Add-on Treatments - Which work & which dont.

‘Add-ons’ or ‘Adjuvant therapies’ are names given to something extra that can be done at the same time as standard fertility treatment to try to increase the chance of success. Most have a reason why they might work but may be unproven or they are expensive for a small potential benefit.

THE STATUS of add-ons can change quite quickly with new information. Our Medical Directors have divided add-ons into three groups - possible benefit, low benefit or unproven, and evidence of no benefit. The HFEA in the UK have their own view on many add-ons, at https://ifqlive.blob.core.windows.

Reasonable evidence for a benefit, or low cost for a possible benefit

Artificial Oocyte Activation (AOA)

AOA can increase the fertilisation rate of eggs. It is limited to couples with no or low fertilisation in a previous ICSI cycle.

Endometrial receptivity Assay (ERA)

ERA looks at 250 genes that are active in a sample of endometrial tissue at the time implantation is expected. If gene expression does not match what is expected, then the day of embryo transfer can be adjusted. There is some evidence this is useful for people who have not become pregnant after the transfer of 2 or 3 embryos.

Embryo Glue

Embryo Glue is a natural substance called hyaluron which is added to the culture medium at embryo transfer. There is reasonable evidence that it increases pregnancy rates, so we do use it routinely at no extra cost. Embryo Glue is standard at Fertility Associates but is an add-on at some other clinics.

Intrauterine infusion of hCG

The infusion of a small amount of the hormone hCG shortly before embryo transfer has been found to increase the chance of a live birth in several studies. The infusion seemed to be more effective for transfer of fresh embryos than thawed embryos. hCG may influence the level of growth factors in the uterus and the immune response of the uterus around the time of implantation.

Luteinising hormone activity (LH)

IVF drugs reduce the amount of LH, so extra LH may improve the response to IVF drugs. There is some evidence that extra LH activity may increase the number of eggs in certain groups of patients.

Pre-implantation Genetic Screening (PGS)

in older women PGS checks the number of chromosomes in an embryo. Embryos with a normal number of chromosomes are more likely to implant and less likely to lead to miscarriage. The benefit shows up in women aged 38 or older. It is covered in detail in the section ‘Choosing the best embryo’.

Sperm Chromatin Structure Assay (SCSA)

SCSA measures DNA damage in sperm. Sperm DNA damage in general is associated with lower embryo quality and lower pregnancy rates. A high SCSA result suggests the man should pay more attention to lifestyle and diet before trying IVF again.

Testosterone

There is some evidence that 21 days or more of testosterone or dehydroepiandrosterone (DHEA) at a low dose may increase the chance of a live birth in women with low ovarian response to IVF medications. The cost is low, and it is unlikely to have an adverse effect.

Time lapse imaging (TiMI)

TiMI uses special incubators which photograph the embryos togive a continuous record of their development without disturbing them. TiMI is covered in detail in the section ‘Choosing the best embryo’ in our pathways book on our website.

Acupuncture

Acupuncture at the time of embryo transfer has been associated with higher pregnancy rates in some studies but not others. A recent well controlled study found no difference between a short course of acupuncture and sessions using dummy needles away from acupuncture points. On balance, combined evidence no longer shows a benefit of acupuncture on pregnancy rates.

Low benefit or unproven

(We wont raise these with you but we can help provide them if you are interested).

Coenzyme Q10 (Co-Q10)

Treating aged mice with Co-Q10 has a remarkable effect on their egg quality, largely cancelling the effects of aging. Preliminary studies have not shown an improvement in pregnancy rates in women. There is limited information on what doses or duration might be appropriate.

IMSI

IMSI involves looking at sperm under high magnification to choose sperm for ICSI. Sperm with irregular features in their head may be more susceptible to DNA damage. Although higher pregnancy rates were reported in earlier studies, later studies have not supported this.

Pre-implantation Genetic Screening (PGS)

in younger women Although PGS should help to choose embryos more likely to implant and less likely to lead to miscarriage for women of any age, in practice it is of no or little benefit in women aged 37 or younger. Exceptions are after repeated miscarriage, or for embryo banking.

‘Colorado protocol’

This is a combination of four low cost add-ons around the time of embryo transfer - low dose aspirin to improve blood flow, low dose prednisone for immunosuppression, antibiotics to guard against low grade infection, and extra estrogen in the second half of the cycle. While some studies of the individual drugs show a benefit, the only well-designed study of all these drugs together showed no benefit.

Reasonable evidence of no benefit

(We discourage these)

Endometrial scratching

This technique arose from the observation that women who had an endometrial biopsy appeared to have a higher than expected pregnancy rate in a subsequent cycle. Recent well-controlled studies have not shown a benefit, and there is a slight chance of infection.

Intralipid infusion

Intralipid is a fat emulsion of soybean oil, egg phospholipids and glycerine that has been used for intravenous nutrition since the 1960’s. Intralipid suppresses some components of the immune system. There is only one small published study, which showed no benefit.

Melatonin

Melatonin is a potent antioxidant, and levels in follicular fluid are related to IVF outcome. Studies are underway to see if taking melatonin can improve pregnancy rates, but the results are unknown. One retrospective analysis of use showed lower pregnancy rates in women using Melatonin.

Natural killer cell therapy

There is a theory that an abnormal immune response may contribute to unexplained infertility, recurrent miscarriage or not becoming pregnant with IVF. However, the immune system within the uterus is complex, and the expert conclusion is that any therapy trying to influence natural killer cells should only be offered as part of university-based research.

Add-on treatments