Clomiphene citrate what misClomiphene : an
useful drug but have to be used rationally.
Points to remember:-Clomiphene: -a) Zuclomiphene (cis form) is the active form of CC , (trade name Goodova) and Zuclomiphene is present
38% in ordinary clomiphene available in the market . Whereas enclomiphene (trans form) is present in 62% in ordinary commercially available CC and this part is virtually inactive.
1)
CC : What is the vices?? Action lasts longer than hMG, i.e. The
blocking action at hypothalamus lasts long due to slow clearance .As hypo is
blocked for E 2 levels by CC so hypo leads
to continued FSH secretion because Hypo considers that there is still oestrogen
lack in the system. Additionally Cc has direct action on the ovaries to promote
oestrogen synthesis.
2)
Virtue:-Increases pulse amplitude
of GnRH.
3)
Virtue:- If basal cycle monitoring
there is short Luteal phase then CC is the drug of choice.
4)
Vices overruled:-:- Nowadays cx
hostility/ poor endometrial receptivity are not believed by specialists.
5)
Vices :--What are the
contraindications of CC? a) Lager follicular cysts> 5 cm. If it is less than
5 cm-one can start CC.
6)
Do LFT enzymes.(like estimating serum creatinine before
prescribing metformin or say estimating Lipid profile (atherogenic lipids) before
initiating COC.
7)
Initiation of CC : Which day of cycle? Ans:-Usually from Day 2/3 .
Though in the decades of seventies & eighties people used to
initiate the drug from cycle day 5 but nowadays day 3 has become a routine procedure . The ground
for early start is that the inhibitory action
of CC on the Endo will pass off to a great extent on day of
implantation. Admittedly it takes about 60-70 days to clear the ingested CC
from the system,. Some group of doctors,
therefore possibly rationally use CC on alt months allowing the major part of previously
ingested CC to go out of system . This,
they believe that will improve endometrium, as CC is reasonably washed off by
day 11 .
8)
Starting dose? Better to start with 100mg CC initially by that one can
diagnose CC resistant. As many as 74% of
women responds to CC 100mg. Life time course 12 cycles.
9)
How to monitor? A) The worst sign as available in monitoring:>On
day 8/9 if serum LH is > 10 i.u. /ml then -> premature LH
surge->poor outcome in that cycle . B) The good worst sign as noticed by evaluating
the cycle is monitoring by serum progesterone on day 21 midluteal phase- if
> 3ng/ml to 10 ng/ml. with echogenic bright endometrium and CL = Ovulation
has occurred.
10)
What about USG on day 2, day 9 & day 13/14?? Is USG (what we call follicular monitoring
cost effective?) I personally prefer USG mentoring at least for first cycle so
that I understand that what is to be done by looking at size of DF, Endo thickness
and appropriate interventions may be taken (adding HMG n day 3/day8/ or day
3,5,8hmg 75) & whether the drug s
working or not. No routine USG. C) After 7 days of last CC tab- can perform
LH surge-urine detection kit-will be +ve. D) After six cycles only 40%
pregnancy rate. Usually limit upto six cycles if young but 3-4 cycles if female
partner is > 30 yrs, \Not to waste time, Child has to be brought up, .
Tips and Tricks in CC induction:-a) if ET is > 6mm then all
right.
b) Reevaluate the woman if no pregnancy after 4 months.
C) If ET is
persistently poor than switch over to Letrozole(if aged below 30 yrs) /hMG(if
aged >30 yrs) /less commonly Tamoxifene.
D) Do not add exogenous estrogens.
Multiple preg rates are 5-8%. So also miscarriage rate.
Alternate dose schedules: i) CC for 10 days. option 2:-ii)
150mg. daily for 8 days.iii) To initiate with 50 mg /day and then go on
increasing the dose every 3 days: total incremental dose will be 250mg /day. But preg rate of
incremental dose is very poor.
Q. 12. Added drugs-Coadminstering some drugs?
a) When to add bromocriptine ?
a) Bromocriptine :- Documented
Hyperprolactinaemia.-
b) But even in undocumented Hyperprolactinaemia.-
i.e. PRL is normal then one can
administer Bromo in presence of Galactorrhoea with normal PRL.& if
persistent lagging of endometrium inspite of
good follicle and other Doppler parameters of Endo remaining same.
b) When to add Decdan?-a) high DHEASO-4 in first half of cycle
b) Empirical Ry – when Chr, anovulation persists.
takes we do>. How can we improve the success>?/
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