Journal of Clinical Medicine

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9 pages, 571 KiB

Open AccessArticle

Exploring the Developmental Potential of Human Germinal Vesicle Oocytes Aiming at Fertility Preservation: Can We Increase the Yields of Competent Oocytes through IVM Combined with Vitrification?

by Xia Hao, Jessie Phoon, Lina Barbunopulos, Mona Sheikhi, Arturo Reyes Palomares and Kenny A. Rodriguez-Wallberg

J. Clin. Med. 2022, 11(6), 1703; https://doi.org/10.3390/jcm11061703 - 19 Mar 2022

Viewed by 1599

Abstract

The rescue in vitro maturation (rIVM) of germinal vesicle oocytes (GVs) has been proposed to improve the total number of mature oocytes in women undergoing fertility preservation. Currently, there is no consensus about the clinical utility of this practice, and heterogeneity in the [...] Read more.

The rescue in vitro maturation (rIVM) of germinal vesicle oocytes (GVs) has been proposed to improve the total number of mature oocytes in women undergoing fertility preservation. Currently, there is no consensus about the clinical utility of this practice, and heterogeneity in the protocols used may influence the final outcomes. This study investigated the developmental potential of mature metaphase II (MII) human oocytes obtained from GVs after rIVM and the impact of applying vitrification at different timepoints either before or after rIVM. After randomization, oocytes were assigned to undergo rIVM and thereafter vitrification or intracytoplasmic sperm injection (ICSI), or to undergo direct vitrification-warming and thereafter rIVM and ICSI. The likelihood of obtaining MII oocytes was just slightly higher in the fresh rIVM group compared to the vitrification-warming-rIVM group. When comparing fresh rIVM that underwent subsequently ICSI, the fertilization and developmental rates up to the blastocyst stage were seen to be reduced in both groups that underwent vitrification either before or after rIVM. Although some blastocysts were obtained in the fresh rIVM-ICSI group, the efficacy of these methods was low overall, suggesting that the further development of protocols for IVM conducted early after denudation is needed to improve the final results of rIVM aiming at fertility preservation. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

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16 pages, 5774 KiB

Open AccessArticle

Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

by Ronald Peek, Lotte L. Eijkenboom, Didi D. M. Braat and Catharina C. M. Beerendonk

J. Clin. Med. 2021, 10(19), 4362; https://doi.org/10.3390/jcm10194362 - 24 Sep 2021

Cited by 2 | Viewed by 1521

Abstract

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. [...] Read more.

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing’s sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

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17 pages, 940 KiB

Open AccessArticle

Oocyte Vitrification for Fertility Preservation in Women with Benign Gynecologic Disease: French Clinical Practice Guidelines Developed by a Modified Delphi Consensus Process

by Blandine Courbiere, Enora Le Roux, Emmanuelle Mathieu d’Argent, Antoine Torre, Catherine Patrat, Christophe Poncelet, Jacques Montagut, Anne-Sophie Gremeau, Hélène Creux, Maëliss Peigné, Isabella Chanavaz-Lacheray, Lara Dirian, Xavier Fritel, Jean-Luc Pouly, Arnaud Fauconnier and on behalf of the PreFerBe Expert Panel

J. Clin. Med. 2021, 10(17), 3810; https://doi.org/10.3390/jcm10173810 - 25 Aug 2021

Cited by 6 | Viewed by 2801

Abstract

International guidelines are published to provide standardized information and fertility preservation (FP) care for adults and children. The purpose of the study was to conduct a modified Delphi process for generating FP guidelines for BGD. A steering committee identified 42 potential FP practices [...] Read more.

International guidelines are published to provide standardized information and fertility preservation (FP) care for adults and children. The purpose of the study was to conduct a modified Delphi process for generating FP guidelines for BGD. A steering committee identified 42 potential FP practices for BGD. Then 114 key stakeholders were asked to participate in a modified Delphi process via two online survey rounds and a final meeting. Consensus was reached for 28 items. Among them, stakeholders rated age-specific information concerning the risk of diminished ovarian reserve after surgery as important but rejected proposals setting various upper and lower age limits for FP. All women should be informed about the benefit/risk balance of oocyte vitrification—in particular about the likelihood of live birth according to age. FP should not be offered in rASRM stages I and II endometriosis without endometriomas. These guidelines could be useful for gynecologists to identify situations at risk of infertility and to better inform women with BGDs who might need personalized counseling for FP. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

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8 pages, 648 KiB

Open AccessArticle

Feasibility of Secondary Follicle Isolation, Culture and Achievement of In-Vitro Oocyte Maturation from Superovulated Ovaries: An Experimental Proof-of-Concept Study Using Mice

by Xia Hao, Amandine Anastácio and Kenny A. Rodriguez-Wallberg

J. Clin. Med. 2021, 10(13), 2757; https://doi.org/10.3390/jcm10132757 - 23 Jun 2021

Cited by 1 | Viewed by 1852

Abstract

Fertility preservation through ovarian stimulation, aiming at cryopreserving mature oocytes or embryos, is sometimes unsuccessful. This clinical situation deserves novel approaches to overcome infertility following cancer treatment in patients facing highly gonadotoxic treatment. In this controlled experimental study, we investigated the feasibility of [...] Read more.

