Stringent criteria needed for germline genome editing of human IVF embryos.

Germline genome editing of IVF embryos is controversial because it is not directly health or lifesaving but is intended to prevent genetic diseases in yet-unborn future offspring. The following criteria are thus proposed for future clinical trials: (i) Due to medical risks, there should be cautious and judicious application while avoiding any non-essential usage, with rigorous patient counseling. (ii) Genome editing should only be performed on the entire batch of IVF embryos without initial PGT screening if all of them are expected to be affected by genetic disease. (iii) When there is a fair chance that some IVF embryos will not be affected by genetic diseases, initial PGT screening must be performed to identify unaffected embryos for transfer. (iv) IVF embryos with carrier status should not undergo germline genome editing. (v) If patients fail to conceive after the transfer of unaffected embryos, they should undergo another fresh IVF cycle rather than opt for genome editing of their remaining affected embryos. (vi) Only if the patient is unable to produce any more unaffected embryos in a fresh IVF cycle due to advanced maternal age or diminished ovarian reserves, can the genome editing of remaining affected embryos be permitted as a last resort.

Regulatory safeguards needed if preimplantation genetic testing for polygenic risk scores (PGT-P) is permitted in Singapore.

Singapore, a highly affluent island city-state located in Southeast Asia, has increasingly leveraged new assisted reproductive technologies (ART) to overcome its dismal fertility rates in recent years. A new frontier in ART is preimplantation genetic testing (PGT) for polygenic risk scores (PRS) to predict complex multifactorial traits in IVF (in vitro fertilisation) embryos, such as type 2 diabetes, cardiovascular diseases and various other characteristics like height, intelligence quotient (IQ), hair and eye colour. Unlike well-known safety risks with human genome editing, there are negligible risks with PGT-P, because there are no man-made genetic modifications that can be transmitted to future generations. Nevertheless, the current efficacy of using PGT-P to select IVF embryos for either increased or decreased probability of developing specific polygenic traits is still far from certain. Hence, the regulatory safeguards proposed here will be based on the assumption that the efficacy of this new technology platform has already been validated. These include: (1) restricting the application of PGT-P only for prevention of clinically relevant polygenic disease traits, (2) securely blocking patients' access to the raw genomic DNA sequencing data of their IVF embryos, (3) validating diagnosis of polygenic disease traits in the prospective parents/grandparents of IVF embryos, and restricting PGT-P only for preventing specifically diagnosed polygenic disease traits and (4) mandating rigorous and comprehensive genetic counselling for IVF patients considering PGT-P. There is an urgent and dire need to prevent abuse of the PGT-P technique, as well as protect the interests and welfare of patients if its clinical application is to be permitted in the country.

Should brain chip implants for memory and cognitive enhancement be banned in competitive national examinations?

In a recent medical breakthrough, Elon Musk's startup company Neuralink implanted the first brain chip in a human patient, purportedly for aiding paralysis. While certainly representing a significant medical milestone for many patients afflicted with debilitating brain and spinal cord injuries, as well as devastating neurodegenerative diseases such as Parkinson's and Alzheimer's, it must be noted that this very same technology can also be manipulated for human memory or cognitive enhancement. What happens if a brain chip were to be developed that can significantly improve either IQ (intelligence quotient) or memory, and these were then implanted in people to enhance their performance in highly competitive national examinations for college entrance or gaining employment in civil service positions? This article therefore discusses the ethical implications of this nascent technology platform, and whether its use in competitive national examinations should be banned.

Counseling Elective Egg Freezing Patients considering Donation of Unused Surplus Frozen Eggs for Fertility Treatment.

