The use of expanded carrier screening of gamete donors

Abstract

STUDY QUESTION What are the sperm and egg donor rejection rates after expanded carrier screening (ECS)? SUMMARY ANSWER Using an ECS panel looking at 46/47 genes, 17.6% of donors were rejected. WHAT IS KNOWN ALREADY The use of ECS is becoming commonplace in assisted reproductive technology, including testing of egg and sperm donors. Most national guidelines recommend rejection of donors if they are carriers of a genetic disease. If the use of ECS increases, there will be a decline in the number of donors available. STUDY DESIGN, SIZE, DURATION A review of the current preconception ECS panels available to donors was carried out through an online search. The genetic testing results of donors from Cryos International were analysed to determine how many were rejected on the basis of the ECS. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on gamete donors and their carrier status was provided by Cryos International, who screen donors using their own bespoke ECS panel. The ECS panels identified through the review were compared to the Cryos International panel and data. MAIN RESULTS AND THE ROLE OF CHANCE A total of 16 companies and 42 associated ECS panels were reviewed. There were a total of 2673 unique disorders covered by the panels examined, with a mean of 329 disorders screened. None of these disorders were common to all panels. Cryos International screen 46 disorders in males and 47 in females. From 883 candidate donors, 17.6% (155/883) were rejected based on their ECS result. Carriers of alpha-thalassaemia represented the largest proportion of those rejected (19.4%, 30/155), then spinal muscular atrophy (15.5%, 24/155) and cystic fibrosis (14.8%, 23/155). LIMITATIONS, REASONS FOR CAUTION Panel information was found on company websites and may not have been accurate. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the need for consistent EU regulations and guidelines that allow genetic matching of gamete donors to their recipients, preventing the need to reject donors who are known carriers. A larger ECS panel would be most beneficial; however, this would not be viable without matching of donors and recipients. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained. J.C.H. is the founder of Global Women Connected, a platform to discuss women’s health issues and the Embryology and PGD Academy, who deliver education in clinical embryology. She has been paid to give a lecture by Cryos in 2019. A-B.S. is an employee of Cryos International. TRIAL REGISTRATION NUMBER N/A

A SWOT analysis of unregulated sperm donation

“…Many recipients and regulators seem to start from the premise that sperm banks should guarantee zero risk. One of the prime examples of this belief is the introduction of mandatory expanded carrier screening for donors (Payne et al, 2021). The gain in risk reduction of ECS is minimal (below 1%) (Pennings, 2020).…”

A case series of adrenoleukodystrophy in children conceived through in vitro fertilization with an egg donor

“…Current American College of Medical Genetics and Genomics guidelines in these cases recommend X-ALD testing be offered to “all pregnant patients and those planning a pregnancy” because of the X-linked inheritance pattern and the prevalence of greater than 1/40,000(3). A recent study demonstrated that expanded carrier screening of gamete donors led to the rejection of 17.6% of donors ( 19 ). Roughly half of those rejected carried 1 of the 4 conditions that American Society for Reproductive Medicine guidelines specifically advise should be required or specifically considered for all gamete donors; however, the remaining variants identified in prospective donors would not have been detected based on current screening recommendations ( 2 , 19 ).…”

“…A recent study demonstrated that expanded carrier screening of gamete donors led to the rejection of 17.6% of donors ( 19 ). Roughly half of those rejected carried 1 of the 4 conditions that American Society for Reproductive Medicine guidelines specifically advise should be required or specifically considered for all gamete donors; however, the remaining variants identified in prospective donors would not have been detected based on current screening recommendations ( 2 , 19 ).…”

An analysis of the outcome of 11 712 men applying to be sperm donors in Denmark and the USA

“…HIV, hepatitis B virus (HBV), Chlamydia trachomatis according to the screening guidelines listed above) and for genetic screening. The Cryos approach to genetic screening of sperm donors has been published recently ( Payne et al , 2021 ) and in 2018 and 2019 included testing for 46 recessive disorders. Applicants who passed the genetic and infectious diseases screening and completed the relevant consent forms were invited to start donating.…”