Complementary Therapies

What is complementary treatment and IVF?

Complementary or adjuvant therapy is additional treatment that can be considered during IVF treatment with the aim of trying to increase pregnancy success, particularly in women who have had multiple unsuccessful IVF cycles.

Complementary or alternative therapies are used by many people to improve their overall physical and emotional health. This could include medicines, such as herbal, vitamin, mineral, homoeopathic, nutritional and other supplements and therapies such as Chinese medicine, chiropractic, naturopathy, osteopathy, acupuncture, homoeopathy, reflexology and aromatherapy.

IVF is a highly successful treatment option for many forms of infertility, however sometimes it takes multiple attempts before success and this can be frustrating. The most important factor impacting the success of IVF is a woman's age and the genetic quality of her eggs. Other contributing factors include quality of sperm and the uterine 'environment.'

Why try complementary therapies?

Complementary therapies, including complementary medicines and hormones aim to try to improve the following outcomes:

  • The number and quality of eggs retrieved in a stimulation cycle
  • The quality of embryos created
  • Uterine environment
  • Sperm quality

At Melbourne IVF, our philosophy of individualised patient care means that a patient may, from time to time, decide with their fertility specialist, to try an adjuvant treatment. It is important to be fully informed about the risks and benefits of each therapy and understand that the use of adjuvant treatments is currently not proven and that safety may not be established. Please speak with your fertility specialist if you require further information or clarification on these treatments.

Summary of complementary therapies

This table outlines the potential role of various adjuvant therapies in IVF practice.  Adjuvant therapies have not been incorporated into established clinical practice to date because they have not yet been confirmed in large scientific studies to be safe and effective.

At Melbourne IVF we are constantly investing in clinical research to ensure we give our patients access to the most advanced science in fertility investigation and treatment to ensure the best possible outcome. 

Therapy or Medication Proposed Use in IVF Safety & Possible Side Effects Efficacy Evidence
Acupuncture To increase pregnancy rates when used during IVF cycle Safe Limited evidence Meta-analysis shows possible benefit with pregnancy in IVF patients
Low Dose Aspirin To improve the implantation rate and decrease miscarriage No/low risk/mild side effects Limited evidence Insufficient evidence of the benefit in pregnancy rates in IVF patients
Heparin To improve the implantation rate and decrease miscarriage No/low risk/mild side effects Limited evidence Studies show inconsistent results Overall, no benefit shown in the pregnancy rate of IVF patients
Melatonin To improve egg and embryo quality No/low risk/mild side effects No evidence Antioxidant effect on egg and embryo quality being evaluated at Melbourne IVF
Testosterone To increase egg numbers and quality in poor IVF responders Moderate risk/moderate side effects No/Limited evidence Currently being trialled at Melbourne IVF
DHEA To increase egg numbers and quality in poor IVF responder Moderate risk/moderate side effects No/Limited evidence Limited small trials with variable results
Growth Hormone To increase egg numbers and the quality in poor IVF responders Moderate risk/moderate side effects No evidence Limited small trials with variable results
Corticosteroids To improve the implantation rate in patients experiencing repeated IVF failure due to underlying immune dysfunction High risk/serious side effects No evidence Currently no evidence Still under research
Endometrial Injury To improve embryo implantation No/Low risk Mild side effects Limited evidence To date, studies have been too small to draw any conclusions
Acupuncture and fertility

Acupuncture has long been used in Eastern Medicine to treat fertility. Many women find acupuncture helpful in reducing stress levels. There are many studies currently being undertaken to determine where acupuncture assists fertility.

Benefits of acupuncture may include:

  • reducing stress during IVF treatment
  • stimulating blood flow to the uterus and ovaries which may influence the menstrual cycle and ovulation
Low dose aspirin

Potential benefit

Low dose aspirin (LDA) has been widely used as a supplementary treatment to IVF particularly in recurrent IVF failure or miscarriages.  LDA thins the blood and relaxes the blood vessels. Research has shown that LDA used in conjunction with heparin helps to improve pregnancy outcomes in women diagnosed with Anti-Phospholipid Syndrome (APS), however not in women who have Anti -phospholipid antibodies (APA)without the syndrome.

Potential side effects

Side effects include indigestion and stomach ulcers. In a small proportion of people breathing difficulties due to an allergic reaction may be experienced.  It is not recommended in patients with asthma.

