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STUDY QUESTION Do defects in sperm chromatin protamination and condensation have an impact on ICSI outcomes? SUMMARY ANSWER Sperm protamination is related to fertilization rates in healthy donors, and the in vitro capacity of sperm to condense their chromatin is linked to blastocyst rates, both associations being more apparent in women <33 years of age. WHAT IS KNOWN ALREADY Previous data on how sperm chromatin damage affects ICSI outcomes are inconsistent. Revealing which sperm factors influence embryo development is necessary to understand the male contribution to ICSI success and to develop novel sperm selection techniques or male-based treatments. Sperm chromatin is mainly condensed in protamines, which are cross-linked through disulphide bridges. This study aimed to determine whether sperm protamination and the integrity of disulphide bonds (condensation) are related to embryo development after ICSI. STUDY DESIGN, SIZE, DURATION The design was a retrospective study with a blind analysis of sperm chromatin. Gametes were divided into two groups: double donation (DD) cohort and single donation (SD) cohort. Samples from 45 semen donors used in 55 ICSI cycles with oocyte donors (age range 19–33 years), generating 491 embryos, were included in the DD cohort. The SD cohort consisted of samples from 34 semen donors used in 41 ICSI cycles with oocytes from healthy females (single-parent families or lesbian couples, age range 20–44 years), generating a total of 378 embryos. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Donor sperm samples from DD and SD cohorts were used for standard ICSI, and embryo development was observed by time-lapse imaging. The incidence of thiol reduction (dibromobimane, DBB) and the degree of chromatin protamination (chromomycin A3, CMA3, indicating non-protaminated regions) in sperm were determined by flow cytometry at 0 and 4 h post-thawing. MAIN RESULTS AND THE ROLE OF CHANCE Percentages ± standard deviation of CMA3 were 21.08 ± 9.09 and 35.01 ± 14.68 at 0 and 4 h post-thawing, respectively, in the DD cohort and 22.57 ± 9.48 and 35.79 ± 12.58, at 0 and 4 h post-thawing, respectively, in the SD cohort. Percentages of DBB+ were 16.57 ± 11.10 and 10.51 ± 8.40 at 0 and 4 h post-thawing (P  <   0.0001), respectively, in the DD cohort and 17.98 ± 10.19 and 12.72 ± 8.76 at 0 and 4 h post-thawing (P  <   0.0001), respectively, in the SD cohort. Female age correlated with fertilization rates, and the relation between sperm chromatin and embryo development was determined through multiple linear regression. While CMA3 was associated with fertilization rates, with no influence of female age, in the DD cohort (β1 = −1.036, P  <   0.001 for CMA3; β2 = 0.667, P  =   0.304 for female age), this was not observed in the SD cohort, where female age had a significant effect, masking the effects of CMA3 (β1 = −0.066, P  =   0.804 for CMA3; β 2 = −1.451, P  =   0.003 for female age). The in vitro capacity of sperm to condense their chromatin after 4 h of incubation was associated with blastocyst rates, independent of female age (DD cohort: β1 = −0.238, P  =   0.008 for %DBB+ variation; β2 = 0.404, P  =   0.638 for female age; SD cohort: β1 = −0.278, P =  0.010 for %DBB+ variation; β2 = −0.292, P  =   0.594 for female age). The in vitro capacity of sperm to condense their chromatin was also related to the time required for the embryo to reach blastocyst stage in the DD cohort (P  =   0.007). Finally, multiple logistic regression showed that both chromatin protamination and condensation, together with the age of the oocyte donors and the embryo recipients, had an impact on pregnancy achievement (P  <   0.01) and on live birth rates (P  <   0.01). LIMITATIONS, REASONS FOR CAUTION The main limitation was the restrictive selection of couples, which led to a relatively small sample size and could influence the observed outcomes. For this reason, and to reduce Type I error, the level of significance was set at P ≤  0.01. On the other hand, the use of cryopreserved samples could also be a limitation. WIDER IMPLICATIONS OF THE FINDINGS This research demonstrated that protamination and condensation of sperm chromatin are related to embryo development after ICSI, but female age could be a confounding factor when oocytes from older females are used. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the European Union's Horizon 2020 Research and Innovation scheme under the Marie Skłodowska-Curie grant agreement No 801342 (Tecniospring INDUSTRY; TECSPR-19-1-0003); La Marató de TV3 Foundation (214/857-202039); the Ministry of Science and Innovation, Spain (IJC2019-039615-I); the Catalan Agency for Management of University and Research Grants, Regional Government of Catalonia, Spain (2017-SGR-1229); and the Catalan Institution for Research and Advanced Studies, Spain (ICREA). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the probability of high-risk genetic matching when assisted reproductive techniques (ART) are applied with double gamete donation, following an NGS carrier test based on a complete study of the genes concerned. We then determine the results that would have been obtained if the genotyping tests most widely used in Spanish gamete banks had been applied. Methods: In this descriptive observational study, 1818 gamete donors were characterised by NGS. The pathogenic variants detected were analysed to estimate the probability of high-risk genetic matching and to determine the results that would have been obtained if the three most commonly used genotyping tests in ART had been applied. Results: The probability of high-risk genetic matching with gamete donation, screened by NGS and complete gene analysis, was 5.5%, versus the 0.6–2.7% that would have been obtained with the genotyping test. A total of 1741 variants were detected, including 607 different variants, of which only 22.6% would have been detected by all three genotyping tests considered and 44.7% of which would not have been detected by any of these tests. Conclusion: Our study highlights the considerable heterogeneity of the genotyping tests, which present significant differences in their ability to detect pathogenic variants. The complete study of the genes by NGS considerably reduces reproductive risks when genetic matching is performed with gamete donors. Accordingly, we recommend that carrier screening in gamete donors be carried out using NGS and a complete study with nontargeted analysis of the variants of the screened genes. [ABSTRACT FROM AUTHOR]

