Lessons Learned and Future Challenges

Abstract

Mild stimulation is defined as the method when exogenous gonadotropins are administered at lower doses, and/or for a shorter duration in gonadotropin-releasing hormone (GnRH) antagonist co-treated cycles, or when oral compounds (antiestrogens, aromatase inhibitors) are used for ovarian stimulation for in vitro fertilization (IVF), with the aim of limiting the number of oocytes obtained to fewer than eight. The ideology that obtaining increased quantity of oocytes leads to better pregnancy rates might be unjustified and contradictory. Retrieval of a modest number of oocytes following mild stimulation is associated with higher implantation rates compared with patients following conventional stimulation. With data to suggest comparable outcomes between mild ovarian stimulation and conventional stimulation protocols but fewer complications, lower costs, and significantly fewer dropouts in mild protocols, there is merit in considering these patient-friendly approaches. The mild stimulation approach, especially when linked to selected single embryo transfer, may represent an important step towards the objective of an easier IVF, more tolerable and problem-free for patients, and cheaper for both patients and the society, with yet an acceptable effectiveness in terms of live birth rates. The issue of embryo cryopreservation is important to consider during discussion of the pros and cons of mild stimulation. Although live birth rates have traditionally been reported per cycle of IVF treatment, more attention is now being given to the cumulative live birth rate from a course of treatment including multiple fresh and frozen embryo transfers. Natural cycle IVF and minimal stimulation IVF are here to stay. The IVF Lite protocol based on a minimal stimulation protocol including Clomiphene citrate and human menopausal gonadotropin (hMG), vitrification, and cryopreserved remote embryo transfers (rET) has yielded much higher pregnancy rates than fresh transfers. IVF Lite includes embryo accumulation and vitrification (ACCU-VIT) over a few cycles for poor responders and older women. For women with previous IVF failures and hyper-responders, we can complete the ACCU-VIT segment in one cycle. IVF Lite is the future of assisted reproduction. In the future, more data on live birth rates in both mild and conventional stimulation IVF is still required for proper and accurate comparison.