DHEA is an androgen (steroid hormone) that helps produce oestrogen and testosterone.

• Use in IVF: As androgen production levels decrease with age, DHEA is believed to be a good supplement to increase oestrogen production which may lead to positive outcomes in IVF patients.
• Possible benefits & supporting evidence: Some studies have stated that DHEA in IVF may have a role in increased follicle development, improved egg quality and pregnancy rates, however there is very insufficient evidence to support this.
• Potential side effects/risks: Acne, hair loss, oily skin, increased energy levels and increased libido are common. More severe side effects from prolonged use include worsening of cardiac arrhythmias and hormone-sensitive tumours, and increased risk of diabetes and bowel cancer.
• Use in Pregnancy: DHEA is a Category D drug and is not safe to use in pregnancy. Category D drugs have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. The use of androgens such as DHEA should only be used prior to an IVF cycle.
• Risk-benefit evaluation: To date, there is limited evidence of the benefits of androgens such as DHEA. Use should be limited to patients who have had prior poor response to standard IVF protocols.

Testosterone is an androgen (steroid hormone) that predominantly stimulates the development of the male reproductive system.

• Use in IVF: Testosterone can be used in IVF patients with the aim of improving the number and quality of the oocytes.
• Possible benefits & supporting evidence: There is some evidence to suggest that testosterone can improve the quality and number of oocytes, as well as promote the growth of larger follicles in poor-responding women. Further studies on larger samples are required to provide more substantial evidence of its effectiveness.
• Potential side effects/risks: The main common side effects from the use of Testosterone is excessive hair growth, acne, and oily skin. Additionally, side effects such as headaches, libido changes, breast tenderness and irritation at the patch site may occur. These are generally reversible based on the dose and duration used. Excessive or prolonged use of Testosterone could result in irreversible deepening of the voice. Side effects can also differ depending on the method of delivery.
• Use in Pregnancy: Testosterone is a Category D drug and is not safe to use in pregnancy. Category D drugs have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. The use of androgens such as testosterone should only be used prior to an IVF cycle.
• Risk-benefit evaluation: To date, there is insufficient evidence of the benefits of androgens such as testosterone. Use should be limited to patients who have had prior poor responses to standard IVF protocols.

Melatonin is a hormone that occurs naturally in the body and is a powerful antioxidant involved in the regulation of sleep patterns.

• Use in IVF: It has been associated with the prevention of damage to a woman’s eggs by oxidative stress, which could lead to an increase in the quality of these eggs and higher fertilisation rates in IVF.
• Possible benefits & supporting evidence: At present, there is limited evidence from the small studies that have been undertaken, showing any benefits of melatonin use in IVF. Larger studies are required to provide conclusive recommendations.
• Potential side effects/risks: Melatonin’s most common side effects are daytime drowsiness, headaches, dizziness, mild anxiety, irritability, and nausea. Other side effects reported include confusion, abdominal pain, and vivid dreams.
• Use in Pregnancy: Currently, there is not enough research to confirm that taking melatonin supplements in pregnancy is safe.
• Risk-benefit evaluation: At present, there is no evidence to conclusively prove Melatonin is of benefit in IVF treatment.

Growth hormone is produced by the pituitary gland. It has many functions including stimulating the growth of tissue and bone (in children) and maintaining metabolism.

• Use in IVF: Growth hormone may lead to a potential improvement in the stimulation of follicles, egg development and egg maturation in an IVF cycle. Growth hormone plays a role in increasing the natural female hormones that play an important role in ovarian function.
• Possible benefits & supporting evidence: Women who have previously experienced poor egg response in past IVF treatment cycles may see some benefit from the use of growth hormone on the number of eggs collected after the use of growth hormone.
• Potential side effects/risks: The most reported side effects include headaches and injection site rashes, along with some joint swelling. Rarer side effects include carpal tunnel syndrome and an increased risk of developing type two diabetes. Long-term use of growth hormone is not recommended as this can lead to significant health concerns such as swelling of extremities and internal organs.
• Use in Pregnancy: Currently, there is not enough research to confirm that taking growth hormone in pregnancy is safe.
• Risk-benefit evaluation: From the small number of studies that have been conducted to date, there has been no significant improvement in pregnancy rates or birth outcomes when growth hormone was used in combination with an IVF cycle. More research and larger studies are required.

Aspirin is a non-steroidal anti-inflammatory drug (NSAID) that is used to reduce pain, aches, fevers, or inflammation.