The majority of women who freeze their eggs for non-medical or social reasons, commonly referred to as elective egg freezing (EEF), do not eventually utilize their frozen eggs. This would result in an accumulated surplus of unused frozen eggs in fertility clinics worldwide, which represents a promising source of donation to infertile women undergoing IVF treatment. Rigorous and comprehensive counseling is needed, because the process of donating one's unused surplus frozen eggs involves complex decision-making. Prospective EEF donors can be broadly categorized into those who have achieved motherhood and those who remained childless and have given up on motherhood aspirations. A two-step systematic counseling protocol is proposed. Firstly, it is imperative to verify and ensure that these women do not want to conceive any children with their surplus frozen eggs before proceeding with further counseling and signing of consent forms. Secondly, various motivating and dissuading factors in the donation of unused surplus frozen eggs should then be comprehensively discussed with egg freezers to facilitate informed decision-making. Key motivating factors for donation include reciprocity in wanting to share the joys of motherhood among egg freezers who already have children, goodwill to help others in need, and avoiding the wastage of surplus frozen eggs after expending so much money, time, and effort. Key dissuading factors include fear of accidental incest between natural and unknown donor-conceived offspring, as well as apprehension of unexpected future contact with unknown donor-conceived offspring due to either donor anonymity being abolished in their jurisdiction or widespread consumer DNA testing.

Islamic Viewpoints on Opportunistic Sex Selection of IVF Embryos upon doing Preimplantation Genetic Testing for Preventing Genetic Diseases.

In recent years, preimplantation genetic testing (PGT) of IVF embryos have gained much traction in clinical assisted reproduction for preventing various genetic defects, including Down syndrome. However, such genetic tests inevitably reveal the sex of IVF embryos by identifying the sex (X and Y) chromosomes. In many countries with less stringent IVF regulations, information on the sex of embryos that are tested to be genetically normal is readily shared with patients. This would thus present Muslim patients with unintended opportunities for sex selection based on personal or social biases without any pressing need or valid medical reason. Additionally, there are other patients who claim using PGT for preventing genetic defects as a pretext or "convenient excuse," with a secret intention to do sex selection when it is banned in their home country. Currently, non-medical sex selection is a highly-controversial and hotly debated issue in Islam, because there is generally a strong preference for having sons over daughters due to widespread cultural norms of elderly parents depending on their sons for financial support, as well as the need for male heirs to continue the family lineage within the backdrop of local patriarchal cultures. There is a risk of gender imbalance and social disequilibrium occurring in Islamic societies due to prevalent sex selection. Hence, the question is whether opportunistic sex selection with PGT would contravene Islamic ethics and principles, which will thus be discussed here.

Sex Reassignment Surgery, Marriage, and Reproductive Rights of Intersex and Transgender People in Sunni Islam.

The traditional gender binary constitutes an integral aspect of Islamic social ethics, which has a pivotal role in shaping religious obligations, legal proceedings, and interpersonal judgments within Muslim communities. Within the familial sphere, this gender binary underscores fundamental responsibilities encompassing parenthood, filial duties, and inheritance rights. Recent years have witnessed a growing challenge to the traditional concept of the gender binary within Islamic societies. This shift is driven by increasing social libertarianism that emphasizes gender fluidity and individual choice. Hence, this article aims to critically scrutinize evolving discussions and controversies about the rights of intersex and transgender individuals, particularly issues relating to sex reassignment or gender-affirming surgery, marriage, and reproduction, from the perspective of the Sunni tradition of Islam. To support the various interpretations and insights presented here, a comprehensive and rigorous analysis is carried out on various religious texts and scholarly sources to elucidate the theological and jurisprudential positions on gender issues. It is thus concluded that Shariah offers greater flexibility in the treatment of intersex individuals compared to those with gender dysphoria because the intersex condition is viewed as a physical impairment that is not the choice of the afflicted individual. By contrast, in the case of individuals with gender dysphoria, they are willfully attempting to change their recognized biological sex, that God had naturally given to them at birth. Therefore, it is recommended that such transgender individuals deserve respectful psychological and social rehabilitation with help and guidance from religious authorities, their families, and communities.

An Ethico-Legal Analysis of Artificial Womb Technology and Extracorporeal Gestation Based on Islamic Legal Maxims.

