AB076. Standardization and individualization in controlled ovarian stimulation

Due to the complexity of controlled ovarian stimulation (COS), in its decision-making process, there are a number of factors that should be taken into consideration, like the choices of gonadotropins (Gn) and gonadotropin releasing hormone (GnRH) analogues, COS and luteal phase support protocols, et al. Based on experience from over 30 years of practice, physicians have come to an agreement that more oocytes resulted from an aggressive COS strategy is not always better, while we should do a comprehensive evaluation about the trade-off between maximal accumulative live birth rate and the medical and monetary burden, including the risk of ovarian hyperstimulation syndrome (OHSS) and high-order multiple gestations. In order to individualize COS treatment, the key is to standardize evaluation and categorization of the patients undergoing COS treatment. All the patients could be generally divided into four categories: normal responders, slow responders, hyper responders and poor responders. Most young patients undergoing COS treatment with undiminished ovarian reserve should be categorized as normal responders. For these patients, large-scale meta-analysis suggests that the optimal daily recombinant follicular stimulating hormone (recFSH) stimulation dose is 150-225 IU/day, and patient-tailored adjustment should done based on individual patients characteristics including basal FSH, Anti-Müllerian hormone (AMH), body mass index and age et al. The definition of the term ‘hyper response’ refers to the retrieval of >15 oocytes and a rapid rise in estradiol levels. Previous history of OHSS and makers of ovarian reserve, in particular AMH and antral follicle counting (AFC) strongly suggest the possibility of showing a high response to a standard COS protocol. The prevalence of hyper response in all IVF cycles is estimated to be 3-6%. Patients with polycystic ovary syndrome (PCOS) have increased Gn sensitivities and present a higher risk of developing OHSS. The narrow margin between an inadequate Gn dose and excessive stimulation (OHSS) is a challenging situation. An inadequate Gn dose is not capable to stimulate multiple follicles development, resulting in cycle cancellation, while excessive ovarian stimulation in these patients commonly leading to a certain degree of OHSS. A low starting dose of Gn, 37.5 IU, is recommended by the consensus on PCOS infertility treatment endorsed by both the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine. Poor ovarian response indicates a reduction in follicular response, at least two of the following features must be present: (I) advanced maternal age (≥40 years) or any other risk factor for poor ovarian response; (II) a previous poor ovarian response (≤3 oocytes with a conventional stimulation protocol); (III) an abnormal ovarian reserve test (i.e., AFC <5-7 follicles or AMH <0.5-1.1 ng/mL). For these poor responders, the supplementation of recLH is beneficial. Significantly more oocytes and better clinical pregnancy rate could be achieved in women treated with recFSH plus recLH vs. recFSH alone. In our reproductive medical center, a comprehensive protocol is employed to better the outcomes of the poor responders, including DHEA pretreatment, oral contraceptive pretreatment, high-dose recFSH priming, supplementation of recLH et al. Besides these categories of patients with different sensitivity to ovarian stimulation, slow responders are featured by no follicles larger than 10 mm and low estradiol level (E2 <180 pg/mL) on the 6(th) day of stimulation. The velocity of their follicle development is also reduced (<2 mm for three consecutive days). According to our practice, adding recombinant luteinizing hormone might be beneficial.