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Is IVF in 2018-less is more? [复制链接]

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只看楼主 倒序阅读 0  发表于: 2018-04-03
Richard Kennedy
International Federation of Fertility and Societies
IFFS
Opening Ceremony for the 30th Anniversary of ART
application in China
Main Meeting Place
31
st, March 11:10-11:40
Richard is a consultant obstetrician and gynaecologist,Clinical Director (Obstetrics) and Deputy Divisional Director at HEFT. Richard has held senior medical leadership roles in the UK and Australia leading service improvement and reconfiguration initiatives. During his consultant career in Coventry
he was Clinical Director (Women’s and Children’s Services), Director of Research and Development and Medical Director / Chief Medical Officer from 2007 -2012. Richard’s clinical specialism is infertility and assisted reproduction, set up the successful IVF unit at UHCW, was Secretary and President of the British Fertility Society, is currently President of the International Federation of Fertility and Societies an NGO of the World Health Organisation.
Is IVF in 2018-less is more?
Richard Kennedy
Assisted Reproduction has changed dramatically in complexity over the last two decades particularly as a consequence of the use of a range of adjuvant therapies – so called “add-ons”. These additions to “standard” ART have also added substantially to the cost of treatment, much if which is born by the patient, sometimes having to pay 2-3x the standard cost of treatment. This has not been matched by increased success and whilst many of these “addons” have minimal risk some pose significant risk to the patient. The consequence of the widespread use of “add-ons”, far from benefitting the infertile, I argue, is in fact decreasing access to treatment and in some cases is leading to catastrophic financial pressure.
A range of “medicinal” compounds and other “non-medical” interventions fall into the broad category of alternative therapies. Within this category fall Chinese Herbal Medicine and Acupuncture. They are widely available to patients generally without the benefit of evidence to support their use. They are not recommended as adjuvants to improve ART success.
Antioxidants include commonly used adjuvants including Vitamin E and C, Omega 3 polyunsaturated fatty acids and pentoxifylline. Some evidence exists to support their use but these findings must be treated with significant caution because of the heterogeneity between the studies, the small number of participants and the small number of live births reported.
Recent reviews have drawn attention to the importance of Vitamin D in reproduction but observational studies have shown no correlation between vitamin D and IVF outcome. However recommendations for dietary intake have been established. The 2011 report from the IOM recommends a 25(OH)D level of at least 50?nmol/l (20?ng/ml) based on positive vitamin D effects on bone health requiring a daily vitamin D intake of 600?IU. South Asian
women are particularly at risk of Vitamin D deficiency and should take supplements during pregnancy.
Aspirin is promoted as a wonder drug for a variety of conditions including reproduction but currently in in the context of ART there is no evidence to support this. As Aspirin is not without risk its routine use is not recommended. Androgens play an important role in reproductive processes and intrafollicular physiology and their role as adjuvants in ART, especially in poor responders has been advocated. DHEA is the most widely used but there is no evidence to support its use in normal responders and three recent reviews drew similar conclusions that there was insufficient evidence to recommend DHEA as routine supplementation in poor responders.
There is some evidence to support the use of Testesterone but the quality of evidence is poor with small trials, heterogeneity, risk of bias. Time lapse imaging (TLI) of embryo development seems intuitively to be a sensible approach to support decision making in embryo selection for transfer but like many adjuvants to standard IVF treatment TLI has been introduced into routine practice without evidence for its benefit. To date there have been no RCTs which have confirmed its benefit.
Assisted Hatching has been widely used as an adjunct to standard ART without evidence to support its us. In the most recent Cochrane review, a modest improvement in clinical pregnancy rates (14 trials included); OR 1.38; 95% CI(1.11-1.70) but no improvement in live birth rates (9 trials included) OR 1.03; 95% CI (0.85-1.26).
A range of interventions are advocated to improve implantation. There is limited evidence to support the use of Hyaluronic Acid supplemented media but the quality of the evidence is low.
Endometrial Injury or “Scratch” is being adopted in many IVF services with limited evidence. It is an invasive procedure, albeit minor and therefore carries some risk. It is often carried out together with a hysteroscopy, another intervention for which there is questionable benefit, that does carry some risk and can add significant cost to the patient. A Cochrane systematic review published in 2015 of 14 studies randomizing 2126 patients found that live
birth rates were increased in those patients with two or more failed embryo transfers. For >/= 1 previous failed ET, RR 1.10, 95%CI 0.91 to 1.33; P value 0.32 and for >/= 2 failed ETs, RR 1.96, 95% CI 1.21 to 3.16; P value 0.006. Bias and heterogeneity was found and the authors concluded that further well designed, adequately powered RCTs were necessary before this intervention could be advocated. Such a study is currently underway in the UK
which will hopefully definitively address whether this intervention is useful and in what context.
Vasodilatation drugs have been advocated in conjunction with ART to improve implantation. These include Sildenafil. Evidence is lacking to support their use and they are not recommended.
Receptivity of the endometrium is the holy grail of infertility treatment. Receptivity has been linked with inflammatory cells found in the endometrium at various stages of the menstrual cycle and a range of immune-modulatory therapies have been tested. They include intravenous immunoglobulin, corticosteroids, Anti TNF alpha and Intralipid. Generally the clinical trials have been on poor quality, worse randomized controlled trials are often absent.
Natural Killer (NK) cells have attracted particular attention. Many of those who advocate measurement of NK cells recommend blood tests to measure peripheral NK cells.Unfortunately peripheral NK cells bear no relation in function to the uterine NK cells and for the latter standardisation of measurement is lacking and even if raised levels of uNK cells are found there is no effective therapy tested through properly controlled studies.
This presentation will present the evidence to date for a range of interventions. The conclusion of this review is that many of the “add-ons” that are in common use have no robust evidence to support them. Some, particularly the immunomodulatory therapies are not without risk and together they add significantly to the cost of treatment. This in turn may deprive patients access to care because of crippling financial burden. There are interventions
which have promise for example morphokinetics and endometrial injury but evidence to date is lacking. Well conducted RCTs are required to provide the evidence to support clinical decision making and until this is available clinicians should avoid advising unproven and costly add-ons or use them only in the context of research studies.



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