Downregulation in IVF

In order to superovulate you properly during your IVF cycle, we first need to downregulate you. This article explains why we need to do this - and how we do so

Superovulation - helping you to grow more eggs - is the heart of modern IVF treatment today. However, when we superovulate you, we also downregulate you ! This can be quite confusing - how can you switch on and switch off the ovaries at the same time ? Won't switching off the ovaries reduce the number of eggs you grow ?

The Effect

It's actually quite simple if you remember that the downregulation does not act on your ovaries - it acts on your pituitary !. We switch your pituitary off, so that we can switch your ovaries on more efficiently. This allows us to ensure that you grow a synchronous cohort of follicles, so that we can retrieve a large number of good quality eggs at the right time - when they are mature, but before you ovulate spontaneously.

The best analogy is that before writing on a blackboard, we need to clean it first. We need to stop your pituitary from producing its own hormones, so that we can make your ovaries grow lots of mature eggs which we can collect at the right time. Not only does this allow a better ovarian response, it also allows us to time egg collection at a convenient hour, so we don't have to do egg collections on Sundays !

There was actually a Lancet article which described the effective use of this protocol published many years ago, titled - Never on a Sunday. Doctors do have a sense of humour ! )

If we did not use downregulation, your follicles might grow at different rates in response to the superovulation ; and if all the follicles do not grow at the same rate, it would be more difficult to collect mature eggs. Even more importantly , downregulation stops you from ovulating on your own.

Precise timing

If you did ovulate spontaneously ( before we are ready to do the egg collection), we would not be able to collect your eggs, as they would be lost in the abdominal cavity , if your follicles ruptured prior to egg retrieval. This would be a nightmare, which thankfully never happens today in a good IVF clinic, because the downregulation is so effective.

This means that we can precisely time egg collection to occur 34-36 hours after the HCG trigger, and you can sleep peacefully , knowing that your follicles would never rupture prior to this time, because you have been downregulated.

In the past, when downregulation was not available, doctors would have to do egg collections even at 2 am - 36 hours after the spontaneous natural LH surge ( which could occur at any time, and was not in the doctor's control).

Downregulation prevents the release of FSH and LH from the pituitary gland during treatment and thus premature ovulation. This therefore gives the doctor much more control over the superovulation phase.

GnRH analogs can be used either in the form of a long protocol ( when they are started from Day 21 of the previous cycle) ; or as a short protocol ( when they are started from Day 1 of the cycle). Another option is to use the newer GnRH antagonists, which act more quickly than the GnRH analogs.
Authored by : Dr Aniruddha Malpani, MD and reviewed by Dr Anjali Malpani.