simple, non-invasive markers of increased risk. Better use of modern imaging techniques will aid considerably in screening for the presence of EOE. Traditional laparoscopy should be limited to cases in which imaging gives rise to suspicion of severity and a stepwise, minimally invasive approach should be used, followed by medical treatment to prevent recurrence. In conclusion, EOE represents a condition necessitating early diagnosis and stepwise management, including medical treatment.

Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial.

BACKGROUND: The success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation. METHODS: We did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078. FINDINGS: Between Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79-1·25; p=0·96). No hysteroscopy-related adverse events were reported. INTERPRETATION: Outpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted. FUNDING: European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.

The Thessaloniki ESHRE/ESGE consensus on diagnosis of female genital anomalies.

STUDY QUESTION: What is the recommended diagnostic work-up of female genital anomalies according to the European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) system? SUMMARY ANSWER: The ESHRE/ESGE consensus for the diagnosis of female genital anomalies is presented. WHAT IS KNOWN ALREADY: Accurate diagnosis of congenital anomalies still remains a clinical challenge because of the drawbacks of the previous classification systems and the non-systematic use of diagnostic methods with varying accuracy, some of them quite inaccurate. Currently, a wide range of non-invasive diagnostic procedures are available enriching the opportunity to accurately detect the anatomical status of the female genital tract, as well as a new objective and comprehensive classification system with well-described classes and sub-classes. STUDY DESIGN, SIZE, DURATION: The ESHRE/ESGE CONgenital UTerine Anomalies (CONUTA) Working Group established an initiative with the goal of developing a consensus for the diagnosis of female genital anomalies. The CONUTA working group and imaging experts in the field have been appointed to run the project. PARTICIPANTS/MATERIALS, SETTING, METHODS: The consensus is developed based on: (i) evaluation of the currently available diagnostic methods and, more specifically, of their characteristics with the use of the experts panel consensus method and of their diagnostic accuracy by performing a systematic review of evidence and (ii) consensus for the definition of where and how to measure uterine wall thickness and the recommendations for the diagnostic work-up of female genital anomalies, based on the results of the previous evaluation procedure, with the use of the experts panel consensus method. MAIN RESULTS AND THE ROLE OF CHANCE: Uterine wall thickness is defined as the distance between the interostial line and external uterine profile at the midcoronal plane of the uterus; alternatively, if a coronal plane is not available, the mean anterior and posterior uterine wall thickness at the longitudinal plane could be used. Gynecological examination and two-dimensional ultrasound (2D US) are recommended for the evaluation of asymptomatic women. Three-dimensional (3D) US is recommended for the diagnosis of female genital anomalies in 'symptomatic' patients belonging to high risk groups for the presence of a female genital anomaly and in any asymptomatic woman suspected to have an anomaly from routine evaluation. Magnetic resonance imaging (MRI) and endoscopic evaluation are recommended for the subgroup of patients with suspected complex anomalies or in diagnostic dilemmas. Adolescents with symptoms suggestive for the presence of a female genital anomaly should be thoroughly evaluated with 2D US, 3D US, MRI and endoscopically. LIMITATIONS, REASONS FOR CAUTION: The various diagnostic methods should always be used in the proper way and evaluated by experts to avoid mis-, over- and underdiagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The role of a combined US examination and outpatient hysteroscopy should be prospectively evaluated. It is a challenge for further research, based on diagnosis, to objectively evaluate the clinical consequences related to various degrees of uterine deformity. STUDY FUNDING/COMPETING INTERESTS: None.

A new approach to the management of ovarian endometrioma to prevent tissue damage and recurrence.

Management of ovarian endometrioma is a matter of debate between those advocating early treatment and those believing that cysts less than 3 cm in diameter should not be submitted to surgery. To explore a new approach to its management capable of preserving future fertility, the molecular pathology of ovarian endometrioma is reviewed and mechanisms by which the endometrioma progressively affects the ovary during reproductive life are summarized. The scope of new therapeutic modalities includes restoring the progesterone receptor ratio using progestin or progesterone receptor modulators and decreasing local oestrogen production through an aromatase inhibitor. In addition, free radical production can be blocked by antioxidants and the autophagic process by increasing apoptosis. Finally, metalloproteinases and relaxin activity, as well as the inflammatory process can be controlled. Many of these pharmacological treatments lend themselves to local administration and can be applied through intracystic drug administration; in fact, the intracystic route has already been tried with recombinant interleukin-2, methotrexate and ethanol; the latter to obtain sclerotization. Specifically, it is proposed that endometrial growth in the endometrioma is suppressed by intra-cystic application of synthetic progestins, such as levonorgestrel or danazol, selective progesterone receptor modulators, such as mifepristone, ulipristal or asoprisnil, without affecting ovarian activity.

