OHSS describes a situation where the ovaries over-respond and have an excessive number of follicles in response to the stimulation drugs that are taken for IVF/ICSI. In severe cases, the body can respond to this over-activity by releasing chemical substances into the bloodstream that cause fluid to move out of the blood and into the spaces around the vessels such as the abdomen and lungs. This makes the blood more concentrated, which puts pressure on the kidneys function, resulting in a dark appearance of the urine.
About one in 20 people undergoing IVF/ICSI will develop some degree of hyperstimulation – usually this is mild.
There are three levels of OHSS:
Note: It is important to advise your doctor of a family history of stroke or blood clots.
These are the symptoms to look out for:
Most moderate to severe cases of OHSS occur when the pregnancy is from a fresh transfer in an IVF/ICSI cycle. The pregnancy hormone hCG plays a role in the cascade of events that cause OHSS. This is why trigger injections that contain this hormone are avoided in treatment cycles that are identified as high risk cases where excessive numbers of follicles have developed. Most pregnancies are unaffected by this condition.
For mild symptoms, contact us at Repromed:
For moderate to severe symptoms where you develop chest or calf pain you should immediately contact us or go to a hospital Accident and Emergency department, then contact the Repromed nurses or leave a message to let us know:
Note: It is important to drink adequate fluids during your IVF/ICSI cycle: two to three litres of water per day.
Yes, some people who are more at risk have:
Prevention is the best form of treatment. If an unexpectedly high ovarian response to the stimulation drugs is encountered early in your cycle, and the chance of OHSS is very high, we may:
Below is a list of medicine or supplements you may have been recommended to take, with details of doses and potential side effects.
Evidence from extensive studies of pregnant people has confirmed that using supplemental folic acid at least one month before pregnancy and during pregnancy, significantly decreases the chance of neural tube defect (spina bifida). Continue taking folic acid until the end of the 14th week of pregnancy. The usual dose is 0.8mg daily or 5mg daily for anyone considered high risk (multiple pregnancy, previous neural tube defect, increased BMI). Reported side effects include nausea and gastric discomfort.
Iodine is an essential nutrient required in small amounts for normal brain development, it is important that unborn babies and infants receive enough iodine. The recommended dose in pregnancy is 0.150 mg (150ug) daily. No side effects have been reported.
There is some evidence that antioxidant preparations in combination with zinc and selenium can improve sperm genetic health. We especially recommend that anyone with abnormal semen tests and those planning to have ICSI, take antioxidant preparations such as CoQ10 for three months prior to treatment. Reported side effect: minor gastric symptoms.
Your specialist may recommend that you take Metformin prior to and during your IVF cycle, where a down regulation cycle is used. It may be indicated if you are known to have Polycystic Ovary Syndrome (PCOS) and has been shown to reduce the risk of hyperstimulation (OHSS) in downregulation cycles. Reported side effects include gastrointestinal upset. Contact your Repromed doctor if you are concerned about the side effects.
This is a synthetic drug that mimics a naturally occurring brain substance known as GnRH. It is routinely administered daily in Down Regulation Cycles to control the growth of follicles and as a trigger injection for some cycles. Reported side effects may include: headaches, local redness and irritation at the site of injection and hot flushes. Rare side effects of muscle weakness, double vision, shortness of breath and chest pains should be reported immediately.
These are synthetic drugs that block receptors in the fertility centre of the brain to prevent the LH hormone from being released so that the ovulation surge is prevented allowing control of follicle growth. Reported side effects may include: redness and itching at the site of injection, nausea and headaches.
Some of these drugs are synthetic while others are highly purified naturally occurring hormone preparations. They are administered during the stimulation phase of the cycle to induce and support the growth of multiple follicles in the ovary. They are given as a subcutaneous injection (just under the skin). Reported side effects may include: enlarged tender ovaries, abdominal distension, breast tenderness, tiredness, vagueness, local redness and irritation at the site of injection, mood changes, Ovarian Hyperstimulation Syndrome (OHSS) – refer to OHSS information.
Medications given in tablet form, to regulate or induce ovulation. Reported side effects: mood changes, hot flushes, abdominal discomfort. Rare side effects of blurred vision, spots or flashes should be reported immediately and the medication stopped.
