Many add-ons are still unproven, with limited or low-quality evidence supporting their effectiveness.

This information summarises the most commonly requested add-ons at Fertility Associates. For more detailed information, please refer to the “IVF Add Ons” resource.

Some of the published research on IVF add-ons is of variable quality and may be unreliable. This guide aims to explain the available evidence in a clear and balanced way, so you can make informed decisions about your care. It also outlines our current recommendations on when these options may be considered.

This  is not intended as a “shopping list” of treatments. Instead, it is designed to support discussions with your specialist. All add-ons must be carefully reviewed and approved by your specialist before use.

We often find “Add Ons” are considered in the setting of Recurrent Implantation Failure and Recurrent Miscarriage, so it is important to define these.

Recurrent implantation failure (RIF) refers to repeated unsuccessful embryo transfers despite the use of embryos expected to have a reasonable chance of pregnancy.

There is no single agreed definition:

• ESHRE recommends defining RIF based on an individual’s predicted chance of success (typically when this exceeds ~60% without pregnancy).
• Many experts (including ASRM-aligned consensus) suggest waiting until at least three transfers of good-quality or euploid embryos have failed before considering this diagnosis.

Importantly, true RIF is thought to be uncommon, and repeated failed transfers are often due to chance rather than an underlying problem.

Recurrent miscarriage (also called recurrent pregnancy loss) is usually defined as having two or more miscarriages.
These losses do not need to happen in a row and can include very early pregnancies confirmed by a positive test.
After two losses, your specialist may recommend further assessment to look for possible underlying causes, although in many cases no clear reason is found.

PGT-A involves taking around 5-10 cells from the outer part of the embryo that becomes the placenta to check whether these cells have the expected number of chromosomes. The number of aneuploid embryos (too many or too few chromosomes) increase with female age. Aneuploidy can often result in implantation failure, miscarriage, or rarely, an ongoing pregnancy with a chromosomal condition (such as Down Syndrome).

Who might consider PGT-A?

• Women aged 38 years or older (especially if ovarian reserve is good)
• Those with recurrent miscarriage or recurrent implantation failure

What benefit might it offer?

PGT-A may:

• Reduce the chance of miscarriage or implantation failure
• Reduce the chance of a pregnancy with a chromosomal condition
• Decrease the time and number of transfers needed to achieve a pregnancy

However, PGT-A does not increase the overall chance of having a baby. Your chance of a baby is the same with or without PGT-A, you simply avoid transferring the aneuploid embryos.

Could it cause harm?

• This is a screening tool and so it is not 100% accurate; <5% of results may be incorrect.
• Mosaic results (cells with a mixture of normal and abnormal chromosome numbers) can cause worry and sometimes require genetic counselling.
• “No results” can occur. Re-biopsy may be possible.
• Thawing an embryo to biopsy, or multiple biopsies, may damage the embryo and reduce its implantation potential.
• Prenatal screening in pregnancy such as maternal serum screening, NIPT, and ultrasound are still recommended.

FA’s current recommendation:

We generally recommend PGT-A is considered for all patients 38 and older, but are happy to discuss its place in your care at any time, particularly in the setting of recurrent miscarriage, implantation failure, or previous births with aneuploidy.

An intravenous infusion containing fats (soybean oil, egg yolk, glycerine).

Who might consider Intralipid?

• Those with recurrent miscarriage
• Those with recurrent implantation failure

What benefit might it offer?

Some theories suggest high natural killer (NK) cell activity may affect implantation. Intralipid has been proposed to reduce NK cell activity, but research has not confirmed this, and studies show mixed results.

Why this may not improve outcomes?

• NK cells normally play an important role in implantation; reducing them may be unhelpful.
• Tests for NK cell levels are not reliable or proven to predict outcomes.
• Most implantation failures and miscarriages are due to embryo chromosome issues, not immune problems.

What does the evidence say?

There is no clear evidence that Intralipid improves live birth rates or reduces miscarriage. Because so little reliable research exists, we also cannot be sure that it won’t reduce the chance of a live birth.

Risks or side effects:

Uncommon side effects: nausea, vomiting, rash, fever, shivering, shortness of breath, headache, flushing, dizziness.

Long term safety is unknown due to limited data.

FA’s current recommendation:

Because of a lack of any clear benefit, our specialists would very rarely recommend this.

