Fertility After Cancer - Part 1

Chemotherapy and cancer drugs

Fertility after cancer - Originally published in February 2004 icon

Fertility after Cancer

What’s the chance of having a child after treatment for cancer?

Fertility after cancer - Part 1 of a vital report that effects the future of many women - and men too.

By Madeleine Kingsley

Family comes firmly first for West Midlands student Louise Lockley. Aged 19, in millenium year, Louise had Ewing’s Sarcoma. She was in for a rocky ride with chemotherapy and surgery but, crucially, her mother Linda came with her to her first oncology consultation. "Louise sat there, too shocked to talk" Linda recalls. "She had a hand-size tumour on her back." But when Dr Peake explained that chemotherapy could damage her fertility, Louise broke down completely. "Getting married and having children has always been top of my priorities" explains Louise now.

Fortunately Linda - who had read about male sperm being frozen before cancer treatment- stepped in at once to enquire if anything could be done to preserve Louise’s eggs. "I had no idea whether this was possible says Linda. "I have a feeling that I was the first person for whom it was done at this hospital’ adds Louise. Although it meant delaying the start of life-saving treatment, and although she was warned that the freezing of eggs was still a highly speculative procedure, Louise opted for an ovarian biopsy under general anaesthetic - and the hope that went with it.

Too many women experience the double-dose anguish of a cancer diagnosis compounded by a question mark over their future fertility. Had Linda Lockley not asked directly, it seems unlikely that Louise would have been offered the chance to bank ovarian tissue or store frozen eggs, "as other girls I met in hospital were distressed to have missed out on the opportunity".

Open quotesLouise opted for an ovarian biopsy under general anaesthet - and the hope that went with itClose quotes

In October 2003, Dr David Lee’s breakthrough research in Oregon brought the likelihood of a pregnancy through ovarian transplant one vital step closer to reality: ovarian tissue was implanted into an infertile rhesus monkey, resulting in an egg harvested to produce a healthy test-tube baby. It this technology can be adapted for humans, young women left infertile, after cancer treatment could indeed be rocking their own cradles. The reality may be five, 10 even 20 years off, but it is certainly in the pipeline.

The fact that doctors, scientists and patients are now starting to consider fertility when battling cancer marks a turn in the medical tide. Treatment has so improved that its no longer preoccupied solely with preventing death. There’s now the luxury of considering how best to help survivors give birth after cancer. And - as we shall explore next month - actually achieving that longed-for outcome. The challenges involved in helping more patients are huge, ranging from the deeply emotional (how difficult it can be for an adolescent boy who may never have had sex to provide sperm for storage) to the legalities of frozen egg storage and the daunting bureaucracy surrounding vital studies. Potential to conceive varies so much according to cancer type - five out of 10 men receiving cisplatin for testicular cancer regain fertility after two years, with the figure rising to eight out of 10 five years on.

icon’s interest in post-treatment fertility is timely, with oncologists increasingly airing a hitherto neglected topic, and research funding acquiring a much higher priority. BACUP, for instance, plans a report later in the year on the levels of emotional and medical support women with cancer and hopes of future childbearing now receive.

"Future fertility can seem a difficult subject to broach with a family where a young person is newly diagnosed" says Dr Mark Brougbam, research fellow in paediatric oncology at the Royal Hospital for Sick Children, Edinburgh. "For adolescent boys, it’s potentially embarrassing to discuss, although they and their families may be thinking about it. And yet it’s a really important issue to raise at an early stage, because, apart from the practical side, a lot of stressed families derive benefit from projecting their thoughts forward to the possibility of a time when treatment is past.’

Open quotesFuture fertility can seem a difficult subject to broach with a family where a young person is newly diagnosedClose quotes

Dr Brougham’s research lies in a particularly challenging field: "We so far have nothing to offer pre-pubertal children in terms of preserving fertility and I am focusing on what might be done for young boys - on whether parts of the testes can be taken and stored and whether, when retrieved, could produce cells to be artificially matured or put back into the testes. The technology to help girls from whom ovarian tissue’s taken, is potentially easier, as they are born with all the oocytes they will have in life. With boys the cells go through major changes before becoming mature sperm, so the technology is at least 10 years off.’ At 32, Dr Brougham says it’s very exciting to work on something so long term. Hopefully, before I retire, preserving fertility in very young patients will be routine practice.’

Dr Mike Hawkins, Reader in Epidemiology at Birmingham University, has already spent 20 years studying survivors of childhood cancer. He is currently working on a mammoth study involving 14,000 of the 18000 recorded UK survivors treated between 1940 and 1991. "This study - the first to follow up effects of cancer treatment, and addressing survivors directly, should tell us more about fertility" be says. It will no doubt expand on the previous work I’ve done through GPs which has already found 3000 children born to survivors.

