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

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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

IUI, ICSI and IVF…huh?

IUI, IVF, ICSI – what do they all mean?

These are all different methods available to try and help couples conceive.  Their names might seem a bit confusing at first, but hopefully this post will try and clear things up a bit!

IUI- Intrauterine Insemination

Also known as artificial insemination, this method can be used in couples affected by ovulation problems or mild endometriosis, as well as problems with the cervix or when there is a male infertility problem such as impotence of premature ejaculation [1].  IUI is not used in couples with ovarian failure, or problems with the fallopian tubes, such as damage or a blockage.

The idea of IUI is that the better sperm (faster moving) are removed from a semen sample and then only these are placed inside the uterus around the time of ovulation in the woman (36-40 hours after), giving the best chance for fertilisation of the egg.  The time of ovulation is the time in the monthly cycle when the egg is released from the ovary (around day 15 of the cycle).  IUI can be used with or without the use of fertility drugs that increase the number of eggs released during ovulation.

A special instrument called a speculum is inserted into the vagina to make space for a small catheter that is inserted into the uterus.  The specially selected sperm are inserted through the catheter in the hope that one will fertilise the newly ovulated egg.  It is a quick and painless procedure that causes little risk to the woman.  This procedure can be carried out multiple times on different cycles if the previous unsuccessful.IUI-process-and-sucess

IVF- In vitro fertilisation

As discussed in the last post, IVF is when the egg and sperm gamete cells are collected from the parents and allowed to fertilise outside of the body in a dish in a laboratory.  The sperm can be left to naturally fertilise the egg, or can be directly inserted into the egg cell.  This is known as Intra-cytoplasmic sperm injection (ICSI).

ICSI- Intra-cytoplasmic sperm injection

Directly injecting a sperm cell into an egg cell means that even men with a low/zero sperm count, or those that have poor sperm motility can father a child.  ICSI can be carried out if previous tries with IVF have been unsuccessful, or the embryos are not fertilised without help.

A semen sample is collected from the man, and the best quality sperm cells are used to fertilise eggs from the woman, outside of the body by embryologists.  Sperm can be collected from a fresh sample or in men unable to do this due to errection problems due to spinal injuries or other disorders a sample can be collected direct from the epididymis using a syringe (where the sperm are located whilst they mature).  Extra sperm collected may be frozen for use later on in future cycles.

The best sperm are used to fertilise an egg, which is then transferred into the woman’s uterus 2-3 days after growing in a lab, exactly the same as in IVF, or after 6 days as a blastocyst transfer.  It is then a waiting game, waiting for the date in which a pregnancy test can be taken to given a result of a positive pregnancy of a failed cycle of IVF…a day that can cause either great joy or disappointment to couples that have gone through these procedures.icsi

Below is a really good youtube clip detailing the ICSI process, as well as other processes such as the collection of eggs during IVF and ICSI.

Counselling is always offered to couples undergoing these assisted reproductive methods as it can often be physically and emotionally draining [2].  Counselling is offered before, during and after IVF treatment (successful or not) to help manage the whole process and dealing with any issues in regards to the couple’s fertility.

References/extra reading

[1]  What is IUI and how does it work, Hfea, available at: http://www.hfea.gov.uk/IUI.html

[2] IVF support, available at: http://www.nhs.uk/Conditions/IVF/Pages/Recovery.aspx