Fertility preservation through ovarian stimulation, aiming at cryopreserving mature oocytes or embryos, is sometimes unsuccessful. This clinical situation deserves novel approaches to overcome infertility following cancer treatment in patients facing highly gonadotoxic treatment. In this controlled experimental study, we investigated the feasibility of in-vitro culturing secondary follicles isolated from superovulated ovaries of mice recently treated with gonadotropins. The follicle yields of superovulated ovaries were 45.9% less than in unstimulated controls. Follicles from superovulated ovaries showed faster growth pace during the initial 7 days of culture and secreted more 17β-estradiol by the end of culture vs controls. Parameters reflecting the outcome of follicular development and oocyte maturation competence in vitro were similar between superovulated and control groups, with a similar follicle size at the end of culture and around 70% survival. Nearly half of cultured follicles met the criteria for in-vitro maturation in both groups and approximately 60% of those achieved a mature MII oocyte, similarly in both groups. Over 60% of obtained MII oocytes displayed normal-looking spindle and chromosome configurations, without significant differences between the groups. Using a validated follicle culture system, we demonstrated the feasibility of secondary follicle isolation, in-vitro culture and oocyte maturation with normal spindle and chromosome configurations obtained from superovulated mice ovaries. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

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Review

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9 pages, 244 KiB

Open AccessReview

Uterus Transplantation: Revisiting the Question of Deceased Donors versus Living Donors for Organ Procurement

by Emily H. Frisch, Tommaso Falcone, Rebecca L. Flyckt, Andreas G. Tzakis, Eric Kodish and Elliott G. Richards

J. Clin. Med. 2022, 11(15), 4516; https://doi.org/10.3390/jcm11154516 - 03 Aug 2022

Cited by 4 | Viewed by 1303

Abstract

Uterus transplantation is a surgical treatment for women with congenital or acquired uterine factor infertility. While uterus transplantation is a life-enhancing transplant that is commonly categorized as a vascular composite allograft (e.g., face or hand), it is similar to many solid organ transplants [...] Read more.

Uterus transplantation is a surgical treatment for women with congenital or acquired uterine factor infertility. While uterus transplantation is a life-enhancing transplant that is commonly categorized as a vascular composite allograft (e.g., face or hand), it is similar to many solid organ transplants (e.g., kidney) in that both living donors (LDs) and deceased donors (DDs) can be utilized for organ procurement. While many endpoints appear to be similar for LD and DD transplants (including graft survival, time to menses, livebirth rates), there are key medical, technical, ethical, and logistical differences between these modalities. Primary considerations in favor of a LD model include thorough screening of donors, enhanced logistics, and greater donor availability. The primary consideration in favor of a DD model is the lack of physical or psychological harm to a living donor. Other important factors, that may not clearly favor one approach over the other, are important to include in discussions of LD vs. DD models. We favor a stepwise approach to uterus transplantation, one in which programs first begin with DD procurement before attempting LD procurement to maximize successful organ recovery and to minimize potential harms to a living donor. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

23 pages, 727 KiB

Open AccessReview

Female Oncofertility: Current Understandings, Therapeutic Approaches, Controversies, and Future Perspectives

by Kim Cat Tuyen Vo and Kazuhiro Kawamura

J. Clin. Med. 2021, 10(23), 5690; https://doi.org/10.3390/jcm10235690 - 03 Dec 2021

Cited by 8 | Viewed by 3129

Abstract

Recent advances in early detection and oncological therapies have ameliorated the survival rate of young cancer patients. Yet, ovarian impairment induced by chemotherapy and radiotherapy is still a challenging issue. This review, based on clinical and lab-based studies, summarizes the evidence of gonadotoxicity [...] Read more.