The information about them is says Dr Hawkins, "very reassuring. Rather like thalidomide, there had been a concern whether the rate of birth defects in these offspring would be higher than average. It is not, not even in the offspring of people who had their gonads irradiated as children or those who had drugs that might mutate germ cells and cause problems in the next generation. The evidence is also reassuring in terms of familial cancers, where again one might anticipate, because of quite mutagenic drugs given, that survivors’ children could be at increased risk of cancer. But if you exclude the particular childhood cancers (such as retinoblastoma) that we’ve known for decades are inherited, there is no evidence of any additional risk." Did ongoing fertility among the 10,000 survivors so far identified relate to the type of cancer suffered?

Not so, says Dr Hawkins, it related more to the treatment and primarily to the extent to which the ovary or testes were in the field of radiation received, to the dosage of chemotherapy, and the age at which it was given, as treatment pre-puberty is much more damaging to fertility than post.

Open quotesThe myth still prevails that cancer and chemo are synonymous with later childlessnessClose quotes

For many laymen, the myth still prevails that cancer and chemo are synonymous with later childlessness. So casual listeners to BBC Radio 4’s The Archers, may have thought the storyline far-fetched in which Ruth Archer had gruelling chemo for breast cancer in 2000, yet a year later fell accidentally pregnant with baby Ben. But this "everyday story of country folk" never embellishes the truth. Medically it was unwise of Ruth not to take precautions for two years after taking toxic drugs that could perhaps harm the foetus, but realistically, says Dr Jane Stewart, consultant at the Newcastle Fertility Centre, "there are lots of precedents for women with breast cancer successfully having babies after treatment. About one third of pre-menopausal women will lose their fertility; one third will retain the facility to conceive for a while before premature menopause sets in and a further third will be unaffected." There is also no evidence that women going onto have babies after remaining cancer-free for two years have an added risk of recurrence.

As a rule of thumb, the younger a woman, the less likely she is to stop ovulating permanently after breast cancer Chemotherapy is also often less harsh than that given to sufferers of other cancers. Women wanting a family should always discuss this and the projected chemo regime with their oncologist ascertain drugs known as "alkylating agents’, of which the most common is cyclophosphamide, are traditionally thought most likely to affect chances of pregnancy. But Professor Michael Seckl, consultant medical oncologist at Imperial College, London, stresses that damage to fertility with even the more toxic forms of chemotherapy may have been greatly overestimated.

According to Breast Cancer Care, women whose breast cancer is oestrogen receptor positive may be offered one of three different treatments (ovarian ablation) to stop their ovaries functioning. Of these, radiotherapy will induce infertility only if applied to both ovaries. Oophrectomy (surgical removal of the ovaries) also spells the end of reproductive potential but the hormone treatment Zoladex offers potentially reversible ablation with periods returning within six months of ending treatment.

Open quotesLouise Lockley has been in remission for three years and has ongoing hopes of bearing four childrenClose quotes

Monthly injections of Zoladex taken over two years is one alternative to chemotherapy that may preserve fertility. Tamoxifen, too, looks like a good friend to women wanting children on recovery. Stimulating the ovaries, it actually makes some women more fertile at the start, though ongoing use inhibits periods during the five year period usually recommended for the drug. You are advised not to conceive whilst on Tamoxifen so this may not be an ideal option for older women whose biological clock is ticking loud. But one, admittedly small study at Cornell Medical Centre in New York City, found that every woman on Tamoxifen remained fertile enough to produce "at least one and in some cases two embryos". Dr Jamie Griffo of NYU Medical Centre observes that Tamoxifen is, at least theoretically, also a safer drug than others currently used. But along with UK oncologists, he calls for further research.

Meanwhile, Louise Lockley has been in remission for three years and has ongoing hopes of bearing four children. "Obviously uncertainty remains, but I seem to be one of the fortunate ones with retained natural fertility as well as stored ovarian tissue . I think the drug I took - Etoposide - is quite toxic, and when my periods resumed after treatment they were, at first, quite irregular. My doctor suggested taking the Pill, but I wasn’t ready for that as a way to rebalance my hormones. I took myself off for a private consultation with a gynaecologist where blood tests and an ovarian scan showed everything to be normal. Obviously I can’t be positive until the time comes to try for a baby, but the picture looks encouraging. At hospital check-ups I heard about another woman who had the same cancer as me, then twins at 28. That news made me cry. I like the idea of having grandchildren to ask me what I did at the millennium. I’d say I was in a lot of pain, but I’m still here - and so are you!"

Chemotherapy and cancer drugs
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