Why clomiphen citrate fails to achieve pregancy in fair number of cases??

1-10-19

Why CC fails in some cases?? What are the reasons why clomiphene is unable to work in few women??- Clomiphene is like a “Post card”(age old time tested drug for induction of ovulation).Gonadotrophin is like Net Banking . What are the unexplored things in CC.??  Unfortunately there been little   research on dynamics at cellular level by CC after it was discovered by Gemzell in 1962. N=o further research Inhibin-A:- Inhibin B, FSH isomers , Activin, Follistatin and 43 growth factors including AMH   

Is there any research on role of Inhibin-A:- Inhibin B, FSH isomers , Activin, Follistatin and 43 growth factors including AMH?? We don’t think and sadly most of us thrown CC in dustbin!!! A sad  state of affairs.  I hope many dignified members will disagree with my statements but here are some few salient points for quick recapitulations on old trusted safe (minimal side effects). Friend (Clomiphene):Q.1. A) Who are the ideal candidates for CC??  Chief Indications:- woman with amenorrhoea or Oligomenorrhoea  but has normal serum oestrogens (eu oestrogenic PCOS-WHO Group II women).

Q.2:- Mode of action: - 1) blocks receptors for oestrogens at the hypothalamus. --- --> Gn RH pulses are maintained-stimulates Pituitary. But in many cases there is preferential excessive release of LHà so better to use micro Prog in previous cycle.

Monitoring:--Point A:-Minimal. The second cycle however should be monitored to note whether CC  is working or not .

What is schedule of  Follicular monitoring inj CC cycle ??  a)  basal scan( day 3),  b) Day 8 scan &  c) finally day 11 and d)  later as indicated .

Q.3. Efficacy Of CC ”- Ovulation rate is about  60% of cases in six cycles but preg rate s only 40%.The discrepancy is  due to 1) Obesity 2) hyperinsulinaemia 3) hyperandrogenic state. CC negatively influences FSH secretion and also reflects the size of Foll cohort. The important members of autocrine- paracrine family consist of inhibin, activin, insulin-like growth factor, vascular endothelial growth factor (VEGF), transforming growth factor alpha (TGF-a), etc. They play important role in modulating gonadotropic effects on ovarian function and ovulation.

A very co-ordinated ovarian endocrine functions are essential for ripe ovum:à Any  disruption  either directly by hormones or  by  above mentioned several autocrine factors through toxins produced by tubercle bacilli (MTB)  or indirectly by adverse immuno-modulatory change in intra- follicular environment. The consequences may be gonadotropin response deficiency, anovulation, endometrial hyperplasia, luteal phase defect, etc.

The trio behind the screen in execution of CC ?? Q.4: What is meant by Inhibin A ?? Ans :-Inhibin-A:- Its level is low in during the most of follicular phase but start rising in latest stage of Follicular  phase and peak in mid-luteal  phase.

’Q.5: What is Inhibin-B? How does    Inhibin –B adversely affct follicular maturation.  Ans;-This protein :-start rising in early Follicular  phase ,paralleling but later than the FSH rise

Q 6; What is Activin:  How does    Activin which modifies the actions of CC  ? – Ans:-It is a promoter of many of the actions of FSH in that it increases FSH secretion ,promotes foll dev, & above all inhibits androgen production.

 Q.7 : What is Follistatin-hiow which modifies the actions of CC      ??:-Ans;- It is an Activin-binding protein, that neutralizes Activin bioactivity. 

Q ,8: What are the growth factors which modifies the actions of CC   ?? Ans;-Growth Factors:- IGF’s I & II, opposed by IGF binding Pro(six in number),TGF family, Epithelial Growth Factor. Similarly AMH growth factor is produced in granulosa  cells ( specially preantral & small antral Follicle).Any suggestion to improve efficacy of CC from dear members??

It is true that there are various kinds of Protocols  related to gonadotrophins . Such gonadotrophins are newly arrived “Internet or E mail “. I wonder, how many of us ever brush up our knowledge on different aspects of CC-which is an old friend .  Most of us will be too happy  to revise chapters on diff gonadotrophins , the impurities , diff moieties in gonadotrophin newer  molecules & routes of administration of Gonadotrophins!!!  But the fact remains that CC has remained and will remain as a trusted friend for at least another two decades till newer safer agent come in. As happens in our family life we seldom ring and enquire health of our good old friends but concentrate on TV /Mobiles/ computers. New things have poured and blurred the chapter of  CC..These are in short how and why CC fails / become resistant.