Perinatal Outcome of Singletons Born after Using a Simplified Low-Cost IVF Culture System and All Singletons Born in Flanders (Belgium) between 2012 and 2020.

BACKGROUND: We developed a simplified IVF culture system (SCS) which has proven to be effective and safe in a selected IVF cohort. METHODS: Preterm birth (PTB) and low birth weight (LBW) of 175 singletons born after using the SCS, 104 after fresh embryo transfer (ET), and 71 after frozen embryo transfer, were compared with all singletons born in Flanders between 2012 and 2020 conceived after natural conception, ovarian stimulation (OS), and assisted reproduction (IVF/ICSI). FINDINGS: The proportion of preterm (<37 weeks) births was significantly higher in the case of IVF or ICSI, followed by hormonal treatment, compared to spontaneous pregnancies. There was no significant difference in PTB between SCS and any of the other groups. Concerning the average birth weight we found no significant difference between singletons born after natural conception and SCS. However, a significant difference in average birth weight was found between SCS singletons and singletons born after IVF, ICSI and hormonal treatment, with a significantly higher birth weight in the SCS group. This difference was also observed in the proportion of babies weighing less than 2500 g, with significantly more LBW babies in the IVF and ICSI group compared to the SCS newborns. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons were found to be comparable with singletons born after natural conception. Compared to babies born after ovarian stimulation and IVF/ICSI, SCS singletons had a lower PTB and LBW rates, although the differences were not significant for PTB. Our results confirm previous reports on reassuring perinatal outcomes after using the SCS technology.

SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients.

BACKGROUND: Short- and long-term implications of SARS-CoV-2 on the quality of the sperm and the results of this on fertility remain largely unknown due to lack of longitudinal studies. In this longitudinal observational cohort study, we aimed to analyse the differential effect and the impact of SARS-CoV-2 infection on different semen quality parameters. METHODS: Sperm quality was assessed using the World Health Organization criteria, DNA damage to sperm cells by quantifying the DNA fragmentation index (DFI) and the high-density stainability (HDS), IgA- and IgG-anti-sperm antibodies (ASA) were assessed with light microscopy. FINDINGS: SARS-CoV-2 infection was associated with sperm parameters that were independent of spermatogenic cycle like progressive motility, morphology, DFI and HDS, as well as spermatogenic cycle dependent parameters such as sperm concentration. Detection of IgA- and IgG-ASA allowed classification of patients in three different groups according to its sequence of appearance in sperm during post-COVID-19 follow-up. The maximum progressive motility was lowest during follow-up in patients without ASA (41.9%), intermediate in patients with only IgA-ASA (46.2%) and highest inpatients who had both IgA- and IgG-ASA (54.9%). INTERPRETATION: SARS-CoV-2 infection was associated with changes of all analysed sperm parameters to a different degree which is also observed in their return to normality and is suggestive of individual variations in the patient's immune system performance. Firstly, sperm production is decreased through temporal immune mediated arrest of active meiosis, and secondly immune induced sperm DNA damage prevents fertilization if transferred to the oocyte. Both mechanisms are temporal, and most sperm parameters return to baseline after infection. FUNDING: AML (R20-014), Femicare.

Promising Perinatal Outcome after Using a Simplified Low-Cost IVF Culture System Specifically Designed for Resource-Poor Countries.

BACKGROUND: Assisted reproductive techniques services are often not accessible to the majority of infertile couples in Low and Middle Income Countries (LMIC) due to high costs. Lowering IVF laboratory costs is a crucial step to make IVF affordable for a larger part of the world population. We developed a simplified culture system (SCS) which has proven to be effective, and the next step is to prove its safety. METHODS: Preterm birth (PTB) and low birthweight (LBW) of 176 singletons born after using the SCS, 105 after fresh embryo transfer (fresh ET), and 71 after frozen embryo transfer (frozen ET) were compared with all IVF/ICSI singletons born in Belgium between 2013 and 2018. When comparing our 105 SCS babies born after fresh ET with all Belgian babies born after conventional IVF only, we also adjusted for 7 risk factors known to influence perinatal outcome, namelythe mother's age, day of transfer, pituitary inhibition protocol, rank of cycles, number of oocytes retrieved, number of embryos transferred, and gender of the baby. FINDINGS: Before adjustment, we found a significantly higher PTB (10.2% vs. 3.8%, OR 2.852, 95% CI [1.042-7.803], p-value 0.0413) and LBW (9.8% vs. 2.9%, OR 3.692, 95% CI [1.163-11.721], p-value 0.0267) in the conventional IVF group versus SCS after fresh ET. After adjusting for seven risk parameters, these differences remained significant (PTB: OR 2.627, 95% CI [1.013-6.816], p-value 0.0471) and LBW: OR 3.267, 95% CI [1.118-9.549], p-value 0.0305). PTB and LBW between both groups was not significantly different for singletons born after frozen ET. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons in FRET cycles are very reassuring and significantly lower compared to babies born after conventional IVF in Belgium. Being aware of its effectiveness, our results offer a good perspective for SCS to become an important tool to implement low-cost IVF in LMIC.