1. Colorado protocol - a combination of aspirin, an antibiotic (e.g., amoxicillin–clavulanate or doxycycline), and a steroid (usually prednisone), taken around the time of embryo transfer.
2. Bondi protocol – a combination of enoxaparin (Clexane) and a steroid (usually prednisone), taken around the time of the embryo transfer and often continued in the first trimester.

Who might consider it?

• Those with recurrent implantation failure
• Those with recurrent miscarriage

What benefit might it offer?

• Steroids may modify immune system activity
• Aspirin and enoxaparin may assist early placental development and implantation
• Antibiotics may treat chronic endometritis
• However, none of these explanations are proven.

Why this may not improve outcomes

• No strong evidence that immune dysfunction or chronic endometritis commonly causes implantation failure or miscarriage.
• Most failed transfers and miscarriages are due to embryo chromosomal issues.
• These medications individually have not been shown to improve live birth rates.

What does the evidence say?

• There has never been a trial done on the Colorado or Bondi Protocol so whether it improves outcomes is unclear.
• Because no research exists, we also cannot be sure that it won’t reduce the chance of a live birth.
• Steroids alone do not improve live birth rates in IVF.

Side effects and potential long-term harm

Common side effects: mood changes, sleep disturbance, nausea, headaches, weight gain, diarrhoea/constipation, dizziness, bruising.

Possible longer-term risks:

• Slightly increased risk of cleft lip/palate in babies exposed to steroids in the first trimester
• Increased risk of gestational diabetes
• Reduced bone density or (very rarely) avascular necrosis with prolonged use

FA’s current recommendation:

Because of a lack of any clear benefit, our specialists would only rarely recommend this, in the absence of other causes or proven treatments for recurrent implantation failure.

PRP is made from your own blood. A centrifuge machine concentrates platelets, growth factors and cytokines, and this plasma is infused into the uterus in a procedure similar to an embryo transfer.

Who might consider PRP?

• Those with recurrent implantation failure
• Those with a thin endometrial lining that has failed to respond to more conventional strategies (e.g. higher dose oestrogen, oestrogen patches)

What benefit might it offer?

• Platelets may stimulate growth and thickening of the endometrium
• Growth factors and cytokines may support healing and reduce inflammation

Why this may not improve outcomes:

• The endometrium already receives platelets naturally; extra platelets may not help.
• Most failed implantations are due to embryo chromosomal issues, not endometrial lining problems.

What does the research say?

• Many studies on this topic have concerns around trustworthiness.
• Current evidence is too limited to know if PRP improves live birth, pregnancy, or miscarriage rates, we also cannot be sure that it won’t reduce the chance of a live birth.

Risks or side effects

• Cramping, discomfort, light bleeding.
• Rarely: infection or hypersensitivity.
• Long-term risks are unknown.
  

FA’s current recommendation:
Thin endometrium is a challenging condition to manage. Studies show successful livebirths will still occur. On a case-by-case basis our specialists may recommend this is considered.

This is a procedure to scratch and disturb the endometrium (lining of the uterus). It involves placing a thin plastic straw called a Pipelle through the cervix and into the uterus. This straw is used to scratch the endometrium by removing a small amount of tissue.

Who might consider it?

• Those with recurrent implantation failure

What benefit might it offer?

• The injury may trigger a healing response and release growth factors, cytokines and immune cells that support implantation.

Why this may not improve outcomes?

• It is usually performed in the cycle before embryo transfer, but the lining sheds at menstruation, so any benefit may not last.
• Most failed implantations are due to embryo chromosomal issues, not lining issues.

What does the evidence suggest?

• High quality research shows no meaningful improvement in live birth rates.
• A large, well designed New Zealand trial found no benefit.

Risks or side effects:

• Cramping or pain during the procedure is common.
• Rare: prolonged bleeding or infection.
• No known long-term harms.

FA’s current recommendation:
Because of a lack of any clear benefit, our specialists would very rarely recommend this.

A procedure where a camera is placed into the uterine cavity to visualise the uterine lining. This can be done in an outpatient setting or under anaesthesia.

Who might consider it?

• Those with recurrent implantation failure

What benefit might it offer?

• May identify subtle abnormalities within the uterine lining not identified with non-invasive imaging (such as ultrasound or saline scan).

Why this may not improve outcomes?

