Clinical utility of chlormadinone acetate (Lutoral™) in frozen‐thawed embryo transfer with hormone replacement

Abstract

Purpose The clinical utility of chlormadinone acetate tablets (Lutoral™), an orally active progestin which has been available since June 2007, was compared to an in‐house vaginal suppository formulation of progesterone used between 2006 and 2007 for assisted reproductive technology (ART). Methods We retrospectively evaluated the efficacy and safety of chlormadinone acetate by comparing the pregnancy rates and the incidences of birth defects and hypospadias in frozen‐thawed embryo transfer cycles using the in‐house vaginal progesterone and those using chlormadinone acetate for luteal phase support. Results The pregnancy rates in the frozen‐thawed embryo transfer cycles were 31.2% (259/831) with vaginal progesterone for luteal phase support and 31.6% (4228/13 381) with chlormadinone acetate (no significant difference). In the cycles resulting in live birth following administration of chlormadinone acetate between July 2007 and December 2015, the incidence of birth defects was 2.8% (80/2893), and the incidence of hypospadias was 0.03% (1/2893). Conclusions These results indicate that the pregnancy rate following frozen‐thawed embryo transfer using chlormadinone acetate for luteal phase support was comparable with that using vaginal progesterone, with no increased risk of birth defects, including hypospadias, which has been a concern following the use of progestins.

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

“…There is only one report in Japan that administration of CMA in early pregnancy did not affect newborn infants. The incidence of hypospadias was only 0.03% and CMA consequently proved to be as safe and effective as virginal progestin tablets 16 . For this reason, at our clinic, we use vaginal progesterone tablets or oral progestins, such as dydrogesterone as progesterone replacement during pregnancy.…”

Two-year cumulative live-birth rates and maximum number of transfer cycles in women aged >40 years

“…A signi cant difference was noted when the p value was ≤ 0.05. Statistical analysis was done using software R (https://www.r-project.org/) [4,5] .…”

“…Embryos that became blastocysts were refrozen and some were transferred in other cycles. All FETs were performed in arti cial hormone replacement cycles, according to the endometrial preparation protocol using transdermal estradiol (Estrana®, Hisamitsu Pharmaceutical, Saga, Japan), combined with chlormadinone acetate (Lutoral®, Fuji Pharma, Tokyo, Japan) 5] . Estradiol treatment was started on the 2nd or 3rd day of the arti cial hormone replacement cycle, and administration of chlormadinone acetate 6 mg/d was started on the 15th day of the cycle.…”

Cryptozoospermia: Should we use ejaculated sperm or surgically retrieved sperm for assisted reproductive technology?

“…In frozen–thawed embryo transfers, artificial hormone replacement cycles were employed, following a specific endometrial preparation protocol using a combination of transdermal estradiol (Estrana®, Hisamitsu) and chlormadinone acetate (Lutoral®, FujiPharma). 3 The treatment with Estradiol began on either the second or third day of the artificial hormone replacement cycle. The endometrial thickness was then measured between days 9 and 11 of the cycle.…”