1,721,311 research outputs found
How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some considerations.
Full text linkControversial opinions exist about the possible mechanisms throughout emergency contraception prevents pregnancy.
Recently, the International Federation of Gynaecology and Obstetrics and the International Consortium for Emergency
Contraception released a Joint Statement declaring that ‘inhibition or delay of ovulation should be their primary and possibly
only mechanism of action’. They still added that ‘Review of the evidence suggests that LNG-ECPs cannot prevent
implantation’. Concerning levonorgestrel-only emergency contraceptive pills effects on ovulation, the Statement based on
seven reference papers which considered a total of only 142 patients, divided into still different subgroups. Basing on their
same references we got quite different conclusions
COME AGISCE IL LEVONORGESTREL NEL PREVENIRE LA GRAVIDANZA QUANDO VIENE USATO COME CONTRACCETTIVO D'EMERGENZA (LNG ECPs)? CONSIDERAZIONI SULLO STATEMENT CONGIUNTO DI ICEC E FIGO.
No full textTransvaginal sonohysterography for the assessment of postpartum residual trophoblastic tissue: is a safe procedure?
No full textUlipristal acetate in emergency contraception: mechanism of action
Full text linkWe would like to discuss the mechanism of action of
ulipristal acetate (UPA, marketed as ellaOne1), an orally
active selective progesterone receptor modulator (SPRM)
licensed for emergency contraception (EC). Each tablet
contains micronized UPA 30 mg (equivalent to unmicronized
UPA 50 mg) [1] and it is effective up to 120 h after
unprotected intercourse.
The developers claim that UPA works by delaying ovulation
and excluding any interference with embryo implantation.
They based this conclusion on four experimental
papers investigating the effects of UPA on ovulation [2] and
on human endometrium [3–5], respectively.
These conclusions are shared by most authoritative international
drug administrations. The USA FDA just adds
that alterations to the endometrium might possibly contribute
to UPA efficacy (http://www.accessdata.fda.gov/
drugsatfda_docs/label/2010/022474s000lbl.pdf), whereas
the European Medicines Agency only mentions ovulatory
delay (http://www.ema.europa.eu/docs/en_GB/document_
library/EPAR_-_Product_Information/human/001027/
WC500023670.pdf). Most respected scientific societies
(http://www.sigo.it/usr_files/home/guidelines.pdf) and
many reviews rely completely on those conclusions [2]
and report that ellaOne1, administered immediately before
ovulation, significantly delays follicular rupture.
However, a careful evaluation of the same studies [2–5]
leads us to question the above statements.
One paper evaluated UPA effects during the fertile
period and stated that UPA can delay follicular rupture
even if given immediately before ovulation [2], a point that
is emphasized in its title.
UPA effects were reported to be highly dependent on
levels of luteinizing hormone (LH) at the time of administration:
before the onset of the LH surge, the ability of UPA
to delay ovulation was 100%; after the onset but prior to the
LH peak, it fell to 78.6%, whereas after the peak, it dropped
to 8.3%.
Moreover, when reporting the interval from UPA intake
to follicular rupture, the authors stated that ‘when UPA
was given at the time of the LH peak, the time elapsed to
rupture was similar to placebo (1.54 0.52 versus
1.31 0.48)’ [2]. This means that when either placebo or
UPA were administered around 2 days before ovulation
their effects were null, which seems the opposite of the
conclusive statement of the paper.
As the fertile days are the 4 to 5 days preceding ovulation
plus the ovulation day itself, we should conclude that
UPA can delay ovulation only when taken in the first fertile
days, whereas in the most fertile days (the pre-ovulatory
day and the 2 days around it) [6], it behaves like a placebo
[2].
In spite of these evident limitations, UPA effectiveness
in preventing pregnancies is very high (80%) and does not
decrease depending on which of the 5 days it is taken after
unprotected intercourse [1,7]. This appears surprising if
we assume that UPA effectiveness is due to an anti-ovulatory
action which decreases as LH levels approach to peak:
we should expect a progressive reduction in its effectiveness
as days elapse.