• Most of these abnormalities will be identified with well conducted non-invasive imaging.

What does the evidence suggest?

• Good quality research shows no meaningful improvement in live birth rates when offered routinely for all patients prior to IVF.
• In patients with recurrent implantation failure it may improve live birth rates.

Risks or side effects:

• If anaesthetic is used there will be small risks associated with this.
• Rare complications include infection, bleeding and perforation (making a hole in the uterus) are complications of hysteroscopy.

FA’s current recommendation:

In the setting of recurrent implantation failure or recurrent miscarriage hysteroscopy is often recommended. We also suggest this if there has been a difficult embryo transfer, as dilatating the cervix may help with subsequent embryo transfers.

hCG is a hormone secreted by the embryo before implantation. An hCG infusion involves placing hCG into the uterine lining directly before embryo transfer.

Who might consider it?

• Those undertaking a day 3 (cleavage stage) embryo transfer.

Why might work?

• May enhance the embryo-endometrium communication and help facilitate implantation.

Why this may not improve outcomes:

• Most embryos that are destined to implant and lead to ongoing pregnancy will have a robust embryo-endometrium interaction, additional hCG may provide little meaningful benefit.

What does the evidence suggest?

• Good quality research shows no benefit when given before blastocyst (Day 5) transfers.
• There may be an improved live birth rate when used before Day 3 (cleavage stage embryos).

Risks or side effects:

• Besides discomfort with insertion there are no risks to the procedure.
• Ectopic pregnancies do not seem to be more common after hCG infusion – though data is limited.
• There does not appear to be any long-term harm associated with the use of hCG infusion.

FA’s current recommendation:

Because of a lack of any clear benefit, our specialists would very rarely recommend this as most of our transfers are day 5 blastocysts.

A group of organic nutrients that includes vitamins, minerals and polyunsaturated fatty acids, which are suggested to reduce oxidative damage. These may include CoQ10, melatonin, myo-inositol, Vitamin (B,C,D,E), omega 3 fatty acids as well as many more.

Who might consider it?

• Anyone undertaking fertility treatment or trying to conceive

• Anyone with previously poor embryology results within an IVF cycle

• Those with male factor infertility or high sperm DNA fragmentation

What benefit might it offer?

Oxidative stress has been implicated in male factor infertility, poor embryo development, infertility, miscarriage and recurrent implantation failure. Antioxidants may reduce oxidative stress.

Why this may not improve outcomes:

Most people who lead a healthy lifestyle will gain antioxidants through their diet.

The egg has been exposed to a lifetime of oxidative stress; it is unlikely that a few months of antioxidant therapy will significantly alter egg quality.

There are many other factors contributing to egg and sperm quality.

What does the evidence suggest?

For both males and females, the evidence is uncertain whether antioxidants improve live birth rates, with no specific type of antioxidant being superior to others. Research in this area is often of very low quality.

Risks or side effects:

Antioxidant use may lead to an increase in gastrointestinal discomfort.

FA’s current recommendation:

If you want to take antioxidants, we have no objections, but the evidence is lacking to say this definitively improves egg, sperm or embryo quality – but likely does no harm either.

The ERA test purports to help identify the best timing for a frozen embryo transfer. It involves taking an endometrial biopsy and analysing it to see whether the lining is “receptive” — meaning ready for an embryo to implant. The results guide the IVF specialist on the ideal day to perform an embryo transfer. The actual transfer is done in a later cycle using a controlled (artificial) preparation cycle.

Who might consider it?

Those with recurrent implantation failure.

What benefit might it offer?

Some research suggests the implantation window might be different in different people.

Why this may not improve outcomes:

The implantation window may vary month to month. The ERA test measures gene expression patterns, a biopsy may not collect a balanced mix of cell types, which could affect the results. If gene expression seems higher or lower than expected it could be due to the make-up of cells sampled rather than a true change in the receptivity.

What does the evidence suggest?

Moderate quality evidence suggests the ERA test does not improve patient outcomes (it does not increase the chance of a baby). Because of this we rarely offer ERA testing at Fertility Associates.

Risks or side effects:

Pain during the biopsy is the most common side effect, other risks are very rare including prolonged bleeding, infection or uterine perforation. There are no known long-term risks to this test.

FA’s current recommendation:

Because of a lack of any clear benefit, our specialists would very rarely recommend this.

