Human oocytes have been fully matured in a laboratory setting for the first time, in a move that could lead to improved fertility treatments and new options for young women with cancer who may be facing chemotherapy that could destroy their ovaries.
The scientists, led by Marie McLaughlin, PhD, of the Institute of Cell Biology, University of Edinburgh, UK, took biopsies from the ovarian cortex of 10 women undergoing cesarean sections and attempted to grow follicles into mature eggs. Their findings were published online January 30 in Molecular Human Reproduction.
The research has given new understanding into how human eggs develop at various stages. In previous studies, scientists have developed mouse eggs to produce live offspring and matured human eggs from a relatively late stage of development.
But this latest study is the first time a human egg has been developed in the lab from its earliest stage to full maturity.
However, outside experts point out that the treatment is inefficient, with only around 10% of the eggs developing to full maturity. Out of 87 immature eggs, only nine developed fully. Also, egg quality has not been tested as none had been fertilized.
Dr McLaughlin and colleagues, who include scientists from the Center for Human Reproduction in New York, acknowledge their work is at a very early stage: "We describe here the successful development of a small number of human oocytes capable of acquiring and expressing a level of development approaching that of an ovulated ovum."
Senior author Evelyn Telfer, PhD, of the University of Edinburgh, says: "Being able to fully develop human eggs in the lab could widen the scope of available fertility treatments."
"We are now working on optimizing the conditions that support egg development in this way and studying how healthy they are. We also hope to find out, subject to regulatory approval, whether they can be fertilized," she noted in a statement from her institution.
How Did They Do it? If Replicated, This Could Be a Seminal Advance
Researchers cultured the follicular tissue from the ovarian biopsies in serum-free media for 8 days and then selected 87 intact follicles of 100–150 µg in diameter (mean 120 µg) for further culture. After a further 8 days, 54 of the 87 follicles had reached the next stage of development (antral). They further selected and matured follicles deemed to be developing properly, and ended up with nine mature oocytes.
They note that although this is a small number of samples, it is "proof-of-concept that complete development of human oocytes can occur in vitro."
More work is needed, however, to see if these eggs are morphologically normal and whether they could potentially be fertilized, they recognize.
Commenting on the research in a statement, Daniel Brison, PhD, scientific director of the Department of Reproductive Medicine at the University of Manchester, says: "This is an exciting breakthrough which shows for the first time that complete development of human eggs in the laboratory is possible, more than 20 years after this was achieved in mice.
"As the authors acknowledge, there is much more important research still to do, but this could pave the way for fertility preservation in women and girls with a wider variety of cancers than is possible using existing methods."
Darren Griffin, PhD, professor of genetics at the University of Kent, Canterbury, says, "The main 'selling point' of this paper is that, in the past, the authors have been successful in developing two stages of the process through which ovary material can be taken and an egg ready for fertilization can be produced."
"Here, they have, through meticulous experimentation, worked out how to complete the third and final stage. This is all proof of principle and small numbers at this stage, but the signs are good."
He adds, "It will be a while until this is implemented in the clinic, but if and when it is, this will be seen as one of the seminal advances."
Hope for Cancer Patients and Those Struggling With Infertility
The advance could one day safeguard the fertility of girls with cancer ahead of potentially harmful medical treatment, such as chemotherapy, the authors say.
Immature eggs recovered from patients' ovarian tissue could be matured in the lab and stored for later fertilization. Conventionally, cancer patients can have a piece of ovary removed before treatment, but reimplanting this tissue can risk reintroducing cancer.
As the study has also improved understanding of how human eggs develop at various stages, it could aid research into other infertility treatments and regenerative medicine.
Aileen Feeney, chief executive of the charity Fertility Network UK, commented: "This research is very much in its infancy, but its potential significance for women and girls hoping to protect their future fertility is huge."
The work was funded by the UK Medical Research Council. The authors have reported no relevant financial relationships.
Mol Hum Reprod. Published online January 30, 2018. Full article
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