Objectives: According to French recommendations, only the caryotype is carried out as a first line in candidates for gamete donation. The prescription of additional genetic tests for variants responsible for serious monogenic diseases is only recommended in the case of call points. However, cystic fibrosis remains the most common genetic disease with serious consequences in childhood. The purpose is to assess the different screening strategies in the Centres d'Études et de Conservation des Œufs et du Sperme humain (CECOS) regarding abnormalities of the Cystic Fibrosis Transmembrane conductance Regulator gene (CFTR)., Method: Our study is based on the analysis of data collected using a questionnaire. Private centres authorised to donate have been excluded from this work., Results: Twenty-six centres participated out of the 33 interviewees. Two centres carry out systematic screening in all their sperm donation candidates while only one centre practises it in its oocyte donation candidates. For the other 23 centres, research is carried out in case of strong clinical suspicions according to personal or family history and when one of the two members of the recipient couple has a known variant. Regarding the molecular analysis technique used, 56.5% of centres use PCR with commercial kits, whereas the other centers use next-generation sequencing., Conclusion: Targeted screening therefore remains widely practiced in France unlike other countries. Moving to expanded systematic screening raises ethical, financial and organisational issues., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Resumen: España es el país europeo donde se realizan más técnicas de reproducción asistida (TRA), alcanzando el 9% de los nacidos. El objetivo de este artículo es introducir el marco legal y analizar algunos aspectos éticos, no exentos de controversia, en relación con el anonimato de los donantes de gametos y la ocultación del origen mediante TRA a los hijos. La legislación española establece el anonimato relativo de los donantes: tanto las receptoras de gametos como los hijos nacidos tienen derecho a obtener información general de los mismos siempre que no incluya su identidad, pero ante situaciones de riesgo para la vida y la salud de los hijos permite su quiebra. Asimismo, se determina un inequívoco derecho a la intimidad y confidencialidad del sometimiento a las TRA. El movimiento tendente a introducir en nuestro país una modificación legislativa que acabe con el anonimato de los donantes de gametos se basa en el derecho de los nacidos a conocer su filiación biológica. Junto con los cambios jurídicos, la actitud de padres y profesionales debe ir modificándose hacia una comunicación más transparente y responsable, en función de las experiencias de los adultos concebidos por estas técnicas, y de los adoptados. Construir valores como la confianza y la verdad en el ámbito de las relaciones familiares desde la responsabilidad requiere colocar a los hijos, grandes olvidados y parte más vulnerable, en el centro del debate. Abstract: Spain is the European country where more assisted reproduction techniques (ART) are performed, reaching 9% of newborns. The objective of this article is to introduce the legal framework and to analyze some ethical questions, not without controversy, in relation to the anonymity of gamete donors and the concealment of origin by ART from their children. Spanish legislation establishes the relative anonymity of donors: both gamete recipients and born children have the right to obtain general information about them as long as their identity is not included, but in situations of risk to the life and health of the children allows your bankruptcy. Likewise, an unequivocal right to privacy and confidentiality of submission to the ART is established. The movement aimed at introducing in our country a legislative amendment that ends the anonymity of gamete donors is based on the right of those children to know their biological origin. Along with legal changes, the attitude of parents and professionals must gradually change towards more transparent and responsible communication, based on the experiences of adults conceived by these techniques, and those adopted. Building values such as trust and truth in the family relationships from responsibility requires placing the children, largely forgotten and the most vulnerable part, at the center of the debate.

