New research suggests that a common chemotherapy drug combination may increase the number of immature eggs in the ovaries. The researchers caution, however, that it is too soon to say how this affects women's fertility. They say more studies should now be done to confirm the findings, look in more detail at the individual drugs involved, and explain the underlying biology.

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If confirmed in further studies, the new findings challenge the accepted view that a woman is born with a fixed number of eggs and cannot grow more in her lifetime.

The small study - reported in the journal Human Reproduction - is the work of a team from the University of Edinburgh in the United Kingdom that analyzed ovarian tissue samples from 14 women who had undergone chemotherapy, and from 12 healthy women.

It is hard to predict if a woman is likely to be fertile after chemotherapy treatment. Damage to eggs and/or fertility can depend on the woman's age, the types of drug, and the drug doses.

If confirmed in further studies, the new findings challenge the accepted view - as others have - that a woman is born with a fixed number of eggs and cannot grow more in her lifetime.

The study concerns a combination of chemotherapy drugs known as ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) that is used to treat Hodgkin's lymphoma (HL) - an uncommon cancer of the lymphatic system.

ABVD is already known to be one of a few chemotherapy regimens that does not affect women's fertility.

The Edinburgh team wanted to investigate this further by examining the follicles in the ovarian tissue of treated patients. Follicles are small fluid-filled cavities in the ovaries that contain immature eggs.

ABVD-treated ovarian tissue had more non-growing follicles

The researchers obtained ovarian biopsies from 13 HL patients (six adolescent and seven adults) and one non-HL patient.

Two of the HL patients and the non-HL patient had received no treatment before biopsy collection.

The other 11 patients (all HL) had undergone one or two chemotherapy treatments before biopsy sampling (eight of them receiving ABVD, the others receiving another combination therapy).

The researchers analyzed the tissue samples and compared them with ovarian tissue from age-matched healthy women. They also examined the developmental potential of follicles by culturing some of the patients' tissue samples for 6 days.

The chemotherapy patients had donated their tissue as part of a procedure for freezing their ovaries for fertility preservation. The healthy patients had donated their tissue while undergoing cesarean section.

The results showed that tissue from eight of the HL patients treated with ABVD had a much higher concentration of non-growing follicles or immature eggs, compared with tissue from age-similar healthy women or the patients treated with a different chemotherapy combination.

The team notes that the ovary tissue in the ABVD-treated samples also appeared to be in a healthy condition - similar to that seen in tissue from the ovaries of young women.

The results also show that follicle growth in the cultured samples occurred in all groups, but development to the secondary stage was very limited in the samples from women treated with ABVD. Also, samples from untreated HL patients grow in a similar way to samples from healthy women.

The researchers suggest the findings should be regarded with caution, because although they analyzed a large number of follicles, the data came from a small number of biopsies from only a few patients. Nevertheless, the results were consistent and could be far-reaching.

The study raises several questions. For instance, does the fact the ABVD chemotherapy appears to increase follicle density in ovarian tissue mean that it could increase the number of mature eggs?

"We need to know more about how this drug combination acts on the ovaries, and the implications of this."

Senior author Prof. Evelyn Telfer

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