OVARIAN STIMULATION IN ASSISTED REPRODUCTION

Abstract

Background. It has passed more than 50 years from the developmental phase of ovulation induction. During this period new medications have been introduced, new protocols and dosage established, but the regimen, that would suit all women, has not been designed yet.

Methods. The success of ovulation induction in assisted reproduction technologies (ART) does not depend only on medications used, but is influenced by contributing key factors, such as woman’s age, characteristics of the menstrual cycle, body mass index, ovarian reserve and concomitant diseases. The first successful pregnancy followed ART in natural cycle without medications. Because of a relatively low success rate natural cycle was replaced in 70’s by protocols that included clomiphene-citrate or gonadotropins. The introduction of gonadoliberin agonists represented the greatest advantage in this field. The use of human menopausal gonadotropins and recombinants: recombinant FSH, recombinant LH and recombinant HCG in combination with GnRH agonists resulted in significantly higher pregnancy rate (cumulative up to 65 %), but also higher multiple pregnancy rate and ovarian hyperstimulation rate. That is why cheaper, less complicated and patient friendly principles have been renewed, including natural cycle, minimal and mild ovarian stimulation (the use of clomiphene-citrate, letrozole and small doses of HMG or rFSH) that enable ovulation induction and pregnancy in about 30 % of treated women. For a half of the century sophisticated protocols of ovarian stimulation have been developed, but recent European recommendations favour the use of less aggressive, cheaper, effective and patient friendly methods of ovulation induction in ART. There are also protocols for low responding ovaries, which we classify as development of three or less follicles 16 mm in size, only one dominant follicle, or if in past there had been previous cancellations of the cycle because of less than three follicles developed in spite of correct stimulation with gonadotropins.

In the literature there are some suggestions how to treat such patients:

– long protocol with higher daily doses of gonadotropins,

– lowering doses of GnRH agonists or stopping the application soon or immediately after stimulation with gonadotropins has started,

– short term use of GnRH agonists in follicular phase,

– sequential use of CC and exogene gonadotropins.

Ovarian response is monitored by serum estradiol determinations and vaginal ultrasound measurement of follicular size together with echographic estimation of endometrial development.

The procedure must comply with each individual and consider her obligations. There should be regular controls, if the dose of gonadotropins is suiting. The application of HCG should be optimized, the hyperstimulation of ovaries should be avoided and the possibility of multiple pregnancies should be lowered. We should also consider the economical side of the use of drugs and the development of the laboratory techniques in reproductive biology.

Conclusions. For a half of the century sophisticated protocols of ovarian stimulation have been developed, but recent European recommendations favour the use of less aggressive, effective and patient friendly methods of ovulation induction in ART