EMMA = Endometrial Microbiome Metagenomic Analysis, evaluates the endometrial microbiome. An endometrial biopsy is taken. It aims to identify the balance of health bacteria (mainly lactobacillus) to other bacteria.

Who might consider it?

• Those with recurrent implantation failure or recurrent pregnancy loss.
• Those with suspected endometrial dysbiosis.

• What benefit might it offer?

It may identify an endometrial microbiome that is negatively impacting implantation.

Why this may not improve outcomes:

It is very difficult to get a non-contaminated endometrial microbiome sample; the vaginal microbiome can contaminate the sample and affect the results. It has yet to be proven that endometrial dysbiosis leads to implantation failure or recurrent miscarriage. We do not know if correcting the dysbiosis improves outcomes, we don´t know what treatment is optimal to correct endometrial dysbiosis.

What does the evidence suggest?

There are no clinical trials on the role of this test, nor subsequent probiotic use if required. The effect of this on live birth rates is therefore unknown.

Risks or side effects:

The endometrial biopsy required for this test can cause pain. Very rarely prolonged bleeding, infection or uterine perforation can occur.

FA’s current recommendation:

More research is emerging about the microbiome. We may recommend the EMMA and ALICE test in the setting of recurrent implantation failure.

ALICE = Analysis of Infectious Chronic Endometritis. An endometrial biopsy is taken which aims to identify if chronic endometritis is present. This is a subclinical infection of the lining of the uterus (meaning a patient will have no symptoms of infection).

Who might consider it?

• Those with recurrent pregnancy loss
• Those with infertility and suspected chronic endometritis

What benefit might it offer?
Chronic endometritis is persistent and mild inflammation of the endometrium. There appears to be a link between chronic endometritis and infertility, so treatment of this condition may improve outcomes.

Why this may not improve outcomes:
There is no standardised or accepted definition of chronic endometritis and the ALICE test has not been externally validated for use. It is uncertain still if treating chronic endometritis, improves outcomes.

What does the evidence suggest?
There are no published randomised controlled trials, so it is unclear if testing for, and treating, chronic endometritis improves outcomes.

Risks or side effects:
The endometrial biopsy required for this test can cause pain. Very rarely prolonged bleeding, infection or uterine perforation can occur.

FA's recommendation:
More research is emerging about the microbiome. We may recommend the EMMA and ALICE test in the setting of recurrent implantation failure.

PRP is made from your own blood. A centrifuge machine concentrates platelets, growth factors and cytokines, and this plasma is injected into your ovaries.

Who might consider it?
Those with low ovarian response, diminished ovarian reserve or premature ovarian insufficiency (early menopause).

What benefit might it offer?
Platelets may help tissues heal and regenerate due to their anti-inflammatory properties. It may cause an improved blood flow, support follicle growth and egg quality.

Why this may not improve outcomes:
It is generally accepted that females are born with all the eggs they will ever have, ovarian PRP is thus extremely unlikely to be able to ¨grow new eggs΅ or rejuvenate the egg supply

What does the evidence suggest?
Only two very small randomised trials are available, both showing no improvement in the chance of a baby. Because they are very small trials, it is unclear if ovarian PRP affects the chances of a live birth. Due to a lack of clear benefit, this add on is not currently offered at Fertility Associates.

Risks or side effects:
Ovarian PRP can be injected into the ovary in a procedure similar to an egg collection or during a laparoscopy. Both of these are invasive procedures and carry a small risk of infection, bleeding and damage to internal organs that surround the ovary.

FA’s current recommendation:
Because of a lack of any clear benefit, and risk of significant injury, our specialists do not recommend this.

TiMi is a specialised embryo incubation system that takes frequent digital images of embryos in culture, and a time-lapse video can be created from these images.

Who might consider it?
Anyone undertaking IVF could consider time-lapse.

What benefit might it offer?
The time-lapse incubator itself may create a more stable environment for embryo culture, limiting exposure to changes in temperature, pH and osmolarity. This is because we don’t need to open the incubator to check on embryo development. It may also be able to use the time-lapse videos to improve embryo selection (picking the embryo with the highest implantation potential first).

Why this may not improve outcomes:
Embryo viability is determined by biology, not imaging. Timelapse imaging can´t change oocyte and sperm quality or the chromosomal status of the embryo.

