The Root of Reduced Fertility in Aged Women and Possible Therapentic Options: Current Status and Future Perspects

Molecular Aspects of Medicine 38 (2014) 54–85

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Molecular Aspects of Medicine

journal homepage: www.elsevier.com/locate/mam

Review The root of reduced fertility in aged women and possible therapentic options: Current status and future perspects

Jie Qiao a,1, Zhen-Bo Wang b,1, Huai-Liang Feng c,1, Yi-Liang Miao d, Qiang Wang e, Yang Yu a, Yan-Chang Wei b, Jie Yan a, Wei-Hua Wang f, Wei Shen g, Shao-Chen Sun h, Heide Schatten i, ⇑ Qing-Yuan Sun b, a Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, People’s Republic of China b State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China c Department of Laboratory Medicine, and Obstetrics and Gynecology, New York Hospital Queens, Weill Medical College of Cornell University, New York, NY, USA d Reproductive Medicine Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA e Department of Obstetrics and Gynecology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110, USA f Houston Fertility Institute, Tomball Regional Hospital, Tomball, TX 77375, USA g Laboratory of Germ Cell Biology, Department of Animal Science, Qingdao Agricultural University, Qingdao 266109, People’s Republic of China h Department of Animal Science, Nanjing Agricultural University, Nanjing 210095, People’s Republic of China i Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA article info abstract

Article history: It is well known that maternal ageing not only causes increased spontaneous abortion and Available online 21 June 2013 reduced fertility, but it is also a high genetic disease risk. Although assisted reproductive technologies (ARTs) have been widely used to treat infertility, the overall success is still Keywords: low. The main reasons for age-related changes include reduced follicle number, compro- Infertility mised oocyte quality especially aneuploidy, altered reproductive endocrinology, and Maternal age increased reproductive tract defect. Various approaches for improving or treating infertility Oocyte in aged women including controlled ovarian hyperstimulation with intrauterine insemina- Ovary tion (IUI), IVF/ICSI-ET, ovarian reserve testing, preimplantation genetic diagnosis and Assited reproductive technology screening (PGD/PGS), oocyte selection and donation, oocyte and ovary tissue cryopreservation before ageing, miscarriage prevention, and caloric restriction are summarized in this review. Future potential reproductive techniques for infertile older women including oocyte and zygote micromanipulations, derivation of oocytes from germ stem cells, ES cells, and iPS cells, as well as through bone marrow transplantation are discussed. Ó 2013 Elsevier Ltd. All rights reserved.

Abbreviations: aCGH, array comparative genomic hybridization; AFC, antral follicle count; AMH, Anti-Müllerian hormone; ART, assisted reproductive technology; BMT, bone marrow transplantation; CC, clomiphene citrate; CGH, comparative genomic hybridization; Dnmt, DNA methyltransferase; FISH, ﬂuorescence in situ hybridization; FSH, follicle-stimulating hormone; DHEA, dehydroepiandrosterone; E2, estradiol; GnRH, gonadotropin-releasing hormone; GV, germinal vesicle; hCG, human chorionic gonadotrophin; HSG, hysterosalpingogram; ICSI, intracytoplasmic sperm injection; IUI, intrauterine insemination; IVF/ICSI-ET, in vitro fertilization/fertilization/embryo transfer; IVIG, intravenous immuno globulin; LDA, low-dose aspirin; LH, luteinzing hormone; MCL, menstrual cycle length; OSCs, oogonial stem cells; P, progesterone; PBD, polar body diagnosis; PGCs, primordial germ cells; PGD/PGS, preimplantation genetic diagnosis and screening; PLI, paternal leukocyte immunization; PZD, partial zona dissection; PR, progesterone receptor; PTEN, phosphatase and tensin homolog; SCNT, somatic cell nuclear transfer; SAC, spindle assembly checkpoint; SC, synaptonemal complex; SMC, structural maintenance of chromosomes; SNP, single nucleotide polymorphism; VEGF, vascular endothelial growth factor. ⇑ Corresponding author. Address: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, #1Beichen West Rd., Chaoyang, Beijing 100101, People’s Republic of China. Tel./fax: +86 10 64807050. E-mail addresses: [email protected], [email protected] (Q.-Y. Sun). 1 These authors equally contributed to this work.

