FIGO statement: Fertility preservation.

Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach.

Assessment of myocardial function in infants conceived by assisted reproductive technologies using deformation imaging over the first year of age: A cohort study.

BACKGROUND AND AIM: There is emerging evidence of cardiovascular remodeling and functional impairment in individuals conceived via Assisted Reproductive Technologies (ART). The aim of this study was to serially assess myocardial function and pulmonary hemodynamic measurements in infants conceived via ART over the first year of age and to compare them to a cohort of spontaneously conceived controls. METHODS: This was a prospective, observational study. Echocardiography was performed at Day 2, 6 months and 1 year of age. Biventricular function was assessed by deformation analysis. Pulmonary artery acceleration time (PAAT) and left ventricular (LV) eccentricity index (LVEI) provided surrogate measures of pulmonary vascular resistance (PVR). RESULTS: Fifty infants conceived via ART were compared to 50 spontaneously conceived controls. There were no differences in baseline infant demographics between the two groups. At 1 year of age right ventricular (RV) basal and RV mid cavity diameters were higher in the ART group. PAATi was lower and LVEI higher in the ART group at 6 months and 1 year. In the ART group, LV global longitudinal strain, LV systolic strain rate, LV early diastolic strain rate and RV free wall strain were lower on Day 2, 6 months, and 1 year of age in comparison to the control group (all p < .05). Within the ART group, on linear regression, maternal age, the type of ART treatment or egg characteristics did not influence PAAT or deformation measurements. CONCLUSION: Our findings suggest that greater cardiovascular surveillance of ART conceived infants may be warranted.

An analysis of the outcome of 11 712 men applying to be sperm donors in Denmark and the USA.

STUDY QUESTION: Is the outcome of donor recruitment influenced by the country in which recruitment took place or the initial identity (ID)-release choice of applicants? SUMMARY ANSWER: More applicants are accepted as donors in Denmark than in the USA and those who choose ID release are more frequently accepted than those who do not. WHAT IS KNOWN ALREADY: The successful recruitment of sperm donors is essential to provide a range of medically assisted reproduction (MAR) procedures, which rely upon donor sperm. However, while much has been written about the medical screening and assessment of sperm donors from a safety perspective, relatively little has been written about the process of recruiting donors and how it works in practice. There are differences in demographic characteristics between donors who choose to allow their identity to be released to their donor offspring (ID release) compared to those who do not (non-ID release). These characteristics may also influence the likelihood of them being recruited. STUDY DESIGN, SIZE, DURATION: A total of 11 712 men applied to be sperm donors at a sperm bank in Denmark and the USA during 2018 and 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Anonymized records of all donor applicants were examined to assess the number passing through (or lost) at each stage of the recruitment process. Statistical analysis was carried out to examine differences between location (Denmark or USA) and/or donor type (ID release versus non-ID release). MAIN RESULTS AND THE ROLE OF CHANCE: Few applicants (3.79%) were accepted as donors and had samples frozen and released for use; this was higher in Denmark (6.53%) than in the USA (1.03%) (χ2 = 243.2; 1 degree of freedom (df); z = 15.60; P < 0.0001) and was higher in donors who opted at the outset to be ID release (4.70%) compared to those who did not (3.15%) (χ2 = 18.51; 1 df; z = 4.303; P < 0.0001). Most candidate donors were lost during recruitment because they: withdrew, failed to respond, did not attend an appointment, or did not return a questionnaire (54.91%); reported a disqualifying health issue or failed a screening test (17.41%); did not meet the eligibility criteria at the outset (11.71%); or did not have >5 × 106 motile sperm/ml in their post-thaw samples (11.20%). At each stage, there were statistically significant differences between countries and the donor's initial ID choice. During recruitment, some donors decided to change ID type. There were no country differences in the frequency in which this occurred (χ2 = 0.2852; 1 df; z = 0.5340; P = 0.5933), but it was more common for donors to change from non-ID release to ID release (27.19%) than the other way around (11.45%) (χ2 = 17.75; 1 df; z = 4.213; P < 0.0001), although movements in both directions did occur in both countries. LIMITATIONS, REASONS FOR CAUTION: No information was available about the demographic characteristics of the applicants, which may also have influenced their chances of being accepted as a donor (e.g. ethnicity and age). Donor recruitment procedures may differ in other locations according to local laws or guidelines. WIDER IMPLICATIONS OF THE FINDINGS: A better understanding of when and why candidate donors are lost in the recruitment process may help develop leaner and more efficient pathways for interested donors and sperm banks. This could ultimately increase the number of donors recruited (through enhanced information, support, and reassurance during the recruitment process) or it may reduce the financial cost to the recipients of donor sperm, thus making it more affordable to those who are ineligible for state-funded treatment. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding from external sources. All authors are Cryos employees or members of the Cryos External Scientific Advisory Committee. TRIAL REGISTRATION NUMBER: N/A.