What does the evidence suggest?
Moderate quality data shows no benefit in the live birth rate or miscarriage rate with the use of time lapse imaging compared to standard embryological culture. It does enable undisturbed embryo culture. There are also benefits to time-lapse in terms of laboratory workflow and allowing patients to view their embryo development.

Risks or side effects:
There are no known long-term risks to this technology.

FA’s current recommendation:
We find timelapse a useful additional data point to assist with embryo selection but need to be clear that using TiMi doesn’t improve your chances of a live birth. There are sound arguments for leaving the embryos undisturbed if possible.

Growth hormone is produced naturally in the body and plays and important role in metabolism and in bone growth. It also helps ovaries develop and mature and helps the eggs that already exist to mature. A manufactured form of this hormone is available for use.

Who might consider it?
Those with poor response to ovarian stimulation, those of advanced female age (≥ 38 years), those with diminished ovarian reserve.

What benefit might it offer?
It may help with egg maturation and thus it could increase the number and quality of eggs retrieved during an IVF cycle.

Why this may not improve outcomes:
It appears to help eggs mature 2-3 months before they are recruited for ovulation. Giving growth hormone during an IVF cycle is likely too late to impact on egg recruitment, growth or quality. It can´t create more eggs and it can´t alter the quality of an egg (chance of chromosome change (aneuploidy) is not changed.

What does the evidence suggest?
It is unclear from the current evidence if growth hormone affects the chance of having a live birth. The trials performed are small with significant limitations that may bias their results.

Risks or side effects:
Common side effects include headache, fluid retention, joint and muscle pain, high blood pressure. When taken within an IVF cycle it is usually given for 4 weeks – in this case it may affect the body’s ability to process and handle glucose – it may cause pre-diabetes for example. Longer term use can be associated with many other risks.

FA’s current recommendation:
Because of a lack of any clear benefit our specialists do not recommend this.

A non-steroidal anti-inflammatory agent that inhibits prostaglandin synthesis. It is taken as a tablet once daily.

Who might consider it?

• Anyone undertaking fertility treatment
• Those with recurrent miscarriage or recurrent implantation failure

What benefit might it offer?
It may improve uterine blood flow and enhance endometrial receptivity to promote implantation.

Why this may not improve outcomes:
Implantation is complex and most causes of implantation failure, miscarriage or unsuccessful fertility treatment are due to embryo factors rather than uterine factors.

What does the evidence suggest?

• Moderate quality evidence suggests no benefit to live birth rate with the routine use of aspirin in patients undergoing IVF treatment.
• Moderate quality evidence suggests no benefit to routine aspirin use to prevent recurrent miscarriage.

Risks or side effects:
Low-dose aspirin is widely used in contemporary clinical practice and is commonly prescribed in pregnancy to reduce the risk of pre-eclampsia. It increases bleeding risk. Side effects include gastrointestinal discomfort, nausea, activation of peptic ulcer, and skin reactions.

FA’s current recommendation:
If you want to take Aspirin we will usually support this however, please do not take low dose aspirin without discussing it with your fertility specialist, especially if you are having an egg retrieval as it may increase your risk of bleeding complications.

Androgen can be used for cycle priming. Preparations used include DHEAS and synthetic testosterone. DHEAS is a given orally in tablet form. Synthetic testosterone is usually administered through the skin (gel or patch). They are given preceding an IVF cycle to try and improve recruitment and response.

Who might consider it?
Patients with diminished ovarian reserve or previous poor response during an IVF cycle.

What benefit might it offer?
Androgens play a crucial role in maintaining adequate follicular steroid production, they also aid in small antral follicle development and they can amplify the effect of FSH on follicular growth.

Why this may not improve outcomes:
There is no agreed upon dose or duration for pre-treatment with androgens. Androgens only act on preantral or small antral follicles and don´t have significant impacts on mature follicles.

What does the evidence suggest?
A recent research review led by Fertility Associates IVF specialists suggested that pre-treatment with synthetic testosterone likely improves the chances of a live birth in patients undergoing IVF who are identified as poor responders. Conversely DHEA likely results in little or no difference in live birth in these patients.

Risks or side effects:
Can cause changes in sexual desire, changes in muscle mass, fat distribution, mood, energy levels and psychological wellbeing.

FA’s current recommendation:
For those who we anticipate may have low egg numbers, testosterone priming is often integrated into your cycle plan.