Drug-free in-vitro activation of follicles and fresh tissue autotransplantation as a therapeutic option in patients with primary ovarian insufficiency

Ferreri, Janisse; Fàbregues, Francesc; Calafell, Josep M.; Solernou, Roser; Borrás, A; Saco, Adela; Manau, Dolors; Carmona, Francisco

doi:10.1016/j.rbmo.2019.11.009

Cited by 46 publications

(28 citation statements)

References 32 publications

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“…Before POI, the ovarian follicle pool reduction begins at a clinical stage known as DOR, a condition that affects 10% of women pursuing pregnancy ( Ferreri et al , 2020 ).…”

Section: In Vitro Activation Of Ovarian Cortexmentioning

confidence: 99%

“…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.…”

Section: In Vitro Activation Of Ovarian Cortexmentioning

confidence: 99%

“…Later, human studies were conducted in patients with POI and DOR. Two case reports that described the performance of this novel technique on 11 patients with DOR ( Kawamura et al , 2020 ) and 14 patients with early stages of idiopathic POI ( Ferreri et al , 2020 ), showed an increase in antral follicle number in multiple growth waves following FSH or HMG treatment and reported successful oocyte retrieval and pregnancy rates of 36% and 28%, respectively.…”

Section: In Vitro Activation Of Ovarian Cortexmentioning

confidence: 99%

“…From birth onwards, the cohort of primordial ovarian follicles decreases progressively, from approximately 2 million to just a few thousand by the age of 40, with the subsequent advent of menopause ( Ferreri et al , 2020 ). It is estimated that ‘natural infertility’ occurs at an average age of 41 years, while ovarian endocrine activity continues until menopause, at an average age of 51 years.…”

Section: Introductionmentioning

confidence: 99%

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

Devenutto

Quintana

2020

Human Reproduction Open

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BACKGROUND Primary ovarian insufficiency (POI) and diminished ovarian reserve are two conditions that affect women’s fertility. Oocyte donation remains an option for these patients; however, the development of certain novel technologies, such as in vitro activation of ovarian cortex (IVA), enables the possibility of activating the pool of resting primordial follicles, increasing the chance of pregnancy. OBJECTIVE AND RATIONALE Here, we review the main pathways (PI3K and Hippo signaling) that govern the activation of primordial follicles and its application through the development of culture systems that support ovarian cortex for autologous transplantation. We also review the available data from case reports regarding outcomes of pregnancy and live birth rates with IVA. SEARCH METHODS A PubMed search was conducted using the PubMed-NCBI database to identify literature pertinent to the pathways involved in the activation of primordial follicles and the outcomes of IVA techniques from 2013 to the present. OUTCOMES Women with POI have around a 5% chance of spontaneous pregnancy. Recently, novel techniques involving the activation of primordial follicles through molecular pathways have been developed, thus increasing the odds of these patients. More recently, the introduction of a drug-free IVA technique has shown to increase the number of antral follicles with successful oocyte maturation after gonadotropin treatment, reaching pregnancy rates over 30%, either through spontaneous conception or by the implementation of assisted reproductive technology. LIMITATIONS The evidence of this review is based on a few small series, so data should be interpreted with caution, and only randomized controlled trials could estimate the real magnitude and success of the procedure. REASONS FOR CAUTION IVA technique remains an experimental strategy, with limited available data and the requirement of invasive procedures. Moreover, possible carcinogenic effects not yet determined after transplantation require special caution. WIDER IMPLICATIONS In view of the results achieved, IVA could provide a promising option for the preservation of fertility in some cancer patients and prepuberal girls where the only alternative is tissue cryopreservation. STUDY FUNDING/COMPETING INTERESTS The authors received no specific funding for this work and declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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“…Before POI, the ovarian follicle pool reduction begins at a clinical stage known as DOR, a condition that affects 10% of women pursuing pregnancy ( Ferreri et al , 2020 ).…”

Section: In Vitro Activation Of Ovarian Cortexmentioning

confidence: 99%

Section: In Vitro Activation Of Ovarian Cortexmentioning

confidence: 99%

Section: In Vitro Activation Of Ovarian Cortexmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Devenutto

Quintana

2020

Human Reproduction Open

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“…The study involving IVC of bovine ovarian cortex demonstrated that PTEN inhibition activated bovine non-growing follicles, but simultaneously increased DNA damage and reduced DNA repair response (27). Recently, a drug-free IVA method was used in infertility treatment for POI patient, leading to successful pregnancies (37). This method may eliminate the negative effect of activation agents on follicles, but it may simultaneously reduce the yield of follicles, which makes it insufficient for subsequent culture use.…”

Section: Initial Stage: In Vitro Activation (Iva) Of Primordial Follimentioning

confidence: 99%

Human Follicle in vitro Culture Including Activation, Growth, and Maturation: A Review of Research Progress

2020

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Fertility preservation has received unprecedented attention nowadays. In addition to cryopreservation and re-implantation of embryos, oocytes, and ovarian tissue pieces, in vitro culture system for follicles/oocytes has been considered as an alternative strategy for fertility preservation. Since the metabolic dynamics and required nutrients are not entirely the same in different stages of follicular development, optimization of each culture step is needed. In this paper, literature regarding culture conditions in three steps were analyzed. Known additives in activation stage included 740Y-P, bpV(HOpic), follicle stimulating hormone (FSH), human serum albumin (HSA), ITS, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and cyclic adenosine monophosphate (cAMP), with different degrees of activation promotion and potential detrimental effect on DNA integrity. For isolated follicles growth stage, actin A, FSH, basic fibroblast growth factor (bFGF), estradiol were proved to improve development or proliferation. As for maturation, addition of growth hormone, melatonin, C-type natriuretic peptide (CNP), GDF9, cilostamide, or forskolin helped to regulate maturation rate or improve oocyte quality. Based on previous sequential culture system for human follicles, optimization is needed to achieve higher maturation rate and better oocyte quality, pursuant to current review, which demonstrated the effects of various additives on different stages.

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Follicle Activation by Physical Methods and Clinical Applications

Devos

Demeestere

Grosbois

2022

Female and Male Fertility Preservation

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Drug-free in-vitro activation of follicles and fresh tissue autotransplantation as a therapeutic option in patients with primary ovarian insufficiency

Cited by 46 publications

References 32 publications

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

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

Human Follicle in vitro Culture Including Activation, Growth, and Maturation: A Review of Research Progress

Follicle Activation by Physical Methods and Clinical Applications

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