The case for mild stimulation for IVF: recommendations from The International Society for Mild Approaches in Assisted Reproduction.

The practice of ovarian stimulation for IVF is undergoing a fundamental re-evaluation as recent data begin to successfully challenge the traditional paradigm that ovarian stimulation should be aimed at the retrieval of as many oocytes as possible, in the belief that this will increase pregnancy rates. An opposing view is that live birth rate should not be the only end-point in evaluating the success of IVF treatment and that equal emphasis should be placed on safety and affordability. The International Society for Mild Approaches in Assisted Reproduction (ISMAAR) committee has carried out an up-to-date literature search, with the evidence being graded according to the University of Oxford's Centre for Evidence-Based Medicine. The recommendations were formulated taking into account the quality of evidence on the efficacy, risk and cost of each intervention. ISMAAR recommends adopting a mild approach to ovarian stimulation in all clinical settings as an increasing body of evidence suggests that mild stimulation is as effective as conventional stimulation, while being safer and less expensive. Mild ovarian stimulation could replace conventional stimulation, thus making IVF safer and more accessible worldwide.

Multiyear outcomes using sibling oocytes demonstrates safety and efficacy of a simplified culture system consistent with use in a low-cost IVF setting.

RESEARCH QUESTION: Can a novel closed simplified IVF culture system be used to achieve outcomes comparable to those obtained with intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: This analysis is part of a non-inferiority prospective study comparing ICSI and a simplified culture system (SCS) for gamete fertilization in a selected group of patients. According to protocol, sibling oocytes in intact cumulus-oocyte complexes were randomly distributed between ICSI and conventional insemination in the SCS. For women, selection criteria included being under 43 years of age and at least six eggs at retrieval. An inseminating motile sperm count ≥1 million was required. The primary outcome measure was ongoing pregnancy rate (>12 weeks) per cycle; secondary outcome measures included fertilization rate, miscarriage rate and implantation rate (ongoing pregnancy rate per embryo). RESULTS: From January 2016 until December 2019, 653 SCS/ICSI cycles were performed yielding a total of 7915 oocytes. The fertilization rate was 61.1% and 50.4% for SCS and ICSI (P < 0.0001), respectively. The ongoing pregnancy rate was 32.0% for SCS and 36.7% for ICSI (P = 0.27). Implantation rate was 30.6% for SCS and 34.4% for ICSI (P = 0.35). The miscarriage rate was 7.5% and 6.5% for SCS and ICSI, respectively (P = 0.75). CONCLUSION: No difference was found in ongoing pregnancy rate, implantation rate and the miscarriage rate between SCS and ICSI in this selected patient cohort.

Perinatal outcome of babies born after using a simplified IVF culture system versus ICSI with sibling oocytes: a prospective cohort study.

