Controlled ovarian stimulation protocols (COC): a personalized approach to succeed

Introduction: the evolution of reproductive technologies

Over the past three decades since the birth of the first child in the world resulting from in vitro fertilization (IVF), reproductive medicine has made enormous progress. At the forefront of these advancements is the development and implementation of a comprehensive range of controlled ovarian stimulation (COS) protocols. These protocols form the cornerstone of most assisted reproductive procedures (ART) programs). They are based on the use of various precisely dosed combinations of gonadotropin-releasing hormone (GnRH) analogs and gonadotropins.

Main objectives of COS

The implementation of these protocols in clinical practice aims to achieve several key interdependent objectives. First, it is to ensure the retrieval of a sufficient, but optimal, number of mature oocytes ready for fertilization; a higher number of oocytes increases the chances of obtaining quality embryos for transfer and cryopreservation. Second, the ultimate goal is to increase the overall live birth rate. Third, it is to optimize and improve the ovarian response, especially in women who show an insufficient response to stimulation (called "poor responders"). Finally, the most important goal is to minimize the risk of developing a severe iatrogenic complication such as ovarian hyperstimulation syndrome (OHSS), which can occur in cases of excessive response. In our blog, we examined the ovarian hyperstimulation syndrome (OHSS) in more detail.

Impossibility of a universal approach

At the current stage of development of reproductive medicine, it has become quite clear that creating a single, universal COS protocol suitable for all patients without exception is impossible. Each woman's physiology is unique. In other words, in each specific clinical case, the applied therapeutic scheme must be strictly individualized. For example, for patients with high ovarian reserve (high AMH, numerous antral follicles), a protocol with GnRH antagonists may be chosen. It provides good control, prevents premature ovulation, and, crucially, allows the use of an ovulation trigger that greatly reduces the risk of OHSS. At the same time, for women with reduced ovarian reserve ("low ovarian reserve"), a "short" protocol with GnRH agonists or protocols using high doses of gonadotropins can be used to recruit the maximum number of available follicles. Our blog discusses this issue in more detail Understanding low ovarian reserve: a comprehensive analysis.

Factors in choosing an individual scheme

The therapeutic scheme is always selected by a reproductive specialist considering a set of parameters. This not only includes the woman's age but also her current endocrine status (levels of FSH, LH, AMH), the assessment of her ovarian reserve (by ultrasound and hormones), her BMI, the history of previous stimulation cycles, as well as all other associated factors and specific conditions, including the cause of infertility.

FAQ (Frequently Asked Questions)

Question: What is COS and what are these protocols based on? 

Answer: COS is a controlled ovarian stimulation, a key step in IVF programs. According to the article, it involves a series of medical protocols based on using different combinations of hormonal preparations: gonadotropin analogs and gonadotropin-releasing hormone (GnRH), to stimulate the growth of multiple follicles in the ovaries.

Question: What are the main objectives of COS in infertility treatment? 

Answer: The main goals are to obtain an optimal number of mature and high-quality oocytes to increase the chances of fertilization and embryo development. The objectives also include increasing the overall live birth rate, improving ovarian response in women with insufficient response, and ensuring patient safety by minimizing the risk of OHSS.

Question: Is there an "ideal" ovarian stimulation protocol for all patients? 

Answer: No, as the article highlights. It is impossible to develop a universal protocol suitable for all patients because of significant individual differences in physiology, ovarian reserve, and reaction to medications.

Question: How do doctors choose the therapeutic scheme if there is no universal protocol?

 Answer: The therapeutic scheme is always strictly individualized. The doctor analyzes numerous factors: age, endocrine status (AMH, FSH levels), ovarian reserve, BMI, and previous treatment history. For example, women with high ovarian reserve are often prescribed a protocol with GnRH antagonists to reduce the risk of PCOS, while women with reduced reserve are prescribed a "short" protocol or a protocol with high doses of gonadotropins for maximal stimulation.