P-734 Low cost antagonist protocol in ivf-icsi cycles using oral ovulation induction agents in developing countries
Authors: Singh M , Singh R 
Published: July 2024

Study question

The study aimed at comparing the cost-effectiveness of a low cost antagonist protocol using oral-ovulation-induction agents with a standard long GnRH-Agonist protocol in IVF-ICSI cycles.

Summary answer

Low cost antagonist protocol using oral-ovulation-induction agents comparing with a standard long GnRH-Agonist protocol in IVF-ICSI cycles is cost-effectiveness in developing countries.

What is known already

IVF-ICSI had always been proved to be costly treatment.

The additional expenditure is mainly due to use of high dose of gonadotrophins in order to get more number of eggs. To cut down the cost,low dose or mild stimulation protocol have been popularized all over the world in last few years. Use of aromatase inhibitors along with low doses of gonadotrophins have been an effective means of mild stimulation protocols for IVF cycles.

Oral ovulogens, reduces the total dose of gonadotrophin required for inducing follicular maturation. We evaluated if incorporation of letrozole could be an effective alternative for low-cost IVF.

Study design, size, duration

A total of 304 patients under 40 years of age were studied between 2018 to 2022

Subsequently, they were randomly divided into two groups. The agonist group underwent standard long GnRH analogue protocol. The antagonist group received oral ovulation inducing drugs (CC/Letrozole) and 0.25mg antagonist injections upto the day of hCG injection, using a flexible start approach.

Participants/materials, setting, methods

A total of 304 patients under 40 years of age were studied between 2018 to 2022. All patients received low-dose OCP before starting treatment. Subsequently, they were randomly divided into two groups. The agonist-group underwent standard long GnRH analogue protocol. The antagonist group received oral ovulation inducing drugs (CC/Letrozole) and 0.25mg antagonist injections upto the day of hCG injection, using a flexible start approach. Follicular development was monitored by vaginal ultrasound and serum estradiol levels.

Main results and the role of chance

There was a significant difference in the gonadotropin usage between the two groups. As a result, the cost of the CC/Letrozole-gonadotropin-antagonist cycle was significantly lower than the long GnRH agonist-gonadotropin protocol. Though the mean number of oocytes retrieved was higher in the long protocol group, yet the clinical pregnancy rate per transfer was the same in both groups.

While comparing for the primary outcomes pregnancy rate and miscarriage rate were comparable between two groups.

It is of particular importance to note that despite 60%reduction of total dose of rFSH in the Let-rFSH group,which entailed significant reduction of the cost of treatment, the outcomes in all major aspects including pregnancy rate were comparable between the groups.

However, numbers of matured follicles, retrieved oocytes and transferable embryos were not statistically different between study and control group in this study.

This prospective study, designed to evaluate the efficacy of oral-ovulogens -FSH as a low-cost IVF protocol, involved an average number of patients; however, the results have been encouraging. We have been successful in reaching our objective to modify an expensive conventional down regulated IVF protocol into one in which the cost was reduced to a larger extent, without compromising the rate of success in developing countries.

Limitations, reasons for caution

Since last Cochrane review, GnRH-antagonist protocol was proved to be a short and simple protocol with good clinical outcome with significant reduction in incidence of severe OHSS and amount of gonadotrophins requirement.

Although, we need more RCTs to come to a conclusion on regular use of such combined protocol.

Wider implications of the findings

Usage of GnRH-antagonist in combination with Oral-Ovulogens offers the advantage of a low-cost economical stimulation in IVF, as compared to an agonist-protocol, with similar pregnancy-rate in developing countries.

It not only offers a cost-saving stimulation-protocol but also reduces side effects like OHSS and multiple pregnancies yet maintain a descent success-rate.

Trial registration number

not applicable