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Research Question: How is the mental health of open-identity gamete donors and their satisfaction with their contributions 14-17 years after acceptance as a donor?, Design: The Swedish Study on Gamete Donation is a longitudinal study comprising women and men who were accepted as donors at seven Swedish university clinics between 2005 and 2008. The latest (fifth) follow-up included 215 open-identity donors (response rate 87%): 123 oocyte donors and 92 sperm donors. The donors answered a questionnaire regarding their perceptions, experiences and expectations after gamete donation 14-17 years previously., Results: The donors were satisfied with the experience of donating, and no differences were detected between sperm and oocyte donors. Oocyte donors were more than twice as likely to feel that family and friends were proud of their donation compared with sperm donors (51% versus 23%, P < 0.001). In total, six donors regretted their donation: four oocyte donors and two sperm donors. Sperm donors were more frequently satisfied with the financial compensation compared with oocyte donors (P = 0.005). No difference in the development of symptoms of anxiety or depression was detected 14-17 years post-donation., Conclusion: Long-term follow-up studies on donors are important for recruiting donors, and for recipients and the children who will be conceived with donated gametes. The results from the current study indicate that donors, generally, have good mental health and do not regret their decision to donate gametes. These findings are reassuring for all parties involved., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Expanded carrier screening (ECS) is a genetic test which informs us of an individual's carrier status in relation to hundreds of serious genetic diseases and to assess the genetic risk to their future offspring. The genetic diseases studied have an autosomal recessive or X-linked inheritance. They are aimed at healthy individuals, regardless of their family, personal or ethnic background. All human beings are carriers of pathogenic variants in one or more genes associated with these genetic diseases. It is estimated that about 2-3% of couples in the general population have a pathogenic variant in the same gene and in consequence are at risk of having children affected by a serious genetic disease. Genetic counselling is necessary and, among other things, will inform the patients about the residual reproductive risk. The application of genetic matching in couples or individuals who need gametes donors allows a significant decrease in reproductive genetic risk. [ABSTRACT FROM AUTHOR]

Medical science has enabled the creation of families through the use of donor conception but some lifelong policy and practice implications are only recently being recognized. Research and practice have shown that donor conception can, for some, carry substantial long-term consequences. In this paper we present findings from a questionnaire-based study that sought to shed light on donor-conceived adults’ and gamete donors’ views on service and support needs when searching for genetic relatives with the aid of DNA testing. The findings demonstrate the complexity and sensitivity of providing services in this newly emerging area of need. Such provision requires collaboration between very different disciplines and agencies (scientific and psychosocial), introduces the potential for blurring of lines of accountability and responsibility, and highlights the challenges of identifying appropriate funding streams. In addition, the findings demonstrate the opportunities and limitations afforded by the use of DNA in identifying unknown genetic relatives. [ABSTRACT FROM PUBLISHER]

Next-generation sequencing (NGS) has the capacity of carrier screening in gamete donation (GD) programs. We have developed and validated an NGS carrierscreening test (qCarrier test) that includes 200 genes associated with 368 disorders (277 autosomal recessive and 37 X-linked). Carrier screening is performed on oocyte donation candidates and the male partner of oocyte recipient. Carriers of X-linked conditions are excluded from the GD program, whereas donors are chosen who do not carry mutations for the same gene/disease as the recipients. The validation phase showed a high sensitivity (>99% sensitivity) detecting all single-nucleotide variants, 13 indels, and 25 copy-number variants included in the validation set. A total of 1,301 individuals were analysed with the qCarrier test, including 483 candidate oocyte donors and 635 receptor couples, 105 females receiving sperm donation, and 39 couples seeking pregnancy. We identified 56% of individuals who are carriers for at least one genetic condition and 1.7% of female donors who were excluded from the program due to a carrier state of X-linked conditions. Globally, 3% of a priori assigned donations had a high reproductive risk that could be minimized after testing. Genetic counselling at different stages is essential for helping to facilitate a successful and healthy pregnancy. [ABSTRACT FROM AUTHOR]

