Ovulation Trigger Strategies in Low Ovarian Reserve (TRIGGERBEST)

Ovulation Trigger Strategies in Women With Low Ovarian Reserve Undergoing Fresh In Vitro Fertilization Cycles: A Prospective Randomized Controlled Trial (TRIGGERBEST)

This study aims to compare different ovulation triggering strategies in women with low ovarian reserve undergoing fresh in vitro fertilization (IVF) cycles.

Ovulation triggering is a key step in IVF treatment, as it determines final oocyte maturation prior to oocyte retrieval.

Participants are randomly assigned to one of three ovulation trigger approaches: human chorionic gonadotropin (hCG) alone, follitropin delta combined with hCG, or dual trigger using a gonadotropin-releasing hormone (GnRH) agonist plus hCG.

The primary objective is to evaluate wether adding follitropin delta at the time of triggering increases the number of matura oocytes obtained, without adversely affecting implantation rates. Pregnancy otucomes following fresh embryo transfer will also be assessed.

The results of this study may help optimize ovulation triggering strategies in women with low ovarian reserve undergoing IVF treatment.

Final oocyte maturation is a critical step in assisted reproductive techniques (ART) and is largely determined by the ovulation triggering strategy. In women with low ovarian reserve, achieving an adequate number of mature oocytes remains a major challenge, even when established trigger protocols are used.

Dual trigger strategies combining hCG and a GnRH agonist are widely used in this population, based on evidence suggesting improved oocyte maturation. However, despite this approach, oocyte yield and maturity often remain suboptimal. The addition of exogenous follicle-stimulating hormone (FSH) activity at the time of ovulation triggering has been proposed as a potential strategy to further optimize final oocyte maturation.

Follitropin delta has a distinct pharmacokinetic profile and provides individualized FSH exposure based on ovarian reserve markers. Its use in combination with hCG at the time of triggering may enhance oocyte maturation without compromising endometrial receptivity.

This prospective, randomized study compares three ovulation triggering strategies in women with low ovarian reserve undergoing fresh IVF cycles: hCG alone, follitropin delta combined with hCG, and dual triggering using a GnRH agonist plus hCG. Participants are randomly assigned to one of the three groups.

The primary outcome is the number of mature oocytes (metaphase II, MII) obtained at oocyte retrieval. Secondary outcomes include the proportion of mature oocytes, biochemical pregnancy rate per embryo transfer, and ongoing pregnancy rate following fresh embryo transfer.

The study aims to generate evidence to optimize ovulation triggering strategies in women with low ovarian reserve.

Inclusion Criteria:

• Signed informed consent.
• Women aged between 18 and 42 years.
• Primary infertility.
• Women with low ovarian response classified within one of the groups defined by the POSEIDON criteria.

Exclusion Criteria:

• More than two previous failed ovarian stimulation cycles.
• Female age >42 years.
• Body mass index (BMI) >35 kg/m².
• Criteria of extremely low ovarian reserve according to the Spanish National Health System exclusion criteria (AMH <0.3 ng/mL and/or antral follicle count <5).
• Male partner age >55 years.
• Severe male factor infertility (total motile sperm count <1 million).
• Previous voluntary sterilization (vasectomy or bilateral tubal ligation).
• Previous healthy child shared by the couple.
• Presence of medical conditions contraindicating pregnancy.
• Risk of ovarian hyperstimulation syndrome (OHSS). If more than 15 follicles are expected on the day of trigger, the patient will be excluded from the study.