• Use in IVF: Low-dose aspirin has been broadly used as an additional treatment in IVF, predominantly with patients who have had recurrent miscarriages.
• Possible benefits & supporting evidence: Aspirin is thought to improve blood flow to the uterus. There is insufficient evidence from studies undertaken to show that low dose aspirin increases the chance of pregnancy or live birth.
• Potential side effects/risks: Side effects could include gastrointestinal ulcers, gastritis, indigestion, headache, nausea, bleeding and bruising. Aspirin may also exacerbate Asthma symptoms therefore the use of aspirin is not recommended in patients who suffer from Asthma.
• Use in Pregnancy: Low-dose aspirin is safe to use throughout pregnancy and is often prescribed for women at high risk of pre-eclampsia.
• Risk-benefit evaluation: Due to the lack of quality evidence, there is little to no benefit from using aspirin as a complementary therapy in IVF.

Heparin is an anticoagulant medication (blood thinner) that is used to prevent blood clotting.

• Use in IVF: The use of heparin in IVF treatment is to prevent thrombosis (clotting) at the implantation site of an embryo. Heparin may be given to patients who have experienced recurrent implantation failure or recurrent miscarriage in hopes of preventing any coagulation complications in early pregnancy.
• Possible benefits & supporting evidence: It is suggested that heparin may improve the intrauterine environment by increasing growth factors to improve the attachment of the embryo to the lining of the uterus.
• Potential side effects/risks: Heparin can cause bleeding, bruising at the injection site, osteoporosis if used over a long period of time and heparin-induced thrombocytopenia. Complications are uncommon when Heparin is used in low doses over short periods of time.
• Use in Pregnancy: There has been no evidence to date that indicates an increased risk in bleeding in pregnancy or in congenital malformations in children born to mothers having taken anticoagulants in pregnancy.
• Risk-benefit evaluation: At present, there is no significant evidence from the research studies that have been completed, to indicate any benefit to increasing implantation, pregnancy rate or overall birth outcome.

Coenzyme Q10 (CoQ10) is an antioxidant that is produced by the body naturally. It produces energy that is imperative for growth and maintenance.

• Use in IVF: Antioxidants such as Coenzyme Q10 are increasingly being used in IVF to improve the natural reproductive potential.
• Possible benefits & supporting evidence: CoQ10 is an important antioxidant within every cell of the body and may improve mitochondrial function in the eggs. Some evidence suggests the use of CoQ10 can be beneficial in improving the ovarian response to stimulation, increasing the number of eggs collected and improving embryo quality.
• Potential side effects/risks: While rare and mild, side effects could include nausea, heartburn, diarrhoea, and low blood pressure.
• Use in Pregnancy: Evidence is lacking as to the safety of taking CoQ10 in pregnancy, therefore it should only be taken if prescribed by a doctor.
• Risk-benefit evaluation: CoQ10 is a powerful antioxidant and whilst there is not substantial evidence of it improving pregnancy outcomes, it may be beneficial to a patient’s wellbeing overall.

Corticosteroids are hormones with strong anti-inflammatory and immunosuppressive properties that can be used to treat a variety of autoimmune and inflammatory conditions.

• Use in IVF: In IVF, corticosteroids are being used to suppress the immune system with the potential to improve pregnancy rates.
• Possible benefits & supporting evidence: It is the opinion of many IVF clinicians and specialists that implantation failure may be linked to an underlying immune dysfunction, for example, the occurrence of natural killer cells in the uterus, which may be reduced using corticosteroids. There is currently very limited evidence that this type of treatment would result in improved pregnancy outcomes.
• Potential side effects/risks: There are many common side effects from corticosteroid use – thinning and discolouration of skin, sleep and mood disturbances, weight gain, acne, increased body hair growth, hair loss. As corticosteroids suppress the immune system, high doses and prolonged use can cause more severe side effects such as infection, delayed wound healing, pregnancy complications, avascular necrosis of the femoral head and Cushing’s Disease. Infections and fever are known to reduce the chance of pregnancy and increase the risk of miscarriage, so the immunosuppressive properties of corticosteroids can have a negative impact on pregnancy outcomes.
• Use in Pregnancy: During pregnancy, there is an increased risk of gestational diabetes and hypertension, as well as a risk of congenital heart defects, cleft lip/palate, and incomplete formation of the anus in the fetus. People with diabetes, GORD/stomach ulcers or glaucoma should avoid using corticosteroids. Furthermore, gradual weaning off corticosteroids is recommended.
• Risk-benefit evaluation: Corticosteroids are not recommended in IVF treatment as there is a distinct lack of sufficient evidence to support any benefit in pregnancy outcomes, and the additional risk of serious and potentially irreversible side effects.

Also referred to as endometrial injury, the endometrial scratch is a procedure where the fertility specialist “scratches” the endometrium using a pipelle catheter.