RESEARCH QUESTION: Is there a difference in perinatal outcome in the same patient cohort for babies conceived following randomization of sibling oocytes allocated to a simplified IVF culture system (SCS) or intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: The study compared the perinatal outcomes of 367 babies born from 1 January 2013 until 31 December 2020 after using split SCS and ICSI insemination of sibling oocytes in a selected group of normo-responsive women, excluding cases of severe male infertility. Primary outcome measures were preterm birth (PTB; <37 weeks' gestation), low birthweight (LBW; <2.5 kg) and small for gestational age (SGA) as a primary outcome parameter while secondary outcome measures included mean birthweight, mean gestational age, extreme prematurity (<32 weeks), very low birthweight (<1.5 kg), perinatal mortality, multiple pregnancy and Caesarean section rate. RESULTS: A total of 105 and 103 singleton babies were born after fresh embryo transfer (FRET) and 71 and 50 singletons after frozen embryo transfer (FET) in the SCS and ICSI groups, respectively. For babies born after FRET, the LBW rate was 2.9% (3/105) for SCS and 7.8% (8/103) for ICSI (P = 0.10). LBW occurred in 4.2% (3/71) and 0% (0/50) of babies born after the transfer of cryopreserved-thawed SCS and ICSI embryos, respectively (P = 0.14). The rate of PTB was 3.8% and 6.8% for SCS and ICSI in FRET cycles (P = 0.33), and 8.5% and 6.0% for SCS and ICSI in FET cycles (P = 0.62). One congenital malformation was found in the SCS FET group. CONCLUSION: There was no difference in perinatal outcome for singleton and twin babies born after SCS and ICSI.

Sperm quality and absence of SARS-CoV-2 RNA in semen after COVID-19 infection: a prospective, observational study and validation of the SpermCOVID test.

OBJECTIVE: To study the contagiousness of sperm and its influence on fertility after recovery from COVID-19 infection. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENT(S): One hundred twenty Belgian men who had recovered from proven COVID-19 infection. INTERVENTION(S): No intervention was performed. MAIN OUTCOME MEASURE(S): Semen quality was assessed using the World Health Organisation criteria. DNA damage to sperm cells was assessed by quantifying the DNA fragmentation index and the high density stainability. Finally antibodies against SARS-CoV2 spike-1 antigen, nuclear and S1-receptor binding domain were measured by Elisa and chemilumenscent microparticle immunoassays, respectively. RESULT(S): SARS-CoV-2 RNA was not detected in semen during the period shortly after infection nor at a later time. Mean progressive motility was reduced in 60% of men tested shortly (<1 month) after COVID-19 infection, 37% of men tested 1 to 2 months after COVID-19 infection, and 28% of men tested >2 months after COVID-19 infection. Mean sperm count was reduced in 37% of men tested shortly (<1 month) after COVID-19 infection, 29% of men tested 1 to 2 months after COVID-19 infection, and 6% of men tested >2 months after COVID-19 infection. The severity of COVID-19 infection and the presence of fever were not correlated with sperm characteristics, but there were strong correlations between sperm abnormalities and the titers of SARS-CoV-2 IgG antibody against spike 1 and the receptor- binding domain of spike 1, but not against nucleotide, in serum. High levels of antisperm antibodies developed in three men (2.5%). CONCLUSION(S): Semen is not infectious with SARS-CoV-2 at 1 week or more after COVID-19 infection (mean, 53 days). However, couples with a desire for pregnancy should be warned that sperm quality after COVID-19 infection can be suboptimal. The estimated recovery time is 3 months, but further follow-up studies are under way to confirm this and to determine if permanent damage occurred in a minority of men.

Negative Impact of Elevated DNA Fragmentation and Human Papillomavirus (HPV) Presence in Sperm on the Outcome of Intra-Uterine Insemination (IUI).

We wanted to determine the sperm DNA fragmentation index (DFI) cutoff for clinical pregnancies in women receiving intra-uterine insemination (IUI) with this sperm and to assess the contribution of Human Papillomavirus (HPV) infection on sperm DNA damage and its impact on clinical pregnancies. Prospective non-interventional multi-center study with 161 infertile couples going through 209 cycles of IUI in hospital fertility centers in Flanders, Belgium. Measurement of DFI and HPV DNA with type specific quantitative PCRs (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) in sperm before its use in IUI. Clinical pregnancy (CP) rate was used as the outcome to analyze the impact on fertility outcome and to calculated the clinical cutoff value for DFI. A DFI criterion value of 26% was obtained by receiver operating characteristic (ROC) curve analysis. Couples with a male DFI > 26% had significantly less CPs than couples with DFI below 26% (OR 0.0326; 95% CI 0.0019 to 0.5400; p = 0.017). In sperm, HPV prevalence was 14.8%/IUI cycle. Sperm samples containing HPV had a significantly higher DFI compared to HPV negative sperm samples (29.8% vs. 20.9%; p = 0.011). When HPV-virions were present in sperm, no clinical pregnancies were observed. More than 1 in 5 of samples with normal semen parameters (17/78; 21.8%) had an elevated DFI or was HPV positive. Sperm DFI is a robust predictor of clinical pregnancies in women receiving IUI with this sperm. When DFI exceeds 26%, clinical pregnancies are less likely and in vitro fertilization techniques should be considered.

