Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. PGT-P makes use of polygenic risk scores for conditions which are multifactorial and are significantly influenced by environmental and lifestyle factors. If current predictions are accurate, then absolute risk reductions range from about 0.02% to 10.1%, meaning that between 10 and 5,000 in vitro fertilization patients would need to be tested with PGT-P to prevent one offspring from becoming affected in the future, depending on the condition and the number of embryos available. Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention; however, clinicians and professional organizations have many reservations. The use of PGT-P raises multiple social and ethical concerns including the need for adequate counseling, the setting of realistic expectations, the application of distributive justice, the impact of environmental and social determinants of health, and the potential exacerbation of health inequities. Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patients' unrealistic expectations regarding "healthiest disease-free" embryos. Furthermore, current evidence lacks long-term outcome data and generalizability. Prior to offering PGT-P to patients, additional clinical validation studies are needed. Also, ethical and social considerations raised by PGT-P should be carefully delineated. Systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable prior to the ethical implementation of PGT-P.
Polygenic risk score analyses on embryos (PGT-P) are being marketed by some private testing companies to parents using in vitro fertilisation as being useful in selecting the embryos that carry the least risk of disease in later life. It appears that at least one child has been born after such a procedure. But the utility of a PRS in this respect is severely limited, and to date, no clinical research has been performed to assess its diagnostic effectiveness in embryos. Patients need to be properly informed on the limitations of this use of PRSs, and a societal debate, focused on what would be considered acceptable with regard to the selection of individual traits, should take place before any further implementation of the technique in this population.
Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS (including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits). Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a society-wide conversation about this technology is made. (Funded by the National Institute on Aging and others.).
For many patients with endometriosis, laparoscopic surgery is the most effective treatment to alleviate severe chronic pelvic pain and improve quality of life. Because endometriosis is common among individuals with infertility, surgery is often considered alongside fertility evaluation and treatment to manage symptoms, identify disease pathology, and restore pelvic anatomy. In patients who desire pregnancy, the decision of whether and when to pursue surgery should be guided by clear medical indications and shared decision making between the patient and their obstetrician-gynecologist. In recent months, however, religious and political groups have sought to reframe this medical decision as an ideologic and moral one, advocating for endometriosis surgery in nearly all patients with infertility and claiming that this can eliminate the need for assisted reproductive technologies. This framework, known as restorative reproductive medicine (RRM), aligns with efforts to promote the "personhood" of fertilized eggs, restrict access to in in vitro fertilization (IVF), and advance endometriosis surgery and lifestyle modifications as "root-cause treatment leading to natural fertility." Recent editorials and issue briefs in the obstetrics and gynecology literature have discussed the serious ethical, medical, and policy implications of RRM, yet there remains an urgent need to address specifically the unfounded claims about endometriosis surgery and its purported advantages over assisted reproductive technology. This article examines the social context of this controversy and reviews the current evidence regarding the indications, benefits, and limitations of endometriosis surgery in the management of infertility. In contrast to RRM's assertions, no evidence supports the adoption of endometriosis surgery as a replacement for IVF or as a primary treatment for infertility. Rather, the role of surgery in fertility care is highly nuanced and depends on each patient's clinical presentation, reproductive goals, and personal priorities.
Infertility affects 1 in 6 people globally (and up to a third of physicians) and is recognized by the World Health Organization and the American Medical Association as a disease. Since 1978, the development of assisted reproductive technology (ART), which is defined as fertility treatments in which gametes or embryos are handled in vitro, has made it possible to overcome otherwise insurmountable barriers to conception and has led to the birth of more than 10 million children worldwide.