Diminished Ovarian Reserve: GH, DHEA and IVF Add-On Evidence

Do growth hormone, DHEA, CoQ10 or L-arginine improve IVF outcomes for women with diminished ovarian reserve? Some studies report more eggs, but live-birth benefits remain uncertain. Current ESHRE guidance discourages GH and DHEA for low responders. The strength of evidence and limitations differ for each add-on.

“From Growth Hormone to DHEA to Help Eggs Grow”… For Women with Diminished Ovarian Reserve, How Far Should We Trust Adjuvant Prescriptions?

Growth hormone, DHEA, CoQ10 and L-arginine have been studied as IVF add-ons; their benefits are not established equally
Select trials show signals of improvement in total oocyte yield and mature eggs, yet definitive live birth efficacy remains uncertain
Adjuvants aim to optimize the microenvironment of existing follicles, not generate new eggs from scratch

Women diagnosed with diminished ovarian reserve (DOR) starting In Vitro Fertilization (IVF) may be offered supplements or medications alongside standard gonadotropin injections.

A proposed regimen may include growth hormone (GH) injections, daily DHEA capsules, Coenzyme Q10 (CoQ10), and L-Arginine together. Depending on the fertility center, transdermal testosterone or other adjunctive therapies may be added to the regimen. From a patient’s perspective, it is only natural to hope: “If I take all of these together, won’t my follicles grow better and increase my chances of getting high-quality eggs?”

However, taking a closer look at the scientific literature reveals that the clinical reality is far from simple.

While select adjuvant therapies demonstrate modest increases in retrieved oocyte counts, mature oocytes, or even clinical pregnancy rates, an increase in cumulative live birth has not been established for the add-ons discussed here. In the management of diminished ovarian reserve, “retrieving a few more eggs” and “increasing the probability of taking home a healthy baby” do not necessarily mean the same thing.

Diminished ovarian reserve and higher FSH doses

The primary reason clinicians turn to adjuvant therapies for women with diminished ovarian reserve is that standard therapeutic options are severely limited.

A low antral follicle count limits the expected response, but dose and egg yield are not a fixed ratio. Higher FSH doses can produce somewhat more eggs in low responders without a proven live-birth benefit. ESHRE advises against doses above 300 IU daily for predicted low responders.

Consequently, reproductive endocrinologists search for alternative biological pathways beyond simply cranking up the gonadotropin dose:

Growth Hormone (GH): Hypothesized to augment follicular responsiveness to FSH.
DHEA: Intended to modify the intra-ovarian androgen microenvironment.
Coenzyme Q10 (CoQ10): Aimed at enhancing mitochondrial bioenergetics.
L-Arginine: Intended to improve local ovarian blood flow.

While these therapies target entirely different biological mechanisms, they share a single premise: attempting to make the microenvironment slightly more favorable for the follicles already present in the ovary. None of these treatments create new eggs.

Growth hormone: IVF trials and current guidance

Among adjuvant therapies for poor ovarian responders (POR), Growth Hormone (GH) is one of the most frequently discussed. GH is thought to act through insulin-like growth factor 1 (IGF-1) and related signaling cascades to enhance granulosa cell function and upregulate follicular sensitivity to FSH.

Indeed, recent clinical trials and meta-analyses have yielded intriguing findings. Across multiple randomized controlled trials (RCTs), adding growth hormone to stimulation protocols in poor responders was associated with a trend toward higher retrieved oocyte numbers, more mature Metaphase II (MII) oocytes, and an increased number of usable embryos. In several pooled analyses, numerical gains in clinical pregnancy and live birth rates were also observed. In the double-blind LIGHT trial published in Reproductive BioMedicine Online in 2019, live birth was 14.5% (9/62) with GH and 13.7% (7/51) with placebo. The trial missed its recruitment target and could not demonstrate a benefit; this does not prove there is no effect.