This paper discusses the attitudes of three groups of stakeholders in the world of assisted reproduction gamete donors, parents who use donated gamete, and offspring conceived with donated gametes with respect to the two issues of donor anonymity and limits on the number of offspring a single donor can produce. The data are drawn from on-line surveys which were made available between May 12, 2104 and August 15, 2014 to gamete donors, donor-conceived offspring, and parents who used donated gametes to conceive. A total of 325 donors (176 egg donors; 149 sperm donors) responded to the survey as did 2134 parents and 419 offspring. The data show that offspring are more opposed to donor anonymity than are parents and donors. Among offspring opposition to anonymity grows as they age. On the other hand, parents are most in favor of limits on numbers of offspring produced by a single donor. Parents worry about health and accidental contact between people conceived from the same donor. [ABSTRACT FROM AUTHOR]

Assisted reproduction (AR), is a phenomenon that expresses the importance of "having" children in our society. Far from a peaceful land, these techniques evoke hybrid feelings. Especially when we talk about gamete donation. In Brazil, donations are anonymous and has been centralized in one bank. Little is known about the donors and their motivations. The way they are chosen is the central theme of this article. The recipients receive a list that contains information such as blood type, ethnic origin, religion, skin color, eye color, height and hobbies. Such information speaks of two sets of information that refer to familiar binomial discussed in anthropology: nature and culture. The aim of this article is to discuss how religious information is important to choose a donor. This debate is situated on the relevance of debates about notions of heredity and transmission for personal and family identity. [ABSTRACT FROM AUTHOR]

Objective To study the personality characteristics of identifiable oocyte donors in a national sample in comparison with normal values. Design Descriptive study. Setting All Swedish donation programmes. Sample In total, 181 women out of 221 donors recruited during 2005-2008. Methods Standardised questionnaires were used to measure personality characteristics. Main outcome measure Demographics, temperament and character inventory (TCI). Results The majority (69%) of the donors had biological children of their own. The results from the TCI indicate that the oocyte donors were all within the normal range of character. With regard to personality, a significant difference was evident between the two groups: oocyte donors showed lower means for harm avoidance and higher scores for persistence than the controls. This indicates that the donors felt less worried, and displayed a lower level of fear of uncertainty, shyness and fatiguability, and a higher level of persistence, than the controls. In the present sample, 29 (16%) of the donors were so-called 'known donors', that is the recipient couples and the donors were known to each other. 'Known donors' displayed a mature and stable character. Conclusion We found that the women who had been accepted for inclusion in this nationwide oocyte donor programme were all well adjusted and mature. [ABSTRACT FROM AUTHOR]

Polymorphic variants on chromosomes are considered 'normal', as heterochromatin has no coding potential and nucleolar organizing regions (NOR) contain genes coding for rRNA. Variants have been reported in infertility and recurrent abortions. With refined molecular techniques, genes for fertility and viability are now thought to reside in heterochromatin. DNA sequence analysis of human chromosome 9 has shown that it is highly structurally polymorphic, with many intrachromosomal and interchromosomal duplications, and contains the largest autosomal block of heterochromatin. Transcriptional activation of constitutive heterochromatic domains of the human genome in response to environmental stress was reported recently. Heat shock triggers the assembly of nuclear stress bodies on the pericentromeric heterochromatin of human chromosomes including chromosome 9. These are characterized by an epigenetic status typical of euchromatic regions. On acrocentric chromosomes, NOR-associated protein count and morphology was reported to separate benign and malignant melanocytic lesions. Hence all variants may not be 'normal'. The present study of karyotyping 842 individuals attending an IVF clinic with primary infertility or repeated miscarriages, showed polymorphic variants in 28.82% of males and 17.19% of females, which was quite high. It is suggested that variants should not be ignored by cytogeneticists. Screening prospective gamete donors for chromosome variants may help enhance the success of IVF. [ABSTRACT FROM AUTHOR]

Objective: To describe and discuss our experience with cystic fibrosis (CF) carrier testing in a donor egg program.Design: Retrospective review.Setting: Community hospital-based assisted reproductive technology (ART) program.Patient(s): Forty anonymous white oocyte donor applicants.Intervention(s): Testing with a DNA mutation analysis panel.Main Outcome Measure(s): Frequency of heterozygotes for CF mutation among the donor applicants and the likelihood of carriers and noncarriers being selected by recipients.Result(s): Five of 40 egg donor applicants (12.5%) were found to be heterozygous for a CF mutation; 35 women (87.5%) tested negative. Two of the five CF carriers (40.0%) were selected by five recipient couples and underwent four donation cycles after the recipients' male partners tested negative. Twenty-nine of the 35 noncarrier donors (82.9%) were matched and underwent 81 egg donation cycles. The likelihood of being selected was lower for CF carriers than for noncarriers.Conclusion(s): Our experience strongly supports the recommendation of routine CF testing of prospective white egg donors. Whereas heterozygosity lowers the probability of a donor being matched, it need not exclude her from the donor pool provided the recipient's partner is not a carrier. Empowering recipients to choose their own donors, focused patient education, and genetic counseling with precise determination of residual risk are important prerequisites for inclusion of CF carriers. [ABSTRACT FROM AUTHOR]

