Survey on ART and IUI: legislation, regulation, funding, and registries in European countries-an update.

Study Question: How are ART and IUI regulated, funded, and registered in European countries, and how has the situation changed since 2018?

Summary Answer: Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding varies across and sometimes within countries (and is lacking or minimal in four countries), and national registries are in place in 33 countries; only a small number of changes were identified, most of them in the direction of improving accessibility, through increased public financial support and/or opening access to additional subgroups.

What Is Known Already: The annual reports of the European IVF-Monitoring Consortium (EIM) clearly show the existence of different approaches across Europe regarding accessibility to and efficacy of ART and IUI treatments. In a previous survey, some coherent information was gathered about how those techniques were regulated, funded, and registered in European countries, showing that diversity is the paradigm in this medical field.

A blended preconception lifestyle programme for couples undergoing IVF: lessons learned from a multicentre randomized controlled trial.

Study Question: What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition?

Summary Answer: This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid-19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes.

What Is Known Already: Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF.

Sperm DNA Fragmentation after Cryopreservation and Sperm Selection Has No Implications for Clinical Pregnancies and Live Births after Intrauterine Insemination with Donor Sperm.

Intrauterine insemination with donor sperm (IUI-D) requires multiple in vitro manipulations such as sperm selection and cryopreservation during which spermatozoa may be exposed to oxidative stress (OS) and other insults that may produce potential damage including sperm DNA fragmentation (SDF). High levels of SDF, referring to damage or breaks in the genetic material of sperm cells, are linked to an increased risk of reproductive failure. This retrospective, observational study set out to evaluate whether SDF assessment could predict clinical outcome in an IUI-D program, where sperm donors are selected on strict conventional semen parameters.

Antioxidants in Male Infertility-If We Want to Get This Right We Need to Take the Bull by the Horns: A Pilot Study.

Antioxidant therapy should be reserved for infertile patients who actually exhibit signs of oxidative stress (OS). Nevertheless, there is no consensus regarding the measure of the primary endpoint and the assay that should be used. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an early marker of sperm DNA oxidation (SDO), was analyzed using flow cytometry, in men at a University hospital setup for infertility treatment.

ART in Europe, 2019: results generated from European registries by ESHRE†.

Study Question: What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2019 as compared to previous years?

Summary Answer: The 23rd ESHRE report highlights the rising ART treatment cycles and children born, alongside a decline in twin deliveries owing to decreasing multiple embryo transfers; fresh IVF or ICSI cycles exhibited higher delivery rates, whereas frozen embryo transfers (FET) showed higher pregnancy rates (PRs), and reported IUI cycles decreased while maintaining stable outcomes.

What Is Known Already: ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF-Monitoring (EIM) Consortium since 1997 and reported in a total of 22 manuscripts published in Human Reproduction and Human Reproduction Open.

Study Design, Size, Duration: Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year.

Semen Thresholds of Normality Established by the WHO Do Not Reveal Genome Instability-A Potential Occult Male Factor.

Semen parameters are unable to inform on the function or fertilizing capacity of the male gamete. Standardized methods are provided by the WHO but, the lower reference limits have reduced sensitivity to predict chances of conception. Subfertile men may be falsely classified as "normal" and a male factor contributing to genome instability may be overlooked.

Is There a Relationship between Sperm DNA Fragmentation and Intra-Uterine Insemination Outcome in Couples with Unexplained or Mild Male Infertility? Results from the ID-Trial.

Background: Sperm DNA fragmentation has been proposed as a candidate test for the assessment of sperm function on the premise that damage to the sperm chromatin is associated with a detrimental reproductive outcome. The objective of our study was to investigate whether sperm DNA fragmentation testing has a prognostic value, and thus can play a pivotal role in selecting future patients for intra-uterine insemination (IUI) therapy.

Methods: This was a prospective cohort study conducted in a University Hospital setting.

Multicentre study on rates and reasons for treatment discontinuation in patients with remaining cryopreserved embryos.

Research Question: What is the discontinuation rate among patients with remaining cryopreserved embryos in Belgium and what are the reasons for discontinuation?

Design: Multicentre, cross-sectional study across 11 Belgian fertility clinics. Patients were eligible (n = 1917) if they had previously undergone an unsuccessful fresh embryo transfer (fresh group) or frozen embryo transfer (FET) (in-between group) and did not start a subsequent FET cycle within 1 year despite having remaining cryopreserved embryos. The denominator was all patients with embryos cryopreserved during the same period (2012-2017) (n = 21,329).

Variability in Sperm DNA Fragmentation in Men with Mild/Unexplained Subfertility in a Prospective Longitudinal Intrauterine Insemination Trial.

