Micro-Trauma Induced Follicular Activation: The Role of Ovarian Pricking in Fertility Enhancement"

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Abstract

Background Women with diminished ovarian reserve (DOR) represent one of the most challenging groups in assisted reproductive technology (ART), often exhibiting poor response to conventional stimulation protocols and limited success in in vitro fertilization (IVF). Strategies aimed at activating dormant follicles have gained increasing attention, particularly approaches that modulate intra-ovarian signaling pathways such as the Hippo pathway. Ovarian pricking, a minimally invasive technique involving targeted disruption of the ovarian cortex under transvaginal ultrasound guidance, has been hypothesized to stimulate follicular activation and improve oocyte yield. This study aimed to evaluate whether ovarian pricking can enhance follicular recruitment and improve subsequent fertility outcomes in women with DOR who had previously failed IVF cycles. Results This prospective study included 24 infertile women aged 30–35 years with AMH levels < 0.5 ng/mL, reduced antral follicle counts, and ovarian volume of 1.5–2 cm³. Ovarian pricking was performed transvaginally under ultrasound guidance using a standard oocyte retrieval needle, followed by estradiol valerate administration and serial monitoring. Of the 24 patients, 22 (91.7%) demonstrated a follicular response, with a significant increase in the mean number of antral follicles from 0.42 ± 0.50 before pricking to 3.96 ± 1.30 post-procedure (t = − 12.274, p = 0.001). Among the 22 responders, 18 (81.8%) exhibited sustained follicular growth during controlled ovarian stimulation with recombinant FSH plus HMG under an antagonist protocol. Oocyte retrieval was successful in all 18, and 16 (88.9%) yielded mature (MII) oocytes. Blastocyst formation was achieved in 8 of these 16 patients (50%), demonstrating the feasibility of the approach in supporting downstream embryonic development. Four women showed an initial response but failed to progress to stimulation. Conclusions Ovarian pricking appears to be a novel and promising adjunct for the management of women with DOR, offering a minimally invasive means of activating dormant follicles and improving follicular recruitment, oocyte maturation, and blastocyst development. The high response rate observed in this study supports its potential clinical utility, possibly through modulation of the Hippo signalling pathway. However, outcomes varied among patients, highlighting the need for individualized treatment strategies. Larger, long-term prospective studies are warranted to validate efficacy, optimize protocols, and define predictors of success, as well as to assess the impact on live birth outcomes.

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