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RATIONALE FOR USE OF LH FOR OVULATION INDUCTION AND SUPER OVULATION
Carrying feelings of love and affection
Krishna IVF Clinic
Ryan and colleagues 1960
Two cell two gonadotrophin
Fsh granulosa cell Lh on theca cell
Role of lh• mid follicular phase
LH the master regulator
Erk1 and Erk2 mediate the luteinizing hormone
Mile stones in development of gonadotropin
18 yrs.
SO MANY BENEFITS?
THEN WHY
SO MANY BENEFITS? THEN WHY
1 BASIC PHYSIOLOGY
2 DIFFERENT PROTOCOLS
3 DIFFERENT DRUGS
4 therapeutic
window
SO MANY BENEFITS? THEN WHY
POTENT HORMONE
1% BOUND
AFTER GNRH 1
IU/L
•LH IS POTENT HORMONE
SO MANY BENEFITS? THEN WHY
NATURAL CYCLE
ANTAGONAGONIST
•LH NEED IS DIFFERENT AT DIFFERENT DAYS
SO MANY BENEFITS? THEN WHY
rec LHHMG
rec FSH
•MEDICATION AS A SOURCE
LH INCREASED
FERTILIZATION
ESTRADIOL LEVELS
LOW LEVEL OF
APOPTOSIS
Therapeutic window
Fsh threshold
Follicular recruitment threshold concept •
Lh threshold
Optimal level for follicular deveopment
LH THRESHOLD >.5 to 1 IU/l
LH Ceiling >5 IU/l
Elevated LH levels negative art
Regan et al 1990
Loumaye et al 2003
Stranger et al 1985
Watson et al 1993
Kolibanakis et al 2003
SUPPRESSED LH LEVELS NEGATIVE EFFECT
Odea et al 2008
Lahound et al 2006
Flemming et al 1996
Westergarad et al 2000
Propst et al 2011.
20
The LH Therapeutic Window Concept
• Follicular growth impaired• Inadequate androgen (and estrogen) synthesis• No full oocyte maturation
LH threshold
Normal follicular growth and development
Normal androgen and estrogen biosynthesis
Normal oocyte maturation
Balasch J, Fábreques F. Curr Opin Obstet Gynecol 2002, 14:265-274
• Suppression of granulosa cell proliferation• Follicular atresia (nondominant follicles)• Premature luteinization (preovulatory follicle)• Oocyte development compromised
LH ceiling
This is where we should be
Therapeutic window
Who needs LH ?
ASIA PACIFIC LH ADBOARD.
Review
Beneficial effect of LH supplementation in ART
Age• Marrs et al;Humaidan
et al 2004
Initial poor responder
Follicular stagnation
• Ferrarettti et al; 2004
Low poor responders• Ruvolo et al. 2007
LH POLYMORPHISIM
Women > 35 years:
26
The number of functional LH receptors decreases with age•Vihko et al,1996
Endogenous LH may become less potent or biologically active•Mitchell et al, 1995
The only group to benefit from LH supplementation with an increase in thenumber of mature eggs collected, improved implantation and pregnancy rates•Marrs et al, 2003; Humaidan et al, 2004
Poor responder
Previous poor response less number of egg
AMHAFC
Poor responder
HYPORESPONDER
POOR RESPONDER HAVE LOWER PROGNOSIS
HYPO RESPONDER HAVE GOOD PROGNOSIS
Hypo responder
LH IN HYPORESPONDER
Hypo responder correction with LH Poseidon Group f&S 2016
How to identify them
On going poor responder add lh• BMI• age • afc
with optimum dose
• AFC good• But not many coming up
lower rate of follicle growth
• day 6• day 8lower e2
LH polymorphism A few words
37
LH and FSH Action on the FollicleTheca externa cells
Theca interna cells
Capillary network Basement membrane
CumulusOophoruscells
OocyteZona pellucida
Granulosacells Follicular
antrum
LH receptorson theca cells
FSH receptors on granulosa cells
E2
FSH
LHA
LH polymorphism 1500 patients 2012 -2016
312 position
• wild• Heterozygous• homozygous
6 base pair insertion
• heterozygous• homozygous
Studied 1500 couple over a period of 4 years
Found the following polymorphism relevant in INDIA
Fshr 29
fshr 307
FSHR 680
Studied 1500 couple over a period of 4 years
Found the following polymorphism relevant in INDIA
LHCGR 680
LHCGR 6 base insertion
LH polymorphism
312 position
• wild• Heterozygous• homozygous
Need LH supplementation
• heterozygous• homozygous
LH polymorphism These are known cause for hypo response
Summary :
Expected poor responder •Hyp-oresponder
•age >35 (agonist and antagonist)•GENETIC MUTATAION
LOW LH ACTIVITY IN THECA &GRANULO CELLL
Summary
Poor responder and hypo-responder are different
•You can improve pregnancy rates
•You identify in a current cycle
•You can analyze from previous cycle
THANK YOU
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