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Sunday, 20 April 2014

IVF regimes explained

There are many protocols that are used in IVF. The commonest ones are
  • Long protocol: In this regime, GnRH analogs are started on the 18th to 21st day of the cycle (contraceptive pills are taken daily from the 2nd day of the period). Once downregulation is confirmed on scan/blood tests, ovarian stimulation is started with daily  injections of FSH or hMG alongside the analog injections. This continues till the leading follicles are 18mm or so. At this point, the last analog injection is given and a trigger injection is given to enable eggs in the follicles to complete their maturation and be ready for "pick-up".  The egg collection is scheduled approximately 36 hours later.
  • Short or Flare protocol: GnRH analog is started on the second day of the cycle and the ovarian stimulation the next day (i.e., 3rd day). The rest of the regime is the same as long protocol. This is particularly used for women with lower ovarian reserve.
  • Antagonist protocol: This is the latest kid on the block. Ovarian stimulation is commenced on the day 2 of the cycle and the daily GnRH antagonist injections are added on the day 6 of stimulation or once the leading follicles are >13mm. Both injections continue till the leading follicles are 17mm or so. On this day, the last antagonist is given followed by the trigger injection. The egg collection is scheduled approximately 36 hours later.
I hope this has clarified the readers' understanding of the different types of protocols that are used in IVF. There are of course subtle variations that exist but this post was to give a broad understanding of the process.

Friday, 18 April 2014

How is ovulation prevented in IVF?

The drama that is enacted in the ovary every month is directed by pituitary (an organ in brain) through messengers FSH and LH (together called Gonadotrophins). The "Director" Pituitary in turn has to act as per the orders of "Grandmaster" Hypothalamus (also a part of brain). Hypothalamus sends its signals to pituitary via messengers called gonadotropin releasing hormones (GnRH). The two medicines used to prevent ovulation during IVF are GnRH analogs and GnRH antagonists.

GnRH analogs (such as Lupride, Buserelin etc.) are substances which have a structure similar to GnRH and cause some response from the pituitary (called flare response) in the form of release of FSH and LH. On being given daily, the flare stops and the pituitary becomes unresponsive and hereafter no release of FSH and LH occurs. This is called down regulation and take about 5 days of injections.

GnRH antagonists (such as Cetrotide and Ganirelix) resemble GnRH molecule but unlike analogs, these elicit no flare response from the pituitary. They are effective immediately in stopping the pituitary from releasing any gonadotropins. 

In IVF, either agonists or antagonists are used alongside ovarian stimulation to prevent premature ovulation from occurring. I will discuss the different protocols used in IVF in my next post....

Sunday, 13 April 2014

Ovarian stimulation in IVF: principles

The concepts of ovarian stimulation are not too complicated. First, let us understand what happens in the when no medications are taken.

In the natural cycle, antral follicles start growing (at the behest of FSH from brain) in the initial part of the menstrual cycle. One of these establishes dominance and only this dominant follicle continues to grow. Reason is when follicles start growing, they release estrogen hormone, levels of which starts increasing due to the contribution from the several follicles. As a reaction to the rising estrogen, brain (in particular pituitary) starts decreasing the amount of FSH that is released. With the decreasing levels of FSH, the smaller follicles' growth slows down and eventually stops. Only the dominant follicle has the ability to survive and grow to eventually ovulate and release the egg.

When we stimulate the ovaries, we do not let the FSH levels drop - by giving the same amount of hormone artificially. This allows even the smaller antral follicles to continue their growth. Stimulation is continued till the biggest two-three follicles are ready for ovulation (size ~18mm). 

The other principle that needs to be taken care of is ovulation. In the natural cycle, ovulation is triggered when estrogen hormone rises to a particular level. Ovulation is caused by way of release of a huge amount of hormone LH - this mechanism is called LH surge. As there is only one follicle that is "allowed" to grow, the threshold level of estrogen that triggers LH surge is not very high. 