The challenges of obesity for fertility: A FIGO literature review.

Obesity has been linked to infertility through several mechanisms, including at a molecular level. Those living with obesity face additional barriers to accessing fertility treatments and achieving a successful pregnancy, which can contribute to their economic and psychosocial stressors. There is scope to further improve care for people living with obesity and infertility with empathy, via a multidisciplinary approach.

Investigating the relationship between body composition, lifestyle factors, and anti-Müllerian hormone serum levels in women undergoing infertility assessment.

BACKGROUND: The impact of lifestyle factors such as adiposity, smoking, stress, exercise, and nutrition on anti-Müllerian hormone (AMH) levels remains an unresolved question. AIMS: This study aims to examine the anthropometric and lifestyle characteristics of women undergoing infertility investigations and to examine the relationship between serum AMH levels and body fat percentage, body mass index (BMI), and lifestyle factors including smoking, alcohol intake, nutrition, exercise, and stress. METHODS: Only women undergoing infertility investigations were included in the study. Those with a diagnosis of polycystic ovary syndrome (PCOS) were excluded. Body fat percentage was measured using the Tanita Body Composition Monitor and BMI calculated. Lifestyle factors were evaluated using the Simple Lifestyle Indicator Questionnaire (SLIQ). RESULTS: Ninety-six women took part in the study. Of these, 35.4% (n = 34) were obese, and 28.1% (n = 27) were overweight according to their BMI. According to body fat percentage, 47.9% (n = 46) were classified as obese. An "unhealthy " SLIQ score was measured in 25% (n = 24) of participating women. There was no relationship between AMH and anthropometric or lifestyle factors, namely, body fat percentage (B = - 0.11, p = 0.76), BMI (B = - 0.14, p = 0.76), smoking [currents smokers (B = - 1.86, p = 0.56), ex-smoker (B = 3.07, p = 0.41)], SLIQ score (B = 0.1.96, p = 0.29), stress (B = 0.12, p = 0.96), exercise (B = - 0.94, p = 0.77), alcohol (B = - 0.94, p = 0.77), or nutrition (B = - 3.14, p = 2.44). CONCLUSIONS: Body fat percentage, BMI, lifestyle choices, and high stress levels do not correlate with AMH levels in women seeking infertility investigations. We identified a high incidence of obesity and low levels of healthy lifestyle scores in our study population. Our study highlights the urgent need for patient education and optimization of pre-pregnancy health.

SARS-CoV-2, fertility and assisted reproduction.

BACKGROUND: In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain. OBJECTIVE AND RATIONALE: This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals. SEARCH METHODS: PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible. OUTCOMES: From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients. WIDER IMPLICATIONS: This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil.

The FIGO ovulatory disorders classification system.

Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical, and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical, and procedural interventions. Collaborative research, effective education, and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to WHO, was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This manuscript describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians, and trainees using the "GAIN-FIT-PIE" mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care, and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.

