Wednesday, 27 May 2020

Enclomiphene -how useful it is?


Q.1:-  When  given choice will you prescribe clomiphene or only active agent as Enclomiphene  ? I understand that many a clinician are biased for those drugs to which she/ he is comfortable or familiar for years together . By contrast there is another group of energetic ,possibly more academic clinicians who  accept  any new drug too quickly before robust data are available,

Who is  your friend - Enclomiphene and Zuclomiphene ??  Ans:-Enclomiphene and Zuclomiphene which e is best ?? Few pharma company  have come up with  Enclomiphene Only —
Q.2:-Enclomiphene Only —why?? Logic:-Clomiphene citrate is a racemic mixture of stereoisomers, Enclomiphene and Zuclomiphene in the ratio of 62% : 38%.
We have to  remember that enclomiphene is the one primarily responsible for ovulation induction, while zuclomiphene is the one primarily responsible for negative effects.
 This  basic informations on pharmaco chemistry prompted many gynaecologists  to prescribe the active pure isomer of clomiphene citrate viz. Enclomiphene for ovulation induction
Q.3: What are the negative  effects with clomiphene citrate if combined form is used?? Ans:- The negative effects commonly encountered are 1)  endometrial thinning in 15-50% of patients, 2) poor cervical mucus and 3) CC  resistance in 15-40% of cases.
Q. 4:--,1:-What is Clomiphene resistance Ans: No ovulation inspite of higher dose of CC.    By contras CC Failure implies:--Ovulation but no pregnancy=(the presumable causes of contd infertility inspite of documented ovulation lliculomeytry) & serum progesterone on day 21-22 is reassuring still no pregancy may be frusta .
Q. 5:-- Causes of CC failure? Why do women fail  conceive despite ovulation??
The known causes of failure to conceive I CC cycle despite documented ovulation are  1)Thin endometrium 2) short implantation window in CC cycles 3) Poor  oocyte quality  due to  persistent high androgens inside  the Liquor Folliculi  in PCO cases 6) Less favourvbale growth factors in granulosa cells I  CC  cycles and sanity receptor induction  in Endometrium.

Q. 6: -CC is ne part but followings are also important like a) Correction of Stress/ daily brisk walking & Exercise/ Eating healthy diets and avoiding street foods and oily foods, Correction  of  elevated PRL,TSH, and insulin by metformin or myoinositol.
Q. 7 : What will be the treatement of C Resistance. The options are 1) May be   letrozole only or with  adjuncts like Myo inositol 2-4 Gm Oc or Metformin 2000mg in divided doses or   2) Letrozole flowed by gonadotrophins from cycle day 8 to day 12 as needed inj hMG(cheap urinary will achieve identical  success) may be tried if age < 27yrs and trying time is < 4 yrs,  3) Drilling. if LH>12 on  day 3of spont cycles & large volumes of  ovaries like > 12 ml
Q. 8:-” If she does not agree for LOD or there are indefinite/ suboptimal indications of LOD  and to add to the problem the alternative agent or protocol of ovulation induction is Chr low dose protocol. then   proceed for Low dose step up R-FSH 50 units till follicular recruitment is visible then maintain that dose & increase if no recruitment.
Q. 9:-Is there any role of CC in Male Subfertility.
Testicular causes:- Male hypogonadism is one of the major reasons of male infertility. About 30 % male factor subfertility suffer from hypogonadism due primarily to testicular cause (low testosterone, high FSH& LH, low inhibin-B)  .This  is often  characterized by deficiency in testosterone hormone production while in  case of secondary hypogonadism, defect lies at the level of hypothalamic-pituitary axis(Low FSH, low LH, high inhibin).
How Clomiphene acts in male subfertility where Leydig cells fails to synthesize adequate Testosterone? Ans; we know that a very large amount testosterone must be synthesized by Leydig cells which will diffuse  to supporting cells called  Sertoli  cells which will pass the freshly locally produced Testosterone to  primary spermatocytes and facilitate mitois of primary spermatocytesà followed by meiotic division . If Testosterone concentration synthesized by Leydig   cells is suboptimal then there will be poor division of  pri spermatocytes.   I this context remember that in case of oocytes mitotic Divion never occurs after birth but  in males mitotic division of gametes continues to occur .
Treating male hypogonadism by accelerating the  endogenous production of testosterone instead of exogenous hormonal preparation is the ideal choice. Thus, the ideal treatment is by blockade of E2 synthesis, secretion of more FSH and LH and up regulation of the testosterone secretion by testes


Investigations in a case of anovulation.
The following women are contraindications for CC:
1) WHO Type 1:-Low levels of FSH & E2,
2) Women who fail to respond to withdrawal bleeds are not the candidates for CC.




  

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