The underlying challenge, however, lies in trial heterogeneity: diagnostic definitions of poor response (ranging from the Bologna criteria to POSEIDON groups), GH dosages, administration timing, and ovarian stimulation protocols vary widely between studies. Furthermore, the overall sample sizes in many of these trials remain relatively modest.

The current ESHRE ovarian stimulation guideline goes beyond saying GH is optional: it advises against its use in low responders through a conditional recommendation based on very low-certainty evidence.

DHEA: early signals versus randomized evidence

At one point, DHEA (dehydroepiandrosterone) was perhaps the most widely publicized adjuvant among women with diminished ovarian reserve. Because DHEA is an adrenal-derived androgen precursor, researchers hypothesized that administering it could elevate intra-ovarian androgen levels, which in turn would stimulate early follicular recruitment and upregulate FSH receptor expression on granulosa cells.

Early observational studies and small pilot series reported increases in egg yields and spontaneous pregnancies, including a 2007 case-control report. Such observations cannot demonstrate that DHEA reverses ovarian aging.

More robust evidence did not confirm a live-birth benefit. A double-blind placebo-controlled trial in BJOG in 2022 included 821 women meeting Bologna poor-response criteria at nine Chinese centers. Live birth after the first transfer was 8.8% with DHEA versus 9.0% with placebo (RR 0.98, 95% CI 0.63–1.51). Cumulative live birth also showed no significant difference.

This explains why ESHRE advises against DHEA before or during stimulation in low responders (a strong recommendation based on low-certainty evidence). A treatment’s widespread clinical popularity does not automatically mean it rests on gold-standard evidence.

CoQ10: egg-yield signals and live-birth uncertainty

In recent years, Coenzyme Q10 has been investigated as an adjuvant in diminished ovarian reserve research. CoQ10 is an electron carrier in the mitochondrial electron transport chain, supporting cellular ATP production.

The human oocyte is one of the most energy-demanding cells in the body. Because mitochondria play a pivotal role not only in oocyte maturation but also in the complex meiotic spindle alignments and cellular divisions of early embryonic development, mitochondrial bioenergetic decline has long been investigated as a core mechanism underlying oocyte aging.

A 2024 meta-analysis of six randomized trials in women with diminished ovarian reserve has shown positive signals: patients supplementing with CoQ10 exhibited modest increases in retrieved oocyte numbers and higher clinical pregnancy rates. For a woman who typically retrieves only one or two eggs, an average gain of even one additional oocyte can be clinically meaningful. However, all included studies lacked blinding and had unclear allocation concealment; positive pooled results require caution.

CoQ10 is not a proven live-birth treatment. In a 2018 randomized trial in Reproductive Biology and Endocrinology, 186 women under 35 with low reserve were assigned to 60 days of CoQ10 or no pretreatment; 169 were analyzed. Egg and embryo measures improved, but live-birth differences were not statistically significant. Lack of blinding, post-randomization exclusions and a primary embryo-quality endpoint limit the conclusions and their relevance to older patients.

L-arginine: limited and conflicting IVF evidence

L-Arginine is a semi-essential amino acid required for the enzymatic synthesis of nitric oxide (NO), a potent endogenous vasodilator. The biological rationale is straightforward: by enhancing blood perfusion to the ovarian stroma and surrounding follicular capillary beds, oxygen and essential nutrients might be delivered more efficiently to developing follicles.

Decades ago, a small randomized study of 34 poor responders in 1999 reported improved ovarian blood flow and enhanced follicular recruitment in poor responders receiving L-Arginine.

The cited evidence remains small and conflicting. A 2002 placebo-controlled trial randomized 37 IVF patients and reported poorer embryo quality and lower pregnancy rates with L-arginine. That different IVF population cannot settle efficacy in DOR, but it cautions against assuming benefit or safety from blood-flow theory alone. Neither small trial establishes a live-birth benefit.

Consequently, there is currently insufficient clinical proof to state that supplementing with L-Arginine reliably improves egg growth or IVF success. While the theory that “better blood flow supports better follicle growth” is biologically plausible, whether that translates into live births remains unverified.

