Dose-Dependent Chlormadinone Acetate Can Suppress Premature LH Surge in Parallel with LH Value Reduction

Abstract

Background: Progestin-primed ovarian stimulation (PPOS) protocol is reported as an alternative method of premature luteinizing hormone (LH) surge suppression. How much dosage of chlormadinone acetate (CMA), a synthetic progestin, is appropriate treatment for this phenomenon? Methods: Retrospective case control study was performed at private assisted reproductive technology (ART) clinic in Japan. Collected data was 231 cycles in patients who underwent either PPOS protocol using 12, 6, 4, or 2 mg of CMA, groups 6C, 3C, 2C, and 1C, respectively (total, 113 cycles), or gonadotropin-releasing hormone (GnRH) antagonist protocol, groups 6A, 3A, 2A, and 1A, respectively (total, 118 cycles). In the CMA group, CMA and human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) were administered simultaneously beginning on menstrual cycle day 3. Serum P, E2, and LH were determined on the day of human chorionic gonadotropin (hCG) administration. Occurrence of premature LH surge was compared between two groups. Pregnancy outcomes were also calculated. Results: Premature LH surge was completely suppressed in CMA groups 6C, 3C, and 2C. On the other hand, this phenomenon was detected in antagonist method groups (5.9%, 7/118). But spontaneous ovulation was not observed in any group, and clinical outcomes are equal to those of GnRH antagonist treatment. Conclusions: Controlled ovarian stimulation (COS) using CMA can be an appropriate alternative progestin for PPOS protocol. Since CMA is an oral medication, this method can be easy to conduct and cost-effective compared with the antagonist method. From our observation, we suggest 4 mg/day of CMA can control the egg retrieval cycle without LH surge occurrence as in other PPOS methods.

Chlormadinone acetate in progestin‐primed ovarian stimulation does not negatively affect clinical results

“…Takeshige et al previously proposed that PPOS using CMA could be an appropriate alternative for COS 10 . To our knowledge, this is the first report on the impact of PPOS with CMA on neonates.…”

“…The moderate antiandrogenic effect of CMA runs a risk of hypospadias for male newborns if taken orally during pregnancy. 9 Takeshige et al previously proposed that PPOS using CMA could be an appropriate alternative for COS. 10 To our knowledge, this is the first report on the impact of PPOS with CMA on neonates. We investigated clinical results, neonatal outcomes, and incidence of congenital deformities between protocols using a GnRH antagonist and using PPOS with CMA in freeze-all cycles.…”

Non‐medical oocyte cryopreservation at a single center in Japan: 8 years of experience

“…A progestin medication, a 2‐mg daily dose of oral tablet chlormadinone acetate (Lutral, Fuji Pharma, Japan), was used with FSH stimulation. The PPOS method can effectively suppress LH surges through the oral intake of progestin, and, in many cases, it prevents severe OHSS, and allows to obtain a number of oocytes close to the target 8 …”

“…The PPOS method can effectively suppress LH surges through the oral intake of progestin, and, in many cases, it prevents severe OHSS, and allows to obtain a number of oocytes close to the target. 8…”