Although the issue of sex selection raises serious ethical concerns, and selection of embryos on the basis of sex, without mitigating reasons such as sex-linked disease, is illegal in many countries, researchers recently announced they had developed a technique that is safe and around 80% effective in producing babies of the desired sex.
Their study’s findings are causing alarm among experts in the field, who say there are many ethical issues.
The Independent reports that for their study, the scientists had set out a technique to separate and select the sperm beforehand, meaning the sex of the embryos could be determined.
They selected sperm based on whether they contained an X chromosome (making female offspring) or a Y chromosome (making male offspring), using density measures.
Sperm containing an X chromosome are slightly heavier than those containing a Y chromosome, the study team suggested.
The researchers, including Professor Gianpiero Palermo from Weill Cornell Medicine in New York, wrote: “Although ethically debatable, expressing a sex preference for offspring is popular among couples, and not limited to those undergoing infertility treatment.
“Sperm sex enrichment, within a protocol of PGT-A, enables the selection of embryos for the desired sex. Our sex selection method does not increase the proportion of additional aneuploid embryos.
“Therefore, it can be regarded as extremely safe as well as efficient, inexpensive and ethically palatable.”
Darren Griffin, professor of genetics at the University of Kent, said: “The issue of sex selection is an ethically fraught one.
“Selection of embryos on the basis of sex, without mitigating reason such as sex-linked disease, is illegal. Separating sperm beforehand may provide a legal loophole in some countries but not the UK.
“There have been numerous methods around for decades, some effective but potentially harmful, others dubious in their effectiveness. The current paper seems to have found a method in which the approach is effective to some degree.
“It involves separation on the basis of density, and the difference in this study compared with previous ones I have seen is that it performs industry standard tests on the sperm and on the embryos.
“I am convinced that the science is sound and that, instead of the usual 50:50 ‘coin toss’ then a couple can get a baby with the desired sex a little under 80% of the time.”
Dr Channa Jayasena, head of andrology at Imperial College London, said: “The results show convincingly that this technique is able to select sperm to determine the sex of embryos made using those sperm.
“However, their technical achievement is insignificant compared with the serious ethical concerns raised by the research.
“The authors clearly describe the understandable ethical concerns of embryo selection and abortion of pregnancies based on (usually female) sex.
“Yet they propose sperm selection as an ‘ethical’ alternative to embryo selection. I find this incredible since sperm selection is just another way of selecting embryos to manipulate the sex of offspring, with detrimental societal implications.
“I am alarmed that such technology might become more widespread in clinical practice. Currently, it is prohibited in the UK to select offspring unless they have a serious medical problem.”
Jayasena added that despite not described in the study, their technique might be adapted in the future to select for other bodily traits, such as sperm containing a gene affecting skin or eye colour.
“This research therefore raises serious ethical concerns which need to be addressed urgently through regulation.”
The small trial was conducted using 1 317 couples, and split into two groups, with 105 men in the study group in which the new technique was used.
According to the study, 59 couples in this group desired female offspring and the technique resulted in 79.1% (231/292) female embryos.
This resulted in the birth of 16 girls without any abnormalities.
Forty-six couples wanting male offspring ended up with 79.6% male embryos (223/280), resulting in the birth of 13 healthy baby boys.
However, in the study, published in the PLOS One journal, the sex of the embryo chosen for transfer was not known.
Study details
A non-randomised clinical trial to determine the safety and efficacy of a novel sperm sex selection technique
Stephanie Cheung, Rony Elias, Philip Xie, Zev Rosenwaks, Gianpiero D. Palermo.
Published in PLOS One on 22 March 2023
Abstract
The desire to have offspring of a specific sex has a long history but has been particularly present with the appearance of assisted reproduction. However, embryo selection raises ethical concerns. Thus, several techniques to select sex-specific spermatozoa have been proposed but carry limitations. There are many variations of each technique, and some are time consuming and costly. Concerns about effectiveness and safety have also rendered many of them unappealing. Therefore, we propose a novel sperm sex selection technique (SST) that appears to be consistently safe and effective.
A single-centre, non-randomised clinical trial was designed. We included 1 317 couples, who were assigned to one of two groups: ICSI/PGTA or ICSI/PGTA+GS. Ejaculates from male partners of couples in the ICSI/PGTA+GS group (n = 105) were processed using SST to enrich spermatozoa for their desired sex. Standard sperm processing was carried out for couples undergoing PGT-A solely for aneuploidy (n = 1,212), comprising the ICSI/PGTA control group.
To validate the efficacy of our technique, we performed an analysis on spermatozoa pre- and post-selection, followed by an assessment of the proportion of the conceptuses’ sex to confirm clinical reliability. We also followed up on ICSI clinical outcomes and child/newborn health to establish the safety of our method. Our main outcome measures included the proportion of spermatozoa and embryos enriched for female and male sex, as well as embryo euploidy rates and ICSI clinical outcomes. These outcomes were compared between the two groups. For the ICSI/PGTA group (n = 1,212) (maternal age, 37.0±4yrs; paternal age, 39.1±6yrs), with ejaculated spermatozoa processed in the standard fashion, 2,303 ICSI cycles (1.2±1) yielded an 81.0% (14,375/17,737) fertilisation. PGT-A results indicated a euploidy rate of 73.1% (n = 3,718) for female and 72.4% (n = 3,054) for male embryos.
These couples achieved a 76.4% (699/915) implantation and 65.2% (597/915) clinical pregnancy rate, with 551 deliveries (48.5% female, 51.5% male). All 105 men in the ICSI/PGTA+GS group had sperm specimens with an equal sex distribution at baseline. Of them, 59 (paternal age, 40.9±6yrs) who desired female offspring obtained an 81.6% enrichment after SST. They underwent 73 ICSI cycles with their partners (maternal age, 37.9±4yrs), achieving a 77.3% (583/754) fertilisation. This resulted in 79.1% (231/292) female embryos that generated a 79.3% (23/29) implantation rate, with 16 singleton deliveries of the desired female sex without major or minor congenital malformations. Forty-six couples (maternal age, 37.3±4yrs; paternal age, 40.7±6yrs) desiring male offspring obtained an 80.8% sperm sex enrichment. They underwent 50 ICSI cycles, achieving a 75.4% (462/613) fertilisation and equivalent proportion of male embryos (223/280, 79.6%). Their implantation was 90.5% (19/21), with 13 singleton deliveries of healthy male offspring. Furthermore, 78.8% (182/231) of female and 66.4% (148/223) of male embryos from the ICSI/PGTA+GS cohort were euploid.
These euploid rates were comparable to those from the ICSI/PGTA group. In couples undergoing ICSI with PGT-A, SST consistently enriched spermatozoa, resulting in a higher proportion of embryos and thus offspring of the desired sex. Moreover, SST did not impair the fertilisation or embryo developmental competence of spermatozoa, nor did it affect offspring health.
See more from MedicalBrief archives:
Unregulated US fertility industry a haven for controversial services
Lack of consideration of sex and gender in clinical trials for COVID-19