3 Parents, 1 Child?!

3 parent

Imagine having a father, a biological mother, ANDDD another genetically related mother. Sounds crazy, but could soon be a possibility.

There has been much talk in the media recently about the new in vitro fertilization method. A ground breaking new method that will eliminate any mutations within mitochondrial DNA that can be passed from mother to child, but at the same time, creating a child from the DNA of 3 adults. After much reading of the many articles on the web, this is my quick summary of what 3 parent IVF involves!

Mitochondrial DNA?

Some diseases such as mitochondrial myopathies (muscle affecting conditions) can be caused by mutations within the mitochondrial DNA, separate to the DNA powerhouse that is the nucleus. It is the nucleus that contains 46 chromosomes, half from the mother and half from the father but it is in the cytoplasm of all but the red blood cell that mitochondria are found. These cells work hard to create energy for the cell to use in various processes, and is also where around 1% of the DNA found in a person is located. The DNA is in a circular form, and contains 37 genes.

And how is it done?

There are two methods that both result in the DNA of the child being passed down from 3 parents, and eliminates any chance of mitochondrial diseases being present in the child. Both methods involve the use of a donor, to get mitochondrial DNA without defects that may cause disease.  Every year, around 1 in 200 children are born with a mitochondrial disease.

The first  method involves creating an embryo with the intended parents sperm and egg, and the pronuclei of this removed and planted into a donor embryo, and is known as a pro-nuclear transfer.  [4]Mitochondrialdisease-creditAusSMC

Image from [4]

The other is  known as a maternal spindle transfer [1].  The chromosomes from an unfertilized egg containing defects within the mitochondrial DNA are taken and transplanted into an empty egg from a donor, and then fertilization is allowed to take place. Experiments using these methods have shown to be successful with eggs able to undergo fertilization in a lab [3].0,,16253959_401,00

Image from [3]

Will everyone be happy about this?

These new methods will help progress science in previously unimaginable ways.  However, regulation of these needs to be strictly observed.  The Human Fertilisation and Embryology Authority (HFEA) in 2008 made an amendment to the HFE 1990 Act, allowing, “regulations to be passed that will allow techniques, which alter the mitochondrial DNA of an egg or embryo, to be used in assisted conception to prevent the transmission of serious mitochondiral disease.” [2] This allows the research into replacement to go ahead but not treatment as of yet, but others have doubts as to whether it should be allowed at all.  Pro-life groups are against the creation and destruction of embryos, and wish for IVF and research on embryos to be abolished.

Others are asking if this is even needed when there are alternative solutions.  Egg donation and PGD (preimplantation genetic diagnosis) [5] are already in use and the consequences of their use known, whereas these new techniques are not totally known, and donor eggs are already high in demand.

I personally believe this is a great idea, enabling infertile couples to have more options into their quest for parenthood.  What do you reckon?

References/extra reading

[1] http://www.dw.de/three-way-ivf-faces-public-consultation/a-1625448

[2] http://www.nhs.uk/news/2012/09September/Pages/Consultation-launched-on-three-parent-IVF.aspx)

[3] http://www.nhs.uk/news/2012/10October/Pages/Three-parent-IVF-creates-viable-human-embryos.aspx

[4] http://www.sciencemediacentre.co.nz/infographics/

[5] Poulton and Oakeshott (2012) Nuclear transfer to prevent maternal transmission of mitochondrial DNA disease, BM,J 345:e6651

Sex Selection- What is it and should it be allowed?

Sex selection for personal reasons is illegal in the UK.  Full stop.  In fact, unless there is a serious medical reason in which would seriously affect the health of the child, it is illegal to choose your future child’s gender.  Is this right? Should couples with 3 boys wanting another child, but this time a girl be allowed to choose the sex of their baby? Or should it be left to mother nature and her mysterious ways? So many questions…

Why?

In some countries, such as India, finding out the sex through ultrasound before birth is illegal, due to the high occurrence of sex-selective abortions, deliberately aborting a foetus as it is of the ‘wrong’ sex, with preference usually shown to males, given that they are able to follow on the family name and allowed to get the family inheritance.  India is an extreme example, take for instance the recent horrific and deadly attack on a 23 year old girl, this shocking article shows the extreme lengths that gender has an effect on people’s lives.

In the past decade many couples have decided to go abroad to become pregnant, spending thousands of pounds to ensure they get their desired child, and sometimes illegally.  American law is less restrictive on these matters and so many have flown across to access this legal sex-selection process [1].human-sex-chromosomes

How can it be done?

