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Article ; Online: Oocyte in vitro maturation: physiological basis and application to clinical practice.

Gilchrist, Robert B / Smitz, Johan

2023 Volume 119, Issue 4, Page(s) 524–539

Abstract: Oocyte in vitro maturation (IVM) is an assisted reproductive technology with a long and sometimes checked history. It is a minimally invasive technique involving the deliberate collection of immature oocytes from patients that have received no or minimal ...

Abstract	Oocyte in vitro maturation (IVM) is an assisted reproductive technology with a long and sometimes checked history. It is a minimally invasive technique involving the deliberate collection of immature oocytes from patients that have received no or minimal ovarian stimulation and the culture of oocytes to maturity in vitro, before standard procedures thereafter. Now, IVM is classified as nonexperimental and is primarily indicated for patients with a high antral follicle count, especially patients with polycystic ovaries or polycystic ovary syndrome, as well as for fertility preservation in cancer patients. In the recent past, IVM practice has had a confusing array of clinical protocols and has been slow to adapt to new scientific insights; however, recently, significant advances have been made in IVM culture methods based on new knowledge from animal studies, combined with defining a simple patient treatment protocol. These improvements have led to significant recent progress in IVM practice to the extent that IVM is now routinely practiced in a growing number of centers with specialized expertise around the world.
MeSH term(s)	Female ; Animals ; Humans ; In Vitro Oocyte Maturation Techniques/methods ; Oocytes ; Reproductive Techniques, Assisted ; Fertility Preservation ; Ovulation Induction ; Polycystic Ovary Syndrome/diagnosis
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80133-1
ISSN	1556-5653 ; 0015-0282
ISSN (online)	1556-5653
ISSN	0015-0282
DOI	10.1016/j.fertnstert.2023.02.010
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Article ; Online: Influence of human chorionic gonadotrophin during ovarian stimulation: an overview.

Smitz, Johan / Platteau, Peter

Reproductive biology and endocrinology : RB&E

2020 Volume 18, Issue 1, Page(s) 80

Abstract: It is widely known that luteinising hormone (LH) and human chorionic gonadotrophin (hCG) are integral in the female reproductive lifecycle. Due to the common binding site and similarity in molecular structure, they were previously thought to have ... ...

Abstract	It is widely known that luteinising hormone (LH) and human chorionic gonadotrophin (hCG) are integral in the female reproductive lifecycle. Due to the common binding site and similarity in molecular structure, they were previously thought to have overlapping roles. However, with the development of both purified urinary-derived and recombinant gonadotrophins, the individual characteristics of these molecules have begun to be defined. There is evidence to suggest that LH and hCG preferentially activate different signalling cascades and display different receptor-binding kinetics. The data generated on the two molecules have led to an improved understanding of their distinct physiological functions, resulting in a debate among clinicians regarding the most beneficial use of LH- and hCG-containing products for ovarian stimulation (OS) in assisted reproductive technologies (ARTs). Over the past few decades, a number of trials have generated data supporting the use of hCG for OS in ART. Indeed, the data indicated that hCG plays an important role in folliculogenesis, leads to improved endometrial receptivity and is associated with a higher quality of embryos, while presenting a favourable safety profile. These observations support the increased use of hCG as a method to provide LH bioactivity during OS. This review summarises the molecular and functional differences between hCG and LH, and provides an overview of the clinical trial data surrounding the use of products for OS that contain LH bioactivity, examining their individual effect on outcomes such as endometrial receptivity, oocyte yield and embryo quality, as well as key pregnancy outcomes.
MeSH term(s)	Chorionic Gonadotropin/pharmacology ; Chorionic Gonadotropin/therapeutic use ; Female ; Humans ; Infertility/epidemiology ; Infertility/therapy ; Male ; Ovulation Induction/methods ; Pregnancy ; Pregnancy Outcome/epidemiology ; Reproductive Techniques, Assisted/statistics & numerical data ; Treatment Outcome
Chemical Substances	Chorionic Gonadotropin
Language	English
Publishing date	2020-08-06
Publishing country	England
Document type	Journal Article ; Review
ISSN	1477-7827
ISSN (online)	1477-7827
DOI	10.1186/s12958-020-00639-3
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Article ; Online: Mouse oocytes restore antral stage partial mechanical denudation in vitro.

Herta, Anamaria-Cristina / Akin, Nazli / Segers, Ingrid / Billooye, Katy / Smitz, Johan / Anckaert, Ellen

Reproduction (Cambridge, England)

2023 Volume 166, Issue 6, Page(s) 369–381

Abstract: In brief: Partially denuded mouse cumulus-oocyte complexes restore likely functional transzonal projections in culture, under meiotic inhibition, with no detectable impact on oocyte competence. This proof-of-concept study constitutes positive premises ... ...