Survival, re-expansion and cell survival of human blastocysts following vitrification and warming using two vitrification systems.

PURPOSE: This study evaluated and compared survival, re-expansion, and percentage of live cells of individual Days 5 and 6 human blastocysts that were vitrified and warmed with the Vit Kit Freeze/Thaw (Irvine Scientific, CA), or with two protocols using the Global Fast Freeze/Thaw Kits (LifeGlobal, Canada). METHODS: Frozen/thawed Day 2-3 or discarded embryos were cultured to blastocyst (culture day 5-6). Group 1 blastocysts were vitrified with the Vit Kit (n = 29) and High Security Vitrification (HSV) devices. Group 2 (n = 47) and Group 3 (n = 48) blastocysts were cryopreserved with the Global Fast Freeze Kit and 0.25 ml straws, using a direct plunge or a -100 °C holding step, respectively. Group 4 (Controls, n = 30) were not vitrified. Blastocysts were subsequently cultured for 24 h, assessed for survival and expansion, and then stained individually with propidium iodide and Hoechst. Live and total cell number was assessed with ImageJ (NIH), and the percentage of live cells calculated for each blastocyst. RESULTS: The percentage of live cells was not different between vitrified and control (non-vitrified) blastocysts, thus vitrification did not affect cell survival. Survival (following thawing and after 24 h culture), re-expansion, and percentage of live cells were not different for blastocysts vitrified and warmed between the two vitrification/warming kits, or between the two protocols for the Global Fast Freeze/Thaw Kits. CONCLUSIONS: Blastocyst vitrification can be achieved with equal success using simplified protocols and cheaper and easy to load freezing straws, providing simultaneously increased safety, and efficiency with lower cost, when compared with vitrification using specialized embryo vitrification devices.

Pathophysiology proposed as the basis for modern management of the ovarian endometrioma.

Present management of the ovarian endometrioma focuses on the size of the cyst and dictates that surgery should not be performed unless this exceeds 3 cm, which neglects the complex pathology of this condition. Studies of ovaries with the endometrioma in situ show progressive smooth muscle cell metaplasia and fibrosis of the cortical layer as the main ovarian lesion. There is no correlation between the size of the endometrial cyst and the degree of ovarian pathology: it is the mere presence of an ovarian endometrioma that has a detrimental impact on the cortical layer's follicle reserve. Cystectomy in young patients with an endometrioma may be particularly detrimental to follicle reserve, with the ovarian parenchyma loss at the time of surgery being related to the cyst's diameter. An underutilized diagnostic procedure, transvaginal hydrolaparoscopy with in-situ inspection of the cyst wall by ovarioscopy, allows careful diagnosis of ovarian pathology and selection of appropriate surgery with minimal invasiveness. Thus, available evidence shows that expectant management may not be the best choice when an endometrioma is suspected. On the contrary, early diagnosis through a minimally invasive technique, followed by early ablative surgery whenever indicated, represents the management of choice to preserve normal ovarian function. Present management of ovarian endometriomata is based on the size of the cyst and dictates that surgery should not be performed unless this exceeds 3cm. We argue that this approach neglects the true pathology of the ovary, since pioneers have studied ovaries with the endometrioma in situ and demonstrated that progressive smooth muscle cell metaplasia and fibrosis in the cortical layer constitute the main features of an endometrioma. There is no correlation between the size of the endometrial cyst and the degree of ovarian pathology: it is in the first place the mere presence of an ovarian endometrioma that has a detrimental impact on follicle reserve. It has been shown that cyst ablation in young patients with an endometrioma may be particularly detrimental to follicle reserve. An underutilized diagnostic procedure, transvaginal needle endoscopy with in-situ inspection after injection of saline suspension into the peritoneal cavity (hydrolaparoscopy) allows careful diagnosis of ovarian cortical pathology by colour changes from pearl-white to dark fibrotic. Thus, available evidence shows that expectant management may not be the best choice when an endometrioma is suspected: the delay in diagnosis causes delay in treatment and progression of the process leading to loss of follicles. On the contrary, early diagnosis through a minimally invasive technique, followed by early ablative surgery whenever indicated, represents the management of choice to preserve normal ovarian function.

