How to use anatgonists to prevent premature rise of LH by rational use of antagonists

How to use anatgonists to prevent premature rise of LH by rational use of antagonists in IUI cycles?? 

 Part 1:- Naitive  GnRH molecules  &  Source of natural GnRH? We know that GnRH is released from a pulsatile manner from mediobasal hypothalamus by neurons located at arcuate nucleus. The normal pulses of GnRH are every 60-120 minutes :--1) the native GnRH has a half life of few minutes only but the synthetic molecules will have few hours and 2) binding affinity at Pituitary will be 100-200 times to Pit –

Part 2 :- Synthetic GN RH agonist:--the native form is stabilized by  changes made in the amino acid molecules of position 6 and position 10. Therefore stability, binding affinity, potency of synthetic GnRH is increased .Within 12 hrs of administration of any agonists there will be 5 fold rise of FSH, 10 fold rise of LH and four fold rise of E2.

When administered continually (GnRH pump) the pit is blocked completely during the entire tr. time frame and but completely reversible by 3-6 weeks.

:-Use of Antagonists in IUI protocol : This is used to prevent premature LH surge from Pituitary, There are two kinds of protocol like Fixed & Flexible .. A) =Fixed (will be in depot form always) and vs. Flexible protocol (always rapid acting form), Antagonists, unlike the agonist do neither cause pit stimulation (whipping)  nor Pit exhaustion. Therefore do not cause immediate suppression of LH & FSH but receptor blockade at the hypothalamus level is immediate. In such cases the trigger is made by Inj agonist 2 doses.  .

 Brand names of Antagonists. Antagonist A) Inj Cetrorelix- Rs. 900/- B)  Inj. Ovurelix- 0.25 mg PFS--Rs. 900/- SUN-C) Inj  Granelerix-o.25 mg Sun-INCA./ d)  Inj Setova-=Zuventus=Rs. 1000/- ).

are administered when then DF is just > 13-14 mm and serum E2 is>200 pg/ml. The antagonist can be administered as :-

a)   Daily dosage schedule e.g.0.25 mg subcutaneous

b)  One depot dose of 3mg which is effective for 4 days i.e. Cetrolix or Ganirelix are commonly used for prevention of release of both LH and FSH.  

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What do we mean  by GNRH analogues: - This means both agonists and antagonists.

What are agonists?  Agonists may be also used as trigger by a single dose of agonist (using the advantage of flare up theory): especially where antagonists have been used for stimulation.

Antagonists =Fixed vs. Flexible protocol.

Antagonists i.e. Cetrolix or Ganirelix are commonly used for prevention of release of both LH and FSH.

Antagonists, unlike the agonist do not cause pit whipping or Pit exhaustion-therefore do not cause immediate suppression of LH & FSH is achievable, Receptor blockade at the hypothalamus level is immediate. We know that GnRH is released from a pulsatile manner from mediobasal hypothalamus by neurons located at arcuate nucleus. The normal pulses of GnRH are every 60-120 minutes.

What do us by GNRH analogues: - This means both agonists and antagonists.

The Antagonists in IUI cycles: Flexible dose protocol.

In this flexible protocol the antagonists are initiated by measuring the diameter. Antagonist A) Inj Cetrorelix-Lokenath-Rs. 900/- B)  Inj. Ovurelix- 0.25 mg PFS--Rs. 900/- SUN-C) InjGranelerix-o.25 mg Sun-INCA./ d)  Inj Setova-=Zuventus=Rs. 1000/)  are administered when then DF is just > 13-14 mm and serum E2 is>200 pg/ml. The antagonist can be administered as :-

c)    Daily dosage schedule e.g.0.25 mg subcutaneous

d)  One depot dose of 3mg which is effective for 4 days. But desired follicular size is not achieved by that time (by 96 hours of first Depot antagonist), and then another few doses of daily dose of antagonists may have to be administered till the HCG (trigger) is administered.

Indications of adding agonists in IUI cycles: - Where to  consider antagonists? What are the distinct advantages of adding antagonists in IUI cycles?

1)   To reduce the premature LH surge.(Inj Decapeptyl-0.1 mg-PFS-Rs.300/-) / Inj Lupride 0.1 mg., To improve the PR. In cases who failed previous cycles of IUI due possibly either to raised v basal P or basal LH.

2)   To avoid week end IUI.

3)   To convert IUI to IVF cycles:-

The Fixed dose protocol of antagonists

The antagonists are initiated on day 7 of the cycle (fixed dose of cycle) disregarding the follicular size or serum E2.  One depot dose of 3mg which is effective for 4 days.

What is the relevance of estimating serum P and LH who had Premature Luteinization?  Ans:-1) First group of failed cycles with raised Progesyerone  value: - The PR will improve in cases where in the first failed where IUI cycle (where antagonists were not used) and there were Premature Luteinization (PL)  with raised serum PP. B) Second group of failed cycles with raised LH: - with raised LH value:-