Recommendations for research
In 2013, the guideline committee made the following recommendations for research. The committee's full set of research recommendations is detailed in the full guideline.
What is the optimum period of expectant management for women of different age groups before invasive treatment such as IVF is considered?
Where there is no known cause for infertility, expectant management increases the cumulative chances of successful conception. However, the chances of a live birth both by natural conception and by using assisted reproductive technology decline with advancing age because of a woman's decreasing ovarian reserve. The guideline currently recommends a shorter period of expectant management for women who are 36 years or older. This is a very crude cut‑off. If there were better evidence it might be possible to customise the period of expectant management based on a woman's age, including longer periods of expectant management for younger women.
Further research is needed to improve embryo selection to facilitate single embryo transfers.
In current IVF practice it is common to transfer more than 1 embryo in order to maximise the chance of pregnancy. As detailed in the guideline, this practice has inherent risks, especially of multiple pregnancy. Embryo selection is based on the assessment of developmental stage and morphological grading criteria in the laboratory. These features are indicative of implantation potential, though the predictive accuracy is relatively poor. However, if prediction of implantation potential could be improved, this would facilitate embryo selection for single rather than double embryo transfer.
Further research is needed to assess the efficacy of adjuvant luteal phase support treatments such as low-dose aspirin, heparin, prednisolone, immunoglobulins and/or fat emulsions.
These interventions are starting to be used in clinical practice in the absence of any RCT evidence of benefit, and even where there is RCT evidence of no benefit. Their use has potential dangers to the treated women. In cases where women are advised to continue taking the preparations until the end of the first trimester there is the additional potential for teratogenicity. Immunoglobulins are also very expensive. It is important that the clinical efficacy of these agents is formally established so that clear statements about whether they should be recommended or are contraindicated can be made.
Is there an association between ovulation induction or ovarian stimulation and adverse long-term (over 20 years) effects in women in the UK?
Women need to be reassured that it is safe to undergo ovulation induction and ovarian stimulation and that these interventions will not lead to significant long-term health issues, especially ovarian malignancy. Both treatments are common in the management of infertile women. The use of ovarian stimulation in IVF is particularly important as IVF is the final treatment option for most causes of infertility. During the course of the review for this guideline update the GDG commented on the paucity of long-term research on the subject, despite the fact that the treatments have been established practice for over 30 years. The longest length of follow‑up in the studies reviewed was 20 years, and the larger studies had shorter follow‑up periods.
What are the long-term (over 20 years) effects of IVF with or without ICSI in children in the UK?
This topic is important in informing patients, service providers and society at large about the potential long-term safety of assisted reproduction. Both IVF and ICSI involve manipulation of egg and sperm in the laboratory, with impacts on the development of the subsequent embryo. However, while the first successful live birth following IVF was over 30 years ago, there is relatively little long-term research on the subject. In the review undertaken in this guideline update, the longest length of follow‑up in the studies reviewed was 20 years, and the larger studies had shorter follow‑up periods.