LH neither too high nor too low

Is the theory of “Two cells – two gonadotrophins still valid?” According to current theories of ovarian physiology, FSH plays a crucial role in follicular recruitment, selection and dominance and LH is an important contributor to dominance, final maturation, follicular rupture and ovulation. The challenge came with the commercial availability of recombinant gonadotrophin preparations (r-FSH, r-LH) that are given to normally ovulating women who in the majority of cases are under pituitary suppression with GnRH analogues.

Nobody knows how much LH activity is necessary for a normal follicular physiology and normal oocyte maturation and ovulation. I agree with what has been published that there is a “threshold of LH” under which ovarian physiology is compromised. But what happens if LH levels are excessively high? It's clear that this situation can affect normal follicular development and we all admit the concept of “LH ceiling” above which follicles enter atresia or are luteinized and oocyte quality is impaired.

From a clinical point of view it is axiomatic that LH supplementation must be used for the induction of ovulation in WHO Group I patients.

Nevertheless, this may not valid for WHO group II patients and for patients under ART for different reasons:

• In PCOS patients, adding exogenous LH activity will increase the risk of developing an OHSS and pregnancy rates will not change. This is why FSH only preparations are better for this group of patients.

• You don't need to measure plasmatic LH levels throughout the follicular phase because this cannot predict the ovarian response to stimulation and the final outcome of the ART cycle.

• In normal IVF patients under pituitary suppression the use of FSH alone is associated with an improvement in the pregnancy rates.

• LH supplementation does not improve treatment outcome and may also have a negative effect irrespectively of IVF patients being under GnRH agonists or antagonists.

• Profound LH suppression in IVF patients under antagonist treatment is associated with higher ongoing pregnancy rates.

• In patients over 35 years, LH supplementation does not improve IVF results and due to the “ceiling effect” it may result in impaired follicular development.

Getting away from the pressure of the pharmaceutical industry and according to current knowledge there is clearly no need to administer an LH supplementation to the majority of IVF normal patients, especially if daily doses of a GnRH agonist with mild ovarian action are used. There is now enough evidence to accept that both threshold and ceiling LH levels exist and frame the “LH window”. The challenge is to use an individualized approach that will assure that LH supplementation will only be given to patients who need it. We are convinced that in order to have an optimal ovarian physiology LH concentrations should be neither too high nor too low.