Clinical implications of congenital uterine anomalies: a meta-analysis of comparative studies.

The clinical implications of congenital uterine anomalies (CUA), and the benefits of hysteroscopic resection of a uterine septum, were evaluated. Studies comparing reproductive and obstetric outcome of patients with and without CUA and of patients who had and had not undergone hysteroscopic resection of a uterine septum, were evaluated. Meta-analysis of studies indicated that the pregnancy rate was decreased in women with CUA (RR 0.85, 95% CI 0.73 to 1.00; marginally significant finding, P = 0.05). The spontaneous abortion rate was increased in women with CUA (RR 1.68, 95% CI 1.31 to 2.15). Preterm delivery rates (RR 2.21, 95% CI 1.59 to 3.08), malpresentation at delivery (RR 4.75, 95% CI 3.29 to 6.84), low birth weight (RR 1.93, 95% CI 1.50 to 2.49) and perinatal mortality rates (RR 2.43, 95% CI 1.34 to 4.42) were significantly higher in women with CUA. Hysteroscopic removal of a septum was associated with a reduced probability of spontaneous abortion (RR 0.37, 95% CI 0.25 to 0.55) compared with untreated women. Presence of CUA might be associated with a detrimental effect on the probability of pregnancy achievement, spontaneous abortion and obstetric outcome. Hysteroscopic removal of a septum may reduce the probability of a spontaneous abortion.

The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies.

STUDY QUESTION: What classification system is more suitable for the accurate, clear, simple and related to the clinical management categorization of female genital anomalies? SUMMARY ANSWER: The new ESHRE/ESGE classification system of female genital anomalies is presented. WHAT IS KNOWN ALREADY: Congenital malformations of the female genital tract are common miscellaneous deviations from normal anatomy with health and reproductive consequences. Until now, three systems have been proposed for their categorization but all of them are associated with serious limitations. STUDY DESIGN, SIZE AND DURATION: The European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE) have established a common Working Group, under the name CONUTA (CONgenital UTerine Anomalies), with the goal of developing a new updated classification system. A scientific committee (SC) has been appointed to run the project, looking also for consensus within the scientists working in the field. PARTICIPANTS/MATERIALS, SETTING, METHODS: The new system is designed and developed based on (i) scientific research through critical review of current proposals and preparation of an initial proposal for discussion between the experts, (ii) consensus measurement among the experts through the use of the DELPHI procedure and (iii) consensus development by the SC, taking into account the results of the DELPHI procedure and the comments of the experts. Almost 90 participants took part in the process of development of the ESHRE/ESGE classification system, contributing with their structured answers and comments. MAIN RESULTS AND THE ROLE OF CHANCE: The ESHRE/ESGE classification system is based on anatomy. Anomalies are classified into the following main classes, expressing uterine anatomical deviations deriving from the same embryological origin: U0, normal uterus; U1, dysmorphic uterus; U2, septate uterus; U3, bicorporeal uterus; U4, hemi-uterus; U5, aplastic uterus; U6, for still unclassified cases. Main classes have been divided into sub-classes expressing anatomical varieties with clinical significance. Cervical and vaginal anomalies are classified independently into sub-classes having clinical significance. LIMITATIONS, REASONS FOR CAUTION: The ESHRE/ESGE classification of female genital anomalies seems to fulfill the expectations and the needs of the experts in the field, but its clinical value needs to be proved in everyday practice. WIDER IMPLICATIONS OF THE FINDINGS: The ESHRE/ESGE classification system of female genital anomalies could be used as a starting point for the development of guidelines for their diagnosis and treatment. STUDY FUNDING/COMPETING INTEREST(S): None.

Elective single versus double blastocyst-stage embryo transfer in women aged 36 years or older: a retrospective cohort study.

