JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):101
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263688

P-89. Excessive FSH and the Early LH Window: An Evidence-Based Approach to Individualizing Controlled Ovarian Stimulation

Katherine Ann Reimão Miller, Gabriel Monteiro Pinheiro¹

¹ Universidade Santo Amaro - São Paulo - SP - Brasil

Objective: The aim of this specialized narrative review is to critically synthesize evidence on the impact of excessive follicle-stimulating hormone (FSH) dosing and the role of early luteinizing hormone (LH) co-treatment during controlled ovarian stimulation (COS), evaluating effects on key reproductive outcomes and proposing practical criteria for individualized protocols.
Methods: A comprehensive search was conducted through PubMed/MEDLINE, Cochrane Library and Scielo, until August 2025, in english, portuguese and spanish, combining the following descriptors with boolean operators (AND/OR): "controlled ovarian stimulation", "IVF" "ICSI", "FSH", "follicle stimulating hormone", "high-dose FSH", "LH", "luteinizing hormone" and "co-treatment". We also hand-searched reference lists of key articles (backward citation tracking). The inclusion criteria for the review was: (i) Women undergoing controlled ovarian stimulation for IVF/ICSI; with special interest in ≥35 years and/ or hypo-responders (low AMH/AFC or prior suboptimal response); (ii) Early LH co-treatment (day-1 LH+FSH) versus FSH alone (including high-dose regimens) or versus late/rescue LH addition; (iii) Randomized controlled trials, prospective/ retrospective cohort studies with appropriate comparators, systematic reviews and meta-analyses; and (iv) reported at least one outcome, such as live birth rate, clinical pregnancy rate, implantation rate, number of mature oocytes, embryo quality and/or stimulation efficiency. The exclusion criteria were: (i) oocyte-donor cycles not applicable to the target profile; (ii) mixed high-/low-response populations without stratified analyses; (iii) single-arm case series or case report; (iv) non-comparative protocols obsolete for current practice; and (v) preclinical/animal studies (used only for background). Records were exported to a reference manager (Zotero) for de duplication exclusion. Articles were firstly screened by titles/abstracts and then full-texts, excluding articles that did not fit in the eligibility criteria. Data extraction used a piloted, standardized form capturing study design, population characteristics, COS/suppression protocols, timing and dosing of FSH/LH, outcomes, and analytical details.
Results: Across the literature, escalating FSH dose beyond individualized requirements shows diminishing returns and has been associated with lower live birth probability when considered as an independent factor, suggesting potential compromise of oocyte competence despite higher oocyte yield. Physiologic data underscore that LH contributes to intrafollicular steroidogenesis and oocyte competence, with clinical relevance in contexts of relative LH deficiency and ovarian aging. Comparative data indicate that modern GnRH agonist and antagonist suppression strategies, after protocol refinements, achieve broadly similar live birth outcomes, supporting the notion that suppression per se does not impair oocyte competence. In selected subgroups (advanced maternal age, hypo-responders, or cycles with prior suboptimal response), early LH supplementation alongside FSH has been associated with improved implantation and clinical pregnancy despite fewer retrieved oocytes, aligning with a shift from "quantity" to "per-oocyte efficiency." However, routine LH addition outside predefined profiles remains of uncertain benefit, and there is no universally validated biomarker to identify ideal candidates or optimal timing. Important evidence gaps include: (i) precise FSH dose–response thresholds beyond which quality declines; (ii) standardized definitions for "hypo-response"; (iii) head-to-head studies isolating the incremental value of LH started from day 1 versus later rescue; and (iv) consistent reporting of embryo euploidy and efficiency indices such as the ovarian sensitivity index.
Conclusion: The emerging clinical paradox is that non-individualized, high-dose FSH can erode per-oocyte efficiency and live birth probability, whereas a refined, physiology-informed approach integrating early LH co-treatment may restore oocyte competence and improve outcomes in carefully selected patients. Current evidence supports personalizing COS by patient profile rather than maximizing oocyte yield. We propose a framework prioritizing (1) baseline ovarian reserve/prior response, (2) conservative FSH dosing calibrated to efficiency metrics, and (3) early LH co-treatment for subgroups (≥35 years, hypo-responders, or cycles with relative LH insufficiency).