The FIGO Ovulatory Disorders Classification System†.

Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding and infertility and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical and procedural interventions. Collaborative research, effective education and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to the World Health Organization (WHO), was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This article describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians and trainees using the 'GAIN-FIT-PIE' mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.

Outcomes of SARS-CoV-2 infected pregancies after medically assisted reproduction.

STUDY QUESTION: What is the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the outcome of a pregnancy after medically assisted reproduction (MAR)? SUMMARY ANSWER: Our results suggest that MAR pregnancies are not differentially affected by SARS-CoV-2 infection compared to spontaneous pregnancies. WHAT IS KNOWN ALREADY: Information on the effects of coronavirus disease 2019 (COVID-19) on pregnancy after MAR is scarce when women get infected during MAR or early pregnancy, even though such information is vital for informing women seeking pregnancy. STUDY DESIGN, SIZE, DURATION: Data from SARS-CoV-2 affected MAR pregnancies were collected between May 2020 and June 2021 through a voluntary data collection, organised by the European Society of Human Reproduction and Embryology (ESHRE). PARTICIPANTS/MATERIALS, SETTING, METHODS: All ESHRE members were invited to participate to an online data collection for SARS-CoV-2-infected MAR pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: The dataset includes 80 cases from 32 countries, including 67 live births, 10 miscarriages, 2 stillbirths and 1 maternal death. An additional 25pregnancies were ongoing at the time of writing. LIMITATIONS, REASONS FOR CAUTION: An international data registry based on voluntary contribution can be subject to selective reporting with possible risks of over- or under-estimation. WIDER IMPLICATIONS OF THE FINDINGS: The current data can be used to guide clinical decisions in the care of women pregnant after MAR, in the context of the COVID-19 pandemic. STUDY FUNDING/COMPETING INTEREST(S): The authors acknowledge the support of ESHRE for the data registry and meetings. J.S.T. reports grants or contracts from Sigrid Juselius Foundation, EU and Helsinki University Hospital Funds, outside the scope of the current work. The other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Attitudes of sperm donors towards offspring, identity release and extended genetic screening.

RESEARCH QUESTION: What is sperm donors' attitude towards offspring, anonymity and extended genetic screening? DESIGN: An online questionnaire for sperm donors was administered at Cryos International in the USA and Denmark between 9 and 30 September 2020. A total of 233 donors (37 in the USA and 196 in Denmark) completed the questionnaire. This study is unique because it was performed in a setting that allows donors to choose to be either ID-release or non-ID-release donors. RESULTS: Most donors had two motives to donate: helping childless people and/or financial compensation. ID-release donors differed significantly from non-ID-release donors in numerous aspects of the donation, including relationships with the offspring, information sharing with others and wanting information about offspring. In general, donors had a very positive attitude towards genetic testing and extended genetic screening. CONCLUSIONS: Offering the possibility for donors to be either ID-release or non-ID-release allows more donors to be recruited than if only one option were available. The multiple differences between the two donor types suggests that these are groups with profoundly different attitudes towards donation. The general attitude of donors towards genetic testing and expanded genetic screening is very positive but further studies on the attitude of candidate donors are needed.

ESHRE guideline: medically assisted reproduction in patients with a viral infection/disease.

