Surgical Approaches of Drug-free in Vitro Activation and Laparoscopic Ovarian Incision to Treat Patients with Ovarian Infertility

Fertility & Sterility
08 Sep, 2020 ,

Researchers sought to provide step-by-step video demonstration of their procedures of drug-free in vitro activation (IVA) for managing patients with premature ovarian insufficiency (POI) or diminished ovarian reserve (DOR), as well as the laparoscopic ovarian incision (LOI) procedure for treating patients with resistant ovary syndrome (ROS). The following four steps were involved in the drug-free IVA: taking away a part of the cortex from one or both ovaries; cutting ovarian cortical pieces into small cubes in vitro; making pockets for ovarian tissue grafting; and grafting ovarian cortical cubes. Only one step was involved in the LOI procedure: cutting ovarian cortex in situ. Ovarian hyperstimulation for at least 1 year followed the two procedures. Per outcomes, a drug-free IVA approach represent an infertility treatment for recent POI or DOR patients. This procedure improved growth of residual ovarian follicles after ovarian tissue fragmentation in vitro, resulting in Hippo signaling disruption. Although symptoms of hypergonadotropic hypoestrogenism were reported by ROS patients similar to that of POI patients, they still had multiple secondary follicles. Follicle growth may enhance with disruption in Hippo signaling in vivo based on cutting ovarian cortex using LOI.

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Abstract

Objective

To demonstrate our procedures of drug-free in vitro activation (IVA) for treating patients with premature ovarian insufficiency (POI) or diminished ovarian reserve (DOR), as well as the laparoscopic ovarian incision (LOI) procedure for treating patients with resistant ovary syndrome (ROS).

Design

Step-by-step video demonstration of the surgical procedures.

Setting

Fertility clinic and reproductive medicine department.

Patients

Women were diagnosed with POI based on recent amenorrhea before 40 years of age or with DOR according to the Bologna criteria, showing growth of a few antral follicles after ovarian stimulation. ROS patients were diagnosed based on amenorrhea with hypergonadotropic hypoestrogenism but showing age-appropriate number of antral follicles under transvaginal ultrasound.

Interventions

The drug-free IVA consists of the following 4 steps: removing a part of the cortex from one or both ovaries; cutting ovarian cortical pieces into small cubes in vitro; making pockets for ovarian tissue grafting; and grafting ovarian cortical cubes. The LOI procedure consisted of only one step: cutting ovarian cortex in situ. Both procedures were followed by ovarian hyperstimulation for at least 1 year. Informed consent was obtained from patients and approval was granted by the Biomedical Ethics Committee of the International University School of Medicine and the Rose Ladies Clinic. The present clinical trial was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).

Main Outcome Measure

Follicle growth.

Results

These procedures can be completed within 1 hour under laparoscopic surgery. There were no complications. In 13 of 15 patients treated with drug-free IVA, increases in antral follicle numbers were found, followed by a higher number of retrieved oocytes for in vitro fertilization. In addition to one spontaneous pregnancy, embryo transfer allowed four live births and one ongoing pregnancy. Five additional patients and one miscarriage patient have cryopreserved embryos for future transfer. We also found follicle growth to the preovulatory stage in seven of 11 ROS patients who have not responded to any endogenous and exogenous follicle-stimulating hormone stimulations for follicle growth prior to LOI treatment, allowing the retrieval of mature oocytes for in vitro fertilization. Four ROS patients became pregnant, followed by the delivery of three healthy infants and one ongoing pregnancy.

Conclusion

A drug-free IVA approach provided an infertility treatment for recent POI or DOR patients. This procedure promoted growth of residual ovarian follicles following ovarian tissue fragmentation in vitro, leading to Hippo signaling disruption. Although ROS patients exhibited symptoms of hypergonadotropic hypoestrogenism similar to that of POI patients, they still had multiple secondary follicles. Hippo signaling disruption in vivo based on cutting ovarian cortex using LOI could promote follicle growth.