  • In vitro fertilisation/ Pre-implantation genetic diagnosis (IVF/PGD)

Take a look at this short video that goes over the basics of PGD:

This is the only really trusted selection method allowed in the UK and is purely to prevent a child being born with a serious medical condition.  Some diseases are genetic, and can be sex-linked, meaning only one sex is affected, though often the other gender can be a carrier.  This is shown in the X-linked recessive disease, Duchenne muscular dystrophy in which only boys are affected, resulting in muscle degeneration, leading onto death at an early age.  A female can survive but be a carrier of the disease, whilst all boys will be affected.

The method requires IVF to be carried out but has an almost 100% chance of getting the desired baby gender.  Before the fertilised egg is transferred into the woman for implantation, the cells are analysed to find out the sex of the embryo.   As described in the video, a needle is inserted into the 3-5 day old blastocyst and a cell taken for analysis.  Only female embryos are taken forward to be implanted, eliminating any risk of the woman carrying a male child with the Duchenne muscular dystrophy.  There is no risk of harming the embryo by carrying out pre-implantation analysis on it.

Pre-implantation diagnosis can be used to select for embryos are of the desired gender, and only these embryos used in the IVF process that follows [2]. This method identifies embryos that contain either only X sex chromosomes (for a girl) or X and Y chromosomes (for a boy) but can also be used to screen for genetic conditions or to identify embryos that are at risk from genetic diseases.  This knowledge can then be used to choose genetically healthy embryos, preventing diseased children in couples that are known to be suffering or carriers of genetically inherited diseases such as cystic fibrosis or Huntington’s disease.  These diseases are caused by a single gene mutation, enabling scientists to easily identify affected embryos.

Pink or blue clothes?babay clothes

Other options, such as a maternal blood sample or an ultrasound scan can be used to carry out prenatal sex testing of the foetus before birth, but these require a growing embryo within the uterus, and so are useful for preparing for the child’s arrival, but no good for the prevention of sex-linked diseases, or for couples wanting to ‘balance’ their families.

So what have we learnt?  Different countries have different beliefs and laws about sex selection, whether for the prevention of children with genetic diseases, or just due to the parent’s desire.  The only reliable way to check pre-implantation is by PGD.

Would PGD prevent the horrific attacks on women in India, or is this completely irrelevant and is society that needs to change, and not the way we chose our child’s gender, and that any child is a blessing? In what situation is PGD acceptable…?

References/extra reading

[1] British couples flying to US for banned baby sex selection, The Telegraph, available at: http://www.telegraph.co.uk/health/healthnews/9504503/British-couples-flying-to-US-for-banned-baby-sex-selection.html

[2] Sex (Gender) Selection, available at: http://www.lajollaivf.com/fertility-treatments/sex-gender-selection-san-diego/

Multiple pregnancy IVF

This news article came out yesterday in The Guardian online, reporting on the use of multiple embryos being transferred into the uterus during IVF.  The article focuses on a study carried out by scientists at the Leicester Infertility Centre.  

A pretty interesting read, and gives the view that using a single embryo in the IVF process has just the same chance as multiple embryos for a healthy live birth, without the risks associated with multiple births, such as high blood pressure and pre-eclampsia.  There is also a much higher risk of twins or triplets being born prematurely, leading to a risky start in life with the possibility health problems after birth and later on in life.

The article says how single embryo transfer should implemented in the UK, reducing multiple birth pregnancies, preventing health risks to the mother and child.

Are Men Needed Anymore?

Came across this the other day- http://www.bbc.co.uk/news/world-us-canada-19879113

Pretty interesting news article.  What would be the consequences of this?  Imagine a world where you can become the father or mother of a child even if your sperm or eggs would not allow you to do so naturally by taking another of your cells and turning into a cell carrying the right DNA to create a child?

sperm around egg

Amazing technology that could give infertile couples another option in the aim for a child.  However, although the research has worked on mice, there is a long way to go until this technique could even be thought of to be used in IVF on a daily basis, the scientists involved have set themselves a target of 2 years to create usable sperm and 5 years for eggs.  I wish them all the very best of luck!

What are your thoughts on this?

Using Drugs in IVF, Yes or No…?

So the last blog mentioned briefly upon how an egg can be fertilised outside of the human body.  But it’s a lot more complicated than this to achieve.  Only 30% of women that undergo IVF actually get pregnant. It is surprising how many couples actually try to get pregnant through IVF considering the physical and mental difficulties that can be experienced, not to mention time, as well as lots of money if privately done.