STUDY QUESTION: What is the recommended management for medically assisted reproduction (MAR) in patients with a viral infection or disease, based on the best available evidence in the literature? SUMMARY ANSWER: The ESHRE guideline on MAR in patients with a viral infection/disease makes 78 recommendations on prevention of horizontal and vertical transmission before, during and after MAR, and the impact on its outcomes, and these also include recommendations regarding laboratory safety on the processing and storage of gametes and embryos testing positive for viral infections. WHAT IS KNOWN ALREADY: The development of new and improved anti-viral medications has resulted in improved life expectancy and quality of life for patients with viral infections/diseases. Patients of reproductive age are increasingly exploring their options for family creation. STUDY DESIGN SIZE DURATION: The guideline was developed according to the structured methodology for the development of ESHRE guidelines. After the formulation of nine key questions for six viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papilloma virus, human T-lymphotropic virus I/II and Zika virus) by a group of experts, literature searches and assessments were performed. Papers published up to 2 November 2020 and written in English were included in the review. Evidence was analyzed by female, male or couple testing positive for the virus. PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. There were 61 key questions to be answered by the guideline development group (GDG), of which 12 were answered as narrative questions and 49 as PICO (Patient, Intervention, Comparison, Outcome) questions. A stakeholder review was organized after the finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: This guideline aims to help providers meet a growing demand for guidance on the management of patients with a viral infection/disease presenting in the fertility clinic.The guideline makes 78 recommendations on prevention of viral transmission before and during MAR, and interventions to reduce/avoid vertical transmission to the newborn. Preferred MAR treatments and interventions are described together with the effect of viral infections on outcomes. The GDG formulated 44 evidence-based recommendations-of which 37 were formulated as strong recommendations and 7 as weak-33 good practice points (GPP) and one research only recommendation. Of the evidence-based recommendations, none were supported by high-quality evidence, two by moderate-quality evidence, 15 by low-quality evidence and 27 by very low-quality evidence. To support future research in the field of MAR in patients with a viral infection/disease, a list of research recommendations is provided. LIMITATIONS REASONS FOR CAUTION: Most interventions included are not well-studied in patients with a viral infection/disease. For a large proportion of interventions, evidence was very limited and of very low quality. More evidence is required for these interventions, especially in the field of human papilloma virus (HPV). Such future studies may require the current recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in MAR for patients with a viral infection/disease, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive any financial incentives, all work was provided voluntarily. A.D. reports research fees from Ferring and Merck, consulting fees from Ferring, outside the submitted work. C.P. reports speakers fees from Merck and MSD outside the submitted work. K.T. reports speakers fees from Cooper Surgical and Ferring and consultancy fees as member of the advisory board BioTeam of Ferring, outside the submitted work. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at  www.eshre.eu/guidelines.).

The calm after the storm: re-starting ART treatments safely in the wake of the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic created a significant impact on medically assisted reproduction (MAR) services. ESHRE decided to mobilize resources in order to collect, analyse, monitor, prepare and disseminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) knowledge specifically related to ART and early pregnancy. This article presents the impact of the SARS-CoV-2 pandemic focusing on reproductive healthcare. It details the rationale behind the guidance prepared to support MAR services in organizing and managing the re-start of treatments or in case of any future wave of COVID-19 disease. The guidance includes information on patient selection and informed consent, staff and patient triage and testing, adaptation of ART services, treatment planning and code of conduct. The initiatives detailed in this article are not necessarily COVID-specific and such action plans could be applied effectively to manage similar emergency situations in different areas of medicine, in the future.

Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners.

With the increase in obesity prevalence among women of reproductive age globally, the risks of type 2 diabetes, gestational diabetes, pre-eclampsia, and other conditions are rising, with detrimental effects on maternal and newborn health. The period before pregnancy is increasingly recognized as crucial for addressing weight management and reducing malnutrition (both under- and overnutrition) in both parents to reduce the risk of noncommunicable diseases (NCDs) in the mother as well as the passage of risk to her offspring. Healthcare practitioners, including obstetricians, gynecologists, midwives, and general practitioners, have an important role to play in supporting women in planning a pregnancy and achieving healthy nutrition and weight before pregnancy. In this position paper, the FIGO Pregnancy Obesity and Nutrition Initiative provides an overview of the evidence for preconception clinical guidelines to reduce the risk of NCDs in mothers and their offspring. It encourages healthcare practitioners to initiate a dialogue on women's health, nutrition, and weight management before conception. While acknowledging the fundamental importance of the wider social and environmental determinants of health, this paper focuses on a simple set of recommendations for clinical practice that can be used even in short consultations. The recommendations can be contextualized based on local cultural and dietary practices as part of a system-wide public health approach to influence the wider determinants as well as individual factors influencing preconception health.