Artificial womb technology for extracorporeal gestation of human offspring (ectogenesis or ectogestation) has profound ethical, sociological and religious implications for Muslim communities. In this article we examine the usage of the technology through the lens of Islamic ethico-legal frameworks specifically the legal maxims (al-Qawaid al-Fiqhiyyah) and higher objectives of Islamic law (Maqasid al-Shariah). Our analysis suggests that its application may be contingently permissible (halal) in situations of dire need such as sustaining life and development of extremely premature newborns, for advancing fetal medicine and avoiding maternal co-morbidities during fetal treatment, and for enabling motherhood for women without functional wombs, or who face grave medical risks in pregnancy. However, its application may be proscribed (haram) for enabling healthy women to avoid pregnancy and childbirth, or to achieve parenthood equity. Specification of these views to particular policy, legal contexts and Fatwa will require multidisciplinary Shariah-based bioethical deliberations between jurists, policymakers, and scientists.

Islamic Perspectives on Elective Ovarian Tissue Freezing by Single Women for Non-medical or Social Reasons.

Non-medical or Social egg freezing (oocyte cryopreservation) is currently a controversial topic in Islam, with contradictory fatwas being issued in different Muslim countries. While Islamic authorities in Egypt permit the procedure, fatwas issued in Malaysia have banned single Muslim women from freezing their unfertilized eggs (vitrified oocytes) to be used later in marriage. The underlying principles of the Malaysian fatwas are that (i) sperm and egg cells produced before marriage, should not be used during marriage to conceive a child; (ii) extraction of mature egg cells from single women being unacceptable; and (iii) fertility preservation in anticipation of late marriage is a conjecture that has not yet occurred. Ovarian tissue freezing can potentially be a more Shariah-compliant alternative to social egg freezing, because once the frozen ovarian cortical tissue sections have been re-transplanted back into the woman, mature egg cells can readily be produced, collected, and fertilized by the husband's sperm only during the period of marriage contract ('akd al-nikah). Unlike accidental mix-ups with frozen eggs, muddling of lineage (nasab) would be automatically avoided in ovarian tissue freezing due to immunological rejection. However, upon critical analysis based on Qawa'id Fiqhiyyah (Islamic Legal Maxims), Maqasid-al-Shariah (Higher Objectives of Islamic Law), and Maslahah-Mafsadah (benefits versus harmful effects on society), elective ovarian tissue freezing by healthy single women for social reasons would likely be a highly contentious and controversial issue within Muslim communities that may conflict with conservative social-religious norms. This thus needs further debate among Islamic jurists in dialogue with medical doctors and biomedical scientists.

Systematic protocol and methodology needed for pre-procedure counselling of elective egg freezing patients in Singapore.

Upon legalization of social egg freezing in Singapore from 2023 onwards, compulsory pre-procedure counselling is mandated for all prospective patients to enable informed choice about whether to undergo the procedure. Being a newly introduced medical procedure in Singapore, there are currently no clear directives on what pre-procedure counselling for elective egg freezing should entail. Due to pervasive media and internet influences, prospective egg freezing patients could be misled into believing that the procedure represents a guaranteed path to future motherhood, contrary to statements by professional bodies such as the American Society for Reproductive Medicine (ASRM) and the British Fertility Society (BFS). Hence, comprehensive counselling is recommended to provide women with evidence-based information (e.g. success rates of social egg freezing for women of their age) to ensure they make informed decisions and to avoid possible decision regret. For this purpose, a systematic protocol and methodology for pre-procedure counselling of women considering elective egg freezing was developed, incorporating flowcharts and decision trees that are specifically tailored to the unique sociocultural values and legal restrictions in Singapore. Questions relating to the why, what, how, where and when of the egg freezing procedure should be addressed, which could serve as a roadmap to facilitate informed decision-making by women considering elective egg freezing.

Sunni Islamic perspectives on lab-grown sperm and eggs derived from stem cells - in vitro gametogenesis (IVG).