Letrozole is an aromatase inhibitor and is most commonly used to induce ovulation in anyone with Polycystic Ovary Syndrome. It works by suppressing oestrogen levels and this results in the pituitary gland producing more follicle stimulating hormone (FSH). It is used in IVF for low ovarian responders to optimise response to stimulation medications and for clients with breast cancer who are undergoing fertility preservation treatment to reduce the oestrogen levels during the cycle. Letrozole is not registered in New Zealand for use in infertility treatment but can be used with specialist recommendation.
This is a synthetic hormone that mimics the action of the hormone, LH. It acts to trigger the maturation and release of eggs from follicles for ovulation or timing for the egg collection. Reported side effects may include: local irritation at injection site, bloating and sore breasts.
This is given instead of an hCG trigger where there is a risk of OHSS or high progesterone levels and no fresh embryo transfer is planned. Reported side effects may include: headaches, local redness and irritation at the site of injection and hot flushes. Rare side effects of muscle weakness, double vision, shortness of breath and chest pains should be reported immediately.
These are inserted into the vagina to boost progesterone levels to support embryo implantation. Reported side effects: vaginal irritation, occasional spotting, sore breasts and mild depression.
This is administered as a vaginal gel and is a source of supplementary progesterone. It is used to enhance the lining of the uterus to support embryo implantation. Reported side effects include: local irritation and vaginal discharge.
Sometimes a cyst can develop during Down Regulation and this is usually detected on blood testing and a scan. A trigger injection of hCG will usually resolve this and the FSH injections can be delayed until blood testing confirms you are ready to start. Occasionally we will recommend that the cycle be stopped and started a month or two later.
Note: For clients undergoing an IUI cycle it is very important to abstain from intercourse if you have overstimulated with greater than three follicles.
If significantly less follicles or no follicles develop, your doctor may advise you to discontinue this cycle and start again with a higher dose of stimulation drugs or a different protocol. Alternatively, you may choose to continue with egg collection with the understanding that there may be fewer or no eggs retrieved. Your AMH levels help us to predict in most cases who will be at risk of under response and a high starting dose of stimulation drugs can be prescribed.
This is rare and would most commonly occur in clients with less than three follicles or very poor ovarian reserve. It can also occur if for some reason the trigger injection was inadequate or incorrectly administered or absorbed. This can be assessed with a blood test.
Most people undergoing IUI have normal semen samples, however on rare occasions the sperm may not have washed-up adequately enough to continue with an insemination. A cut off of 2M/ml is usually applied in these cases.
Premature ovulation before egg collection is very unusual and is reported in 1 in 200 cycles. Premature progesterone rise can occur in 5–10% of cycles, this can occur but most commonly where there is a rapid increase in oestrogen levels and follicular growth. It can also be common in clients who have a very low AMH (ovarian reserve). If the progesterone level in the blood has been noted to be raised prior to trigger, your doctor will usually advise a Freeze Only cycle with no fresh transfer. This is because the progesterone can have an effect on the lining of the endometrium which reduces the chance of embryo implantation. It is best to delay the transfer to a future cycle where the uterine environment is more favourable.
About a third of IVF cycles result in what is called a Freeze Only cycle, where all high-quality embryos are frozen without a fresh transfer occurring. The three most common reasons why these are carried out are:
A Freeze Only cycle requires the embryos to be cultured in the laboratory until Day 5 or 6 when they have the best chance of being successfully frozen at the blastocyst stage (>60-cell stage). Approximately 30–40% of fertilised embryos reach the blastocyst stage by Day 5 but they need to be of a high grade for them to be frozen. A very quick-freezing process called Vitrification is used to create a glass-like state in the embryo cells that protects them from ice crystal damage. The embryos then are stored in liquid nitrogen until the client is ready to have a Frozen Embryo Transfer cycle.
We expect more than 98% of blastocysts to survive the freezing/thawing. It is reassuring to know that thawed embryos have approximately a 40% chance of resulting in a pregnancy. This is because firstly they were considered high quality embryos before they were frozen and secondly, they are being transferred in either a natural or manufactured cycle where the hormone levels in the uterus are most receptive to embryo implantation.
