What is IVF?
In vitro fertilisation is a form of assisted reproductive technology which involves the combination of human eggs and sperm outside of a woman’s body. Prepared ova and sperm cells are cultured together in the laboratory overnight. The resulting fertilised eggs are allowed to develop to the 8-cell stage – typically 2-3 days – before being graded and selected for transfer into the woman’s uterus, with the ultimate aim of a successful pregnancy.
When was IVF pioneered?
The world’s first baby conceived using IVF – Louise Brown – was born in the UK on 25 July 1978. The technique was developed for humans by Patrick Steptoe and Robert Edwards of the Centre for Human Reproduction in Oldham. This work built upon the successful mammalian in vitro fertilisation research of Chinese-American scientist Min Chueh Chang, who demonstrated the technique in 1959 by implanting black rabbit embryos conceived in the lab into a white rabbit.
What fertility issues is it designed to overcome?
Lack of reproductive success can be due to many factors, including low sperm count, poor sperm or egg quality, or inefficient transport of eggs from ovary to uterus. IVF was originally intended to address problems of blocked fallopian tubes, but it has proved to be useful for many types of infertility, including unexplained infertility.
• increase the number of eggs available for fertilisation at one time
• overcome motility issues by placing eggs directly in contact with sperm
• allow the creation of multiple embryos
• observe and select embryos for the highest likelihood of survival
Normally, only one ovarian follicle matures to produce a single egg during each menstrual cycle. IVF uses synthesised hormones to stimulate the production of multiple eggs simultaneously. These eggs are removed directly from the ovary and placed in contact with sperm. Because multiple eggs are ripened at once, IVF can condense many months’ worth of attempts at spontaneous conception into a single, intensive effort.
How are embryos graded and selected for implantation?
Eggs are assessed by their appearance under the microscope following fertilisation. The resulting embryos are assigned a grade based on the number and regularity of cells, how quickly they divide, degree of fragmentation and other cell characteristics.
Any nonviable or abnormally developing embryos can be discarded in favour of those with a greater likelihood of survival. Embryos with a regular, unfragmented appearance have a higher likelihood of successfully implanting. However, the science of embryo selection is not standardised, and grading criteria can vary from clinic to clinic.
Regardless of which criteria are used, there is always a chance that a high grade embryo may fail to implant or develop once transferred to the uterus. Equally, a low grade embryo may develop into a perfectly healthy child.
What happens to embryos that are not implanted?
Embryos that are of good quality but are not selected for transfer can be frozen for future attempts using liquid nitrogen. This process is called cryopreservation. The embryos are placed in a cryoprotectant fluid that replaces much of the water in the cells, to help prevent freezing damage.
The mixture is then cooled using liquid nitrogen, either gradually – using a controlled-rate freezer – or through a process called vitrification, which lowers the temperature of the cells extremely rapidly so that ice crystals do not have time to form. The frozen embryos are stored in freezers at -196 degrees Celsius, where they can be maintained for years. When the embryos are needed for another round of treatment, they are gradually thawed in a reversal of the freezing process.
Some sustain damage during freezing or thawing and do not survive. Around 60 – 70% can be expected to remain viable if frozen correctly. Even when the embryos appear healthy, pregnancy rates from IVF using frozen embryos are lower than those using fresh embryos. However, there is no evidence to show that babies born from frozen embryos have any lasting health consequences associated with spending time in the deep freeze.
Should the couple choose not to attempt another pregnancy, the embryos can be donated to medical research, donated to another couple, or taken out of storage and allowed to perish.
How successful is IVF?
Rates of success vary widely, influenced largely by factors such as maternal age and the number of embryos implanted, as well as other complicating factors related to the cause of infertility. Pregnancy rates per cycle of IVF decline sharply as the age of the woman increases, from in the region of 40 – 50% for women under 35 to approximately 5-10% for women over age 40.
It can be difficult to compare success rates across fertility clinics. Some clinics use statistics that include chemical pregnancies, which are pregnancies confirmed by blood or urine test, or clinical pregnancies, which are confirmed using ultrasound.
It is important to distinguish these from pregnancy rates that count live births only. This is because the ongoing risk of miscarriage will likely lead to a lower live birth rate than what the initial pregnancy rates reflect.
Are pregnancies at higher risk following IVF?
Due to the common practice of transferring multiple embryos simultaneously to increase chances of a successful pregnancy, women undergoing IVF have a much higher than usual incidence of twins or triplets.
In general, pregnancies involving multiples incur a significantly higher risk of miscarriage, stillbirth, preterm delivery, low birth weight and other serious complications when compared to singleton pregnancies. For this reason, many fertility clinics are now encouraging the transfer of a single embryo at a time, especially in women under 37.
However, even when only a single embryo is transferred, the likelihood of that embryo dividing to become identical twins is increased in IVF for reasons that are not yet understood.
IVF in NZ
* About 25% of NZ couples have problems conceiving and about 5% have in vitro fertilisation treatment.
* Approximately 2500 IVF treatments are completed each year
* IVF costs between $8000 and $12000
* Our public health system funds 2 treatment cycles per eligible couple
* Each year about 1.5% of all children born in NZ are IVF babies
This Science Byte was reviewed by John Hutton (Fertility Associates Wellington and University of Otago Wellington School of Medicine and Health Sciences) and Wayne Gillett (Associate Professor, Women’s and Children’s Health, Obstetrics & Gynaecology, Health Sciences, Dunedin School of Medicine)