Abstract	In brief: Partially denuded mouse cumulus-oocyte complexes restore likely functional transzonal projections in culture, under meiotic inhibition, with no detectable impact on oocyte competence. This proof-of-concept study constitutes positive premises for improving the developmental competence of human capacitation (CAPA)-in vitro maturation (IVM) oocytes with inadequate somatic cell connections. Abstract: In vitro oocyte culture might be the sole option for fertility preservation in some patients. This relies on constant oocyte-somatic bidirectional communication, and its precocious disruption alters oocyte competence. In non-human chorionic gonadotropin-triggered human in vitro maturation (IVM), retrieval of cumulus-oocyte complexes (COCs) by needle aspiration from the targeted small follicles (2-8 mm) leads to the collection of some partially denuded (PD) COCs with poor developmental competence. Hypothetically, re-establishing connectivity in these COCs could rescue oocyte quality. To test this, we used a well-characterized mouse preantral follicle culture system. On day 8, at antral stage, in part of the follicles, the oocytes were mechanically denuded while in other follicles in vitro grown oocytes were replaced with age matched fully stripped in vivo grown ones. The denuded oocytes were cultured on top of the somatic compartment until day 12, when oocyte-somatic reconnection was assessed. Furthermore, to better mimic the current biphasic IVM setup, fully surrounded (FS) COCs were collected from 19- to 21- day-old unprimed mice. Following partial mechanical denudation, COCs were cultured under meiotic inhibition for 2-4 days, to test oocyte-cumulus cell (CC) reconnection. Meiotic and developmental competence endpoints were compared between reconnected and FS-cultured COCs. We concluded that (i) in vivo- and in vitro- grown antral oocytes reconnect with in vitro-grown somatic companions; (ii) PD-COCs restore the FS morphology in culture, under meiotic inhibition; and (iii) oocyte quality from reconnected and intact cultured COCs is comparable. These observations encourage translational work to rescue partially denuded oocytes in human IVM.
MeSH term(s)	Female ; Humans ; Animals ; Mice ; Ovarian Follicle ; In Vitro Oocyte Maturation Techniques ; Oocytes ; Meiosis ; Cumulus Cells
Language	English
Publishing date	2023-10-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-23-0191
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Article ; Online: The Role of Mitochondria in Oocyte Maturation.

Kirillova, Anastasia / Smitz, Johan E J / Sukhikh, Gennady T / Mazunin, Ilya

Cells

2021 Volume 10, Issue 9

Abstract: With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of ... ...

Abstract	With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for continuous transcription and translation, the availability of the right number of functional mitochondria is crucial. There is a correlation between the quality of oocytes and both the amount of mtDNA and the amount of ATP. Suboptimal conditions of in vitro maturation (IVM) might lead to changes in the mitochondrial morphology as well as alternations in the expression of genes encoding proteins associated with mitochondrial function. Dysfunctional mitochondria have a lower ability to counteract reactive oxygen species (ROS) production which leads to oxidative stress. The mitochondrial function might be improved with the application of antioxidants and significant expectations are laid on the development of new IVM systems supplemented with mitochondria-targeted reagents. Different types of antioxidants have been tested already on animal models and human rescue IVM oocytes, showing promising results. This review focuses on the recent observations on oocytes' intracellular mitochondrial distribution and on mitochondrial genomes during their maturation, both in vivo and in vitro. Recent mitochondrial supplementation studies, aiming to improve oocyte developmental potential, are summarized.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Humans ; Mitochondria/physiology ; Oocytes/cytology ; Oocytes/physiology ; Oogenesis ; Oxidative Stress ; Reactive Oxygen Species/metabolism
Chemical Substances	Antioxidants ; Reactive Oxygen Species
Language	English
Publishing date	2021-09-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10092484
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Article ; Online: Genome-wide assessment of DNA methylation alterations induced by superovulation, sexual immaturity and in vitro follicle growth in mouse blastocysts.

Saucedo-Cuevas, Laura / Ivanova, Elena / Herta, Anamaria-Cristina / Krueger, Felix / Billooye, Katy / Smitz, Johan / Kelsey, Gavin / Anckaert, Ellen

Clinical epigenetics

2023 Volume 15, Issue 1, Page(s) 9

Abstract: Background: In their attempt to fulfill the wish of having children, women who suffer from fertility issues often undergo assisted reproductive technologies such as ovarian stimulation, which has been associated with adverse health outcomes and ... ...