A picture of medically assisted reproduction activities during the COVID-19 pandemic in Europe.

STUDY QUESTION: How did coronavirus disease 2019 (COVID-19) impact on medically assisted reproduction (MAR) services in Europe during the COVID-19 pandemic (March to May 2020)? SUMMARY ANSWER: MAR services, and hence treatments for infertile couples, were stopped in most European countries for a mean of 7 weeks. WHAT IS KNOWN ALREADY: With the outbreak of COVID-19 in Europe, non-urgent medical care was reduced by local authorities to preserve health resources and maintain social distancing. Furthermore, ESHRE and other societies recommended to postpone ART pregnancies as of 14 March 2020. STUDY DESIGN SIZE DURATION: A structured questionnaire was distributed in April among the ESHRE Committee of National Representatives, followed by further information collection through email. PARTICIPANTS/MATERIALS SETTING METHODS: The information was collected through the questionnaire and afterwards summarised and aligned with data from the European Centre for Disease Control on the number of COVID-19 cases per country. MAIN RESULTS AND THE ROLE OF CHANCE: By aligning the data for each country with respective epidemiological data, we show a large variation in the time and the phase in the epidemic in the curve when MAR/ART treatments were suspended and restarted. Similarly, the duration of interruption varied. Fertility preservation treatments and patient supportive care for patients remained available during the pandemic. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Data collection was prone to misinterpretation of the questions and replies, and required further follow-up to check the accuracy. Some representatives reported that they, themselves, were not always aware of the situation throughout the country or reported difficulties with providing single generalised replies, for instance when there were regional differences within their country. WIDER IMPLICATIONS OF THE FINDINGS: The current article provides a basis for further research of the different strategies developed in response to the COVID-19 crisis. Such conclusions will be invaluable for health authorities and healthcare professionals with respect to future similar situations. STUDY FUNDING/COMPETING INTERESTS: There was no funding for the study, apart from technical support from ESHRE. The authors had no COI to disclose.

A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or obese. First line medical ovulation induction therapy to improve fertility outcomes is letrozole, whilst other less efficacious ovulation induction agents, such as clomiphene citrate, metformin, and metformin combined with clomiphene citrate, may also be considered. Metformin combined with clomiphene citrate is more effective than clomiphene citrate alone. In obese women with PCOS, clomiphene citrate could be used in preference to metformin alone whilst clomiphene citrate could be added to metformin alone in order to improve reproductive outcome in all women with PCOS. Gonadotrophins, which are more effective than clomiphene citrate in therapy naïve women with PCOS, can be considered a first line therapy in the presence of ultrasound monitoring, following counselling on the cost and the potential risk of multiple pregnancy.

A brief update on the evidence supporting the treatment of infertility in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. AIMS: This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018. MATERIALS AND METHODS: International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages. RESULTS: Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed. CONCLUSION: This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

A Review of Second- and Third-line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome.

In clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, either metformin combined with clomiphene citrate or gonadotrophins could be used as a second-line pharmacological therapy, although gonadotrophins are more effective. Gonadotrophins could also be used as a second-line pharmacological therapy in anovulatory women with PCOS and clomiphene-citrate-failure. Laparoscopic ovarian surgery can also be used as a second-line therapy for ovulation induction in anovulatory women with clomiphene-citrate-resistant PCOS and no other infertility factors. The usefulness of letrozole as a second-line pharmacological treatment for ovulation induction in clomiphene-citrate-resistant women with PCOS requires further research. In terms of improving fertility, both pharmacological anti-obesity agents and bariatric surgery should be considered an experimental therapy in anovulatory women with PCOS and no other infertility factors. Where first- or second-line ovulation induction therapies have failed, in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) could be offered as a third-line therapy in women with PCOS in the absence of an absolute indication for IVF/ICSI. For women with PCOS undergoing IVF/ICSI treatment, the gonadotropin-releasing hormone (GnRH) antagonist protocol is preferred and an elective frozen embryo transfer strategy could be considered. In assisted conception units with sufficient expertise, in-vitro maturation (IVM) of oocytes could be offered to women with PCOS.

