Response to 'Ovarian tissue grafts to combat the menopause' by Dr Melanie Davies

Due to the limited space offered by BioNews we can only take up a few but highly significant points raised by Dr Melanie Davies (see BioNews 1011). Readers are referred to a fuller discussion, which is in response to the British Menopause Statement and currently submitted for publication.

Background

The work of ProFaM specialists is based on nearly 20 years and over 5000 reported cases of human ovarian tissue cryopreservation (OTC); followed by over 300 transplantations, which succeeds decades of animal research (1); and is recognised by Dr Davies in her comment, 'ovarian tissue freezing is a valuable option for children and young women facing cancer treatments that will destroy fertility'.

Graft Survival

Ovarian tissues have been transplanted in 318 patients (360 ovarian transplants) over the past 15 years, with survival from only a few grafted strips in single transfer episode reported from two to 10 years, and a mean duration of 5.5 years (2,3,4). This data is based on a range of patient conditions and technical variances from different centres. 

ProFaM removes a third to half of the outer cortex of an ovary using advanced, state of the art technologies resulting in as consistent as possible prepared strips. Storing from a minimum of four to eight (often more), if based on published work (and all its variances) a single transplant episode to restore ovarian function lasts for a mean of 5.5 years, then 20 years of continued hormone production is plausible; especially as ProFaM will work with healthy patients of all ages within the reproductive years. 

Surgery is not without risk.

We agree that no medical or surgical intervention, including laparoscopy, IVF and hormone replacement therapy (HRT) – see Royal College of Obstetrics and Gynaecology (RCOG) and NICE statement about HRT – is without risk; and patient counselling is essential.

Laparoscopy is quite safe surgery and recommended by all medical authorities for diagnosis and treatment of conditions affecting the quality of life, such as infertility and endometriosis (NICE guideline).  Laparoscopy is also a recognised surgery for many conditions with an existing non-invasive alternative like tubal ligation (RCOG guideline). Every day in each hospital all around the world, laparoscopy is provided safely for different indications including quality of life condition of less magnitude than the impact of menopause (Department of Health statistics). 

Nearly 25 percent of women of reproductive age will have an intervention that will provide safe access for the ovary without need for laparoscopy, for which OTC at that stage is also an option.  

 'It is an attractive idea to "give back your own hormones", modern hormone replacement therapy (HRT) is based on oestradiol which is bio-identical.'

A recent Editorial, 'BMS Consensus Statement' in the Post Reproductive Health Journal (5) states: '"bioidentical" is often used as a marketing term by clinics'. They are 'precise duplicates of hormones such as estradiol E2, estriol E3, estrone E1, progesterone...' but there are concerns around 'absence of medical evidence to support the practice of combining E1 and E3 with E2', absence of warnings on the products regarding potential risks and side effects.'; the dosage of oestrogen, and 'issues related to purity, potency and safety'. Further salutary information can be found at ref 5.

Indeed, ovarian tissue cryopreservation should be compared against the current standard of HRT. HRT is associated with a small but significant risk of thromboembolism, stroke, heart disease (in older women) and breast cancer. The NHS information site states: 

'Taking combined HRT (oestrogen and progestogen) is associated with a small increased risk of breast cancer – some studies have suggested that for every 1,000 women taking combined HRT, there will be around five extra cases of breast cancer and 'Oestrogen-only HRT can increase the risk of womb cancer (also called endometrial cancer).

However, the latest study in the Lancet indicates the breast cancer risk may be significantly higher (from 5/1000 to 20/1000 for oestrogen plus daily progestagen preparations). The authors conclude: 'In western countries there have been about 20 million breast cancers diagnosed since 1990, of which about 1 million would have been caused by MHT' (HRT). (6)

So is OTC any safer?  It has to be implied; but it is implied by those women who are ok with the premenopausal state, but who cannot take the pharmacological approach when menopause hits. 

Furthermore, HRT does not resolve menopausal symptoms in all women; and not all women can tolerate HRT. It has been reported that 18 percent of patients of premature menopause discontinue the HRT because of side effects. Furthermore, for many women who, for clinical reasons, are prevented from considering HRT, OTC could be considered, albeit with very specific case-by-case assessment.

'Egg and embryo freezing are well-established techniques'

Egg and embryo freezing cannot be grouped together. Egg freezing is indeed a viable option but it is well recognised that a minimum of 20-30 eggs need to be stored (live birth per egg around 8 percent in women under 36 years and 3 percent in women 36-39 years; equating to 29.6 oocytes per live birth). This would require on average three cycles of stimulation, at a cost of over £15,000 (7). Plus, there are the necessary several rounds of egg collection, with attendant risks on each occasion, as well as multiple gonadotrophin stimulation rounds and the associated visits to the clinic for blood tests and monitoring. This compares to OTC which does not require any drug regimen, and a single visit to the hospital at a mutually agreed time at any point in the cycle.