We evaluated if elective single-blastocyst transfer (eSBT) could be adopted in women aged 36 or older. In this retrospective cohort, women aged ≥36 years received IVF ovarian stimulation cycles and had ≥ two blastocysts. A total of 240 women underwent eSBT and 189 double-blastocyst transfer (DBT) in the first transfer cycle. The subsequent frozen-thawed embryo transfer cycles were a combination of single- and double- blastocyst transfers. Analysis was stratified for patients in age groups 36-37, 38-39 and ≥40, considering the quality of the blastocyst transferred. The cumulative live birth rates (cLBR) were 74.2% (178/240) versus 63.0% (119/189) after eSBT versus DBT, respectively (aOR: 1.09 (0.68, 1.75)). Time to live birth did not vary significantly between the two groups (HR: 0.85 (0.68, 1.08)). The total number of children born was 194 after eSBT (162 singletons and 16 pairs of twins) versus 154 (84 singletons and 35 twins) after DBT. The odds ratios for preterm birth (0.37 (0.21-0.64)), and low birth weight (0.31 (0.16, 0.60)) were all lower in eSBT. In women aged ≥36 years, cLBR following single- versus double- blastocyst transfer was comparable while the odds of multiple live births and adverse perinatal outcomes were reduced.

The 10 "Cardinal Sins" in the Clinical Diagnosis and Treatment of Endometriosis: A Bayesian Approach.

Evidence-based data for endometriosis management are limited. Experiments are excluded without adequate animal models. Data are limited to symptomatic women and occasional observations. Hormonal medical therapy cannot be blinded if recognised by the patient. Randomised controlled trials are not realistic for surgery, since endometriosis is a variable disease with low numbers. Each diagnosis and treatment is an experiment with an outcome, and experience is the means by which Bayesian updating, according to the past, takes place. If the experiences of many are similar, this holds more value than an opinion. The combined experience of a group of endometriosis surgeons was used to discuss problems in managing endometriosis. Considering endometriosis as several genetically/epigenetically different diseases is important for medical therapy. Imaging cannot exclude endometriosis, and diagnostic accuracy is limited for superficial lesions, deep lesions, and cystic corpora lutea. Surgery should not be avoided for emotional reasons. Shifting infertility treatment to IVF without considering fertility surgery is questionable. The concept of complete excision should be reconsidered. Surgeons should introduce quality control, and teaching should move to explain why this occurs. The perception of information has a personal bias. These are the major problems involved in managing endometriosis, as identified by the combined experience of the authors, who are endometriosis surgeons.

No clinical relevance of the height of fundal indentation in subseptate or arcuate uterus: a prospective study.

The American Fertility Society has classified the arcuate uterus as a minor malformation with a benign clinical behaviour. The aim of this prospective study was to verify whether there is any scientific basis for this differentiation. Patients with at least one early miscarriage and a subseptate or arcuate uterus were admitted for hysteroscopic metroplasty. Patients were allocated to a subseptate uterus group, with an indentation of 1.5 cm or more, or an arcuate uterus group, with a smaller indentation. The miscarriage rates after metroplasty were similar between the two groups (14.0% in the subseptate uterus group versus 11.1% in the arcuate uterus group). Before metroplasty, the miscarriage rates were significantly higher in subseptate uterus group, as well as in the arcuate uterus group (both P<0.001). According to these results, there is no evidence to support that the arcuate uterus has a different effect on the reproductive outcome in comparison to the subseptate uterus, neither before nor after surgical correction of the anomaly. Since there is no scientific basis for a separate classification of the arcuate uterus, a review of the classifications of uterine congenital anomalies should be considered as necessary. Congenital uterine malformations have been classified by the American Fertility Society (AFS) since 1988. Although the AFS classification received wide acceptance and is still the most broadly used system, it is associated with various limitations in effective categorization of the anomalies. It is interesting that, until now, none of the other available options have been able to effectively replace the AFS system. Numerous papers indicate septate or subseptate (partial septate) uterus (AFS class V) is a possible cause of an unfavourable pregnancy outcome. Arcuate uterus (AFS class VI), a slight malformation similar to septate uterus, should differ from septate or subseptate uterus, because this 'minor' malformation should behave benignly with respect to the septate uterus. The aim of this study was to scientifically validate the difference between the arcuate and subseptate uterus in their effect on reproductive outcome through the results of a metroplasty in both groups of patients. A group of 96 patients, who underwent metroplasty after at least one early miscarriage, was divided into two groups according to the severity of the congenital uterine malformation. Our results indicate that there are no differences in pregnancy outcome after metroplasty either in patients with septate or arcuate utera. The poor pregnancy outcome in women with septate uterus seems not to be correlated to the dimension of the septum itself. There are no scientific bases for a separate classification of the arcuate uterus and it is proposed that a review of the classification of uterine congenital anomalies is necessary.