With so many new options of IVF, things can sometimes get confusing but it is definitely worth researching all areas, to find out the right treatment for the individual.  In this blog I am going to go over the use of drugs in IVF, and when they are needed, and who will benefit from them.

Natural Cycle IVF

Natural cycle IVF is when he woman’s cycle is monitored closely, allowing the removal of an ovum at the correct time of month.  This egg can then be fertilised and placed into the uterus, establishing implantation of the blastocyst, and allowing the embryo to develop into a foetus and so on. This method differs from IVF, as no hormone drugs are given prior to egg collection.  There are many reasons for not using fertility drugs, ranging from health reasons, some cancer patients may be at risk from ovarian hyper-stimulation that can be dangerous, whilst others may have religious reasons, or do not want to have excess embryos destroyed as a result of their treatment [1]. The chances of having a successful birth are lower than that of stimulated IVF, as you are relying on the body to correctly behave as it should, which is not always consistent! This said though, the risks associated with a natural cycle IVF treatment are much lower, and no risk of twins or triplets!natural cycle baby

IVF using drugs

3075injection

These drugs are given to allow several eggs to be produced at the same time from the ovary.  IVF treatments carried out with drugs given usually have a higher success rate, due to a higher number of eggs available for collection and fertilisation.   This method is called Mild IVF and produces about 2-7 eggs that can be used to create embryos for implantation. The women that opt for the natural IVF are usually concerned about the side effects of these ovarian stimulating drugs due to health conditions, or want their pregnancy to be as natural as possible without drug intervention.

What drugs are given?

Fertility drugs- These help trigger egg production (ovulation induction).  Gonadotrophin-releasing hormone (GnRH) analogues are given by injection or tablet from.  They are pituitary agonists that prevent the normal cycle from occurring.

Hormone injections- These are injected daily for 12 days and help stimulate multiple egg production from the ovaries.  Gonadotrophin hormones such as follicle stimulating hormone (FSH) and luteinising hormone (LH) are used.  Hormone levels in the blood are monitored, allowing the IVF clinic to detect the best time to harvest the mature eggs.  Human chorionic Gonadotrophin (hCG) stimulates the release of the eggs and is naturally made in the developing placenta of the embryo in early development.

What next?

For the female:  After the eggs have matured and are ready for collection an anesthetic is given and eggs removed from the ovaries using a hollow needle that is attached to a probe that enables ultrasound scanning. The eggs are located on the follicles using the probe.

For the male:  The sperm is collected from a fresh sample provided by the man.  These can then be frozen, to be used at a later date, or used as fresh sperm in the IVF process.  Once collected, the sperm is washed and best sperm chosen for use.  It is not normal practice for men to be given fertility drugs during a normal course of IVF.

Drugs for embryo transfer

To prepare the uterus for the implantation of the blastocyst, progesterone is give to the woman.  This thickens the uterus lining, allowing a successful implantation.

Using a catheter, 1-2 embryos are placed within the uterus to prevent multiple pregnancies of more than twins, but enough to hopefully get a successful cycle of IVF.

So it all depends on the patient really, making the decision whether to use drugs or not, and whether this choice is the best for you, in regards for your health, beliefs, and the best possibility of getting pregnant.

References/extra reading

[1] http://www.hfea.gov.uk/natural-cycle-ivf.html

Alternatives to ovarian hyperstimulation. Natural cycle IVF, available at: http://books.google.co.uk/books?hl=en&lr=&id=l-TdGJX2zEMC&oi=fnd&pg=PA173&dq=natural+cycle+ivf&ots=8L16QOTGrw&sig=1Z0s_EoKK_AhDBT7NKY_XAA7olU#v=onepage&q=natural%20cycle%20ivf&f=false

Efficacy of natural cycle IVF: a review of the literature, available at: http://humupd.oxfordjournals.org/content/8/2/129.short

Male Infertility

Carrying on from the last blog, in which I looked at female infertility, male infertility is also a cause for infertile couples, accounting for approximately half of infertile couples.

Sperm quality/quantity is often the problem in male infertility.  However, aging does not play a major role in infertility in men as it does in women, with accounts of men fathering children much later on in life.  The risk of congenital abnormalities with increasing parental age is not as well known about as it for women, but the risks are still present.

Sperm count/qualitysperm

It has been found that in 19% of couples suffer from a low sperm count or low quality.  Once again, there are many factors that can lead to poor sperm, such as excessive weight. Those that are overweight or obese (with a body mass index of 25 or above) are at an increased risk of low sperm count/quality.  Studies into the effect of nicotine on both female and male rats with sperm analysis, fertility, litter size and weight being analysed [1].  The results showed a significant decline in sperm motility and number, as well as a reduced libido in the male rats.  However, more recent studies have found no difference in sperm quality between smokers and non smokers.  The BBC article, which can be found here, http://www.bbc.co.uk/news/health-18407647 indicates no relationship between smoking and infertility, but still advisable not too, with studies having not considered DNA quality or size and shape of the sperm.

