Clinical Outcomes of Drug-Free in Vitro Activation (IVA) with Modified Surgical Technique in Patients with Diminished Ovarian Reserve

Study Objective Patients with critically diminished ovarian reserve have few remaining follicles and using donated eggs becomes the only chance of getting pregnant. Kawamura et al. have invented a method for the activation of dormant follicles using PI3K stimulator and PTEN inhibitors, but later showed that ovarian tissue fragmentation alone with returning to the contralateral ovary could also lead to follicular growth. Our purpose was to optimize infertility treatment in patients with diminished ovarian reserve using a new modified surgical technique with ipsilateral ovarian tissue reimplantation. Design Prospective study, Level II. Setting National Medical Research Center. Patients or Participants 70 patients with diminished ovarian reserve and no successful results from previous treatment, including ART methods. Interventions Bilateral ovarian cortex biopsy via laparoscopy, ovarian tissue fragmentation in aliquots of 1 mm2, and hysteroscopy with endometrial biopsy were performed in all patients, followed by histological examination. Collected tissue fragments were grafted into a formed space between the ovarian cortex and medulla ipsilaterally. To date 40 patients underwent ovarian stimulation after at least a one-month postoperative period. Measurements and Main Results Our study demonstrated at least a triple increase in estradiol level in 5 days after surgery, progressive decrease in gonadotropins levels, increase in the number of growing follicles in all patients after our modified surgical approach. 31 out of 40 patients have responded to ovarian stimulation. Moreover, in 25 out of 31 patients we revealed an increase in the number of oocytes, fertilization rates, and high-quality embryo rates. 10 patients became pregnant after the surgery (3 spontaneous pregnancies, 7 - after ovarian stimulation). Conclusion Our data shows that drug-free IVA with our modified surgical technique is associated with favorable clinical outcomes for infertility treatment in patients with diminished ovarian reserve.