Adjuncts in the IVF laboratory: where is the evidence for 'add-on' interventions?

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add-on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high-quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further pediatric and long-term follow-up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories, including embryo glue and adherence compounds, sperm DNA fragmentation, time-lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching. We examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients.

Patients with cancer at the margins of reproductive age had reduced levels of anti-Müllerian hormone compared with patients experiencing infertility.

OBJECTIVE: To compare the ovarian reserves between female patients with cancer and patients experiencing infertility. METHODS: A retrospective age-matched observational study was performed at Rotunda Hospital, Dublin. The study group included data from all female oncology patients attending for oocyte or embryo cryopreservation between January 1, 2009 and December 31, 2013. Anti-Müllerian hormone (AMH) levels were recorded at patients' initial visits before beginning chemotherapy or radiotherapy. The control group included patients without cancer who had their AMH levels recorded to investigate fertility or as a baseline level prior to beginning assisted reproductive treatment. RESULTS: The records of 118 oncology and 5231 control patients from the study period were identified. There was no difference in AMH levels between patients in the oncology and control groups aged 30-38years; however, significantly lower AMH levels were observed in patients in the oncology group aged 29years and younger (17.89pmol/L vs 23.35pmol/L; P=0.015), or at least 39years (2.65pmol/L vs 5.87pmol/L; P=0.028). CONCLUSION: Before commencing chemotherapy or radiotherapy, patients in the oncology group at the margins of reproductive age had a diminished ovarian reserve compared with the control group. This should be considered when planning optimal doses of follicular stimulating hormone as part of controlled ovarian-stimulation regimes performed for embryo or oocyte cryopreservation prior to chemotherapy or radiotherapy.

Serum estradiol:oocyte ratio as a predictor of reproductive outcome: an analysis of data from >9000 IVF cycles in the Republic of Ireland.

PURPOSE: The purpose of this study was to evaluate the serum estradiol (E2) per oocyte ratio (EOR) as a function of selected embryology events and reproductive outcomes with IVF. METHODS: This retrospective analysis included all IVF cycles where oocyte collection and fresh transfer occurred between January 2001 and November 2012 at a single institution. Patients were divided by three age groups (<35, 35-39, and ≥40 years) and further stratified into nine groups based on EOR (measured in pmol/L/oocyte). Terminal serum E2 (pmol/mL) was recorded on day of hCG trigger administration, and fertilization rate, cleavage rate, number of good quality embryos, and reproductive outcomes were recorded for each IVF cycle. RESULTS: During the study interval, 9109 oocyte retrievals were performed for 5499 IVF patients (mean = 1.7 cycles/patient). A total of 63.4 % of transfers were performed on day 3 (n = 4926), while 36.6 % were carried out on day 5 (n = 2843). Clinical pregnancy rates were highest in patients with EOR of 250-750 and declined as this ratio increased, independent of patient age. While the odds ratio (OR) for clinical pregnancy where EOR = 250-750 vs. EOR > 1500 was 3.4 (p < 0.001; 95 % CI 2.67-4.34), no statistically significant correlation was seen in fertilization, cleavage rates or number of good quality embryos as a function of EOR. CONCLUSIONS: Predicting reproductive outcomes with IVF has great utility both for patients and providers. The former have the opportunity to build realistic expectations, and the latter are better able to counsel according to measured clinical parameters. A better understanding of follicular dynamics and ovarian response to gonadotropin stimulation could optimize IVF treatments going forward.