Abstract	Background: In their attempt to fulfill the wish of having children, women who suffer from fertility issues often undergo assisted reproductive technologies such as ovarian stimulation, which has been associated with adverse health outcomes and imprinting disorders in children. However, given the crucial role of exogenous hormone stimulation in improving human infertility treatments, a more comprehensive analysis of the potential impacts on DNA methylation in embryos following ovarian stimulation is needed. Here, we provide genome-wide DNA methylation profiles of blastocysts generated after superovulation of prepubertal or adult mice, compared with blastocysts derived from non-stimulated adult mice. Additionally, we assessed the impact of the in vitro growth and maturation of oocytes on methylation in blastocysts. Results: Neither hormone stimulation nor sexual maturity had an impact on the low global methylation levels characteristic of the blastocyst stage or was associated with extensive DNA methylation alterations. However, we found hormone- and age-associated changes at specific positions but dispersed throughout the genome. In particular, we detected anomalous methylation at a limited number of CpG islands. Additionally, superovulation in adult mice was associated with alterations at the Sgce and Zfp777 imprinted genes. On the other hand, in vitro culture of follicles from the early pre-antral stage was associated with globally reduced methylation and increased variability at imprinted loci in blastocysts. Conclusions: Our results indicate a minimal effect of ovarian stimulation of adult and prepubertal mice on the DNA methylation landscape attained at the blastocyst stage, but potentially greater impacts of in vitro growth and maturation of oocytes. These findings have potential significance for the improvement of assisted reproductive techniques, in particular for those related to treatments in prepubertal females, which could be crucial for improving human fertility preservation strategies.
MeSH term(s)	Animals ; Female ; Mice ; Blastocyst/metabolism ; DNA Methylation ; Hormones/metabolism ; Oocytes/metabolism ; Superovulation
Chemical Substances	Hormones
Language	English
Publishing date	2023-01-16
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-023-01421-z
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Article ; Online: Non-invasive cumulus cell analysis can be applied for oocyte ranking and is useful for countries with legal restrictions on embryo generation or freezing.

Adriaenssens, Tom / Van Vaerenbergh, Inge / Van Landuyt, Lisbet / Verheyen, Greta / De Brucker, Michaël / Camus, Michel / Platteau, Peter / De Vos, Michel / Reis, Maria / Van Hecke, Elien / Rosenthal, André / Smitz, Johan

PloS one

2024 Volume 19, Issue 1, Page(s) e0297040

Abstract: Research question: Can a strategy for scoring oocyte quality, based on cumulus cell (CC) gene expression, prioritize oocytes with the highest implantation potential, while limiting the number of embryos to be processed in culture and the number of ... ...

Abstract	Research question: Can a strategy for scoring oocyte quality, based on cumulus cell (CC) gene expression, prioritize oocytes with the highest implantation potential, while limiting the number of embryos to be processed in culture and the number of supernumerary embryos to be vitrified? Design: An interventional, blinded, prospective cohort study was retrospectively analyzed. In the original study, patients underwent a fresh Day3 single embryo transfer with embryos ranked based on morphology and CC gene expression (Aurora Test). The additional ranking of the embryos with the Aurora Test resulted in significant higher clinical pregnancy and live birth rates. Now it is investigated if the Aurora Test ranking could be applied to select oocytes. The effect of an Aurora Test based restriction to 2 and 3 2PN or MII oocytes on clinical pregnancy and other outcomes, was analyzed in two subsets of patients with all 2PN (n = 83) or all MII oocytes (n = 45) ranked. Results: Considering only the top three ranked 2PN oocytes, 95% of the patients would have received a fresh SET on Day3 resulting in 65% clinical pregnancies. This was not different from the pregnancy rate obtained in a strategy using all oocytes but significantly reduced the need for vitrification of supernumerary embryos by 3-fold. Considering only top-ranked MII oocytes gave similar results. Conclusions: In countries with legal restrictions on freezing of embryos, gene expression of CC can be used for the selective processing of oocytes and would thus decrease the twin pregnancy rate and workload, especially for embryo morphology scoring and transfers as the handling and processing of lower competence oocytes is prevented, while improving the ART outcome.
MeSH term(s)	Pregnancy ; Female ; Humans ; Freezing ; Retrospective Studies ; Prospective Studies ; Embryo Transfer ; Cumulus Cells/metabolism ; Oocytes/metabolism ; Pregnancy Rate ; Vitrification ; Cryopreservation/methods
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0297040
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Article ; Online: Redox Biology of Human Cumulus Cells: Basic Concepts, Impact on Oocyte Quality, and Potential Clinical Use.