If your doctor feels that you have over responded to the ovarian stimulation drugs and are at risk of developing OHSS, then the type of Trigger injection you will be given may be changed and a Freeze Only cycle will be recommended. See OHSS section for further information.
The majority of egg collections are performed after you have been given some strong pain relief medication through a vein in your arm and local anaesthetic has been administered into the wall of the vagina with a needle. This is called local and anaesthetic sedation, so that you are responsive to instructions but very drowsy. Your heart rate and level of pain is closely monitored and more relief is given as you need it. Most people cope well during this process and many do not even remember the procedure after it is over. It is extremely rare to have any negative effects during the sedation, and afterwards you can expect to be tired and sometimes nauseous.
Approximately 5–10% of people undergoing IVF/ICSI will require the procedure to be performed under a general anaesthetic due to difficulties in accessing the ovaries or occasionally if the procedure cannot be tolerated under sedation. This is where an anaesthetist uses medication to completely put a patient to sleep so they are not conscious. It requires taking control of the airways so that oxygen is supplied to allow normal breathing to occur. Note that this is an additional cost – refer to the fee schedule.
The ovaries are surrounded with important structures including the bowel, bladder and major blood vessels. The needle used to remove the eggs is guided into position by the doctor using an ultrasound scan. There is a very low risk of damage to these structures approximately 1 in 2,500. If this occurs it may require urgent abdominal surgery.
As the egg collection needle is passed through the vaginal wall and into the ovary there is a small risk that bacteria can be introduced at this time. It can also occur when the embryo transfer catheter is passed through the cervix and into the uterus. The risk of this occurring has been reported to be less than one case in every 500 people undergoing an egg collection. This possibility is increased with the presence of an endometriotic cyst in the ovary at the time of treatment, so antibiotics are usually given at the time of the egg collection to reduce the chance of this occurring in these people.
Please inform the nurses if you have had any vaginal infection or thrush in the months leading up to your treatment. They will assess if you need to have this treated to reduce the risk of pelvic infection.
When sperm is not present in the ejaculate, surgical sperm retrieval may be possible. This is usually performed under local anaesthetic and sedation and takes about 15 minutes. We normally give you antibiotics at the time of the procedure to minimise the risk of infection and there is a 1% risk of haematoma (bleeding) after the procedure.
You are putting all your trust in us to care for your eggs/sperm and embryos while you undergo this very technical range of procedures. We want to assure you that firstly we honour that trust, and secondly that the quality of our techniques and processes meet the very highest international standards as they are assessed and accredited by auditors every year. There are however risks with any highly technical procedures and the following are a list of things that either clients wonder about or need to be aware of.
It is very important to be aware that over the course of six days from egg pickup, there is always a drop off in the numbers of viable eggs and embryos. So for example, someone undergoing ICSI might experience:
Day 0 – egg collection
12 follicles present, where 10 eggs are collected but only 8 are mature enough to be injected
4 high quality embryos
3 high quality embryos
2 high quality embryos (blastocysts) – one is transferred back to the uterus and one is frozen
This is an example only and not to be used as an expected or typical outcome.
IVF and ICSI involves a number of complex handling stages where the eggs, sperm and embryos are contained within and transferred between, test tubes, dishes, catheters, freezing devices and injection pipettes. The equipment undergoes strict daily monitoring and is alarmed for all malfunctions. In the past 25 years of our laboratory staff’s experience, the risk of an accident or equipment malfunction is very rare (1/1000). Protocols, staff competencies and quality assurance are rigorously monitored and reviewed so that errors are absolutely minimised.
It may be natural for clients to be concerned about the accuracy and reliability of IVF clinics to protect against the possibility of a “mix up” with their own eggs, sperm, and embryos. Our clients can be confidently assured that we use the best internationally renowned golden benchmark of cross witnessing systems to prevent these kinds of errors from occurring. The RI witness program which was implemented at Repromed in 2021 uses radio frequency identification tags on all embryo culture dishes, sperm pots, and client ID tags which are continuously monitored by electronic equipment to detect any mismatches of eggs, sperm, embryos, and clients, before an error can occur. For all other manual processes, we have strict policies and procedures that are monitored and audited by our Quality Manager, who is responsible for ensuring the witnessing procedures are adhered to, and staff are annually audited for compliance to our Patient Identification and Gamete/Embryo Chain of Custody Policies. An external auditing authority, RTAC (Reproductive Technology Accreditation Committee), also annually audits the clinic for compliance to these policies.