Social sperm freezing.

Increased paternal age has been associated with lower fertility and higher genetic risk for the offspring. One way to prevent these consequences is to freeze sperm at a young age. Social sperm freezing could be developed in a way similar to social oocyte freezing. The main difference between freezing oocytes and sperm is that social sperm freezing is much less focussed on fertility preservation and much more on avoiding increased genetic risk. Contrary to what some people seem to believe, sperm freezing is more complicated than it looks at first sight. This article considers three practical aspects: freezing, storage and testing. It is concluded that the remedy (cryopreservation) may itself cause damage to the quality of the spermatozoon and to its genetic integrity, thus undoing the possible benefits in terms of fertility and health of offspring.

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.).

IVF and other ART in low- and middle-income countries: a systematic landscape analysis.

BACKGROUND: Infertility affects 48.5 million couples worldwide with a prevalence estimated at 3.5-16.7% in low- and middle-income countries (LMIC), and as high as 30-40% in Sub-Saharan Africa. ART services are not accessible to the majority of these infertile couples due to the high cost of treatments in addition to cultural, religious and legal barriers. Infertility and childlessness, particularly in LMIC, have devastating consequences, which has resulted in considerable interest in developing affordable IVF procedures. However, there is a paucity of evidence on the safety, efficiency and ability to replicate techniques under different field conditions, and how to integrate more affordable ART options into existing infrastructures. OBJECTIVE AND RATIONALE: This review was performed to investigate the current availability of IVF in LMIC and which other ART options are under development. This work will unfold the landscape of available and potential ART services in LMIC and is a key element in positioning infertility more broadly in the Global Public Health Agenda. SEARCH METHODS: A systematic literature search was performed of articles and gray literature on IVF and other ART options in LMIC published between January 2010 and January 2020. We selected studies on IVF and other ART treatments for infertile couples of reproductive age (18-44 years) from LMIC. The review was limited to articles published after 2010, based on the recent evolution in the field of ART practices in LMIC over the last decade. Citations from high-income countries, including data prior to 2010 and focusing on specialized ART procedures, were excluded. The literature search included PubMed, Popline, CINHAL, EMBASE and Global Index Medicus. No restrictions were applied with regard to study design or language. Two reviewers independently screened the titles and abstracts, and extracted data. A search for gray literature was performed using the 'Google' search engine and specific databases (worldcat.org, greylit.org). In addition, the reference lists of included studies were assessed. OUTCOMES: The search of the electronic databases yielded 3769 citations. After review of the titles and abstracts, 283 studies were included. The full texts were reviewed and a further 199 articles were excluded. The gray literature search yielded 586 citations, most of which were excluded after screening the title, and the remaining documents were excluded after full-text assessment due to duplicate entries, not from LMIC, not relevant or no access to the full document. Eighty-four citations were included as part of the review and separated into regions. The majority of the studies were observational and qualitative studies. In general, ART services are available and described in several LMIC, ranging from advanced techniques in China to basic introduction of IVF in some African countries. Efforts to provide affordable ART treatments are described in feasibility studies and efficacy studies; however, most citations were of low to very low quality. We found no studies from LMIC reporting the implementation of low-cost ART that is effective, accessible and affordable to most of those in need of the services. WIDER IMPLICATIONS: The World Health Organization is in a unique position to provide much needed guidance for infertility management in LMIC. This review provides insight into the landscape of ART in LMIC in various regions worldwide, which will guide efforts to improve the availability, quality, accessibility and acceptability of biomedical infertility care, including ART in these countries.

WHO fact sheet on infertility gives hope to millions of infertile couples worldwide.

