Mixed hMG–rFSH Infertility Protocol for AMH-Based OHSS Control

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Solution Overview

Problem

Current assisted reproductive technology (ART) protocols for patients over 35 years old lack individualization, leading to suboptimal outcomes in terms of oocyte quality and increased risk of ovarian hyperstimulation syndrome (OHSS), particularly with mixed protocols of follitropin delta and human menopausal gonadotropin (hMG).

Innovation Solution

A mixed protocol of individualized dosing of highly purified human menopausal gonadotropin (hMG) and recombinant human follicle-stimulating hormone (rFSH) with α2,3- and α2,6-sialylation, tailored to patients aged 35-40 based on anti-Müllerian hormone (AMH) levels and body weight, adjusting doses according to serum estradiol levels during stimulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a mixed protocol of hMG and FSH is used to stimulate multiple follicular development, then the number of oocytes produced increases, but the risk of ovarian hyperstimulation syndrome (OHSS) increases

Engineering Contradiction:
Improvenumber of oocytes producedVSAvoidrisk of OHSS
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by using individualized dosing based on AMH levels and body weight. The FSH dose is calculated as 0.09-0.19 μg per kg body weight per day, and hMG dose is individualized based on AMH levels. This personalized approach optimizes the stimulation intensity to maximize oocyte yield while maintaining safety by preventing excessive ovarian response that leads to OHSS.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If standard COS regimens are used without individualization, then the treatment protocol is simple to implement, but the oocyte quality and pregnancy rates are suboptimal

Engineering Contradiction:
Improvesimplicity of protocol implementationVSAvoidoocyte quality
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by determining AMH levels and calculating individualized dosing parameters before starting the COS cycle. This pre-treatment assessment allows the protocol to be tailored to each patient's ovarian reserve, ensuring optimal oocyte quality from the outset while maintaining clear dosing guidelines that facilitate implementation.

Inventive Principle:
Principle #10Preliminary action

3Productivity

If higher doses of gonadotrophins are administered to stimulate follicular development in patients over 35, then the ovarian response may be improved, but the risk of OHSS and treatment complications increases

Engineering Contradiction:
Improveovarian responseVSAvoidsafety of treatment
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by using AMH levels and body weight as dosing parameters. For patients over 35, the FSH dose is individualized at 0.09-0.19 μg per kg body weight per day, and hMG dosing is adjusted based on AMH levels. This personalized approach ensures adequate ovarian response in older patients while preventing excessive stimulation and associated safety risks.

Inventive Principle:
Principle #35Parameter changes

4Manufacturing precision

If a mixed protocol of hMG and FSH is used, then better quality oocytes and embryos are obtained, but the treatment complexity and dosing adjustment requirements increase

Engineering Contradiction:
Improveoocyte qualityVSAvoidtreatment protocol complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by calculating individualized dosing parameters based on AMH levels and body weight before treatment initiation. The FSH dose is predetermined as 0.09-0.19 μg per kg body weight per day, and hMG dosing is established based on AMH levels. This pre-planning simplifies the actual treatment execution while maintaining the benefits of mixed protocol for oocyte quality.

Inventive Principle:
Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This protocol significantly increases the number of good-quality blastocysts obtained without compromising safety, reducing the incidence of OHSS, and minimizing the need for dose adjustments, particularly benefiting patients aged 35-40 years.

Implementation Method 1

recombinant human follicle-stimulating hormone (rFSH) with α2,3- and α2,6-sialylation

Methodology Applied
Scientific EffectHormone-receptor interaction:

Implementation Method 2

administration of gonadotrophins, such as menotropin (e.g., human menopausal gonadotropin (hMG)) and follicle stimulating hormone (FSH) alone or in combination with luteinising hormone (LH) activity to stimulate multiple follicular development

Methodology Applied
Scientific EffectGonadotrophin stimulation:

Implementation Method 3

COS requires administration of a GnRH analogue (GnRH agonist) or GnRH antagonist prior to and/or during stimulation to prevent a premature LH surge which may induce ovulation before planned oocyte retrieval

Methodology Applied
Scientific EffectHormone regulation:

Data Source

PatentUS20250241993A1Mixed protocol for treatment of infertility
Publication Date: 2025.07.31 FERRING BV

AI summary

Methods, uses and products including a recombinant human follicle stimulating hormone (rFSH) including α2,3- and α2,6-sialylation and menotropin (human menopausal gonadotropin or hMG) for use in the treatment of infertility in a patient of age≥35 are described.