Other factors affecting fertility

Smoking and obesity are factors that can be controlled, but some men suffer from disorders that detrimentally effect the testis and sperm production (spermatogenesis).

The sperm found in some men might be perfectly healthy, and instead there is a problem with the release of the sperm, whether this be due to problems with getting an erection, or problems with ejaculating.  There may be physiological or psychological reasons for this, and is usually treatable after a visit and treatment options from a doctor.

Previous medical illness may have an effect on fertility.  Certain drug treatments or surgery can affect fertility, as well as radiotherapy and chemotherapy. Depending on which drug was given, as well as dose can affect the risk.  Sperm can be preserved before these treatments in order for semen to be available later on if the man wishes to have a child.

Bacterial infections can also cause infertility.  The scarring caused by the infection, and the possibility of the tubes within the epididymis connecting to the vas deferens being blocked can have a detrimental effect.  The vas deferens is the transport system for the sperm that are ready to be ejaculated.

IVF can help couples in which the man has an infertility problem, by making the fertilisation of the egg as easy as possible by the sperm, whether this be by directly injecting the sperm into the egg, or allowing natural fertilisation but giving the sperm the best chance it can get at reaching the egg through use of a catheter.

[1] Oyeyipo I, Yinusa R, Emikpe B and Bolarinwa A (2011), Effects of Nicotine on Sperm Characteristics and Fertility Profile in Adult Male Rats: A Possible, Journal of Reproduction & Infertility, 12(3):48

http://www.hfea.gov.uk/infertility.html

Female Infertility

Definition: when a couple who are having regular unprotected sex are unable to conceive.

The time it takes to conceive can be extremely variable throughout couples, ranging from weeks to years.   Infertility can be caused by so many factors, and can wide ranging effects on couples, physiologically as well as a psychological effect.

A range of factors can affect fertility in women, ranging from acquired to genetic.  Factors such as age (fertility starts to decrease after the age of 35), smoking (chemicals prevent correct oestrogen production) and sexually transmitted diseases, as well as eating disorders that increase/decrease body weight (affecting correct oestrogen production) can all affect fertility, as well as some medical treatments including chemotherapy, as well as deliberate contraceptive methods.

Genetic factors can also lead to mutations in genes involved with fertility, such as the FSHB gene [1], encoding the beta subunit of the Follicle Stimulating Hormone (FSH).  Incorrect gene product can lead to amenorrhea, the lack of a menstrual period, and so unable to conceive due to lack of ovulation.

Conditions within the female reproductive system can affect fertility, and these can be caused by genetic or acquired factors.  Physiological problems such as polycystic ovary syndrome, blocked fallopian tubes and endometriosis are to name a few, as well unknown causes.  Drugs or surgery can be used to solve some of these problems and regain fertility, but in others IVF can be carried out to become pregnant.

Polycystic ovary syndrome (PCOS)

PCOS is a frequent, possibly genetic problem in women, leading to menstrual disorders and infertility, due to lack of ovulation. Those that suffer from PCOS have follicles develop within their ovaries, altering the very fine hormonal balance and often preventing ovulation.  The causes of PCOS are not totally clear, with several factors thought to play a role in the cause.  It is found that suffers are insulin resistant, leading to increased levels of insulin within the body, causing the ovaries to produce too much testosterone.  These high insulin levels play havoc with the ovaries, causing follicles to develop.

A high level of luteinising hormone (LH) is sometimes found within women with PCOS. LH is a hormone that works in line with insulin to control testosterone levels, but also stimulates ovulation.  [2]PCOS

PCOS can be treated to reduce the health risks by losing weight if needed, reducing testosterone and insulin levels through medication. For those inflicted with infertility, these efforts may be enough to restart a normal menstrual cycle.  If not, ovulation-inducing medication can be given, and assisted reproductive methods such as IVF can be used in those still unable to conceive naturally.

References/extra reading

[1] Grigorova M, Rull K and Laan M (2007) Haplotype Structure of FSHB, the Beta-Subunit Gene for Fertility-Associated Follicle-Stimulating Hormone: Possible Influence of Balancing Selection, Annals of Human Genetics, 71(1):18-28

[2] http://www.patient.co.uk/health/Polycystic-Ovary-Syndrome.htm