• Use in IVF: The endometrial scratch procedure aims to improve the receptivity of the endometrium and increase the rate of implantation.
• Possible benefits & supporting evidence: The procedure is thought to increase the chances of implantation due to the scratching triggering an inflammatory response within the endometrium. It is unclear exactly how this occurs, and there is limited reliable evidence at this time to support the theory. Further controlled trials are required.
• Potential side effects/risks: It is common for women to have mild bleeding, cramping and pelvic pain similar to that of period pain. In very rare cases, pelvic infection or uterine perforation could occur.
• Use in Pregnancy: N/A – Endometrial scratch is done prior to fertility treatment and should not be performed during pregnancy.
• Risk-benefit evaluation: Although there is limited sufficient evidence of its efficacy, the endometrial scratch procedure may be recommended to patients who have had recurrent implantation failure.

Endometrial Receptivity Analysis (ERA) is a diagnostic test designed to identify the most optimal window of time that the endometrium is receptive to embryo implantation.

• Use in IVF: ERA is carried out at the time an embryo transfer would usually take place. Similar to the endometrial scratch procedure, a biopsy is taken to analyse the endometrium’s gene expression.
• Possible benefits & supporting evidence: It is thought that some women may not receive an embryo transfer at a time when the endometrium is most receptive, and therefore ERA can provide a more personalised embryo transfer time in the hope of increasing the chance of pregnancy. However, there is limited evidence to support whether ERA is superior to the standard timing of embryo transfer.
• Potential side effects/risks: Some bleeding, cramping and pelvic pain are common, but usually mild. In very rare cases, pelvic infection or uterine perforation could occur.
• Use in Pregnancy: N/A – ERA testing is done prior to the embryo transfer procedure and should not be performed during pregnancy.
• Risk-benefit evaluation: Women with recurrent implantation failure may be recommended ERA by their fertility specialist, with the caveat that its effectiveness is unproven and further studies are required.

• Use in IVF: PRP is used to help improve the uterine lining (endometrial) thickness and/ or the endometrial receptivity to improve pregnancy outcomes.
• Possible benefits & supporting evidence: PRP has been used to assist in the treatment of recurrent implantation failure experienced over multiple IVF cycles and for patients who have a thin endometrium. Some studies have shown improvements in endometrial thickness which could lead to increased pregnancy rates, however further studies are required to provide more conclusive evidence.
• Potential side effects/risks: Potential side effects that may occur from the phlebotomy include mild pain at the site of the blood collection, some mild bruising or bleeding at the site, and possible localised irritation or infection. From the PRP procedure patients may experience mild cramping, pain, bloating/swelling or spotting. More serious side effects such as possible fever, infection and cervical shock are possible but are extremely rare.
• Use in Pregnancy: N/A – PRP is typically undertaken 48 hours prior to the anticipated embryo transfer and should not be performed during pregnancy.
• Risk-benefit evaluation: There is limited conclusive evidence of the effectiveness of PRP. The evidence base will continue to grow as the therapy is used more frequently and studies are undertaken, so patients should have detailed discussions with their fertility specialist about whether PRP is suitable for them.

G-CSF is a glycoprotein that stimulates bone marrow to produce specific types of white blood cells. The use of G-CSF is usually prescribed for patients with neutropenia who have a high risk of infection.

• Use in IVF: It is thought that G-CSF can play a role in helping to improve embryo implantation in IVF by increasing the blood flow to the endometrium and promoting the regeneration of cells. G-CSF can be administered via intrauterine infusion or subcutaneous injection.
• Possible benefits & supporting evidence: It has been suggested that the use of G-CSF may improve IVF outcomes by increasing endometrium thickness, particularly for those with persistent thin endometrium. However, there is insufficient evidence that G-CSF improves pregnancy rates at this stage and further studies are required.
• Potential side effects/risks: Fever, pain, nausea, syncope, cough and headaches could occur. Whilst rare, more severe side effects could include chest pain, hypoxemia and anaphylaxis.
• Use in Pregnancy: N/A – when used in IVF, G-CSF is done during the cycle and not performed during pregnancy.
• Risk-benefit evaluation: Some studies have shown that G-CSF can improve endometrial thickness, however further studies need to be undertaken and as such, fertility specialists may recommend the use of G-CSF for patients who are fully informed about the lack of substantial evidence.

Assisted hatching is an advanced scientific IVF technique where a laser is used to create a small gap in the outer layer of the embryo (zona pellucida).

• Use in IVF: In some situations, the zona pellucida is abnormally thick. Usually done three days after fertilisation, assisted hatching creates the opening for the embryo to break through to facilitate the implantation into the uterus.
• Possible benefits & supporting evidence: The less difficulty the embryo has in hatching, the better its chance of attaching or implanting into the wall of the uterus. This gentle and safe procedure is widely available to patients prior to embryo transfer.
• Potential side effects/risks: Interfering with the natural hatching process makes the embryo more susceptible to damage. Incomplete hatching and risk of Monozygotic twins is also possible, although rare.
• Use in Pregnancy: N/A – Assisted hatching is done prior to the embryo transfer.
• Risk-benefit evaluation: Assisted hatching may improve clinical pregnancy rates for patients who have had recurrent unsuccessful cycles, poor quality embryos or who are aged over 37 years old. However, studies undertaken show inconclusive evidence of increased live birth rate. Assisted hatching may be recommended by a fertility specialist for patients with recurrent implantation failure.

