Poor prognosis in cycles following ‘‘genuine’’ empty follicle syndrome Serdar Coskun a, *, Samira Madan b , Ibtihal Bukhari b , Saad Al-Hassan b , Rafat Al-Rejjal b , Khalid Awartani b a Departments of Pathology and Laboratory Medicine, King Faisal Specialist Hospital & Research Center, P.O. Box 3354, MBC 10, Riyadh 11211, Saudi Arabia b Departments of Obstetrics & Gynecology, King Faisal Specialist Hospital & Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia 1. Introduction Failure to retrieve oocytes from mature ovarian follicles despite meticulous aspiration and repeated flushing following ovulation induction for in vitro fertilization (IVF) treatment has been previously described, and called empty follicle syndrome (EFS) [1]. In the literature, the incidence of unsuccessful oocyte retrieval ranges from less than 1% to 7% [2,3]. The underlying mechanism of EFS remains hypothetical. It has been suggested that it is not a syndrome, but rather a sporadic event that cannot be predicted by the pattern of ovarian response either sonographically or hormonally [4]. The underlying patholo- gy is unknown; however, it has been earlier suggested that EFS might reflect dysfunctional folliculogenesis with an altered follicular steroid profile [5]. Others have interpreted EFS solely as a drug-related syndrome, resulting from an abnormality in the biological activity of some batches of human chorionic gonado- trophin (hCG) [6,7] or human error related to injections [8]. However, these hypotheses fail to explain the recurrence of the syndrome in certain patients [1,9–11]. Stevenson and Lashen [2] classified EFS as either false or genuine according to the demonstration of optimal levels of hCG on the day of oocyte retrieval. They define the genuine EFS as failure to retrieve oocytes from mature ovarian follicles after ovarian stimulation for IVF after apparently normal follicular development and steroidogenesis in the presence of optimal beta hCG levels on the day of oocyte retrieval [2]. While van Heusden et al. [12] challenged the presence of any genuine EFS, Desai et al. [13] recently showed microscopic evidence for genuine empty follicles. What is essentially important during counselling of couples who have had EFS is the significance of this event to their future fertility. Along this line, Zreik et al. [11] reported poor prognosis in patients with EFS in both recurrence and no recurrence groups. Lorusso et al. [14] also raised an important question as to whether the occurrence of EFS is an indicator of an unfavorable outcome for future cycles. Their answer was a confirmatory one in their small case series of three patients. The aim of this study was to further investigate the prognosis of patients with EFS in their subsequent IVF cycles. 2. Materials and methods A retrospective study was performed at a tertiary care referral centre. Data from an IVF database from January 2000 to December 2004 were used to identify patients with EFS. EFS was defined as no oocytes retrieved during follicular aspiration despite performing multiple flushes of the follicles in good responder patients undergoing IVF ovarian stimulation, with at least five mature follicles (15 mm) seen in the ultrasound scan on the day of hCG. Patients with negative urine hCG on the day of EFS occurrence were excluded from the analysis. Controlled ovarian hyperstimulation and oocyte retrieval procedures were performed as described earlier [15]. EFS cases were reviewed for patient and cycle characteristics for the cycle in which EFS occurred. All future cycles for patients with EFS were also reviewed. Clinical pregnancy rate per started cycle was taken European Journal of Obstetrics & Gynecology and Reproductive Biology 150 (2010) 157–159 ARTICLE INFO Article history: Received 11 October 2009 Received in revised form 8 December 2009 Accepted 3 February 2010 Keywords: Empty follicle syndrome IVF Pregnancy Prognosis ABSTRACT Objectives: The aim of this study was to investigate the prognosis in future IVF cycles of patients with empty follicle syndrome (EFS). Study design: EFS cases and their future cycles were reviewed. Clinical pregnancy rate per started cycle was taken as the primary outcome in assessing the future outcome in IVF treatment cycles. Results: A total of 3023 patients underwent 5238 IVF treatment cycles. Twenty-six patients (1%) had a total of 58 (1%) cycles of EFS. Thirteen women went through 32 further IVF treatment cycles following the diagnosis of EFS, yielding only two clinical pregnancies, giving a clinical pregnancy rate of 6.25% per started cycle. In addition, four patients had recurrence in a total of 15 cycles. Conclusions: The occurrence of EFS will indicate poor IVF success in subsequent IVF cycles. Patients with ‘‘genuine EFS’’ should be counselled about the outcome of their future IVF cycles. ß 2010 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +966 1 442 3779; fax: +966 1 442 4280. E-mail addresses: serdar@kfshrc.edu.sa, serdarcoskun@hotmail.com (S. Coskun). Contents lists available at ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb 0301-2115/$ – see front matter ß 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2010.02.013