ORAL CONTRACEPTIVE PILL PRETREATMENT IN POLYCYSTIC OVARY SYNDROME PATIENTS UNDERGOING IVF/ICSI USING THE GONADOTROPHIN RELEASING HORMONE ANTAGONIST PROTOCOL (A RANDOMIZED CONTROLLED TRIAL)

Abstract

Compared with GnRH agonist long protocols, the introduction of GnRH antagonist protocols for controlled ovarian hyperstimulation has offered a great opportunity to reduce the duration of treatment and the consumption of gonadotrophins (Al-Inany and Aboulghar, 2001). However, GnRH antagonist protocols are cycle-dependent (Albano et al., 1997; Olivennes et al., 1998; The ganirelix dose-finding study group, 1998; Huirne and Lambalk, 2001), which makes scheduling IVF or ICSI cycles difficult. Moreover, there is a slight reduction in the number of retrieved oocytes compared to the GnRH agonist protocol (Al-Inany and Aboulghar, 2001), For these reasons, more attention has been paid to the potential use of steroid pretreatments to schedule IVF cycles, modulate the hormonal environment before starting COH, and thereby synchronize the follicular cohort before stimulation. Indeed, combined oral contraceptive pills (OCP) (Huirne et al., 2006; Rombauts et al., 2006; Cédrin-Durnerin et al., 2007), progestogens alone (Frydman et al., 1986; Wardle et al., 1986; Gerli et al., 1989; Biljan et al., 1998) and natural estrogens alone (De Ziegler et al., 1998) have been largely used for many years to program GnRH antagonist cycles. Nevertheless, outcomes of OCP pretreatment in GnRH antagonist cycles showed ongoing pregnancy rate was significantly reduced in OCP-pretreated women, with an odds ratio ranging between 0.74 – 0.80. Paradoxically, each of the components of combined OCP in isolation did not show this detrimental effect (Farquhar et al., 2017). Consequentially, in the 2020 ESHRE guideline, combined oral contraceptive pill pretreatment in the GnRH antagonist protocol is not recommended due to reduced efficacy (strong recommendation); whereas pretreatment with either estrogen alone or progesterone alone is probably not recommended for improving efficacy or safety (conditional recommendation), but is probably acceptable for scheduling purposes given the data on efficacy and safety. Despite being the first-line recommended COH protocol in women with PCOS (Teede et al., 2018; The ESHRE Guideline Group on Ovarian Stimulation et al., 2020), data regarding the efficacy or safety of steroid pretreatment for its scheduling in such population is scarce. Overall data suggest that there is a scope to revisit the concept of scheduling GnRH antagonist cycles by steroid pretreatment, especially in women with PCOS. Hence, the purpose of this prospective observational study was to assess the effect of OCP pretreatment on pregnancy outcomes in women with PCOS undergoing IVF/ICSI using GnRH antagonist protocol. Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. It is the major cause of anovulatory infertility, menstrual disturbances, and hirsutism. In addition, PCOS is also associated with metabolic disturbances, central to which is peripheral insulin resistance and compensatory hyperinsulinemia (Dunaif, 1997; Ehrmann, 2005). These endocrinal and metabolic abnormalities appear to have an influence on the development of anovulation in women with PCOS, but these factors do not exclude the possibility of an intrinsic abnormality of folliculogenesis in PCOS.