von Mengden, Lucia / Klamt, Fabio / Smitz, Johan

Antioxidants & redox signaling

2019 Volume 32, Issue 8, Page(s) 522–535

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Animals ; Antioxidants/metabolism ; Biology/methods ; Cumulus Cells/metabolism ; Cumulus Cells/physiology ; Female ; Fertilization in Vitro/methods ; Humans ; Oocytes/metabolism ; Oocytes/physiology ; Oxidation-Reduction ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism
Chemical Substances	Antioxidants ; Reactive Oxygen Species
Language	English
Publishing date	2019-12-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2019.7984
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Article ; Online: In vitro

Herta, Anamaria C / Lolicato, Francesca / Smitz, Johan E J

Reproduction (Cambridge, England)

2018 Volume 156, Issue 1, Page(s) F59–F73

Abstract: The currently available assisted reproduction techniques for fertility preservation (i.e. ...

Abstract	The currently available assisted reproduction techniques for fertility preservation (i.e.
MeSH term(s)	Female ; Fertility Preservation/methods ; Fertilization in Vitro/methods ; Humans ; In Vitro Oocyte Maturation Techniques/methods ; Ovarian Follicle/cytology ; Vitrification
Language	English
Publishing date	2018-06-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-18-0173
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Article ; Online: Protective Effects of Antioxidants on Cyclophosphamide-Induced Ovarian Toxicity.

Barberino, Ricássio S / Silva, Regina Lucia S / Palheta Junior, Raimundo C / Smitz, Johan E J / Matos, Maria Helena T

Biopreservation and biobanking

2022 Volume 21, Issue 2, Page(s) 121–141

Abstract: The most common limitation of anticancer chemotherapy is the injury to normal cells. Cyclophosphamide, which is one of the most widely used alkylating agents, can cause premature ovarian insufficiency and infertility since the ovarian follicles are ... ...

Abstract	The most common limitation of anticancer chemotherapy is the injury to normal cells. Cyclophosphamide, which is one of the most widely used alkylating agents, can cause premature ovarian insufficiency and infertility since the ovarian follicles are extremely sensitive to their effects. Although little information is available about the pathogenic mechanism of cyclophosphamide-induced ovarian damage, its toxicity is attributed to oxidative stress, inflammation, and apoptosis. The use of compounds with antioxidant and cytoprotective properties to protect ovarian function from deleterious effects during chemotherapy would be a significant advantage. Thus, this article reviews the mechanism by which cyclophosphamide exerts its toxic effects on the different cellular components of the ovary, and describes 24 cytoprotective compounds used to ameliorate cyclophosphamide-induced ovarian injury and their possible mechanisms of action. Understanding these mechanisms is essential for the development of efficient and targeted pharmacological complementary therapies that could protect and prolong female fertility.
MeSH term(s)	Female ; Humans ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Cyclophosphamide/adverse effects ; Ovarian Follicle ; Primary Ovarian Insufficiency/chemically induced ; Primary Ovarian Insufficiency/prevention & control ; Primary Ovarian Insufficiency/pathology
Chemical Substances	Antioxidants ; Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2022-06-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2593993-2
ISSN	1947-5543 ; 1947-5535
ISSN (online)	1947-5543
ISSN	1947-5535
DOI	10.1089/bio.2021.0159
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Article ; Online: Luteinizing hormone and human chorionic gonadotropin: a review of their varied clinical applications in assisted reproductive technology.

Choi, Janet / Smitz, Johan

Expert review of endocrinology & metabolism

2014 Volume 10, Issue 1, Page(s) 87–100

Abstract: Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are often viewed as interchangeable from a functional standpoint because they are highly homologous members of the same glycoprotein hormone family that share a common α-subunit and receptor. ...

Abstract	Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are often viewed as interchangeable from a functional standpoint because they are highly homologous members of the same glycoprotein hormone family that share a common α-subunit and receptor. However, technological advances yielding highly purified and recombinant gonadotropin preparations have revealed that LH and hCG fulfill different roles, both endogenously and when administered exogenously. These differences are becoming more apparent as the individual hormones are incorporated into the treatment of infertility - a therapeutic area that is continually advancing with the introduction of new agents and emerging clinical trial data. This review examines the unique attributes of LH and hCG that drive their distinctive applications in the treatment of female infertility.
Language	English
Publishing date	2014-11-24
Publishing country	England
Document type	Journal Article
ISSN	1744-8417
ISSN (online)	1744-8417
DOI	10.1586/17446651.2015.969711
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