Optimal Stimulation of Hypo-responders Undergoing in Vitro Fertilization (IVF)

Summary

Stimulation is a key step of in vitro fertilization (IVF). Typically, injectable gonadotropins are used for stimulation, and their dose is individually determined to avoid hypo- as well as hyper-response. Despite the individualization some patients respond with a lower-than-expected number of oocytes. If the low response is unexpected based on the baseline parameters or if an unusually high dose of gonadotropins is needed to achieve a proper response we talk about "hypo-response". In such cases if the first treatment fails and a repeat attempt is planned typically even more gonadotropins, the combination of luteinizing hormone (LH) with follicle stimulating hormone (FSH) or the use of the more potent recombinant preparations are considered. The benefits of these approaches however have not been studied properly in hypo-responders. The studies have used various criteria to identify hypo-responders, have used various gonadotropin doses and have evaluated different outcome parameters. Live birth was only studied in one trial.

It is also known that in a different cycle the same patient is likely to have a slightly different response to the same type and dose of drugs. Therefore, the question arises whether a hypo-responder in one treatment is expected to have hypo-response again if the treatment is similarly carried out in a different cycle. Do we need to change/ increase the gonadotropin dose if based on age and ovarian reserve otherwise we would expect a normal response? Furthermore, if we consider a change should we increase the dose of FSH or should we combine it with LH?

Therefore the aim of this randomized controlled trial is compare an unchanged medication regimen to increased dose of FSH vs the combination of FSH and LH in hypo-responder patients identified based on POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria (Gr 1 and 2: retrieval of 9 or fewer oocytes in patients with an anti-Müllerian hormone (AMH) level ≥ 1.2 ng/ml or antral follicle count (AFC) ≥ 5 and age \<35 years \[Group (Gr) 1\] or ≥35 years \[Gr2\]). Hypo-responder patients will be randomized to:

1. Same gonadotropin dose as in previous treatment (recombinant(r) FSH) \['control group'\]
2. The same dose as in the previous cycle but in the form of FSH + LH combination (rFSH:rLH 2:1 ratio) \['additional LH group'\]
3. A dose increase of 75 international unit (IU) compared to the dose in the previous treatment. \['higher dose FSH group'\] The primary outcome parameter to study is live clinical pregnancy. In addition, baseline demographic, stimulation and further clinical outcomes (pregnancy rate, miscarriage rate, live birth rate) will be compared.

Conditions

• Hypo-responder
• Infertility (IVF Patients)
• OVARIAN STIMULATION

Interventions

DRUG

use of combination of recombinant FSH and recombinant LH

in this arm the patients will use the combination of recFSH:recLH in the same dose as in her prior cycle

DRUG

higher dose recFSH

in this arm the patient will use an additional 75 IU/day recFSH compared to her previous drug dose

DRUG

unchanged dose

in this groups the patient will receive the same recFSH dose as in her prior cycle

Sponsors & Collaborators

• Dunamenti REK Gyor Clinic

  collaborator UNKNOWN

• Dunamenti REK Pannon Clinic

  collaborator UNKNOWN

• University of Szeged, Hungary

  collaborator UNKNOWN

• Dunamenti REK Istenhegyi IVF Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-01

Primary Completion

2026-08-31

Completion

2027-03-01

Countries

• Hungary

Study Locations