Besides, we wonder how UPA, if taken after ovulation,
could delay a follicular rupture that may have already
occurred up to 4 days earlier. This suggests that the
effectiveness of UPA relies on other mechanisms, particularly
on its endometrial effects.
Experimental studies conclude that the threshold for
altering endometrial morphology is lower than that
for altering folliculogenesis [3–5]. The inhibitory effect
of UPA acts directly on the endometrial tissue through
its inactivation of progesterone receptors [8] and is
observed even after a single administration of its lowest
dose.
When unmicronized UPA (1–100 mg) was administered
in the mid-follicular phase, a time preceding the fertile
days, all doses inhibited luteal phase endometrial maturation
in a similar way. This effect was long lasting: it was
observed even in the very delayed luteal phases following
the coalescence of a new leading follicle and persisted until
the next menstrual flow [3]. This means that all unprotected
intercourse occurring in that cycle after UPA intake
might end in fertilization but with no chance for implantation.
If unmicronized UPA (10–100 mg) was administered in
the early luteal phase [4], there was always a significant
reduction in endometrial thickness, without effects on
luteal hormones. Moreover, the highest doses, 50 mg –
equivalent to ellaOne1 – and 100 mg, significantly inhibited
the endometrial expression of progesterone-dependent
markers of luteal phase differentiation. Peripheral node
addressins were significantly reduced, which is associated
with implantation failure [9]. The trophoblasts, in fact,
initiate implantation by binding to endometrial addressins
through their own L-selectins [10].
When, at last, unmicronized UPA was administered in
the mid-luteal phase, at single doses of 1–200 mg, the
highest dose consistently induced early endometrial
bleeding. This effect was also observed in 50% of the
women treated with 50 mg, the dose equivalent to
ellaOne1 [5].
Thus, evidence shows that UPA endometrial effects can
interfere with embryo implantation and that the high
efficacy of ellaOne1 in EC is probably a result of these
endometrial effects, rather than the anti-ovulatory effects.
References
1 Glasier, A. et al. (2010) Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and metaanalysis. Lancet 375, 555–562
2 Brache, V. et al. (2010) Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum. Reprod. 25, 2256–2263
3 Stratton, P. et al. (2000) A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum. Reprod. 15, 1092–1099
4 Stratton, P. et al. (2010) Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB2914. Fertil. Steril. 93, 2035–2041
5 Passaro, M.D. et al. (2003) Luteal phase dose–response relationships of the antiprogestin CDB-2914 in normally cycling women. Hum. Reprod. 18, 1820–1827
6 Wilcox, A.J. et al. (1995) Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N. Engl. J. Med. 333, 1517–1521
7 Fine, P. et al. (2010) Ulipristal acetate taken 48–120 hours after intercourse for emergency contraception. Obstet. Gynecol. 115, 257–263
8 Blithe, D.L. et al. (2003) Development of the selective progesterone receptor modulator CDB-2914 for clinical indications. Steroids 68, 1013–1017
9 Foulk, R.A. et al. (2007) Expression of L-selectin ligand MECA-79 as a predictive marker of human uterine receptivity. J. Assist. Reprod. Genet. 24, 316–321
10 Genbacev, O.D. et al. (2003) Trophoblast L-selectin-mediated adhesion at the maternal–fetal interface. Science 299, 405–40
Sperm maturity and the extent of DNA degradation in sperm fractions prepared by various methods
No full textNeonatal outcome in intrauterine growth restricted and small for gestational age fetuses
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Metodo di misura automatico per una arteria di un feto ed in particolare per l'aorta addominale e dispositivo ecografico per una arteria di un feto, in particolare per la realizzazione di tale metodo
No full textA longitudinal study of the middle cerebral artery pulsatility index and peak systolic velocity: is there a correlation between their trends and fetal demise?
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