ICSI requires that the egg is injected with a glass needle that contains a single sperm and some eggs can be damaged during this delicate process. The membranes of eggs can be especially fragile and do not respond well to being injected. The incidence of the egg not surviving this process is approximately one egg in every 10.
This can be equally due to either the sperm or egg quality. The eggs retrieved in an IVF cycle always range in their stage of maturity, some can be immature and unable to be fertilised or injected, while others are over mature and deteriorate. Usually the embryologist can provide a visual assessment of these variables which may provide some explanation behind the lower than expected fertilisation. In other cases it may be lower than expected sperm quality or quantity on the day that is responsible for the poor fertilisation. Occasionally a second sample may be requested, to increase the quantity of sperm for fertilisation. The risk of having total failed fertilisation during a cycle is approximately one case in every 35 IVF/ICSI cycles.
This occurs in approximately 5% of eggs and is described as an unbalanced number of cell nuclei (pronuclear 1PN or 3PN). Three pronuclear eggs are discarded immediately as they have a high chance of abnormal development. In some cases the abnormal fertilisation is caused by more than one sperm entering the egg by chance, and in others cases, it is due to a dysfunction of the egg during the fertilisation process.
Embryo quality originates from the sperm and egg quality and some embryos have the ability to survive better in culture than others. The embryologists assess the embryo quality on Day 2 and early on Day 3 to decide if a client should have a transfer on Day 3 or Day 5. Embryos that are high quality after being cultured through to Day 5 have a higher probability of creating a pregnancy partly because they have demonstrated they are actively growing and viable. There is however a relatively high risk (>50%) that clients may not have any embryos surviving until Day 5 if the numbers of high quality embryos on Day 3 are low (i.e. less than three). In these cases, the embryologist will advise the client to have a transfer on Day 3 to avoid this risk. The embryos remaining in culture after a Day 3 transfer, are grown on until Day 5 and 6 when they can be assessed for freezing, however the chance that there may be no embryos reaching this stage, are again, relatively high. Approximately one case in every 80 cycles there are no normal quality embryos to transfer fresh.
Embryos and eggs are frozen using a process called Vitrification. The embryos/eggs are attached to a freezing rod by surface tension in a tiny drop of fluid then stored in liquid nitrogen at -196°C. This is also a delicate operation which involves several steps where the embryo or egg can become damaged even when all the procedures are carried out correctly with highly experienced staff. There is an accepted 5% risk that an embryo or egg could either rupture on the freezing device or become dislodged and lost during the freezing or thawing process.
Freeze Only cycles are carried out for three common reasons:
a) excessive follicle development and risk of OHSS
b) premature rise in progesterone before the egg collection
c) the development of health issues (such as the need for surgery).
The fertilised eggs will routinely be cultured through to Day 5 or 6 when their quality is assessed for suitability to freeze.
It’s important that clients undergoing Freeze Only cycles are clear that this does not mean Freeze-All, as just like all other IVF/ICSI cycles, only high quality blastocysts can be successfully frozen. The freeze rate is therefore dependent on the embryo quality and development. At Repromed the average number of embryos frozen in Freeze Only cycles is two but is again age dependent. The chance that there will be no embryos frozen in a Freeze Only cycle is between 10–15%.
Standard IVF/ICSI cycles involve the creation of several embryos to produce the best chance of selecting a high-quality embryo for transfer. A large proportion of these embryos will contain chromosome abnormalities which cannot be detected without performing more complicated procedures such as genetic diagnosis. On average, 40% of embryos are non-viable or fail to develop normally and show clear signs of arresting their development by Day 5 or 6. This makes them unavailable for either embryo transfer or freezing. This is a normal occurrence in IVF/ICSI treatment and natural conception (without IVF) where the majority of embryos either fail to implant or miscarry. Clients undergoing IVF/ICSI will however, be required to consider the disposal of these non-viable/non-functional or developmentally arrested embryos by selecting one of three options in the IVF/ICSI Procedures Consent Forms.