The biological variability of semen and sperm DNA fragmentation (SDF) parameters in a longitudinal intrauterine insemination (IUI) trial over multiple IUI cycles was investigated. A TUNEL assay was used for SDF testing, both before and after density gradient centrifugation. A significant age effect was observed: while semen parameters deteriorated with advancing age, on average, higher SDF values were observed for older males.

Obese outbred mice only partially benefit from diet normalization or calorie restriction as preconception care interventions to improve metabolic health and oocyte quality.

Study Question: Can diet normalization or a calorie-restricted diet for 2 or 4 weeks be used as a preconception care intervention (PCCI) in Western-type diet-induced obese Swiss mice to restore metabolic health and oocyte quality?

Summary Answer: Metabolic health and oocyte developmental competence was already significantly improved in the calorie-restricted group after 2 weeks, while obese mice that underwent diet normalization showed improved metabolic health after 2 weeks and improved oocyte quality after 4 weeks.

What Is Known Already: Maternal obesity is linked with reduced metabolic health and oocyte quality; therefore, infertile obese women are advised to lose weight before conception to increase pregnancy chances. However, as there are no univocal guidelines and the specific impact on oocyte quality is not known, strategically designed studies are needed to provide fundamental insights in the importance of the type and duration of the dietary weight loss strategy for preconception metabolic health and oocyte quality.

The LH endocrine profile in gonadotropin-releasing hormone analogue cycles.

What does the evolution of serum luteinizing hormone (LH) levels look like throughout the follicular phase of cycles in which gonadotrophins and gonadotropin-releasing hormone (GnRH) analogues in the context of ovarian stimulation for assisted reproduction technologies (ART) were used? This was a retrospective, observational cohort study in a tertiary infertility clinic. 1303 patients aged between 18 and 43 years of age were included with a total of 2200 cycles for ART, using GnRH-analogues for pituitary down-regulation stimulated with human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rec-FSH). Follicular evolution of LH during ovarian stimulation in different treatment protocols was modeled as repeated measures.

Sperm as a Carrier of Genome Instability in Relation to Paternal Lifestyle and Nutritional Conditions.

Endogenous and exogenous factors can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. The extent to which men with and without subfertility are exposed to several adverse lifestyle factors and the impact on sperm DNA fragmentation (SDF), sperm chromatin maturity (condensation and decondensation), stability (hypo- and hypercondensation) and sperm aneuploidy are assessed in this study. Standardized assays employing flow cytometry were used to detect genome instability in 556 samples.

Single-embryo transfer implies quality of care in reproductive medicine.

This review appraises evidence on the difference between single- and double-embryo transfer (SET, DET) in assisted reproductive technology (ART) regarding the four healthcare quality dimensions most important to fertility patients and doctors. Regarding safety, not only does DET create the uncontested perinatal risks of twin pregnancies, but compelling evidence has added that singleton pregnancies after a vanishing twin also have poorer perinatal outcomes. SET is as effective as DET, as shown by meta-analyses of randomized controlled trials, comparing two cycles of SET versus DET and shown by cumulative live birth rates of entire ART trajectories of up to six cycles.

Live birth after additional tubal flushing with oil-based contrast versus no additional flushing: a randomised, multicentre, parallel-group pragmatic trial in infertile women with at least one patent tube at hysterosalpingo-foam sonography (HYFOIL study).

Introduction: Tubal patency testing is an essential part in the fertility workup of many subfertile women. Hysterosalpingography (HSG) has long been the test of choice in many clinics. There is evidence from a large randomised multicentre trial and from a recent meta-analysis that women who had HSG using oil soluble contrast medium (OSCM) had higher rates of ongoing pregnancy compared with women who underwent this procedure using water contrast.

Diet normalization or caloric restriction as a preconception care strategy to improve metabolic health and oocyte quality in obese outbred mice.

Background: Maternal metabolic disorders are linked to reduced metabolic health and oocyte quality. Obese women are advised to lose weight before conception to increase pregnancy chances. However, as human studies show no univocal guidelines, more research is necessary to provide fundamental insights in the consequences of dietary weight loss on oocyte quality.

Peak retrograde flow a potential objective management tool to identify young adults with varicocele 'at risk' for a high sperm DNA fragmentation.

Introduction: Determining which patients are negatively affected by varicocele would enable clinicians to better select those men who would benefit most from surgery. Since conventional semen parameters, have been limited in their ability to evaluate the negative effects of varicocele on fertility, specialized laboratory tests have emerged.

Objective: To identify clinical and ultrasound parameters (including PRF) which would negatively influence standard and functional semen variables in young adults with a varicocele.

Systematic development of a mobile preconception lifestyle programme for couples undergoing IVF: the PreLiFe-programme.

Study Question: Can we develop a preconception lifestyle programme for couples undergoing IVF that is in line with their needs.

