There is a renewed scientific interest in a more natural approach to IVF cycles.
More than 50 peer reviewed papers have been published in the last five years addressing natural, modified natural and milder approaches to ovarian stimulation in IVF cycles. Better understanding of ovarian physiology in relation to ovarian follicular growth and maturation, advances in ultrasound technology (eg Doppler) and clinical availability of GnRH antagonist (a hormone used to block spontaneous ovulation), have allowed ovarian stimulation to be started in a natural menstrual cycle (i.e. without forced follicular recruitment) and have given us the opportunity to develop novel, gentler approaches to ovarian stimulation. Advances in embryology, ultrasound technology and endocrinology are making the natural cycle and mild stimulation IVF more successful and increasingly relevant to everyday practice.
This approach is much needed because not only are we entering an era of single embryo transfer but also we are increasingly aware of the need to put the health, safety and welfare of the woman right at the top of the agenda when it comes to Assisted Reproduction Technology (ART).
The conventional approach to ovarian stimulation in IVF treatment is aimed at maximizing the number of oocytes available for fertilisation, in order to generate several embryos for selection and transfer. The potentialclinical problems associated with ovarian stimulation include ovarian hyperstimulation syndrome (OHSS).
The prevalence of severe Ovarian Hyperstimulation Syndrome (OHSS) ranges from 0.5-5% of cycles andcan be associated with severe symptoms requiring hospitalization. Furthermore the impact of such side effects can influence many patients to say “never again”. The long term effects of conventionally stimulated cycles are not conclusive. Most of the long-term studies are based on the effects of clomiphene citrate (clomid) treatment and detailed long term analyses of the effects of gonadotrophins (IVF drugs) related to dosage are not available and are urgently needed. Less well known are the effects of ovarian stimulation and the resultant very high levels of oestrogen concentrations on the quality of eggs and endometrium (lining of womb).
There is a substantial scientific evidence suggesting adverse conditions in the endometrium (lining of womb) for implantation of the embryo and an increase in chromosome abnormalities in eggs following high dosages of ovarian stimulation used in IVF cycles.
Finally the cost of treatment is higher with conventional ovarian stimulation protocols due to higher daily dose and cumulative dose of drugs. The treatment cycle is prolonged by nearly two weeks due to suppression of ovaries leading to unpleasant menopausal symptoms. Natural and Mild IVF are fitted in a woman’s spontaneous cycles. Natural and modified natural cycle IVF have specific applications in women with damaged or blocked tubes, in older women, poor responders, those with failed implantation and in those where stimulating drugs are to be avoided ( in women with cancer).
The success rates (live birth rates) of natural/modified natural cycle IVF can be lower per cycle (10-17% per cycle) but cycles can be repeated in subsequent cycles (up to 3-4 cycles) to achieve success rates similar to stimulated cycles. A recent Lancet paper has shown that cumulative pregnancies resulting in term live birth after one year were 43.4% with mild IVF compared to 44.7% with conventional IVF.In addition, mild IVF might lessen patient discomfort, costs and multiple births and risks associated with multiple births. The role of IVM is limited to young women with PCOS and needs further trials.
Modified natural cycle and Mild stimulation IVF are already popular in many countries and will be widely used globally in the future.
Definitions are described below:
| Terminology | Aim | Methodology |
| Natural cycle IVF | Single oocyte | No medication |
| Modified Natural cycle IVF | Single oocyte | hCG only Antagonist & FSH add-back |
| Mild stimulation IVF | 2-7 oocytes | Low dose FSH, oral compounds & antagonist |
| High stimulation IVF (Conventional) | ≥8 oocytes | Agonist or antagonist High FSH dose |
It is my view that tailored protocols (natural, modified natural, mild) should become standard during IVF treatment cycles in order to make treatments safer, low-risk, more patient-friendly and cost-effective. Women should receive information about all options during consultation. The HFEA must provide information and outcome of natural/mild IVF in Patients’ Guide. It would also help to get more IVF cycles funded on the NHS.What’s more, the scientific evidence supports this.
For more information contact:
www.createhealth.org