These options include:
Very occasionally (one case in every 350 cycles) the embryologists will detect a microbial contamination in a client’s embryo culture, usually on the day of fertilisation check (Day 1). The microorganism can be bacterial or fungal and originate from either the semen sample or vagina during the egg collection. Once the samples have been tested by microbiology, the affected person is required to take antibiotics before undergoing future treatment. Contaminated embryos often do not develop normally and the doctor will assess if a fresh transfer is advisable.
You can minimise the chance of egg and sperm microbial contamination by:
A pregnancy loss can be hugely emotional and you may need a support person at this time – someone who is understanding and available to help you through this time of loss. Our counsellors are here to support you
Pregnancy loss after fertility treatment occurs at a similar rate that occurs in the general non-IVF population. The loss rate is directly related to age and past obstetric and medical history. For example, a quarter of pregnancies miscarry in people less than 35 years. The loss rate gradually increases to half of the pregnancies in people 40 years and over.
Some vaginal bleeding may occur in the early stages of many pregnancies. A blood test may be done to check hormone levels are rising appropriately. Pelvic discomfort/period type pain in early pregnancy is very common as your ovaries will still be enlarged.
From the most current statistics from all Australian and New Zealand clinics we know that:
This is a positive pregnancy test that does not result in an ongoing pregnancy and occurs at a rate of around one case in every 5 IVF/ICSI pregnancies. Repromed staff closely monitor your results to ensure that you are supported through this difficult time.
This is a loss of the pregnancy after there has been evidence of a growing fetus in the uterus by ultrasound scan. It is often associated with abnormal genetic or foetal development. Anyone having a miscarriage may experience abdominal cramps and or persistent bleeding. If you develop any of these symptoms, go immediately to a hospital Accident and Emergency department, then contact the Repromed nurses or leave a message to let us know.
This pregnancy is where no foetal heartbeat is visible at the 6–8 week scan. At some stage of development the fetus has stopped growing and blood tests would not necessarily have detected this.
When a non-viable pregnancy is determined, your doctor will discuss and recommend whether you should wait for a period (which may be heavy or painful), medical management with tablets and a referral to a early pregnancy unit or have a curette (this may enable products of conception to be tested for possible chromosome abnormalities). Regular blood tests may be needed until there is no pregnancy hormone (hCG) remaining in the blood before another IVF treatment can be started.
This is a pregnancy that implants outside the uterus, most commonly in the fallopian tubes. Transferring embryos directly to the uterus doesn’t exclude an ectopic pregnancy. Such a pregnancy cannot continue and surgical intervention is required. Early diagnosis further minimises tubal damage and usually means the tube can be removed with minimally invasive surgery (laparoscopically).
Contact the nurses immediately if you experience any strong cramping in your abdomen or bleeding after a positive pregnancy test. For severe pain, go immediately to a hospital Accident and Emergency department, then contact the Repromed nurses or leave a message to let us know.
Most people having IVF treatment in Aotearoa will have one embryo transferred to minimise the risk of having a multiple birth which is associated with higher risks. However even when one embryo is transferred there is still a very small chance (1% overall) that the embryo may split into two and result in a twin pregnancy. With IVF treatment, when more than one embryo is transferred, the chance of a multiple pregnancy is much higher (and may be as high as 50% chance of twins).
Multiple pregnancies are associated with increased risks of pregnancy complications, preterm delivery and small for dates babies and therefore long-term health consequences for the child.
Multiple pregnancies can be a cause of problems for both you and baby. Some of the problems for the baby can be:
Some problems include:
Please note, at Repromed, it is our policy to transfer ONE embryo per public or privately funded IVF/ICSI or Frozen Embryo Transfer (FET) cycle.
Assisted Reproductive Technology (ART) is being used with increasing frequency with over five million babies born since 1976. The prevalent use of ART worldwide has enabled large-scale studies of developmental outcomes in babies, including the risk of birth defects. Overall the results of these studies have been reassuring particularly with respect to the growth and neurological development of babies conceived through IVF.