ESHRE certification of ART centres for good laboratory and clinical practice.

STUDY QUESTION: Three years after the start of the ESHRE ART Centre Certification (ARTCC) programme, what is the current state of the system, in terms of the interest expressed in it and experiences during the assessment of ART services? SUMMARY ANSWER: As of 1 December 2021, 25 European ART centres have been involved in the various stages of certification and the most common recommendations from inspectors were the need for documented training, verification of competencies for all staff members, verification of laboratory and clinical performance indicators, implementation of a quality management system and avoidance of overusing ICSI and add-ons. WHAT IS KNOWN ALREADY: European Union (EU) legislation has included ART activities in the EU Tissue and Cells Directives (EUTCDs). Following inspections by national EUTCD authorities, many details regarding documentation, laboratory environment, handling of reproductive cells and tissues, traceability, coding and patient testing have become standardized. However, the EUTCDs do not cover all ART-specific aspects. For this reason, the ARTCC was established to focus on peculiar areas, including relevant staff qualifications, training, continuing professional development, workload, equipment suitability, (non)-evidence-based laboratory and clinical methods used, treatment approaches according to ESHRE guidelines, recommendations and laboratory and clinical key performance indicators. STUDY DESIGN SIZE DURATION: The article reviews the state-of-the-art of the ESHRE certification of ART centres for good clinical and laboratory practice over an initial 3-year period of operation, including the number of ART centres involved in the different stages of certification and the most common recommendations by inspectors. PARTICIPANTS/MATERIALS SETTING METHODS: In 2016, the ARTCC working group began to establish a new ESHRE ARTCC programme. Since then, the working group has organized 4 preparatory courses and appointed 37 inspectors (19 clinicians, 17 embryologists and one paramedical). A tool to verify compliance with ESHRE recommendations for good laboratory and clinical practice was developed. The ARTCC has been open for applications since September 2018. In Step 1, the applicant enters basic information about the ART centre, staff and ART activities into the application platform. After review and approval, the applicant is given the opportunity to enter Step 2 and provide detailed online checklists on general, laboratory, clinical services and clinical outcomes. Two inspectors (one clinician and one embryologist) independently evaluate the submitted checklists. The condition to proceed to evaluation is a positive mean score (at least 66%) from each of the four checklists. In Step 3, a live site visit (or virtual owing to the coronavirus disease 2019 (COVID-19) pandemic) is organized and the inspectors prepare a final report with appropriate recommendations. The application may be rejected at any time if the criteria required to advance to the next stage are not met. The ARTCC programme is currently available for European countries listed in ESHRE internal rules, available on the ESHRE website. The certificate is valid for 3 years, after which an application for renewal can be submitted. MAIN RESULTS AND THE ROLE OF CHANCE: Over a 3-year period (until 1 December 2021), 63 ART centres from 25 countries started applying through an online platform. So far, 38 applications did not progress owing to lack of completion of the initial application within a 1-year period or because applications came from non-European countries. Of the remaining 25 applications, 8 centres have been inspected and 7 centres have been certified. The most common recommendations given by inspectors to assessed centres were the need for documented training, verification of competencies, skills and continuing professional development for all staff members, verification of laboratory and clinical performance indicators and implementation of a quality management system. The inspectors identified some recurring areas of medically assisted reproduction that deviate from good practice: the overuse of ICSI, preimplantation genetic testing for aneuploidies, freeze-all and other add-ons. They often reported that the clinical outcomes could not be objectively assessed because of non-inclusion of the started cycles or the frequent use of freeze-all cycles. LIMITATIONS REASONS FOR CAUTION: No major modifications have been made to the application platform and checklists since the early stages of the certification programme. However, in this short time, quite a few changes in clinical practice have occurred, especially concerning the more frequent use of the 'freeze-all' strategy. As a result, problems arose in the evaluation of clinical outcomes. In addition, because of the COVID-19 pandemic, site visits were substituted by the implementation of virtual visits. While this enabled the certification programme to continue, it is possible that certain critical details that would have been noticed during a traditional site visit may have been overlooked. WIDER IMPLICATIONS OF THE FINDINGS: Regular monitoring of the observations of ARTCC inspectors and analysis of their reports is certainly useful to harmonize inspectors' criteria in the assessment process and to identify chronic deficiencies in clinical and laboratory practice. Non-conformities can be addressed by ESHRE through guidelines and recommendations, as well as through discussion with EU institutions and competent authorities. STUDY FUNDING/COMPETING INTERESTS: The ARTCC programme was developed and funded by ESHRE, covering expenses associated with the meetings. The Steering Committee members who are the authors of this article did not receive payments for the completion of this study. The inspectors were remunerated for their work with an honorarium. The authors have no conflicts of interest to declare.

