In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients

Abstract

Context: Recently, two patients with primary ovarian insufficiency (POI) delivered healthy babies after in vitro activation (IVA) treatment followed by auto-transplantation of frozen-thawed ovarian tissues.

Objective: This study sought to report the first case of live birth after IVA treatment following fresh ovarian tissue grafting in patients with POI, together with monitoring of follicle development and serum hormonal changes.

Design: This was a prospective observational cohort study.

Setting: We performed IVA treatment in 14 patients with POI with mean age of 29 years, mean duration since last menses of 3.8 years, and average basal FSH level of 94.5 mIU/mL.

Interventions: Prior to IVA treatment, all patients received routine hormonal treatments with no follicle development. We removed one ovary from patients with POI and treated them with Akt stimulators. We improved upon early procedures by grafting back fresh tissues using a simplified protocol.

Main outcome measures: In six of the 14 patients (43%), a total of 15 follicle development waves were detected, and four patients had successful oocyte retrieval to yield six oocytes. For two patients showing no spontaneous follicle growth, human menopausal gonadotropin treatment induced follicle growth at 6-8 months after grafting. After vitro fertilization of oocyte retrieved, four early embryos were derived. Following embryo transfer, one patient became pregnant and delivered a healthy baby boy, with three other embryos under cryopreservation.

Conclusion: IVA technology can effectively activate residual follicles in some patients with POI and allow them to conceive their own genetic offspring. IVA may also be useful for treating patients with ovarian dysfunction including aging women and cancer survivors.

Figure 1.

Follicle growth patterns and oocyte retrieval for six POI patients after IVA treatment. Pink ovals with an inner dot indicate spontaneous follicle growth whereas red ovals with an inner dot indicate hormonal induced follicle growth. Right upward arrows indicate follicle growth. Upward arrows pointing to one or two dots indicate successful retrieval of oocyte. A, spontaneous follicle growth with or without E/P. B, GnRH agonist followed by HMG treatment. C, HMG treatment with or without E/P pretreatment. spontaneous; induced; live birth; frozen embryo.

Figure 2.

Hormonal profiles for six POI patients showing follicle growth after the IVA procedure. Serum levels of estradiol, FSH, and LH (left y-axis) were measured and plotted together with follicle diameters (right y-axis) estimated based on ultrasound monitoring. X-axis represents the number of days after ovarian grafting. Hormonal treatment protocols are also shown. A, spontaneous follicle growth. B, GnRH agonist followed by HMG treatment. C, HMG treatment with or without E/P pretreatment. Abbreviations: E-P, pretreatment with estrogen and progesterone; GnRH-a, GnRH agonist; opu, ovum pickup.

Figure 3.

Serum AMH levels in five patients with POI showing follicle growth. Serum AMH was measured before and at different times after grafting.