Although the consequences of infertility are often severe in LMIC (Low and Middle Income Countries), national and international health strategies have always focussed on reducing total fertility rates while infertility care has received no attention at all. Access to infertility care can only be achieved when good quality but affordable infertility care is linked to more effective family planning programmes. Only a global project with respect to socio-cultural, ethical, economical and political differences can be successful. The 2020 WHO fact sheet on infertility cannot be misunderstood; global access to high-quality services for family planning including fertility care is one of the core elements of reproductive health. Different strategies are presented.

Long-Term Reproductive Outcomes after Hysteroscopic Treatment of Dysmorphic Uteri in Women with Reproductive Failure: An European Multicenter Study.

OBJECTIVE: To evaluate the long-term reproductive outcomes in patients with dysmorphic uterus treated by hysteroscopic metroplasty with miniaturized instruments. DESIGN: Retrospective multicenter cohort study. SETTING: Tertiary care university hospitals. PATIENTS: The study was conducted on 214 women with a dysmorphic uterus (T-shaped, infantilis, or other type of dysmorphic uterus according to the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy classification system) with history of primary unexplained infertility (group 1) or repeated (>2) early miscarriages (group 2). Dysmorphic uteri were diagnosed by office hysteroscopy and 3-dimensional transvaginal ultrasound (3D-TVS). INTERVENTIONS: All patients underwent in office hysteroscopic metroplasty using a continuous-flow hysteroscope with a 5 Fr operating channel introduced into the uterine cavity using the vaginoscopic approach. Longitudinal incisions were performed on the fibromuscular constriction rings in the isthmic area and in some cases on the other uterine walls with a 5 Fr bipolar electrode or scissors. At the end of the procedure, an antiadhesive gel was applied into the uterine cavity to minimize adhesion formation. Postsurgical assessment of the uterine cavity was carried out through office hysteroscopy and 3D-TVS. All patients were followed for at least 24 months. MEASUREMENTS AND MAIN RESULTS: The metroplasty was completed in all cases, resulting in a significant increase of uterine cavity volume (100%) and optimization of uterine morphology in 211 of 214 women (98.6%). After 60 months, the overall clinical pregnancy rate was 72.9% (n = 156/214), and the live birth rate was 80.1% (n = 125/156). Specifically, 74 of 156 women (47.4%) conceived spontaneously (with a median time to pregnancy of 5.5 months), of whom 32.4% had previously failed 1 or more attempts at in vitro fertilization/intracytoplasmic sperm injection. CONCLUSION: Our long-term follow-up data demonstrate that the hysteroscopic correction of dysmorphic uteri may result in a high live birth rate in women suffering from unexplained infertility or repeated miscarriages.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination.

OBJECTIVE: To study the influence of human papillomavirus (HPV) virions present in different sperm fractions of male partners of women undergoing IUI on fertility outcome. DESIGN: Prospective noninterventional multicenter study. SETTING: Inpatient hospital fertility centers. PATIENT(S): Seven hundred thirty-two infertile couples undergoing 1,753 IUI cycles with capacitated sperm. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Biochemical and clinical pregnancy rate in IUI cycles with HPV-positive or HPV-negative semen. RESULT(S): Five hundred seventy-three infertile couples undergoing 1,362 IUI cycles were enrolled. Work-up of the 1,362 sperm samples that were used for IUI generated 3,444 separate sperm fractions. Each of the sperm fractions was tested with quantitative polymerase chain reaction for 18 different HPV types (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, and 68). HPV prevalence in sperm was 12.5%/IUI cycle. When infectious HPV virions were detected in sperm, a significant decrease in clinical pregnancies was observed when compared with HPV-negative cycles (2.9% vs. 11.1 %/cycle). Above a ratio of 0.66 HPV virions/spermatozoon no pregnancies occurred (sensitivity 100%, specificity 32.5%). CONCLUSION(S): Women inseminated with HPV-positive sperm had 4 times fewer clinical pregnancies compared with women who had HPV-negative partners. Detection of HPV virions in sperm is associated with a negative IUI outcome and should be part of routine examination and counseling of infertile couples. EUROPEAN CLINICAL TRIALS DATABASE NUMBER: 2017-004791-56.

Limits of current male fertility testing.

