Drug-free in vitro activation for primary ovarian insufficiency

Abstract 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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Primary ovarian insufficiency: from basis of pathogenesis to treatment perspectives

Voprosy ginekologii akušerstva i perinatologii ◽

10.20953/1726-1678-2021-5-100-107 ◽

2021 ◽

Vol 20 (5) ◽

pp. 100-107

Author(s):

E.N. Andreeva ◽

◽

Yu.S. Absatarova ◽

R.R. Akhmatova ◽

E.V. Sheremetieva ◽

...

Keyword(s):

Early Diagnosis ◽

Ovarian Tissue ◽

Reproductive Potential ◽

Primary Ovarian Insufficiency ◽

Cochrane Library ◽

Ovarian Insufficiency ◽

Autoimmune Pathology ◽

In Vitro Activation ◽

Selection Of

The review of literature data on primary ovarian insufficiency (POI), its autoimmune aspect, determination of markers for early diagnosis of the disease, treatment options and implementation of reproductive plans was carried out. Autoimmune and genetic aspects of pathogenesis, markers of autoimmunity in ovarian tissue, which may be promising for early diagnosis in risk groups of patients with autoimmune pathology, were considered; information on the incidence of nosology in other autoimmune diseases, which will also allow to identify POI at early stages, was provided. This article provides information about a new direction in reproductive surgery – drug-free in vitro activation based on primordial follicle activation by modulating biological signaling pathways. This procedure may have a long-term perspective for realizing reproductive potential without the use of donor eggs. The literature search was performed in domestic (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The selection of sources was made within a limited period from 2016 to 2021. However, given the insufficient knowledge of the chosen topic, the selection of sources was dated from 2009. Key words: autoimmune oophoritis, hypergonadotropic hypogonadism, primary ovarian insufficiency, in vitro activation

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Interest of the use auto-transplantation of the ovarian cortex after dormant follicles in vitro activation (IVA) in patients with premature ovarian insufficiency (POI)

Fertility and Sterility ◽

10.1016/j.fertnstert.2019.07.1104 ◽

2019 ◽

Vol 112 (3) ◽

pp. e386

Author(s):

Khaled Mahmoud ◽

Hanen Elloumi ◽

Mohamed Khrouf ◽

MED Habib BEN Aribia ◽

Khaled Terras ◽

...

Keyword(s):

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Ovarian Cortex ◽

In Vitro Activation

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Homozygous Inactivating Mutation inNANOS3in Two Sisters with Primary Ovarian Insufficiency

BioMed Research International ◽

10.1155/2014/787465 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Mariza G. Santos ◽

Aline Z. Machado ◽

Conceição N. Martins ◽

Sorahia Domenice ◽

Elaine M. F. Costa ◽

...

Keyword(s):

Rna Binding ◽

Mutational Analysis ◽

Primordial Germ Cells ◽

Embryonic Cell ◽

Primary Ovarian Insufficiency ◽

Primary Amenorrhea ◽

Female Reproduction ◽

Ovarian Insufficiency ◽

Rna Interaction

Despite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis ofNANOS3in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lys mutation inNANOS3was identified in two sisters with primary amenorrhea. The substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 andin silicomolecular modelling suggests destabilization of protein-RNA interaction.In vitroanalyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. The identification of an inactivating missense mutation inNANOS3suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology.

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