Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture.
BACKGROUND
Current methods of hormonal emergency contraception (EC) are ineffective in preventing follicular rupture when administered in the advanced pre-ovulatory phase. This study was designed to determine the capacity of ulipristal acetate (UPA), a selective progesterone receptor modulator developed for EC, to block follicular rupture when administered with a follicle of >or=18 mm.


METHODS
This was a double-blind, crossover, randomized, placebo-controlled study. Thirty-five women contributed with UPA (30 mg. oral) and a placebo cycle. Serial blood sampling for luteinizing hormone (LH), estradiol and progesterone measurements and follicular monitoring by ultrasound were performed before and for 5 days following treatment. Follicular rupture inhibition was assessed in the overall study population and in subgroups of women stratified by when treatment was administered in relation to LH levels (before the onset of the LH surge, after the onset of the surge but before the LH peak or after the LH peak).


RESULTS
Follicular rupture failed to occur for at least 5 days following UPA administration in 20/34 cycles [59%; 95% confidence interval (CI) (40.7-75.4%)], whereas rupture took place in all cycles within 5 days of placebo intake. When UPA was administered before the onset of the LH surge, or after the onset but before the LH peak, follicle rupture had not occurred within 5 days in 8/8 (100%) and 11/14 [78.6%; 95% CI (49.2-95.3)] cycles, respectively. In contrast, when UPA was given after the LH peak, follicle rupture inhibition was only observed in 1/12 [8.3%; 95% CI (0.2-38.5)] cycles.


CONCLUSIONS
This study demonstrates that UPA can significantly delay follicular rupture when given immediately before ovulation. This new generation EC compound could possibly prevent pregnancy when administered in the advanced follicular phase, even if LH levels have already begun to rise, a time when levonorgestrel EC is no longer effective in inhibiting ovulation.
Brache
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V
PROFAMILIA, Nicolas de Ovando & Calle 16, Santo Domingo 10401, Dominican Republic. biomedica@codetel.net.do
Cochon
L
L
Jesam
C
C
Maldonado
R
R
Salvatierra
A M
AM
Levy
D P
DP
Gainer
E
E
Croxatto
H B
HB
D000328:Adult; D044363:Contraception, Postcoital / Q000009:adverse effects / Q000379:methods*; D003283:Contraceptives, Postcoital, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D005498:Follicular Phase / Q000097:blood / Q000187:drug effects*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D009649:Norpregnadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009929:Organ Size; D006080:Ovarian Follicle / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D034445:Ovulation Inhibition / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D013223:Statistics as Topic; D013997:Time Factors; D014463:Ultrasonography; D055815:Young Adult
D003283:Contraceptives, Postcoital, Synthetic; D009649:Norpregnadienes; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; C094854:ulipristal; D007986:Luteinizing Hormone