In the current approach to male fertility testing, basic semen analysis has limitations as a predictor of fertility status, and the technology is fraught with variability. Nonetheless, it remains the cornerstone of the evaluation of the male infertility, and we recommend adherence to most recent World Health Organization guidelines. Although the current sperm function tests (bioassays) have important drawbacks, they are still valuable as research tools. Sperm quality assays with analysis of sperm DNA fragmentation need further investigation before they can be recommended for routine clinical use. The answer to the many current challenging questions relies on identifying spermatogenesis pathologies and the resulting sperm dysfunctions at the cellular and molecular levels. New discoveries may bring answers or new avenues to explore.

IUI: review and systematic assessment of the evidence that supports global recommendations.

BACKGROUND: IUI with or without ovarian stimulation (OS) has become a first-line treatment option for many infertile couples, worldwide. The appropriate treatment modality for couples and their clinical management through IUI or IUI/OS cycles must consider maternal and perinatal outcomes, most notably the clinical complication of higher-order multiple pregnancies associated with IUI-OS. With a current global emphasis to continue to decrease maternal and perinatal mortality and morbidity, the World Health Organization (WHO) had established a multi-year project to review the evidence for the establishment of normative guidance for the implementation of IUI as a treatment to address fertility problems, and to consider its cost-effectiveness for lower resource settings. OBJECTIVE AND RATIONALE: The objective of this review is to provide a review of the evidence of 13 prioritized questions that cover IUI with and without OS. We provide summary recommendations for the development of global, evidence-based guidelines based upon methodology established by the WHO. SEARCH METHODS: We performed a comprehensive search using question-specific relevant search terms in May 2015. For each PICO (Population, Intervention, Comparison and Outcomes) drafted by WHO, specific search terms were used to find the available evidence in MEDLINE (1950 to May 2015) and The Cochrane Library (until May 2015). After presentation to an expert panel, a further hand search of references in relevant reviews was performed up to January 2017. Articles that were found to be relevant were read and analysed by two investigators and critically appraised using the Cochrane Collaboration's tool for assessing risk of bias, and AMSTAR in case of systematic reviews. The quality of the evidence was assessed using the GRADE system. An independent expert review process of our analysis was conducted in November 2016. OUTCOMES: This review provides an assessment and synthesis of the evidence that covers 13 clinical questions including the indications for the use of IUI versus expectant management, the sperm parameters required, the best and optimal method of timing and number of inseminations per cycle, prevention strategies to decrease multiple gestational pregnancies, and the cost-effectiveness of IUI versus IVF. We provide an evidence-based formulation of 20 recommendations, as well as two best practice points that address the integration of methods for the prevention of infection in the IUI laboratory. The quality of the evidence ranges from very low to high, with evidence that may be decades old but of high quality, however, we further discuss where critical research gaps in the evidence remain. WIDER IMPLICATIONS: This review presents an evidence synthesis assessment and includes recommendations that will assist health care providers worldwide with their decision-making when considering IUI treatments, with or without OS, for their patients presenting with fertility problems.

Motivations and attitudes of candidate sperm donors in Belgium.

OBJECTIVE: To study the motivation and attitudes of a candidate sperm donor population in Belgium. DESIGN: Anonymous survey. SETTING: Tertiary referral infertility center. PATIENT(S): One hundred candidate sperm donors applying to the center for a first semen analysis between April 2013 and March 2016. INTERVENTION(S): Invitation to complete an anonymous questionnaire. MAIN OUTCOME MEASURE(S): Demographic characteristics, recruitment methods, motivations and attitudes toward payment, donor anonymity, disclosure to offspring, donation to lesbian couples and single women, views on the donor children and social aspects of sperm donation. RESULT(S): The majority of our candidate donor population were older men with a partner who were donating sperm for altruistic reasons. The financial compensation was only an important motivational factor in 31% of the candidate sperm donors. Eighty-two percent of the men said they were willing to reveal nonidentifying information about themselves to donor offspring, but only 26% were willing to donate nonanonymously. The wish to receive certain information about the recipient family and the donor offspring was linked to men who had a partner and a child of their own. CONCLUSION(S): The wish to receive and donate information depends on the characteristics and beliefs of the candidate donors. Also, the donor's characteristics were linked to the acceptance of meeting the offspring in the future: the donors with a partner and donors who said they would donate without financial reimbursement were less willing to meet the donor offspring.