Vaginal progesterone supplementation has no effect on ongoing pregnancy rate in hCG-induced natural frozen–thawed embryo transfer cycles Dimitra Kyrou a, *, Human M. Fatemi a , Biljana Popovic-Todorovic a , Etienne Van den Abbeel b , Michel Camus a , Paul Devroey a a Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium b Department of Embryology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium 1. Introduction The first successful pregnancy following frozen–thawed em- bryo transfer (FET) was described in 1983 by Trounson and Mohr [1]. However, the question which of cycle regimens should be advocated for the preparation of the endometrium remains unanswered. Different approaches with regard to endometrial preparation with gonadotropins/GnRH agonists, clomiphene citrate, exogenous administered estrogens and progestatives for controlled cryo-thawed embryo transfer have been described around the world [2,3]. The most common modalities for FET are natural cycle or endometrial preparation with exogenous estrogen and progesterone, with or without the addition of a GnRH agonist [4–7]. In the recent Cochrane review by Ghobara and Vandekerc- khove [3], no conclusions could be drawn due to the lack of sufficient prospective randomized trials assessing the different methods of endometrial preparations prior to FET. Different IVF centres around the world using the natural cycle for FET, administer human chorionic gonadotropin (hCG) to induce the ovulation for planning the FET. Administration of hCG for FET timing has been accepted as the standard of care for patients who are undergoing FET in natural cycle. Studies in menopausal women have demonstrated that LH values were reduced after an hCG injection [8]. As LH is essential for the maintenance and normal steroidogenic activity of the human corpus luteum [9] abnormal LH secretion may account for a defective luteal phase in ovarian stimulation. The human chorionic gonadotropin (hCG) administered for the final oocyte maturation could potentially cause a luteal phase defect by suppressing the LH production via a short-loop feedback mechanism [8]. However, the administration of hCG did not downregulate the LH secretion in the luteal phase of normal, unstimulated cycles in normo-ovulatory women [10]. European Journal of Obstetrics & Gynecology and Reproductive Biology 150 (2010) 175–179 ARTICLE INFO Article history: Received 1 December 2009 Received in revised form 19 January 2010 Accepted 15 February 2010 Keywords: Luteal phase support Vaginal progesterone supplementation Frozen embryo transfer Natural cycle Human chorionic gonadotropin ABSTRACT Objective: The purpose of this study is to assess the effect of luteal phase supplementation (LPS) on pregnancy rates in human chorionic gonadotropin (hCG)-induced natural frozen–thawed (FET) cycles. Study design: All performed hCG-induced natural FET cycles from January 2006 until August 2007 were retrospectively identified. The study group consisted of 452 cycles: 243 supplemented with progesterone administration (600 mg natural micronized progesterone in three separate doses) and 209 without progesterone. Analysis was limited to cycles where embryos were cryopreserved on day 3. Final oocyte maturation was achieved by hCG when endometrial thickness of 7 mm and a follicle of 17 mm were present on ultrasound. Results: No statistically significant differences were observed in ongoing pregnancy rate between the two groups (22% versus 21%, p = 0.8; difference +1%; 95% confidence interval (CI): 6.5 to +8.7). The non- significant effect of the presence or not of luteal support on pregnancy rate was confirmed by logistic regression (odds ratio (OR): 0.9, 95% CI: 0.54–1.47, P = 0.64). A previous pregnancy following fresh embryo transfer (OR: 6.04, 95% CI: 3.63–10.02, P = 0.001) and increased endometrial thickness (OR: 1.25, 95% CI: 1.11–1.41, P = 0.001) significantly affected the achievement of ongoing pregnancy, whereas the association between embryo score and achievement of pregnancy was marginally significant (OR:0.28, 95% CI: 0.08–0.97, P = 0.05). Conclusion: There is no convincing evidence to support the use of LPS in hCG-induced natural FET cycles, since there is no luteal phase defect. Further prospective randomized studies are necessary to confirm these findings. ß 2010 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: V.U.B/C.R.G., Laarbeeklaan 101, 1090 Brussels, Belgium. Tel.: +32 2 477 6699; fax: +32 2 477 6333. E-mail address: mimikyrou@yahoo.gr (D. Kyrou). 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.2010.02.038