It’s possible that in some studies reporting an increased risk of birth defects, they may be related to conditions that underlie infertility. It’s also possible that there may be aspects of treatment that can influence growth and development of the embryo. The major risk from ART involves the practice of transferring more than one embryo and thereby having a multiple pregnancy with the associated risks as listed above. That is why Repromed has a policy of one embryo for transfer to minimise negative outcomes on the children and mother as much as possible.
Most of the babies born through IVF worldwide are only just reaching reproductive age. The potential long-term effects of assisted conception are therefore not yet fully known. As mentioned above, the physical, mental and social development in IVF children is similar to those conceived naturally based on evidence from several large studies. Some studies suggest that IVF children may be slightly taller but the differences are minor.
On average, IVF children are born earlier, and have a lower birth weight if they are a fresh embryo transfer or a higher birth weight if they are a frozen embryo transfer than the standard population, even for single births. This is thought to be due to a variety of factors including the underlying cause of infertility, parental age and effect of the ovarian stimulation drugs on implantation. The chance of congenital abnormalities in children born after IVF or ICSI appears to be slightly higher (four per 100 births) than with children conceived naturally (three per 100 births).
There is no conclusive evidence to link IVF with a specific abnormality, although some studies (2013) have suggested that some “imprinting” disorders are more prevalent after IVF/ICSI. Imprinting refers to changes in the way that some genes in our genetic make-up are expressed due to environmental pressures on the eggs/sperm or embryo. These disorders are extremely rare in the general population (one case in every 30,000 people) so it is very difficult to assess the exact impact that IVF has on the prevalence. But there are reports that estimate a 12 times greater likelihood of IVF children having one of the imprinting disorders called Beckwith-Wiedmann syndrome. It is however thought to be due to errors already present in the genetic material of sperm and eggs and not caused by the procedure itself.
There does not appear to be any additional increased risk of abnormalities in children following freezing of eggs, sperm or embryos. The chance of a major chromosomal abnormality such as Down’s syndrome, is not increased with the IVF procedure and the risk is related primarily to ovarian and sperm quality gradually declining with age.
The chance of miscarriage is slightly higher with advancing paternal age and infertility.
There is some evidence that sperm DNA damage (fragmentation) may reduce the chance of pregnancy from treatment and increase miscarriage risk. People with non-obstructive azoospermia (absence of sperm) or severe oligospermia (less than one million per ml) may have a genetic cause of their infertility with an abnormal gene on the Y chromosome. It is still unknown if male children conceived through ICSI may therefore inherit the same genetic abnormality present in their father and may have the same sperm production problem.
People who have azoospermia due to congenital absence of the vas deferens (CBAVD) carry the gene for cystic fibrosis. We screen both partners for cystic fibrosis when the male could have CBAVD to determine any potential risk. There may be a slightly higher risk of chromosomal abnormality (0.5%) with ICSI particularly an abnormal number of X and Y chromosomes in the naturally conceived population (0.25%). People needing ICSI may have an increased risk (1–2%) of having a child with a genetic abnormality that may not be recognisable at birth.
Large published studies involving the follow-up of tens of thousands of people having IVF, have shown that there is no evidence of increased risk from IVF of ovarian and breast cancer. There is also no link between the number of treatment cycles or type of medication used and increased cancer incidence. Studies on the incidence of cancer in children conceived from ART, indicate the incidence is the same as in children conceived naturally.
We do recommend you have annual reviews that include breast and pelvic examination. If you have a family history of breast or ovarian cancer, please advise your doctor. Regular screening, such as an annual mammogram, may be recommended depending on your age and family history.
Some people worry that the fertility drugs and collection of many follicles may cause them to go into early menopause, however, there is no evidence that this is the case. The egg collection procedure
only takes the number of eggs that would regularly start to grow but die off naturally each month. It is thought that many people undergoing IVF over the age of 39 often already have a low ovarian reserve of eggs and may be destined to enter menopause early.
Megan leads the nursing team through the continually changing face of IVF. She works in a multidisciplinary team, providing the essential organization between the doctors and laboratory and ensuring communication between all departments.
Megan started her IVF nursing career in the United Kingdom, working in two large London clinic’s before returning to New Zealand. She is also the Secretary of Fertility Nurses of Australasia.