Pregnancy after drug-free in vitro activation of follicles and fresh tissue autotransplantation in primary ovarian insufficiency patient: a case report and literature review

Abstract

BackgroundThe aim of this report was to describe a case of pregnancy after drug-free in vitro activation (IVA) of follicles and fresh tissue autotransplantation in primary ovarian insufficiency (POI) patient and to review the pertinent literature.MethodsWe present a case in wich a 32 - years old patient with POI became pregnant after IVA without tissue culture and with ovarian tissue transplantation. We also reviewed the literature using Pubmed database.Case presentationPretreatment with estradiol/progesterone stopped the day before surgery. The removal of the ovarian cortex and autotransplantation were performed by laparoscopy in the same surgical act. Ovarian fragments were transplanted in contralateral ovary and peritoneal pocket near to the ovary. Immediately after surgery GnRH agonist together HMG injections started, leading the growth of 3 preovulatory follicles and the retrieval of two mature eggs. After IVF two embryos were transferred and singleton pregnancy was established and currently she is 25 weeks pregnant.ResultsA total of 51 patients with POI in whom an in vitro activation of ovarian tissue was performed, were collected from the revieew of the literature. In 29.4% of them, follicular development was obtained and in 4 of them a pregnancy. In all of them, a combined technique (fragmentation and activation) was performed in two laparoscopies. No case has been reported successfully after drug-free in vitro activation.ConclusionsThis is the first report about a case with pregnancy after drug-free in vitro activation of follicles and fresh tissue autotransplantation in POI patient.

In vitro activation of ovarian cortex and autologous transplantation: A novel approach to primary ovarian insufficiency and diminished ovarian reserve

“…This procedure, which does not require the culture of ovarian tissue, could offer a less invasive treatment with a single surgical act and without the need of in vitro chemical activation. According to our review, the chance of pregnancy was 34.6% (9 out of 26 patients) ( Fabregues et al , 2018 ; Ferreri et al , 2020 ; Kawamura et al , 2020 ). Recently, an uncontrolled trial conducted in 20 women under 39 years with DOR failed to detect increased activity of the fragmented ovarian tissue.…”

“…Subsequent studies indicated that even simple fragmentation of the ovarian cortex could interfere with the Hippo pathway and hence restore the growth of ovarian follicles ( Fabregues et al , 2018 ; Ferreri et al , 2020 ; Kawamura et al , 2020 ). In summary, the Hippo pathway regulates cell proliferation and apoptosis and thereby organ size by performing a negative growth control.…”

“…Since patients with DOR, or at the initial stages of POI, have spontaneous activation of dormant primordial follicles reaching the secondary stage, subsequent follicular growth could be achieved using simplified in vitro activation, by just performing ovarian tissue fragmentation in a single surgical act, without the requirement of culture with stimulant drugs. For patients with residual secondary follicles, sole fragmentation of the ovarian cortex (causing interruption of the Hippo pathway) is likely to be enough to promote follicular growth ( Fabregues et al , 2018 ).…”

Successful Spontaneous Pregnancy and Live Birth in a Woman With Premature Ovarian Insufficiency and 10 Years of Amenorrhea: A Case Report

“…The main features of our cases were as follows: a 31-year-old female with 10 years of amenorrhea spontaneously conceived and delivered a healthy baby without ART; there are very few similar cases available for reference. Almost all accessible case reports described women who achieved pregnancy under intervention, including HRT (5-8); ovulation induction (9); donor egg in vitro fertilization (10); ovariectomy for ovarian tissue cryopreservation, followed by in vitro activation (IVA) for infertility treatment (11); immediate ovarian stimulation and in vitro fertilization (12); drug-free in vitro activation of follicles and fresh tissue autotransplantation (13), and autologous grafting of cryopreserved ovarian cortex at an orthotopic site (14), etc. A 29year-old Indian woman with primary amenorrhea characterized by a few episodes of withdrawal bleeding with HRT in the past was considered to be POI; she completed a full-term pregnancy without any assisted reproductive measures, however, the authors did not show the duration of amenorrhea and the FSH level, so the POI described lacks diagnostic evidence (15).…”

New Surgical Ways to Recover Lost Ovarian Functions in Premature Ovarian Insufficiency in Women of Reproductive Age

“…Исследователями во главе с F. Fabregues, представляющими Institut Clinic of Gynecology, Obstetrics and Neonatology, Institut d'Investigacions Biomèdiques August Pi I Sunyer (Барселона), применена хирургическая методика drug-free in vitro activation для активации функции яичников у пациентки с ПНЯ с последующим достижением беременности. Отличительными особенностями операции стали модификация процесса реимплантации, который, помимо интраовариального доступа, был выполнен подбрюшинно, и использование полимерного состава N-Hexyl-2-Cyanoacrylate как альтернативы шовного материала [13].…”