Management of endometrioma prior to IVF: compliance with ESHRE guidelines.

Management of endometrioma before IVF remains controversial. As well as some measurable benefits from surgical treatment, there are also potential risks that should be discussed with the patients to help them make an informed decision. When surgery is compared with expectant management, there appear to be no statistically significant differences in pregnancy rate and ovarian response to exogenous stimulation. The objectives of this European Society of Human Reproduction and Embryology (ESHRE)-sponsored survey were to acquire knowledge of current strategies for the management of endometrioma (>3 cm) prior to IVF and to explore adherence to ESHRE guidelines. A validated, peer-reviewed online questionnaire made of 14 questions was sent to 396 members of the ESHRE Special Interest Groups (Reproductive Surgery and Endometriosis/Endometrium), with a response rate of 27%. Surgical management is the most common treatment (82.2%), with drainage and excision of the cyst wall being the preferred surgical approach (78.5%). Monthly depot gonadotrophin-releasing hormone analogues are the preferred choice of medical treatment of endometriomas before IVF, with an average duration of treatment of 3 months. The findings demonstrate that surgery remains the commonest treatment offered for women with endometrioma before IVF. This is in line with the recommendations of the ESHRE guidelines.

Possible role of endometriosis in the aetiology of spontaneous miscarriage in patients with septate uterus.

A recent study found a significant correlation between endometriosis and non-obstructive forms of Müllerian anomalies. Other studies described an increased miscarriage rate in patients with endometriosis. This study assessed the effect of endometriosis on pregnancy outcome in a group of patients with endometriosis and septate uterus. Spontaneously achieved pregnancies were taken into consideration. The outcome of 179 infertile women who underwent surgery for septate uterus was analysed in a retrospective study. Stage I or II endometriosis was found by laparoscopy in 36 patients. The pregnancy outcomes, before and after metroplasty, of the group of 36 patients with septum and endometriosis were compared with the pregnancy outcomes of 143 patients with septate uterus with no endometriosis. Before metroplasty the incidence of pregnancy loss was 67% in patients without endometriosis and 75% in patients with endometriosis and the difference was not significant. After metroplasty, no significant differences have been found between the two groups, suggesting that endometriosis could be an occasional finding not influencing pregnancy outcome.

Current knowledge about the management of congenital cervical malformations: a literature review.

The prevalence of congenital cervical agenesis or dysgenesis ranges from 1/80,000 to 1/100,000, and in about 50% of these cases it coexists with congenital vaginal agenesis. This narrative review summarizes the contemporary knowledge in the field of conservative surgical restoration of the reproductive tract. The management of congenital cervical malformations aims to [1] provide relief from the obstructive symptoms, [2] establish normal sexual function, and [3] preserve the uterus for future fertility. In cases of cervical agenesis and vaginal aplasia, the surgical approach involves the creation of neovagina, the creation of neocervix, and then subsequent restoration of the continuity of the genital tract. In cases where vagina is not congenitally absent, the surgical approach involves either a direct uterovaginal anastomosis or initial creation of neocervix and then subsequent restoration of the continuity of the genital tract. The neocervix can be surgically created with small intestinal submucosa, split-thickness skin graft, full-thickness skin graft, peritoneal flap, or vaginal mucosa lined with a polytetrafluoroethylene graft. Most of the published cases report long-term menstruation and sporadic pregnancies. Conservative surgery of cervical congenital malformations could serve as a first-line treatment. Sexual function and menstruation are established in the majority of patients. Extirpatory surgery may be preserved for surgical failures after initial restoration of the continuity of uterus-cervix-vagina or in cases with more complex anatomy.