There is a renewed scientific interest in a more natural approach to IVF cycles. More than 50 clinical papers have been published in the last five years addressing natural, modified natural and milder approaches to ovarian stimulation in IVF cycles.
This article on mild IVF treatment is written by Geeta Nargund, FRCOG, Consultant in Reproductive Medicine at St. George’s Hospital, London.
Better understanding of ovarian physiology in relation to ovarian follicular growth and maturation, advances in ultrasound technology (for example the Doppler technique) 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 0.5-3% of cycles andcan be associated with severe symptoms requiring hospitalization. Severe OHSS can be potentially fatal. 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. There is 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 and embryos 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 own menstrual cycle.
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). Low dose hCG could be used in low stimulation IVF cycles in women with PCOS to avoid severe OHSS and its complications.
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 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 will reduce patient discomfort, risks of ovarian hyperstimulation syndrome and costs and multiple births and the additional risks associated with multiple births. The role ofIn Vitro Maturation (IVM) is currently 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.