Study question: Does a fixed-dose combination of oral hyaluronic acid (HA) and alpha lipoic acid (ALA), administered during IVF/ICSI, improve clinical pregnancy rates in women with primary infertility? Summary answer: Combined periconceptional supplementation with HA and ALA was associated with a clinical pregnancy rate of 88.9% per embryo transfer, approximately double published global IVF/ICSI benchmarks, with 100% biochemical-to-clinical conversion and no adverse events attributable to either agent. What is known already: Global IVF/ICSI clinical pregnancy rates remain constrained to 35–45% per transfer cycle. HA is integral to endometrial extracellular matrix remodelling during the implantation window and has been associated with modest improvements in ART outcomes when used as an embryo transfer medium additive. ALA is a mitochondria-targeted amphipathic antioxidant with demonstrated efficacy in reducing reactive oxygen species burden during ovarian stimulation. No prospective clinical study has evaluated their combined use. Study design, size, duration: Prospective observational case series at a single specialist reproductive medicine centre in Mumbai, India (September–November 2025). Ten women with primary infertility were consecutively enrolled; nine were evaluable after one exclusion for PGT-identified chromosomal embryo anomaly precluding transfer. Participants/materials, setting, methods: Women aged 22–42 years with confirmed primary infertility scheduled for IVF or ICSI with fresh or frozen embryo transfer. The intervention was a fixed-dose combination tablet containing HA 200 mg and ALA 100 mg, administered orally twice daily (total daily dose: HA 400 mg, ALA 200 mg), initiated concurrent with controlled ovarian stimulation and continued through the luteal phase. The primary outcome was clinical pregnancy rate per embryo transfer, defined as visualisation of an intrauterine gestational sac on transvaginal ultrasound at 6–7 weeks gestation. Binomial 95% confidence intervals were calculated using the Wilson score method. Main results and the role of chance: Clinical pregnancy rate was 88.9% (8/9; 95% CI 51.8–99.7%) per embryo transfer. Biochemical pregnancy rate was 88.9% (8/9; 95% CI 51.8–99.7%); biochemical-to-clinical conversion was 100% (8/8; 95% CI 63.1–100%). All eight clinical pregnancies were ongoing at last follow- up. Mean endometrial thickness at transfer was 9.0 mm (SD 0.9; range 7.5–10.0 mm). All nine evaluable participants had triple-line (trilaminar) endometrial morphology. No adverse events attributable to HA or ALA were recorded. The wide confidence intervals reflect the small sample; results are considered hypothesis- generating. Limitations, reasons for caution: The small evaluable sample (n = 9), single-centre design, and absence of a concurrent randomised control arm preclude causal inference. The independent contributions of HA and ALA cannot be disentangled. The live birth rate was not available due to the short follow-up period. Findings may not generalise to other clinical settings. Wider implications of the findings: The magnitude, internal consistency, and mechanistic plausibility of these findings provide justification for a well-powered, double-blind, placebo-controlled RCT evaluating the HA and ALA combination in women undergoing IVF/ICSI, with live birth rate as the primary endpoint. Study funding/competing interests: This study received no external funding. No conflict of interest is declared. Study funding/competing interests: This study received no external funding. No conflict of interest is declared. Trial registration number: Not applicable (observational case series).
Tasneem Bano2* Veena Shinde1 (Mon,) studied this question.