How IVF procedure works.IVF procedure is a multistep process where the woman’s natural menstrual cycle is firstly downregulated, i.e. suppressed and timing artificially controlled (most commonly using birth control pills and a drug like Lupron or Synarel).
Then the ovaries are stimulated to produce more mature eggs than the normal one per cycle with injectable medications, then the eggs are then collected with a minor surgery and mixed (IVF) or injected with sperm (ICSI) in a laboratory before embryo(s) are transferred back into the woman anywhere from two to five days later. Additional medications are also given to support the second half of the cycle to optimise the chance of a pregnancy occurring.
Finally, generally a blood pregnancy test will be performed around two weeks after the transfer, and if positive, the medications will need to be taken for up to 12 weeks of pregnancy before the placenta is mature enough to take over.
There are several other types of IVF procedures, including antagonist protocols and flare protocols that skip the downregulation phase in a bid to maximise the number of eggs collected. They are typically utilised in those with a history of poor response to IVF procedure, have a raised FSH or who are older. These protocols use a type of drug known as GnRh antagonist to prevent premature ovulation during the stimulation phase instead of GnRh agonists and downregulation first.
The key phases of a typical (downregulation) IVF cycle are therefore:
In more detail:
IVF Procedure - DownregulationThe downregulation phase is designed to suppress natural ovarian activity, usually using the contraceptive pill, so that timing of the menstrual cycle can be controlled.
Additionally to this, the centres in the brain responsible for releasing hormones called follicle stimulating hormone (FSH) and luteinising hormone (LH) that are responsible for stimulating the ovaries to make and ovulate mature eggs in a normal menstrual cycle need to be suppressed. This is because if they were not, inappropriate early ovulation could happen during the subsequent stimulation phase of IVF due to the higher than normal levels of estrogen made by many maturing follicles at once.
To do this a drug of the type known as a GnRh agonist (such as Synarel, which is inhaled like a sinus medication, or Lupron, which is given by injection) is given once or twice daily. This has the effect of causing the brain to release all of its stores of FSH and LH during downregulation, and then keeps them low so that premature ovulation cannot occur.
At the end of the downregulation phase, the birth control pills are stopped, but the Lupron or Synarel continues to be taken. The woman will then have a period, followed by a vaginal ultrasound scan to confirm that the ovaries are suppressed and the lining of the womb is thin.
IVF Procedure - StimulationOnce the downregulation has been completed, the ovaries will need to be stimulated to produce more eggs than would normally happen in a natural cycle. To do this, artificial forms of FSH are given by injection (they are not absorbed orally, so injection is necessary) daily. This will stimulate the antral follicles (eggs ready to develop into more mature form) in the ovaries to grow, and unlike in a natural cycle where follicles compete for FSH and only the ‘strongest’ is ovulated, many will usually grow.
The Lupron or Synarel from the downregulation phase will also be continued to be taken until the end of the stimulation phase so that premature ovulation does not occur.
The FSH dosage is carefully adjusted based upon either the results of the number and size of the follicles growing in the ovaries on vaginal ultrasound and/or blood tests of the level of estrogen in the blood made by the growing eggs.
Without careful monitoring (especially in younger women with polycystic ovarian syndrome) there is the risk of a potentially serious complication known as OHSS (ovarian hyperstimulation syndrome) where too many eggs are made and estrogen levels are very high.
If OHSS occurs, depending on the severity, the woman may be more closely monitored, or eggs may be retrieved and no embryos transferred (being frozen for transfer in a later cycle after the OHSS has resolved), or the trigger injection may not be given and the entire cycle cancelled.
The duration of stimulation depends on the response to the FSH, but is typically in the range of ten to fourteen days. At the end of this phase when there the follicles are of a mature size an injection of HCG is used to artificially mimic the natural hormonal surge of LH that would occur to trigger maturation of the eggs and ovulation (if the woman had not been suppressed with the Lupron/Synarel).
The timing of this injection is critical, as if it is given too early before egg retrieval the eggs will be ovulated into the fallopian tubes and lost, and if given too close to egg retrieval will not have had time to work and the eggs may not be able to be retrieved or may still be immature. Typically the timing is 36 hours before retrieval, so it is important to follow your clinic’s instructions precisely.
IVF Procedure - Egg Retrieval (ER)This part of the IVF cycle involves a minor surgery, usually with sedation, where a fine needle is passed through the walls of the vagina and into each ovary under ultrasound guidance to collect the mature eggs.
The eggs and fluid aspirated from each follicle are collected into test tubes and passed directly to an embryologist who will separate the eggs using a microscope and then either mix them with sperm, allowing fertilisation to happen naturally, or if the count is very low or there are other sperm problems single sperm may be carefully directly injected into each mature egg.
Generally the retrieval procedure itself is only fairly minor despite being the most fearsome sounding part of the IVF procedure cycle, taking around half an hour. Once the eggs are retrieved the woman will spend 1-2 hours in the recovery room and then go home. Some cramping and discomfort is common, but it is not usually severe enough to require more than minor analgesics such as paracetamol/acetaminophen.
