Couple of
year back there has been formation of a society called “The international
society for mild Approaches in Ovulation induction”. . This is also called “mild
IVF” protocols. In such protocols eggs collected are admittedly less in number
& in most cases the number of oocytes collected range from 2 to 7. This
differs from “conventional IVF” where the aim is to retrieve 8 or more oocytes. The very idea of MOS-IVF is to minimize the expenses by
using smaller doses of hormones for stimulation then
a conventional protocol.
Advantages of MOS over standard IVF::
1) less inj days 2) so patient
preference, MOS demands only small amounts of gonadotropins, unlike the
standard protocol, and is therefore not as aggressive. 3) decreased cost per
fresh IVF cycle, 4) OHSS rate very
low . WE know that few women, such as polycystic
ovaries (PCO), are particularly predisposed to developing OHSS even with long
down regulation programme. This is truer for cases of PCO. 5) In addition to the aforementioned advantages,
MOS also results in reasonably good pregnancy outcome. Although the number of
oocytes collected by this approach is less, the quality of both oocyte and
embryo is better than that achieved with the conventional protocol. 6)
Endometrial Receptivity seems to be better due possibly a n acceptable balance
between oestrogen & progesterone, In
multiple follicle development in conventional protocol there is a dominance of
oestrogen due to many middle size follicles ,This causes an adverse ratio with
progesterone (oestrogen dominate in Endo level)
and nidation is interfered with abnormal cascade of even due to
prevailing hyperoestrogenism,
A)
Pretreatment
late Luteal E2 supplementation?? à This was followed by . administration of clomiphene citrate for 5 days, and 225 IU
HP HMG and GnRH antagonist form cycle day 6 onward to prevent
premature or unschedulked LH surge. What is the protocol then?? Ans;- In real
terms., mild stimulation protocol can involve Drug 1:- Pretreatment will low
cost (E2 alone late luteal of previous cycle- adv to use barriers) in that cycle followed by Drug 2 :-
clomiphene in combination with Drug 3:-human menopausal gonadotropin (HMG), Drug
4: and GnRH antagonist form cycle day 6 onward to prevent
premature or unschedulked LH surge. , By adherence with this protocol of MOS
- which yields better outcomes compared
to HMG alone (46% vs 25.9%). These
findings were in congruity with another report which showed ovulation and
pregnancy rate to be 82% and 21% respectively in women who underwent MOS using
clomiphene in conjunction with hMG. Moreover, the average cost was much lower
(one-third) than the hMG-only protocol.
Further, the
combination of clomiphene citrate with lower
dose of hMG plus GnRH antagonist is more cost effective than the conventional
ovarian stimulation in women with poor ovarian response, undergoing
Intracytoplasmic sperm Injection (ICSI).
Taking this
notion a step further, Devroey et al reported that when MOS is used, the
endometrial receptivity becomes better. In light of this, clinical outcomes
yielded by MOS appear to be better than those achieved with the standard
protocol. This was evidenced in a prospective, open, rondomized study which
demonstrated remarkably higher implantation rate (21.5 vs14.5 %), pregnancy
rate (37.7 vs23.4%), and delivery rate (32.8 vs20.1%) in MOS group than
standard protocol group (figer2). Based on these data it is worthwhile to
consider mild stimulation during ART programs.
randomized
to receive a conventional mid-luteal long GnRH agonist treatment with HP HMG
starting on day 2 of the cycle at a dose of 300 IU/day. Besides, in the study
group,
The exact
protocol ?? Can we or should we pre-treatment with luteal E2 supplementation??
Ans: Possibly yes. Such drug was administrated followed by clomiphene citrate
for 5 days, and 225 IU HP HMG and GnRH antagonist form cycle day 6
onward. The cost of ovarian stimulation per cycle was far lesser with clomiphene citrate ovarian
stimulation group in comparison to the conventional group. Similar results were
demonstrated in another study which also showed that ovarian stimulation with
clomiphene citrate is less expensive than ovarian than the usual high dose of
gonadotropins, in women with compromised ovarian selected for in vitro
fertilization.
However in a
recent prospective cohort study, a fixed dose protocol of clomiphene citrate at
a dose of 100 mg/d from cycle 3 to7 in combination with low doses of
gonadotropins and GnRH antagonist is found to reduce patient discomfort, risk,
and treatment cost in mild stimulation protocol. The cumulative delivery rate with
100 mg dose of clomiphene citrate was reported to be considered as a realistic
option for good-prognosis of the patients undergoing IVF.
Have any
member used “micronized form of clomiphene “
--for ovarian stimulation? Is it available in Indian market ?? Why Micronization of CC ?? The efficacy of clomiphene for
mild stimulation can be increased when its micronized from is used. Many drugs
which are poorly water soluble show limited oral bioavailability. With micronization, both dissolution rate
bioavailability can be enhanced. Moreover, improved digestive absorption and
consequently better clinical efficacy have been reported with the use of micronized
drugs. Based on these data, it appears logical to use the micronized form of
clomiphene for ovarian stimulation.
The benefits
of micronizaton are:--
. Increases
dissolution rate of drug
. Enhances
absorption
.Improves
bioavailability
.Increases
clinical efficacy
Future of
MOS with clomiphene citrate
Several
recent reports have described clomiphene citrate in combination with GnRH
antagonist as a viable alternative to exogenous FSH in good-prognosis patients.
Alterations in the revived clomiphene citrate protocols have given pregnancy
rates per started cycle of 21-29%. In case
of substantial reduction in treatment cost allowing its use in low-resource
settings, oral compounds like clomiphene citrate alone is preferred with no
luteal phase support.
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