Artificial Oocyte Activation (AOA) is a laboratory procedure where the oocytes are artificially stimulated by adding the chemical calcium ionophore to the culture media to initiate the development of the embryo.

• Use in IVF: The addition of calcium ionophore to culture media may mimic oocyte activation, a process that is typically triggered when the egg and sperm meet, starting the embryo development process.
• Possible benefits & supporting evidence: In patients who have had previous fertilisation failure, it is thought that if fertilisation is successful with AOA then embryo implantation and pregnancy rates would be similar to that of ICSI. However, there is insufficient evidence at this time to conclusively prove this.
• Potential side effects/risks: Simulating the activation of eggs artificially could theoretically result in embryos having an abnormal number of chromosomes, which may potentially lead to miscarriage, however there is not enough evidence to support this.
• Use in Pregnancy: N/A – AOA is done during a treatment cycle.
• Risk-benefit evaluation: Given the complexity of artificially inducing oocyte activation and limited evidence to support its effectiveness, fertility specialists should be cautious when recommending AOA to their patients.

Embryo Glue is a transfer medium that is enriched with a glycoprotein named hyaluronan.

• Use in IVF: The embryo selected for transfer is placed in a small volume of this glue-like medium, then loaded into the catheter and released into the uterus. Embryo Glue does not make the embryo “stickier” in any way but maximises the chances of implantation into the uterus.
• Possible benefits & supporting evidence: Research shows that hyaluronan plays an important role in assisting embryos to implant. Hyaluronan is a naturally occurring substance found in the uterine cavity and fallopian tubes. Studies have shown an increase in the implantation rate and pregnancy rate when the embryo transfer media has contained hyaluronan
• Potential side effects/risks: There are no known risks or side effects.
• Use in Pregnancy: N/A – Embryo Glue is used for the embryo transfer procedure only.
• Risk-benefit evaluation: There is some evidence to suggest that females aged over 38 show the most benefit, with a significant increase in pregnancy rates, when a transfer medium with hyaluronan is used (Balaban et al., 2004). There have also been studies indicating embryos that were frozen and thawed may have increased pregnancy rates through the use of a hyaluronan-enriched transfer medium.

Preimplantation genetic testing for aneuploidy (PGT-A) screens embryos for the number of chromosomes. A small sample of chromosomes. By definition ‘aneuploidy’ is the presence of an abnormal or unbalanced number of chromosomes.

• Use in IVF: PGT-A is used to help select embryos with the right number of chromosomes, by taking a small sample of cells from the embryo to be sent for genetic testing.
• Possible benefits & supporting evidence: PGT-A may increase IVF conception rates by helping to identify the embryos most likely to produce a pregnancy, allowing them to be prioritised for transfer. Additionally, PGT-A can reduce the incidence of miscarriage, reduce the risk of a live-born child with a chromosomal abnormality and reduce the number of IVF cycles necessary to achieve a successful outcome.
• Potential side effects/risks: The chances of these occurring are usually minimal, but possible risks include damage to the embryo, inconclusive or misdiagnosis, and having no normal embryos.
• Use in Pregnancy: N/A – In-cycle procedure only.
• Risk-benefit evaluation: PGT-A may increase IVF conception rates by helping to identify the embryos most likely to produce a pregnancy, allowing them to be prioritised for transfer. PGT-A does not diagnose any specific diseases but looks more generally at the chromosomal makeup of the embryo.

EmbryoGen/BlastoGen are new sequential culture media used in the laboratory to optimise embryo development by supporting metabolic and physiological phases before implantation.

• Use in IVF: Fertilised and cleavage-stage embryos (zygote to day three) are cultured with EmbryoGen, followed by the culture to the blastocyst stage with BlastoGen. For the embryos cultured with this system, BlastoGen is the recommended medium for embryo transfer.
• Possible benefits & supporting evidence: There have been many studies that have shown a significant increase in the survival of transferred embryos, increase in pregnancy rates and lower miscarriage rates. It is suitable for all patients.
• Potential side effects/risks: There are no known negative effects of culture embryos in these culture media.
• Use in Pregnancy: N/A – In-cycle procedure.
• Risk-benefit evaluation: Improvement of embryo culture has contributed significantly to the increase in the overall success rates in assisted reproductive technology (ART). EmbryoGen and BlastoGen are recommended for patients who have experienced recurrent biochemical pregnancy loss, miscarriage recurrent implantation failure or unexplained infertility.