Introduction
Due to advanced reproductive age, genetic and, iatrogenic factors, diminished ovarian reserve (DOR) patients are becoming a large proportion of assisted reproductive technology (ART) practices. The prevalence of DOR increased from 19% to 26% during 2004 to 2011 in US ART Population[1].
Ovarian stimulation has been undeniably one of the biggest breakthroughs in ART. The conventional ovarian stimulation protocol aims to provide the maximum number of oocytes retrieved for fertilization and thus several embryos for selection[2]. In past 30 years, many attempts have been proposed to improve the IVF outcomes in DOR patients, however, the clinical prognosis of DOR patients remains poor regardless. We must realize that a good oocyte can merely be encountered occasionally and randomly for this group of patients with very poor ovarian reserve.
In this context, mild/minimal stimulation protocol has been raised and proven effective, but controversial. According to the proposed definition by the International Society for Mild Approaches to Assisted Reproduction (ISMAAR) in 2007, the term mild stimulation may apply in three scenarios: (i) when oral compounds (anti-estrogens or aromatase inhibitors) are used (alone or with gonadotropins)[3] (ii) when stimulation is performed with low gonadotropin doses[4] and (iii) in case of delay in the start of stimulation (shorter duration) in a GnRH antagonist cotreated cycle[5]. The American Society for Reproductive Medicine recommended that in patients who are considered to be poor responders, ‘strong consideration’ should be given to a mild ovarian stimulation protocol (≤150 IU FSH) due to lower costs and comparable pregnancy rates[6](ASRM, 2018). Montoya-Botero P et al. concluded that mild/minimal stimulation could be considered as an option in low prognosis poor responder patients, given that it results in similar fresh and cumulative live birth rate (CLBR) [7].
In this article, we aim to investigate the effectives of minimal stimulation protocol women in comparison with conventional ovarian stimulation protocol on severe DOR women. We compared the outcomes in women seeking minimal stimulation protocol according to the patient’s previous IVF/ICSI(below as IVF) history, we then stratified patients according to numbers of previous cycles done. We compared the clinical outcomes and propose that if a DOR patient is seeking fertility treatment, when is wise to turn to minimal stimulation protocol IVF after no more than two conventional stimulation cycles.