The day after retrieval, the eggs are examined to determine how many have successfully fertilised, and they are monitored thereafter to see how they continue to divide and help decide the day of transfer.
IVF Procedure - Transfer
Depending on local protocol (some countries/clinics routinely only do day 2 transfers, some prefer day 5 if possible) the number of mature eggs retrieved, embryos made, and the quality and rate of division of the embryos, the day of transfer will vary.
Generally speaking, the pregnancy rate is higher for embryos that grow well to day five than for embryos that are transferred on day two. This is because on day two it can still be too early to tell which embryos have genetic errors which will cause them to stop dividing early in development. IVF procedure is often likened to a process of attrition where A eggs are collected, of which B subset will be mature, of which C sub-subset will fertilise of which D sub-sub-subset will develop, and so on. This is the reason that the aim of the stimulation phase is to develop several mature eggs, with the aim of generating not only enough embryos to transfer, but ideally having leftover embryos to freeze and be used in a subsequent frozen embryo transfer as these cycles are less complicated.
Typically transfer will be anywhere from the second to fifth day post retrieval. In that time a woman will also start taking progesterone either by intramuscular injection, or via pessary into the vagina to prepare the lining of the uterus fully for the embryo(s) to be transferred in order to maximise the chance of pregnancy.
The decision on the number of embryos to transfer is often a difficult one. Many women transfer two, especially if having twins is not a personal concern. Couples who have experience infertility welcome the possibility of a twin pregnancy for entirely understandable reasons.
Transferring more embryos can increase the odds of pregnancy, but also increases the odds of multiple pregnancy, which in turn carry increased risks to both the mother and baby(ies) compared to singleton pregnancies.
Because of this, and continued improvement in the technology of IVF such that pregnancy rates are acceptable, even with transferring only one embryo (especially in younger women), there is increasing emphasis on transferring one, maximally two, embryos in most cases.
As with all things, individual history may vary how many embryos are transferred back into the uterus, but as the risks to the pregnancy increase significantly with each additional baby that is carried, the decision needs to be carefully weighed.
IVF Procedure - Luteal SupportIf progesterone is not given after retrieval, the body will not act as it normally would to mature the lining of the uterus or support and early pregnancy because the natural cycle has been suppressed. It is therefore routine to supplement the second half of the cycle (luteal phase) post-retrieval with progesterone.
Progesterone may be given either via daily intramuscular injection into the large muscles of the buttocks, or by vaginal pessary several times a day. This is continued up until the pregnancy test approximately two weeks after retrieval.
Our many TTC readers have listed their IVF pregnancy symptoms here.
IVF Procedure - Pregnancy Test
Generally a blood pregnancy test is used to determine the exact level of pregnancy hormone (beta hCG). Success rates do vary from clinic to clinic, it is best to check your local clinic’s statistics for the odds of pregnancy depending on number of embryos transferred, your age and other factors in your cycle (eg day 2 vs. day 5 transfer).
If the pregnancy test is negative, the progesterone injections or pessaries will be stopped and a period will occur. If it is positive, the progesterone will need to be continued for the first trimester until the placenta is mature enough to make enough of the hormone to support the developing pregnancy.
It is common to wonder if there are possibly twins from a high beta number. Here and here are some examples of online charts listing the beta hCG values found in early pregnancy.
There is a wide range of normal values of beta hCG in early pregnancy and additionally the ranges for twins and singletons do overlap, so whilst a high beta is suggestive that you may be carrying twins an ultrasound scan at six weeks pregnancy will be more informative.
By this stage it should be possible to see the number of gestational sacs, embryos and fetal heart pulsations. Earlier than this point, it may be possible to see gestational sacs, and possibly yolk sacs, but the embryo and the heartbeat are not yet big enough to be clearly visible.
IVF Procedure - Frozen Embryo Transfer (FET)Finally, although it is emotionally very difficult when the result for a fresh cycle is negative, if there are frozen embryos left over it is still possible to achieve pregnancy without another full cycle, albeit with somewhat lower success rates (probably because the freezing and thawing process, although performed very carefully, may cause damage to the embryo).
There are several way in which an FET can be performed, ranging from monitoring for ovulation in women with regular menstrual cycles and simply placing the embryos back at the appropriate time post ovulation, to supplementing the second half of the menstrual cycle with additional progesterone, to artificially creating a cycle by giving estrogen and then estrogen+progesterone to suppressing first with Lupron and then performing an artificial cycle. Mostly this process is less complex than a fresh IVF as there is no stimulation phase, no egg retrieval and less monitoring.
My own twins were the result of my second FET. Although it often feels hopeless to think that pregnancy may occur when the fresh cycle did not work, it can happen.
In conclusion, to those of you reading who are still battling infertility or undergoing IVF procedure, I extend my sympathies and wish you the very best of luck.
It isn’t an easy journey, but it is rewarding.
For more information on IVF procedure and infertility, you can visit Mission Impossible Infertile Also recommended is Stirrup Queens for information and support.
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