A small number of animal studies have suggested more recently that LDA may have subtle adverse effects on embryo development in the uterine lining.

Risk and benefit assessment

To date there is insufficient evidence to show that the use of LDA in IVF improves the pregnancy rate. 

There is also some question about the safety of LDA and no good evidence of efficacy.

Heparin

Potential benefits

Hypercoagulation (thickening) of maternal blood due to the autoimmune disorder Antiphospholipid Syndrome (APS) is associated with recurrent miscarriage. Heparin thins the blood and improves pregnancy outcomes in women who have APS. Heparin is sometimes given to women who have experienced repeated IVF failure based the theory that potentially altered maternal blood coagulation status and micro clot formation could interfere with different stages of embryo implantation.

Possible side effects

Side effects of heparin include bruising at injection sites, bleeding, heparin-induced thrombocytopenia (HITs) and osteoporosis. Low dosages over short time duration are usually not associated with major complications.

Risks and benefit assessment

There are inconsistent results from research about the benefits of Heparin in IVF patients.  A large study performed at Melbourne IVF did not show any benefit of using Heparin in patients with IVF implantation failure who also tested positive for APA antibodies.

To date, the safety profile of Heparin is good however this is a lack of good evidence of its benefit.

Melatonin

Potential benefits

Melatonin is a naturally occurring hormone involved in the regulation of circadian rhythm (sleep pattern).  It is a powerful antioxidant that decreases oxidative stress.  Oxidative stress contributes to the depletion of the ovarian egg reserve.   Melatonin is thought to be involved in different ovarian processes and this is supported by observations that disruptions in circadian rhythmicity, as observed in female shift workers for example, are associated with menstrual dysfunction.  Melatonin can also induce a resurgence of regular ovulation in perimenopausal women.

Melatonin is also thought to be involved in egg maturation and there is some evidence to suggest its role in the protection of nuclear and mitochondrial DNA. 

There is an association between higher melatonin levels in the follicular fluid surrounding the oocyte (egg) collected during IVF and apparent less oxidative stress damage to the egg.  A 2008 study demonstrated that the administration of melatonin to IVF patients improved their fertilisation rates and increased the number of good quality embryos. 

Possible side effects

The ideal dosage and duration of treatment is unknown but melatonin is generally well tolerated with few side effects.   Common side effects include daytime sleepiness, dizziness, headaches, nausea and vivid dreams.  Other less commonly observed effects are abdominal discomfort, mild anxiety, irritability, confusion and short-lasting feelings of depression.  It is important to note that melatonin can interact with various medications including anticoagulants, immunosuppressants, medications for diabetes, antihypertensives and sedatives. 

Risk and benefit assessment

There are presently no large conclusive studies showing benefits of melatonin in the IVF population.  The 2008 study showing an increased fertilization rate only involved a small number of patients.  Limited conclusions can be drawn from small studies and more studies are required for the assessment of any potential long term beneficial or harmful effects. 

The safety profile of Melatonin is reasonable however there are various side effects.  To date, evidence of its benefit has not been proven.

Testosterone

Potential Benefits

Testosterone is an androgen (male sex steroid hormone) that is primarily secreted by the ovaries of females and the testes of males. Testosterone is essential for health and well-being and is required for oestrogen synthesis. The proposed mechanism of action is similar to DHEAS in preventing smaller ovarian follicles from degeneration and promoting growth of larger follicles.

Previous studies have suggested that testosterone plays a critical role in early follicular development and granulosa cell proliferation in the ovary. It stimulates early stages of follicular growth and increases the number of pre-antral and antral follicles. Increased intra-ovarian concentration of testosterone may enhance the responsiveness of ovaries to Follicle Stimulating Hormone (FSH).

Early evidence suggests that transdermal testosterone pre-treatment may increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. A meta-analysis from 2012 on androgen use in IVF showed that transdermal testosterone was the only androgen observed to have a benefit.

Possible side effects

Excessive hair growth and acne are the major adverse reactions that have been reported and are quite common. Both of them are dose and duration related and generally reversible. With excessive use of any androgens there may rarely be deepening of the voice which may be irreversible. No adverse effects or any congenital malformations were identified in any of the relevant studies when testosterone was given by skin patch route of administration in low dose. 

Risk and benefit assessment

Although the latest evidence suggests there is potential benefit in using testosterone in poor responders, the evidence is still limited. Only two randomized studies with a total of 163 patients were involved. Although no adverse effects or congenital malformations were reported in these patients, the safety of the medication is yet to be established.