An exciting development in the field of assisted reproductive technologies is In Vitro Gametogenesis (IVG) that enables production of functional gametes from stem cells in the laboratory. Currently, development of this technology is still at an early stage and has demonstrated to work only in rodents. Upon critically examining the ethical dimensions of various possible IVG applications in human fertility treatment from a Sunni Islamic perspective, together with benefit-harm (maslahah-mafsadah) assessment; it is concluded that utilization of IVG, once its efficacy and safety are guaranteed, could be permissible by strictly adhering to Islamic ethical principles related to marriage, biological/genetic relatedness, sexual intercourse, and moral status of the embryo/fetus versus that of the gamete. As a result, IVG will be acceptable for treating primary infertility, age-related infertility, and preventing genetic diseases. However, it will be unacceptable for application in posthumous reproduction, donor gametes, genetic enhancement, and procreation in same-sex couples.

Singapore needs to update regulation of frozen egg donation after permitting social egg freezing.

With social egg freezing being permitted in Singapore, there is expected to be an accumulated surplus of unused frozen eggs (vitrified oocytes) available for donation in coming years. A comprehensive update of current healthcare regulations pertaining to frozen egg donation is needed to resolve various pertinent ethical issues. In particular, the issue of egg donor anonymity should be addressed, together with the lack of sharing of medical and family information about the donor to prospective recipient patients and donor-conceived offspring. Rigorous and comprehensive genetic testing of prospective egg donors must be mandated to protect the welfare of recipient patients. Older women above 35 years of age should be required to have at least one child, before being allowed to donate their unused frozen eggs, to prevent any future regret and psychological problems of remaining childless, while being unsure of whether they have an unknown genetic offspring out there. New regulations drafted to address these ethical issues must also prevent potential conflicts of interests. For example, fertility doctors soliciting and encouraging former patients to donate their unused frozen eggs face an obvious conflict of interest, because additional medical fees will be earned by performing the egg donation procedure on other patients. A centralized donor registry should be established by the Singapore government to oversee the distribution and allocation of donated unused frozen eggs to infertile IVF patients. Such a registry could also facilitate sharing of vital health information about the donor to recipient patients and donor-conceived offspring.

Is social egg freezing (oocyte cryopreservation) for single women permissible in Islam? A perspective from Singapore.

Elective egg freezing (oocyte cryopreservation) for fertility preservation - commonly referred to as social egg freezing or non-medical egg freezing, will be permitted in Singapore from 2023. There is a need for clear religious directives on social egg freezing for the minority Muslim population in Singapore, due to conflicting Fatwas on this medical procedure that were issued in different Islamic countries, in particular Egypt and Malaysia. Although social egg freezing would be beneficial for the fertility preservation of many single Muslim women who are unable to start a family due to various personal circumstances, there are also various potential risks and harms of this medical procedure at the individual and societal level. Hence, based on Maqasid Al-Shariah, by which preventing harm takes precedence over securing benefit in medical treatment (Tadawi), it is posited that social egg freezing should be classified as Makruh, which is permissible but discouraged in Islam.

Investigations of oocyte in vitro maturation within a mouse model.

This study attempted to develop a 'less meiotically competent' murine model for oocyte in vitro maturation (IVM), which could more readily be extrapolated to human clinical assisted reproduction. Oocyte meiotic competence was drastically reduced upon shortening the standard duration of in vivo gonadotrophin stimulation from 48 h to 24 h, and by selecting only naked or partially naked germinal vesicle oocytes, instead of fully cumulus enclosed oocyte complexes. With such a less meiotically competent model, only porcine granulosa coculture significantly enhanced the oocyte maturation rate in vitro, whereas no significant enhancement was observed with macaque and murine granulosa coculture. Increased serum concentrations and the supplementation of gonadotrophins, follicular fluid and extracellular matrix gel within the culture medium did not enhance IVM under either cell-free or coculture conditions. Culture medium conditioned by porcine granulosa also enhanced the maturation rate, and this beneficial effect was not diminished upon freeze-thawing. Enhanced IVM in the presence of porcine granulosa coculture did not, however, translate into improved developmental competence, as assessed by in vitro fertilization and embryo culture to the blastocyst stage.