Sequential clomiphene/corifollitrophin alpha as a technique for mild controlled ovarian hyperstimulation in IVF: a proof of concept study
Mild controlled ovarian hyperstimulation (COH), combined with oocyte retrieval (OR) under local anaesthesia (LA), may provide low-impact IVF. Since a single injection of corifollitrophin alfa (CFA) provides 7 days of COH, we hypothesised that clomiphene-citrate (CC) followed by CFA may provide adequate COH response from one single FSH injection. Therefore, the aim was to assess IVF outcomes after a novel clomiphene citrate/CFA (CC/CFA) protocol, compared to women undergoing standard rFSH COH protocols (good prognosis comparative cohort:GPCC) in a 1:2 matched design.
Materials and methods
In this pilot study of 25 patients (ANZCTR id:ACTRN12612000740897, MINIVA:Minimal_Stimulation_in_IVF), we examined the effectiveness of oral clomiphene (100 mg-days 2–6) followed by CFA in a GnRH antagonist protocol producing a single injection COH stimulation regime. All OR were conducted under LA pre-ovarian block. Cycle outcomes were compared to a matched good prognosis comparative cohort (GPCC) undergoing standard rFSH COH.
Mild stimulation was achieved with less oocytes being collected compared to the GPCC (6.4 ± 0.7 vs. 10.7 ± 0.9, p < 0.001), resulting in a reduced number of good quality embryos available for transfer/cryopreservation (3.7 ± 0.6 vs. 5.7 ± 0.5, p = 0.01). While embryo quality was similar between the two groups, endometrial thickness was significantly lower in the group receiving CC/CFA. Pregnancy rates were significantly lower in the CC/CFA cohort compared to GPCC (31.8 vs. 57.1%, p = 0.04) and 44% of CC/CFA participants required supplemental rFSH in order to achieve the hCG trigger criteria.
Sequential clomiphene CFA protocol does not appear to be an optimal regime for low impact IVF treatment as it does not provide adequate COH from a single CFA injection and results in lower fresh embryo transfer pregnancy rates and fewer embryos for cryopreservation.
KeywordsClomiphene Corifollitrophin alfa IVF Controlled ovarian hyperstimulation
- 1.Theraputic goods administration product approval for CCF. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-07204-3.
- 3.Devroey P, Boostanfar R, Koper NP, Mannaerts BMJL, IJzerman-Boon PC, Fauser BCJM, et al. A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2009;24(12):3063–72.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Balen AH, Morley LC, Misso M, Franks S, Legro RS, Wijeyaratne CN, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016;22(6):687–708.CrossRefPubMedGoogle Scholar
- 13.Australian Public Assessment Report for Corifollitropin alfa. T.G. In: Administration; 2010.Google Scholar
- 16.van der Linden, M., et al., Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev, 2015(7): p. CD009154.Google Scholar
- 22.Iliodromiti S, Blockeel C, Tremellen KP, Fleming R, Tournaye H, Humaidan P, et al. Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support: a retrospective multicentre study. Hum Reprod. 2013;28(9):2529–36.CrossRefPubMedGoogle Scholar