Recent advances in early detection and oncological therapies have ameliorated the survival rate of young cancer patients. Yet, ovarian impairment induced by chemotherapy and radiotherapy is still a challenging issue. This review, based on clinical and lab-based studies, summarizes the evidence of gonadotoxicity of chemoradiotherapy, the recent approaches, ongoing controversies, and future perspectives of fertility preservation (FP) in female patients who have experienced chemo- or radio-therapy. Existing data indicate that chemotherapeutic agents induce DNA alterations and massive follicle activation via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Meanwhile, the radiation causes ionizing damage, leading to germ cell loss. In addition to the well-established methods, numerous therapeutic approaches have been suggested, including minimizing the follicle loss in cryopreserved ovarian grafts after transplantation, in vitro activation or in vitro growing of follicles, artificial ovarian development, or fertoprotective adjuvant to prevent ovarian damage from chemotherapy. Some reports have revealed positive outcomes from these therapies, whereas others have demonstrated conflictions. Future perspectives are improving the live birth rate of FP, especially in patients with adverse ovarian reserve, eliminating the risk of malignancy reintroducing, and increasing society’s awareness of FP importance. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

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15 pages, 955 KiB

Open AccessReview

In Vitro Maturation of Oocytes Retrieved from Ovarian Tissue: Outcomes from Current Approaches and Future Perspectives

by Chloë De Roo and Kelly Tilleman

J. Clin. Med. 2021, 10(20), 4680; https://doi.org/10.3390/jcm10204680 - 13 Oct 2021

Cited by 17 | Viewed by 3313

Abstract

In vitro maturation (IVM) of transvaginally aspirated immature oocytes is an effective and safe assisted reproductive treatment for predicted or high responder patients. Currently, immature oocytes are also being collected from the contralateral ovary during laparoscopy/laparotomy and even ex vivo from the excised [...] Read more.

In vitro maturation (IVM) of transvaginally aspirated immature oocytes is an effective and safe assisted reproductive treatment for predicted or high responder patients. Currently, immature oocytes are also being collected from the contralateral ovary during laparoscopy/laparotomy and even ex vivo from the excised ovary or the spent media during ovarian tissue preparation prior to ovarian cortex cryopreservation. The first live births from in vitro-matured ovarian tissue oocytes (OTO-IVM) were reported after monophasic OTO-IVM, showing the ability to achieve mature OTO-IVM oocytes. However, fertilisations rates and further embryological developmental capacity appeared impaired. The introduction of a biphasic IVM, also called capacitation (CAPA)-IVM, has been a significant improvement of the oocytes maturation protocol. However, evidence on OTO-IVM is still scarce and validation of the first results is of utmost importance to confirm reproducibility, including the follow-up of OTO-IVM children. Differences between IVM and OTO-IVM should be well understood to provide realistic expectations to patients. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

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15 pages, 1019 KiB

Open AccessReview

Hot Topics on Fertility Preservation for Women and Girls—Current Research, Knowledge Gaps, and Future Possibilities

by Kenny A. Rodriguez-Wallberg, Xia Hao, Anna Marklund, Gry Johansen, Birgit Borgström and Frida E. Lundberg

J. Clin. Med. 2021, 10(8), 1650; https://doi.org/10.3390/jcm10081650 - 13 Apr 2021

Cited by 5 | Viewed by 4322

Abstract

Fertility preservation is a novel clinical discipline aiming to protect the fertility potential of young adults and children at risk of infertility. The field is evolving quickly, enriched by advances in assisted reproductive technologies and cryopreservation methods, in addition to surgical developments. The [...] Read more.

Fertility preservation is a novel clinical discipline aiming to protect the fertility potential of young adults and children at risk of infertility. The field is evolving quickly, enriched by advances in assisted reproductive technologies and cryopreservation methods, in addition to surgical developments. The best-characterized target group for fertility preservation is the patient population diagnosed with cancer at a young age since the bulk of the data indicates that the gonadotoxicity inherent to most cancer treatments induces iatrogenic infertility. Since improvements in cancer therapy have resulted in increasing numbers of long-term survivors, survivorship issues and the negative impact of infertility on the quality of life have come to the front line. These facts are reflected in an increasing number of scientific publications referring to clinical medicine and research in the field of fertility preservation. Cryopreservation of gametes, embryos, and gonadal tissue has achieved quality standards for clinical use, with the retrieval of gonadal tissue for cryopreservation being currently the only method feasible in prepubertal children. Additionally, the indications for fertility preservation beyond cancer are also increasing since a number of benign diseases and chronic conditions either require gonadotoxic treatments or are associated with premature follicle depletion. There are many remaining challenges, and current research encompasses clinical health care and caring sciences, ethics, societal, epidemiological, experimental studies, etc. Full article

(This article belongs to the Special Issue The State of the Art in Fertility Preservation for Adults and Children)

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