Oocyte donation is a technique in full expansion in the field of human reproduction. The main problem with this technique is the shortage of oocytes. In our programme, prospective donors are selected from anonymous, well-informed university students over 18 years of age, who give their informed consent in writing. Before being accepted as donors, the candidates' personal and family medical histories were taken and they were given a gynaecological examination, genital ultrasonography, and analysed for syphilis, acquired immune deficiency syndrome, hepatitis B and C, coagulation factor VIII, fetal haemoglobin and karyotype. The donors received economic compensation of about 750 euros. Over the last 6 years, 554 medical histories have been taken. Fifty-eight candidates (10.5%) were rejected because of previous family or personal pathologies. Only 243 out of 496 (49%) continued the study. Sixteen candidates (7%) were rejected as a result of gynaecological problems and ultrasonographic results; and 12 (4.9%) as a result of their blood test results; 215 donors were accepted (38.8% of the original population). Other options for recruiting oocyte donors are commented on and we argue that the methodology described here is the most suitable one. [ABSTRACT FROM PUBLISHER]

A continuing feature of gamete donation is the scarcity of available donors. A strategy to improve the meagre supply of gametes would be to adjust the donation procedure to the wishes and desires of the donors. However, giving donors the right to direct their gametes to certain groups of recipients goes against the general rule that donors relinquish all rights and duties. Moreover, allocation by the donor might very well run counter to the rules of distributional justice. On the other hand, the allocation right can be supported by the principle of autonomy and by the donor's interest in and contribution to the process. The position is taken that the donors should have the right to direct their gametes to categories accepted as relevant by the moral and religious communities in their society. They should not be given the right to add their own categories to the exclusion list. If donors are not allowed to allocate their gift, they should at least be informed as to which categories of recipient are treated by the hospital to enable them to decide whether they want to donate gametes. [ABSTRACT FROM AUTHOR]

Spain is the European country where more assisted reproduction techniques (ART) are performed, reaching 9% of newborns. The objective of this article is to introduce the legal framework and to analyze some ethical questions, not without controversy, in relation to the anonymity of gamete donors and the concealment of origin by ART from their children. Spanish legislation establishes the relative anonymity of donors: both gamete recipients and born children have the right to obtain general information about them as long as their identity is not included, but in situations of risk to the life and health of the children allows your bankruptcy. Likewise, an unequivocal right to privacy and confidentiality of submission to the ART is established. The movement aimed at introducing in our country a legislative amendment that ends the anonymity of gamete donors is based on the right of those children to know their biological origin. Along with legal changes, the attitude of parents and professionals must gradually change towards more transparent and responsible communication, based on the experiences of adults conceived by these techniques, and those adopted. Building values such as trust and truth in the family relationships from responsibility requires placing the children, largely forgotten and the most vulnerable part, at the center of the debate., (Copyright © 2021 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

This response challenges the notion that paying more money, in whatever form, will overcome the anxieties of gamete donors regarding the removal of anonymity. An overview of the literature on payment and donor recruitment indicates that this is a complex issue. That literature does provide 'pointers' to the types of persons who should be 'targeted' in an information sharing and non-payment system. The experience in Sweden, both in relation to donor recruitment and parents' information-sharing with their children, is clarified, as the evidence is not always presented accurately. [ABSTRACT FROM AUTHOR]

This paper discusses the attitudes of three groups of stakeholders in the world of assisted reproduction gamete donors, parents who use donated gamete, and offspring conceived with donated gametes with respect to the two issues of donor anonymity and limits on the number of offspring a single donor can produce. The data are drawn from on-line surveys which were made available between May 12, 2104 and August 15, 2014 to gamete donors, donor-conceived offspring, and parents who used donated gametes to conceive. A total of 325 donors (176 egg donors; 149 sperm donors) responded to the survey as did 2134 parents and 419 offspring. The data show that offspring are more opposed to donor anonymity than are parents and donors. Among offspring opposition to anonymity grows as they age. On the other hand, parents are most in favor of limits on numbers of offspring produced by a single donor. Parents worry about health and accidental contact between people conceived from the same donor.