Infertility (IVF Patients), Infertility Assisted Reproductive Technology, Infertile Patients, Infertility Drugs, Infertile Women Undergoing IVF or ICSI, Infertility, Stimulation in the Ovary, Infertile Women Undergoing ART, Controlled Ovarian Simulation, Infertile Women Undergoing Assisted Reproductive Technology (ART)
Conditions
Keywords
Human Chorionic Gonadotropin (hCG), Infertility, Female Infertility, Gonadotropins, Assisted Reproductive Technology (ART), Controlled Ovarian Stimulation (COS), Ovarian Stimulation
Brief summary
This study evaluates a more affordable medication protocol for ovarian stimulation during in vitro fertilization (IVF). Standard IVF protocols use medications called gonadotropins to stimulate the ovaries to produce multiple eggs, but these medications can be very expensive and create a barrier to treatment. This clinical trial tests whether substituting a significant portion of these standard medications with human chorionic gonadotropin (hCG) is just as effective. Researchers will compare the number and quality of eggs and embryos produced by women using the experimental hCG protocol versus those using the standard gonadotropin protocol. The main goal is to determine if the hCG method can provide similar clinical outcomes and safety profiles while significantly reducing the overall financial cost of IVF treatment.
Detailed description
Ovarian stimulation is a critical phase in assisted reproductive technologies (ART), but the high cost of recombinant gonadotropins remains a significant barrier to the accessibility of care for many patients. Human chorionic gonadotropin (hCG), due to its structural similarity to luteinizing hormone (LH), binds to LH/hCG receptors and can effectively support steroidogenesis and folliculogenesis when administered in sub-trigger doses. This prospective, randomized, single-blind trial is designed as a non-inferiority study to demonstrate that an hCG-based stimulation protocol is equivalent to standard controlled ovarian stimulation. While standard protocols rely on the continuous administration of follicle-stimulating hormone (FSH) or FSH/LH, the experimental protocol introduces 200 IU of hCG (without FSH) to replace standard gonadotropins once the main cohort of follicles reaches 11 to 12 millimeters in size. Both treatment arms will utilize a fixed gonadotropin-releasing hormone (GnRH) antagonist protocol starting on day 6 of stimulation, followed by a dual trigger for final oocyte maturation. To minimize bias and ensure objective results, the embryologists evaluating oocyte morphology, fertilization rates, and blastocyst development will be blinded to the treatment arm assignments. If moderate or severe ovarian hyperstimulation syndrome (OHSS) is suspected in the experimental group, the protocol incorporates safety measures, including switching to a GnRH agonist trigger and utilizing a "freeze-all" strategy. By thoroughly comparing these methods through both intention-to-treat (ITT) and per-protocol (PP) analyses, researchers aim to validate an individualized treatment approach. Proving the non-inferiority of this alternative protocol could potentially reduce the medication cost of an IVF cycle by 30 to 60 percent, providing clinicians with a flexible, cost-effective tool without compromising clinical efficacy or patient safety.
Interventions
Administered in sub-trigger doses of 200 IU (without FSH) as a substitute for LH activity and to support folliculogenesis
DRUGGnRH antagonist
Administered starting on the 6th day of stimulation as part of a fixed antagonist protocol
Administered to induce final oocyte maturation before retrieval
DRUGGonadotropins (FSH or FSH/LH)
Standard follicle-stimulating hormone (FSH) or FSH/LH preparations administered continuously at doses ranging from 100 to 225 IU/day.
Sponsors
LTD "EKODNIPRO", Medical centre Medical Plaza Dnipro
LTD "Yuzko"
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
to minimize bias, the study employs a single-blind outcome assessment design. The embryologists responsible for evaluating oocyte and embryo quality, as well as the personnel assessing clinical pregnancy and live birth rates, will be completely blinded to the participants' assigned treatment groups.
Intervention model description
This is a prospective, randomized, parallel-group, non-inferiority trial. Participants are allocated to one of two treatment groups (Group A or Group B) using block randomization (block size of 6) stratified by the participating institution. Allocation concealment is ensured through the use of Sequentially Numbered Opaque Sealed Envelopes (SNOSE). Due to the distinct differences in medication administration regimens between the two groups, the study is open-label for the patients and the treating physicians. However, to minimize bias, the study employs a single-blind outcome assessment design. The embryologists responsible for evaluating oocyte and embryo quality, as well as the personnel assessing clinical pregnancy and live birth rates, will be completely blinded to the participants' assigned treatment groups.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Women of reproductive age between 18 and 40 years. * Clinical indications for the induction of superovulation (undergoing ART/IVF programs). * Patients with all variants of ovarian reserve. * Body Mass Index (BMI) up to 35 kg/m². * Provision of informed consent to participate in the research study.
Exclusion criteria
* Presence of ovarian endometriomas. * History of severe Ovarian Hyperstimulation Syndrome (OHSS) in previous cycles. * Presence of severe endocrine disorders. * History or presence of oncological diseases. * Any medical contraindications to hormonal stimulation. * Severe male factor infertility (specifically cryptozoospermia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of oocytes retrieved (oocyte yield) | Day of oocyte retrieval (typically 34-36 hours after trigger administration) | The total count of oocytes retrieved following the controlled ovarian stimulation protocol |
| Proportion of Mature Oocytes (MII Rate) | Day of oocyte retrieval | Description: The percentage of retrieved oocytes that have reached the Metaphase II (MII) stage, evaluated according to the standardized ESHRE/ALPHA (Istanbul Consensus, 2025 update) criteria |
| Fertilization Rate | Day 1 following oocyte retrieval | The percentage of mature oocytes (MII) that are successfully fertilized. |
| Embryo Quality | Day 3 and Day 5 following oocyte retrieval | The percentage of good quality cleavage-stage embryos and good quality blastocysts, assessed according to the standardized ESHRE/ALPHA (Istanbul Consensus, 2025 update) criteria. |
| Total Dose of Gonadotropins/hCG | From Day 1 of stimulation up to the day of trigger administration (approximately 10-14 days) | The total cumulative dose in International Units (IU) of gonadotropins or hCG administered throughout the entire stimulation cycle |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Pregnancy Rate | Approximately 4 to 6 weeks following embryo transfer | The percentage of patients who achieve a clinical pregnancy following embryo transfer |
| Live Birth Rate | Approximately 9 to 10 months following embryo transfer | The percentage of patients who achieve a live birth |
| Incidence of Ovarian Hyperstimulation Syndrome (OHSS) | From the day of trigger administration through the luteal phase/early pregnancy | The frequency of moderate and severe OHSS cases, classified according to RCOG/ESHRE criteria |
| Average Duration of Stimulation | From Day 1 of stimulation up to the day of trigger administration (approximately 10-14 days) | The total number of days the stimulation medications were administered. |
| Endometrial Thickness | On the day of trigger administration | The thickness of the endometrium measured in millimeters (mm) via ultrasound |
| Cost of Stimulation Protocol per Cycle | At the completion of the stimulation protocol (day of trigger) | An economic evaluation calculating the total cost of all medications consumed during the stimulation cycle, initially recorded in UAH and converted to USD. |
Countries
Uganda, Ukraine
Contacts
PRINCIPAL_INVESTIGATOROleksandr O. Plyh, MD
LTD "EKODNIPRO"
Outcome results
None listed