To date, the safety profile of Testosterone has not been established and there is no proof it has any benefit.

DHEA - Dehydroepiandrosterone

Proposed benefits

Dehydroepiandrosterone (DHEA) is a weak androgen (male sex hormone) that is converted to testosterone in the body. Dehydroepiandrosterone sulphate (DHEAS) is the sulphate version of DHEA and is found predominantly in the blood.  Both work as precursors for the intracellular production of oestrogen and androgens. Androgens may have specific roles in the smaller follicles protecting them from degeneration and promoting them to grow.

Some controlled studies have demonstrated that DHEA may have a role in follicle development but no evidence to date suggests that this helps produce more follicles or results in better quality eggs.

Since 2000, there have been several small studies suggesting a possible improvement in ovarian response and pregnancy rates in IVF.  Two randomised controlled studies demonstrated positive effects but they have to be interpreted with caution due to the methodology used.  Another recent study suggested that DHEAS administration may improve the genetic quality of embryos and decrease miscarriage rates. It is important to note that these studies do not currently provide sufficient evidence for safety or efficacy.

Potential side effects  

Side effects may include oily skin, acne and hair loss. Some patients have noticed improved energy levels and an increased libido while on DHEA. There has been a single report of a post traumatic seizure one month after DHEA supplementation. Prolonged use of DHEA can worsen cardiac arrhythmias and hormone sensitive tumours. There may be an increased risk of bowel cancer and diabetes with prolonged use.

Risk and benefit assessment

There is currently a lack of robust evidence showing a benefit from supplementing DHEA in IVF. The ideal dosage and duration of supplementation is unknown and the safety of administration has not been proven.

Due to the lack of evidence and possible adverse side-effects, DHEAS is not recommended for use in patients undergoing fertility treatment unless patients are enrolled in a clinical trial or after extensive discussion with their fertility specialist. 

To date, the safety of DHEA has not been established and there is a lack of evidence of its benefit.

Growth hormone

Potential benefits

Growth hormone (GH) has the potential to increase the effects of gonadotropins (the hormones which stimulate follicle and egg development) in the ovary by increasing a chemical called IGF -1. IGF-1 plays an important part in ovarian function by helping the activity of different enzymes including aromatase and 7 beta oestradiol.  It also affects progesterone production and LH receptor formation. IGF-1 has also been found to stimulate follicular development, oestrogen production and oocyte (egg) maturation.

Some studies of women who previously had a poor response to IVF treatment suggested there may be some beneficial effect on egg numbers at oocyte retrieval. However, there is currently no evidence that GH supplementation has any impact on pregnancy rates or the chance of giving birth to a healthy baby.

Possible side effects

Common adverse reactions may include injection site rashes and headaches. More rarely, patients can experience joint swelling and pain, carpal tunnel syndrome and an increased risk of diabetes.

Excessive use of GH may lead to acromegaly (a syndrome of body overgrowth) with swelling of the extremities and internal organs, particularly the heart and kidneys. GH has occasionally been associated with Hodgkin's lymphoma.

Risk and benefit assessment

A meta-analysis study looking at combined data from ten studies of 440 couples has shown that GH was not helpful in increasing pregnancy and birth rates when used routinely as an adjunct to IVF. This study however did not examine the use of GH in patients who had already failed to conceive in previous IVF cycles.

Currently there is a controlled clinical trial is being carried out across Australian IVF centres to investigate the use of GH during a stimulation cycle for poor responders of IVF. Melbourne IVF is contributing the largest number of patients to this study. The results will hopefully shed more light on whether there is any benefit to the use of GH for patients who respond poorly to conventional IVF treatment.

To date, the safety of GH is has not been well established.

Corticosteroids

Potential benefit

Glucocorticoids are steroid hormones with potent anti-inflammatory and immunosuppressive properties. It has been suggested that the use of glucocorticoids may improve the intra-uterine environment and embryo implantation in some patients. This has been linked to the immune cells in the uterus called Natural Killer (NK) cells.

Elevated NK cells in the uterus or the blood of some patients are thought to be associated with recurrent implantation failure.  There is currently no evidence to support this. However, there is a theory for patients with IVF implantation failure that by suppressing the immune system with steroids the numbers of Natural Killer cells may be reduced.