Contents

1. Introduction ...... 55 2. Reasons for fertility impairment with maternal ageing...... 56 2.1. Follicle number decreases with maternal ageing ...... 56 2.2. Endocrine factors causing low fertility ...... 57 2.3. Reproductive tract factors related to infertility...... 57 2.4. Embryo quality decreases with maternal ageing ...... 59 2.5. Poor oocyte quality dominantly affects embryo quality ...... 59 2.5.1. Oocyte aneuplidy increases with maternal ageing ...... 59 2.5.2. Why is oocyte aneuploidy increased with maternal ageing? ...... 60 2.5.3. Ooplasmic quality is compromised with maternal ageing: mitochondria dysfunction in aged oocytes ...... 60 2.5.4. Loss of oocyte polarity in aged oocytes...... 61 2.6. Epigenetic and imprinting gene alterations in oocytes with maternal ageing ...... 61 3. Possible treatments and improvement of age-related infertility in women...... 63 3.1. Controlled ovarian hyperstimulation with intrauterine insemination ...... 63 3.2. Ovarian reserve testing ...... 63 3.2.1. Histological assessment of ovarian reserve...... 64 3.2.2. Ovarian reserve assesement by endocrine factors ...... 64 3.2.3. Ultrasound markers of ovarian reserve ...... 64 3.2.4. Ovarian stimulating tests ...... 64 3.3. Prevention of miscarriage ...... 64 3.3.1. Progesterone administration ...... 65 3.3.2. Human chorionic gonadotropin (hCG) administration ...... 65 3.3.3. Immunotherapy ...... 65 3.3.4. The use of aspirin and heparin ...... 65 3.4. In vitro fertilization/intracytoplasmic sperm injection and embryo transfer...... 65 3.5. Preimplantation genetic diagnosis (PGD) and screening (PGS) ...... 66 3.6. Polar body diagnosis (PBD)...... 66 3.7. Oocyte donation ...... 68 3.8. Imaging of human oocytes by the Polscope ...... 68 3.9. Oocyte and ovary tissue cryopreservation before maternal ageing ...... 69 3.9.1. Oocyte cryopreservation before maternal ageing ...... 69 3.9.2. Ovary tissue cryopreservation before maternal ageing ...... 70 3.10. Caloric restriction improves ageing-associated low fertility...... 71 4. Potential future techniques that may rescue female infertility...... 71 4.1. Manipulation of oocytes in assisted reproduction ...... 71 4.1.1. Cytoplasmic injection and mitochondria transfer...... 71 4.1.2. GV transfer ...... 72 4.1.3. Spindle-chromosomal complex transfer ...... 72 4.2. Zygote manipulation ...... 73 4.3. Stem cells: derivation and differentiation of oocytes ...... 73 4.3.1. Oogonial stem cells or germ stem cells in the ovary ...... 73 4.3.2. Derivation of oocytes from ES cells ...... 74 4.3.3. Differentiation of oocytes from iPS cells ...... 75 4.3.4. Bone marrow transplantation and fertility recovery ...... 75 5. Concluding summary and future perspectives ...... 76 Acknowledgment ...... 76 Reference ...... 76

1. Introduction

With the world’s industrialization, more and more women postphone marriage, childbearing and first birth due to their career priorities, advanced education, contraception, artificial abortion, and financial concerns. The number of women bear- ing children in their 30- and 40-year age range is clearly increased which is the age range when female fertility is signifi- cantly decreased. It has been predicted that the likelihood of infertility of a woman at age 35 is just below 20%; at age 40 it is about 40%; and at age 45 it is 80% (Jansen, 1984). It is estimated that about 50% of the early embryos undergo miscarriage before or directly after implantation, and in such cases women are not aware of being physiologically pregnant. After pregnancy is established, about 15% of the clinical preg- nancies terminate by miscarriage, usually in the first trimester (Jones and Lopez, 2006). The risk of miscarriage increases sig- nificantly with advancing maternal age. Several studies have shown an increase in the risk of spontaneous abortion in Download English Version: https://daneshyari.com/en/article/1995661

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