Summary Answer: A mobile preconception lifestyle programme was systematically developed based on expert opinion, literature and needs of IVF-patients.

What Is Known Already: A healthy lifestyle prior to conception is not only beneficial for the general health of couples, but evidence on its importance for their reproductive health and the health of their children is also emerging.

Evolution of cumulative live birth and dropout rates over six complete IVF/ICSI cycles: a large prospective cohort study.

Research Question: How do cumulative live birth rates (CLBR), cumulative multiple live birth rates (CMLBR) and dropout rates over six IVF and intracytoplasmic sperm injection (ICSI) cycles change over time?

Design: Prospective longitudinal cohort (n = 16,073 patients; 48,946 cycles) starting a first fresh assisted reproductive technology cycle between 1 January 2014 and 31 December 2016, with follow-up until 31 December 2017. Outcomes between the periods 2014-2017 and 2009-2012 were compared.

Results: Conservative estimates of CLBR after six complete cycles were significantly higher in women younger than 35 years after every cycle: one to three, adjusted P-value [p adj] < 0.

Time intervals between semen production, initiation of analysis, and IUI significantly influence clinical pregnancies and live births.

Purpose: Does IDEF mapping help monitor the technical process of IUI and explore the potential improvements which might contribute to increased pregnancy and live birth rates?

Method: Retrospective analysis of 1729 homologous IUI cycles of couples attending a fertility clinic in a university hospital setting. Standardized conventional semen parameters were analyzed and the semen samples prepared via discontinuous density gradient centrifugation.

Results: There was no significant association between sperm concentration, motility and morphology (analysis phase), and pregnancy outcome.

Is there a temporal trend in semen quality in Belgian candidate sperm donors and in sperm donors' fertility potential from 1995 onwards?

Background: A recent meta-regression analysis reported a temporal trend in sperm count showing a significant decline in sperm count between 1973 and 2011. This decline is thought to affect fecundity. Moreover, semen quality is considered of key interest to public health given its association with all-cause male morbidity/mortality.

Sperm nuclear maturity and chromatin stability in subfertile patients: Density gradient centrifugation is fair but non-discriminative in selecting the right population.

Multiple technologies exploring chromatin structure anomalies have been applied during the last decade to evaluate fertility disorders and to increase the predictive value of sperm analysis for procreation in vivo and in vitro. Our aim was to implement sperm nuclear maturity and nuclear chromatin stability as a functional test for male infertility diagnosis and to compare it with a fertile group. As semen processing is an integral part of assisted reproductive technologies the impact of density gradient centrifugation in selecting sperm based on nuclear maturity and stability was also analyzed.

The role of sperm DNA fragmentation testing in predicting intra-uterine insemination outcome: A systematic review and meta-analysis.

There is a growing body of literature that recognizes the importance of sperm DNA fragmentation as a candidate test for the assessment of sperm function and thus male reproductive potential. Research on the subject has mostly been focused on couples undergoing IVF/ICSI treatment whilst much uncertainty still exists about the relationship between sperm DNA fragmentation and IUI. This study systematically reviews the literature, aiming to define the value of sperm DNA fragmentation measurement in predicting clinical pregnancy outcome in couples undergoing intra-uterine insemination From inception until March 2018, the relevant databases were searched for studies investigating the relationship between sperm DNA fragmentation as measured by SCSA, TUNEL, SCD or Comet assay and pregnancy outcome after IUI.

Effectiveness of a mobile preconception lifestyle programme in couples undergoing in vitro fertilisation (IVF): the protocol for the PreLiFe randomised controlled trial (PreLiFe-RCT).

Introduction: Infertility and in vitro fertilisation (IVF; with or without intracytoplasmic sperm injection) result in considerable emotional and financial burden. Increasing evidence suggests that lifestyle factors, including diet, physical activity and personal well-being, are associated with IVF-success rates. Currently, IVF is not routinely combined with a lifestyle programme.

DNA fragmentation in concert with the simultaneous assessment of cell viability in a subfertile population: establishing thresholds of normality both before and after density gradient centrifugation.

Purpose: TUNEL assay is the most common, direct test for sperm chromatin integrity assessment. But, lack of standardized protocols makes interlaboratory comparisons impossible. Consequently, clinical thresholds to predict the chance of a clinical pregnancy also vary with the technique adopted.

Free Testosterone Reflects Metabolic as well as Ovarian Disturbances in Subfertile Oligomenorrheic Women.

Background: Diagnosing polycystic ovary syndrome (PCOS) is based on ovulatory dysfunction, ovarian ultrasound data, and androgen excess. Total testosterone is frequently used to identify androgen excess, but testosterone is mainly bound to sex hormone-binding globulin (SHBG) and albumin. Only 1-2% of nonprotein-bound testosterone (so-called free testosterone) is biologically active and responsible for androgen action.