In the context of ovarian stimulation, multiple follicles are growing and releasing estrogen, as such the level of estrogen required to "trigger" the response is reached quickly. In order to prevent LH surge interfering with the ovarian stimulation, we have to use one of two medications - GnRH analogues (such as Buserelin, Lupride, etc.,) and GnRH antagonists (such as Cetrotide and Ganirelix). These medications are quite different in the way they can be used and I will discuss these in the next post.

Thursday, 10 April 2014

What is IVF?

In vitro fertilisation or IVF is increasingly being used to help people who face difficulty in conceiving. IVF also called test-tube baby treatment is the treatment in which embryos are created in petri dishes (originally made of glass hence the name in vitro) outside of the human body and these embryos are then transferred in the uterus after growing them for a few days.

IVF when it started in 1978 was done without any stimulation and had a low success rate. The advent of injectable medicines (such as hMG and FSH) enabled retrieval of more eggs from which more embryos can be created and good quality embryos can be selected. The process is intensive and the fertility specialist will need to monitor the patient very closely throughout the treatment. It is extremely important for patients to understand what is happening and to follow instructions very carefully as this can affect the end result.

The process of IVF is a complicated one and I will talk about it over the next few posts. There are essentially the following steps:
  • Ovarian stimulation (in some protocols down-regulation step precedes this)
  • Egg collection
  • IVF
  • Embryo transfer

Sunday, 6 April 2014

IUI: What is it?

In the simplest terms, Intrauterine insemination (IUI) consists of inserting sperms into the uterus at or around the time of ovulation. IUI is often offered to infertile couples as a first option as it is less expensive and less stressful.

Why IUI?
The logic of IUI is to ensure that the sperms are present in the reproductive tract during the first 24 hours after ovulation. This is because the egg stays alive and can fertilise only during this 24 hour time period. In order to make the process more efficient fertility specialists often advise ovarian stimulation in conjunction with IUI. If ovarian stimulation is done with daily injections of FSH or hMG, it is recommended that the lady takes progesterone in the form of pessaries for at least 14 days for hormonal support of the impending pregnancy.

What happens naturally?
Sperms make up less than 5% of the volume of the semen that is produced. These sperms are a mix of motile and immotile (but live) as well as dead sperms. These sperms are suspended in a fluid along with substances that are nutritive and protective. The function of the fluid is to transport the sperms to the vagina. From there only the sperms can swim up, these are filtered by the cervix (the neck of the womb) while the rest of the fluid comes out. 

What happens in IUI?
Processing of the semen is done to isolate motile sperms, these moving sperms are then suspended in fresh medium and released into the uterus. The procedure is NOT painful but the insertion of fluid into the uterus may cause muscles of the uterus to contract. This will cause cramping pain similar to that experienced during periods.

How many times?
IUI can be done once or on two consecutive days by different fertility specialists. This is usually decided by the specialist and so far studies have not been able to show which is better.

Friday, 4 April 2014

Ovulation induction in special circumstances

In the introductory post on Ovulation induction, I had mentioned that there are some special circumstances where ovulation does not occur due to a problem in the hypothalamus. In the normal individuals, the hormones FSH and LH (the common term for these two together is Gonadotrophins) are released from the pituitary gland in brain and their role is to enable the growth of follicles in the ovary culminating in ovulation. This action of pituitary gland is controlled by another organ in the brain called hypothalamus with the help of hormones called Gonadotrophin releasing hormones. 

When the "circuitry" in the hypothalamus is faulty, the ovaries fail to work. There is no hormone producing activity in the ovary and so the cyclical growing and shedding of womb lining (menstrual cycle) does not occur. This condition is called Hypothalamic Hypomenorrhoea or Hypogonadotrophic hypogonadism (hypo hypo in short). Ovulation induction in such women can only be done by giving FSH and LH injections to artificially stimulate the ovaries. The crucial point to remember is that the ovulation induction in these ladies must be done by the 'old-fashioned' stimulating injections called HMG (Human menopausal gonadotrophins) which contains both FSH and LH. Recombinant FSH in such women will not be helpful.