Potential side effects

Common side effects of steroid use include thinning and discolouration of the skin, weight gain, sleep disturbance and mood changes. Steroids have also been shown to increase pregnancy complications such as gestational diabetes and maternal hypertension. There is a slightly increased risk of congenital heart defects and cleft lip/palate in babies born to women who have taken steroids during pregnancy, particularly in the first trimester.

Prolonged steroid use increases the risk of infection and delays wound healing. There is a risk of a rare but serious complication called ‘avascular necrosis of the head of the femur’ in which the top of the hip bone becomes eroded and is permanently damaged.

Importantly, stopping steroids suddenly can be associated with serious complications and this type of medication needs to be withdrawn slowly under medical supervision.

Risk and benefit assessment

The potential risk of serious complications and side effects along with the current lack of scientific evidence means that steroids are currently not routinely recommended during IVF treatment. 

To date, there are significant concerns with the safety of cortico steroids as well as no evidence of its benefit.

Endometrial injury

Endometrial ‘scratch’, also known as endometrial injury or biopsy is a procedure to induce mechanical injury to the endometrium by pipelle endometrial biopsy or hysteroscopy and curette. It has been proposed as a procedure to improve endometrial receptivity and implantation rate in women undergoing in vitro fertilization (IVF) treatment. (Barash et al., 2003, Karimzadeh et al., 2009, Huang et al., 2011). This procedure is offered by many fertility clinics to infertile women, most commonly those suffering from RIF (Lensen et al., 2016).

What is the evidence?

Previously, low quality evidence has suggested that endometrial injury may improve IVF success, especially in women with previous implantation failure (Vitagliano et al., 2018).
Clear evidence has been provided by a randomized, controlled study that was published at the New England Journal of Medicine recently. This multicentre trial involving a total of 1364 women has shown that endometrial scratching does not improve live birth rate in women undergoing IVF when compared to no endometrial intervention. (Lensen et al., 2019)

Possible side effects

It is common to experience period-like cramps or pelvic pain during and after the procedure. These are usually short-lived side effects. Rarer complications include uterine perforation and infection. Sometimes the procedure is required to be performed under sedation or general anaesthetic.

Risk and benefit assessment

As there is clear evidence now that endometrial scratching does not improve pregnancy rate in standard IVF, it is no longer recommended. However, in women with recurrent implantation failure, your specialist may still recommend performing an outpatient pipelle biopsy or hysteroscopy with endometrial biopsy to investigate for endometrial causes of implantation failure, such as endometritis, polyps, adhesions etc.

Multivitamins and fertility

Many multivitamins are considered beneficial to overall well-being, including:

  • Antioxidants – may protect cells from damage by free radicals in environmental and other toxins.
  • Coenzyme Q10 – an important antioxidant and ‘energy nutrient’ within every cell.
  • Vitamin E – an antioxidant that may promote circulation to the reproductive system, including to the placenta,
  • Vitamin C – an antioxidant important within the ovary itself and egg maturation and ovulation.
  • Mixed carotenoids – vitamin A (retinoid) is involved in creating DNA. In small amounts it is essential for healthy fetal development, particularly for the immune system and eyes.
  • Manganese – involved in enzyme functions that have antioxidant effects and transfer genetic information.
  • Zinc – an important nutrient for a healthy reproductive system and involved in sexual development, ovulation and the menstrual cycle.
  • Selenium – an antioxidant that supports normal conception.
  • Omega-3 fatty acids – a woman’s fat tissue stores retain a reserve of these fatty acids for the developing fetus
  • B-vitamins – B12, B6 and folate are three B vitamins significant for the reproductive system.

If you would like to try complementary therapies while also seeking medical support for conception, it is important that you discuss this with your fertility specialist. Acupuncture and vitamin supplements are generally considered to be compatible with most fertility treatments, though some complementary medicines may interfere.

Additional resources

The Preconception Health Special Interest Group and the Fertility Coalition - A partnership between the Victorian Assisted Reproductive Treatment Authority (VARTA), Jean Hailes for Women’s Health, Robinson Institute and Andrology Australia, and Your Fertility – have produced the following fact sheets summarising current evidence relating to factors affecting fertility and Assisted Reproductive Technology outcomes.

> Complementary therapies & medicines to improve fertility and emotional well-being

> Zinc & Selenium supplements and subfertility

> Folic acid, Iodine and Vitamin D supplements in preconception and pregnancy