30spotlight
MD Singapore May 2011
Fertile Future
Fertility Preservation Techniques
Dr Kelly Loi
Fertility problems may arise due to problems in the female or the male reproductive system. Female infertility reasons can broadly be divided into 1) ovulation disorders, eg, caused by polycystic ovaries, 2) endometriosis and 3) tubal disease. In secondary infertility, it is possible that a patient had an underlying health problem when she conceived before, but was fortunately not affected then.

Age is an important contributing factor to infertility. Although the evidence is less strong compared to women, men may also become less fertile as they get older. In men, the quantity and quality of sperm may deteriorate with time, making it difficult for them to reach and fertilise an egg. This can occur as a result of poor diet or lifestyle habits as well as chronic illnesses such as diabetes and raised blood pressure.

The likelihood of conceiving ranges from 20% a month in a woman in her late 20s to 8% in the late 30s. Even the success rate of artificial reproductive treatment is affected by age and pregnancy rates fall with increasing age, from 40% in women < 35 years to just 10% in women over 40 years.

Women are born with a fixed number of eggs. With increasing age, there is a fall in ovarian reserve, ie, the number of functioning follicles or eggs left in the ovaries. In cases of early menopause, the eggs run out much sooner than usual. In addition, there is also a decline in the quality of eggs, with an increased risk of genetic abnormalities. This, in turn, results in an increased risk of miscarriage. Women under the age of 35 years have about a 15% chance of miscarriage while those 35-45

years old have a 20-35% chance of miscarriage.

With increasing age, our general health also tends to decline. Existing conditions may worsen or new illnesses may develop, which can have an impact on fertility too.

Referring to a Fertility SpecialistEarly diagnosis and treatment of infertility is crucial in the successful management of a couple seeking infertility treatments. Infertility is defined as the inability to conceive after one year of unprotected sexual intercourse. Ideally, the frequency of intercourse should be two to three times a week.

Up to 90% of couples should have conceived by the end of the 1st year of trying. At this point,

if they still have not conceived, further investigations are warranted. However, older couples should be referred to a specialist earlier, particularly in the case of women over the age of 35. It would be prudent to refer them to a specialist after six months of trying to get pregnant.

An early referral is also indicated if a female patient has a history of amenorrhoea (no periods), oligomenorrhoea (infrequent periods), dysmenorrhoea (painful periods), pelvic inflammatory disease (PID) or previous surgery. In such scenarios, the likelihood of gynaecological disorders is high and she should seek specialist advice sooner rather than later. A history of menstrual irregularity could indicate an ovulation problem

Medical Advice for Patients Trying to Conceive
For couples
  • Try to start planning for a family as early as possible
  • Maintain a normal weight, exercise and eat a diet rich in fruits, vegetables and antioxidants
  • Stop smoking as smoking impairs sperm quality and female smokers are 1.6 times more likely to be infertile
  • Limit alcohol intake to two drinks per day
For women
  • Limit coffee intake to one cup a day as high levels of caffeine are associated with decreased fertility and an increased risk of miscarriage
  • Take folic acid to prevent certain birth defects
For men
  • Wear loose-fitting undergarments
  • Avoid extremely hot temperatures, such as hot tubs or saunas
  • Use lubricants which are suitable for conceiving
MD Singapore May 2011
30spotlight
which would benefit from ovulation induction medications. Painful periods may indicate the presence of endometriosis, ovarian cysts or fibroids, which may benefit from surgery to improve her fertility status. A history of PID or previous pelvic surgery may cause tubal disease which would then require tubal surgery to unblock the tubes, or in vitro fertilisation to bypass the tubal blockage. Fertility Preservation for Cancer PatientsTreatments for cancer – such as chemotherapy and radiotherapy – may damage fertility. In such cases, sperm and eggs can be frozen before treatment starts in order to prolong fertility.

Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. It has been estimated that by 2010, one in 250 young adults will be childhood cancer survivors (Blatt, 1999). Quality of life is an important issue for cancer survivors and fertility after cancer treatment is often a concern. With the recent success and advances made in fertility preservation for cancer patients, international guidelines now recommend that these options should be discussed with the patient. If a young patient is diagnosed with cancer, it is important to let them know early about such possibilities.

The strategies to preserve fertility in women with cancer include frozen storage of embryos, storage of oocytes for future in vitro fertililisation and storage of ovarian tissues.

Cryopreservation of embryosCryopreservation of embryos is the most established technique but requires ovarian stimulation, oocyte retrieval and in vitro fertilisation, all of which takes about two to five weeks. This may not be practical for many cancer patients and
exposure to the high oestrogen milieu during ovarian stimulation with gonadotrophins is undesirable in patients with oestrogen-sensitive tumours such as breast cancer. It is also not an option for pre-pubertal girls as well as to women who do not have a partner and do not want to use donor sperm to fertilise their eggs. However, if embryos are frozen, the pregnancy success rate per thaw cycle for non-cancer cases is well-documented at around 20%.Cryopreservation of oocytesCryopreservation of mature oocytes requires ovarian stimulation and will also delay cancer therapy. Without ovarian stimulation, a reasonable number of immature oocytes may be retrieved. The current trend is to retrieve these immature oocytes and mature them in vitro before freezing them by vitrification. Vitrification refers to a method of 'rapid freezing' to prevent ice crystal formation in the eggs which tends to destroy the egg cells. To date, results are increasingly encouraging, with a live birth rate of around 4% per thawed oocyte.Ovarian tissue cryopreservation and transplantationIn recent years, there have been an increasing number of reports in the literature of successful restoration of fertility after auto-transplantation. In such cases, before cancer treatment is commenced, ovarian tissue is surgically removed and frozen. If the patient is diagnosed to have premature menopause following cancer treatment but is keen to get
pregnant, the frozen ovarian tissue can be thawed and transplanted back into the patient. At least 10 live births so far have been reported following such transplantation.Fertility preservation for malesSemen cryopreservation is an established technique for adult males, but is difficult in adolescents. For adolescents as well as prepubertal boys, testicular tissue may be harvested prior to gonadotoxic cancer therapy and cryopreserved. Because of the absence of mature gametes, cryopreservation of immature tissue is the only way of preserving fertility in young boys. Testicular tissue banking may therefore be promising for fertility preservation in pre-pubertal boys undergoing oncological treatment, although this is still in experimental stages.ConclusionsA survey conducted on the attitudes of our local Singaporean patient population published in the Journal of Reproductive Medicine in 2010, indicated that there is an interest in fertility preservation, and that the medical information received may influence the attitudes of our patients. Greater emphasis should therefore be placed on counselling the patient on fertility preservation during the treatment planning process. To preserve the full range of options, fertility preservation approaches should be considered as early as possible during the treatment planning process.MD
Dr Kelly Loi underwent medical training at the University of Oxford and completed attachments at John Hopkins Hospital, Baltimore, and Massachusetts General Hospital, Harvard University, Boston. She has also undergone advanced training in Belgium in fertility preservation for cancer patients, under one of the foremost experts in this field, Professor Jacques Donnez. Dr Loi is accredited by the Ministry of Health to perform assisted reproductive care and in vitro fertilisation for patients as well as advanced gynae-laparoscopic and reproductive surgery. She is the Medical Director of Health & Fertilty Centre for Women at Paragon Medical Centre (www. healthfertility.com.sg, Tel: 6235 5066).