Why combined add-ons make benefit hard to identify

If growth hormone, CoQ10 and other add-ons are started together, the effect of any single ingredient becomes difficult to identify.

Consider a scenario: a woman retrieves only one egg in her initial IVF cycle. For her subsequent cycle, she starts growth hormone injections, takes DHEA, CoQ10, and L-Arginine, and her physician switches her gonadotropin medication. At retrieval, she obtains three eggs.

From the patient’s standpoint, the intuitive reaction is: “The new cocktail of supplements worked.”

From a medical standpoint, however, it is impossible to isolate the true cause. Was it the growth hormone? The altered gonadotropin protocol? Or did her ovaries simply begin that month with a naturally higher baseline antral follicle count?

The human ovary does not start from the exact same baseline every month. This inherent physiological variability makes evaluating the true individual efficacy of adjuvant therapies exceedingly difficult.

Egg quantity, egg quality and live birth

One of the most critical phrases that patients with diminished ovarian reserve must interpret with care is “improving egg quality.”

An increase in retrieved oocytes can be directly counted. The number of mature MII oocytes and successfully fertilized 2PN embryos can be verified under a microscope.

True biological “egg quality,” however, is vastly more complex.

Even if an adjuvant regimen leads to more usable blastocysts, that does not necessarily mean it has corrected underlying chromosomal aneuploidy or halted cellular aging. In clinical trials to date, there is no definitive proof that these adjuvant therapies can reverse age-related meiotic non-disjunction or significantly reduce embryonic chromosomal errors.

This is why live birth rate remains the ultimate benchmark in reproductive medicine. If an intervention yields more eggs or higher fertilization rates without translating into an increased likelihood of taking home a baby, the clinical value of the treatment changes.

Can add-ons replenish ovarian reserve?

For women navigating diminished ovarian reserve, none of these agents—whether growth hormone, DHEA, CoQ10, or L-Arginine—has been shown clinically to replenish the ovarian egg reserve.

Their proposed mechanisms concern the hormonal, bioenergetic or vascular environment of existing follicles. A proposed mechanism does not establish clinical benefit.

Very low AMH and a low antral follicle count suggest a low response, but do not set an exact ceiling on the number of eggs retrieved. A supplement combination cannot be promised to turn one expected egg into ten.

The cornerstone of care for diminished ovarian reserve remains tailoring an evidence-based stimulation protocol suited to the patient’s age, baseline antral follicle count, AMH, and prior ovarian response history.

Weighing the evidence for each IVF add-on

Biological hypotheses and limited egg yields help explain research interest in adjuvants. They do not establish that prescribing an add-on improves live birth.

Women with diminished ovarian reserve face limited treatment avenues. For a patient who has undergone multiple cycles yielding only one or two eggs, securing even a single additional oocyte can mean the difference between having an embryo available for transfer and facing cycle cancellation.

Any discussion of an add-on should separate research signals from demonstrated benefits and include uncertainty, cost and possible harms. It should not present GH as an ESHRE-endorsed treatment for selected low responders.

However, patients should understand the distinct levels of evidence behind each agent:

Growth Hormone: Trials are mixed; ESHRE conditionally advises against use in low responders.
DHEA: ESHRE advises against use in low responders; a large placebo-controlled trial found no live-birth benefit.
CoQ10: Some trials report better egg or embryo measures, but bias and uncertain live-birth benefit limit confidence.
L-Arginine: Lacks adequately powered clinical trials to establish its utility.

What patients should discuss with their fertility team

In the end, success does not depend on taking as many pills or injections as possible.

What matters is understanding whether a prescribed therapy is an established, proven treatment or an adjunctive option being explored for its potential benefits.

As of 2026, reproductive medicine has yet to discover a universal magic pill capable of restoring egg quality and guaranteeing a live birth for every patient.

The clinical frontier in managing diminished ovarian reserve is shifting away from asking “What else can we add to the prescription?” toward identifying “Which specific subgroup of patients can genuinely benefit from targeted adjuvant therapy?”