A Good Egg (And Sperm)
When you’re trying to conceive, many factors are important, including the genetic health of your eggs and your partner’s sperm. Dr Guy Gudex, fertility expert and Medical Director at Repromed, tells of advances in genetic testing techniques and how they apply to preconception and pregnancy.
The importance of the genetic health of both eggs and sperm at the time of fertilisation has long been recognised, and there has been an increasing understanding of the importance of the environment before and around the time of conception. The mum-to-be’s environment can permanently change the function of a gene, influencing, for example, immunity and the risk of cancer in her child. Diet and nutrition are likely to play a role in this. While a baby’s genes are inherited directly from its parents, how these genes express themselves is controlled through epigenetic changes to the DNA. The most commonly studied epigenetic changes researched are chemical marks called “methylation”, which are placed on the genes and changes in methylation can often prevent expression of certain genes. Because methylation requires a defined set of nutrients, a mother’s nutrition and diet before and during pregnancy can affect the setting of these changes, thus affecting the baby’s gene function permanently. A mother’s risk of miscarriage and the chance of having a baby with a chromosome abnormality such as Down syndrome increases when the mum is older than 35 and here in New Zealand, there’s been a significant increase in the number of women having babies in their mid- to late-30s – yet the best chance of becoming pregnant is when a woman is in her mid-20s through to early 30s.
MELATONIN AND FERTILITY
New research suggests that melatonin plays an important role in several physiological processes, including fertility. Melatonin is a hormone produced by the pineal gland in the brain. Recent studies indicate that healthy melatonin levels are necessary for optimal fertility, and that melatonin acts as an antioxidant in the ovaries, removing free radicals and preventing cellular damage. There is some evidence that melatonin improves embryo quality, presumably by improving egg genetic health. There was also some evidence of improved pregnancy rates if the woman takes a melatonin supplement during her cycle of IVF.
The genetic testing of embryos for chromosome abnormalities is called Preimplantation Genetic Screening (PGS), and the technology that allows this has recently become quicker, cheaper, and more accurate. PGS involves removing a few cells from a day 5 embryo, then analysing the cells. The embryo is then frozen to allow time for the results to become available, and to be able to select the healthiest embryo. PGS is of particular interest to couples who are undergoing IVF and have experienced recurrent miscarriage, recurrent implantation failure, or where the mum is over the age of 35 and has a higher risk of a baby with a chromosome problem.
SPERM GENETIC HEALTH
The genetic health of a dad-to-be’s sperm is also important. Sperm DNA fragmentation increases in men who are aged 35 to 40 or older, and also in men who smoke or are obese. Increased sperm DNA damage is associated with reduced fertilisation rates, reduced embryo quality, and reduced pregnancy rates, as well as higher rates of miscarriage and childhood diseases. Assessing sperm DNA damage can help predict the chances of success with IVF and other assisted reproduction techniques. Testing is now available to assess both sperm DNA fragmentation and the level of aneuploidy (abnormal chromosome numbers) in sperm. Sperm DNA fragmentation is most commonly tested on a fresh sample of sperm, using the techniques Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) or Sperm Chromatin Structure Assay (SCSA). DNA fragmentation testing costs $250-450 depending on the type of test used, and the results take two to three working days. A result of more than 20% of DNA fragmentation is considered abnormal. Sperm Aneuploidy Testing (SAT) is now available in New Zealand, with the first test done at Repromed Auckland in September 2015 in partnership with IGENZ, a private genetic testing laboratory based in Parnell. SAT is a diagnostic test to evaluate the percentage of sperm with chromosome abnormalities in a sperm sample. An increase in sperm with chromosome abnormalities has been associated with a decrease in pregnancy rates and a higher miscarriage risk in couples undergoing IVF. SAT can help in the reproductive genetic counselling of infertile couples in order to assess the optimal approach to helping them conceive. In a couple with a history of recurrent miscarriage and recurrent implantation failure at IVF, and in men with significantly impaired sperm parameters, it is particularly useful.
HOW TO IMPROVE SPERM HEALTH
For men, lifestyle changes like quitting smoking and losing weight can help to reduce sperm fragmentation, as can treatment with antioxidants. Most studies have confirmed that antioxidants have a favourable effect on sperm genetic health, including motility (the ability of sperm to move properly through the female reproductive tract to reach the egg), and can improve the chances of pregnancy with assisted conception. A diet containing vitamin C, vitamin E, folic acid, zinc, and selenium have all shown to have beneficial antioxidant effect.
Conversely, a diet with a heavy intake of meat and dairy products has been shown to decrease sperm quality. This may be because of the increased saturated fats found in meat and particularly cheese products. A study from the UK shows that eating fruits and vegetables can improve fertility in men, with the ideal being more than five servings per day.
GENETIC SCREENING IN PREGNANCY
Non-Invasive Prenatal Screening (NIPS) is another area where there has been significant advances in genetic testing. When a woman becomes pregnant, some of the baby’s DNA crosses the placenta into the maternal bloodstream. This foetal blood can be detected in a sample of maternal blood, and then analysed for some of the conditions caused by chromosome changes, such as Down syndrome, the most common chromosome condition seen in children and adults. NIPS can screen for:
- Down syndrome (an extra chromosome 21)
- Edwards syndrome (extra chromosome 18)
- Patau syndrome (extra chromosome 13)
- Sex chromosome conditions such as Turner syndrome (X chromosome missing) and Klinefelter syndrome (extra X chromosome)
The majority of pregnant women in New Zealand undergo the publicly funded First Trimester Combined Screening (FTCS), commonly called the “12-week scan”. FTCS includes an ultrasound at between nine weeks and 13 weeks plus six days of pregnancy, which measures the fluid-filled space at the base of the baby’s neck (nuchal thickness), and a maternal blood test which measures the levels of hormones B-HCG and PAPP-A.
Nuchal thickness is increased when the baby has certain conditions. With NIPS, a negative result means that none of the chromosome conditions tested for were detected, and that no further invasive testing is required unless recommended by your doctor or midwife.
If a positive result is obtained, then usually an amniocentesis or chorionic villus sample (CVS) will be recommended. These highly accurate tests can take place from as early as 10 weeks through to 20 weeks of pregnancy.
A scan at seven to 10 weeks of pregnancy can determine the gestational date of your pregnancy; however, it is still recommended that pregnant mums consider having the 12-week ultrasound scan to check the baby’s anatomy, and the most important scan at 18-20 weeks, to check the baby’s growth and physical development are normal.