Subfertility

Recent Advances in Management and Prevention

Rehana Rehman, Aisha Sheikh

• Publisher: Elsevier
• Year: 2020
• ISBN:
  9780323759465
• Topic: Medizin
• Subtopic: Gynäkologie, Geburtshilfe & Hebammen

With the increased prevalence of subfertility(any form of reduced fertility with prolonged time of unwanted non-conception) and the numberofsubfertilepatients turning to assisted reproductive clinics for help, Subfertility: Recent Advances for Management and Preventionisa much-neededresource for today's health care providers.Written by doctors with extensive expertise in the areas of reproductive physiology and endocrinology, it provides adescription of the methods for achieving conception, an overview of the causes of subfertility and how to detect them, a review of the psychological impact of subfertility, guidelines for the treatment of subfertility, and a look at assisted reproductive technologies.

• rovides aholistic approach to the causes and treatment of subfertility, with guidance on selecting patientson the basis ofovarian reserve/sperm parameters and the management of special endocrine abnormalities likepolycysticovariansyndrome, endometriosis, and thyroid disorders.
  
  

• Offers a concisereview of the most recent advances for improving assisted reproductive techniques.
  
  

• Coversreproductive physiology and the causes of subfertility, with special focus on endocrine abnormalities that lead to subfertility.
  
  

• Consolidates today's available information on this timely topic into a single, convenient resource.
  
  

Chapter 1: Anatomy and embryology of male and female reproductive systems

Ahmed Sayed Mettawi Clinical Nutrition Service, 6th of October University Hospital, 6th of October City, Giza, Egypt

Abstract

This chapter provides a review of the clinically relevant anatomy and embryology of the reproductive systems of both males and females.

Keywords

Anatomy; Embryology; Congenital anomalies; Internal genitalia; External genitalia; Genital; Urogenital; Reproductive

Chapter outline

• Embryology of the male and female reproductive systems
  • Germ cell specification
  • Germ cell migration and the concurrent genital ridge development
  • The indifferent stage, the bipotential gonad, and the gonadal differentiation
    • Gonadal relocation and descent
  • Sexual duct differentiation
  • External genitalia and other accessory glands differentiation
• Anatomy of the male reproductive system
  • Testes and spermatogenesis
    • Microstructure
    • Spermatogenesis
    • Vascular supply, neural supply, and lymphatic drainage
  • The epididymis
  • The vas deferens
  • The accessory glands
  • The penis
    • Vascular supply, neural supply, and lymphatic drainage
  • The scrotum
• Anatomy of the female reproductive system
  • The ovaries
    • Microstructure
    • Vascular supply, neural supply, and lymphatic drainage
  • Upper genital tract (uterus, cervix, and fallopian tubes)
    • Vascular supply, neural supply, and lymphatic drainage
  • The vagina
    • Vascular supply, neural supply, and lymphatic drainage
  • The vulva
• References

Embryology of the male and female reproductive systems

Embryonic sexual differentiation is a very delicate process (Fig. 1.1) that starts with the genotypic determination at the time of fertilization (i.e., XY or XX) and then concludes in a manner that depends on how the gametes influence the phenotype (i.e., culminating in final pubertal and brain development events).¹ It is worth noting that most information—especially information pertaining to genetics—have been derived from mouse models since studies on human tissues are few in number and also since it has been pointed out that the developmental stages and global gene expression of both species are comparable [i.e., few exceptions exist like how SOX2 (sex-determining region Y-box 2) and SOX17 are two different transcription factors utilized by the primordial germ cells (PGCs) of the mouse and human species, respectively].^2,3 Sex determination has long been thought to have a predetermined default path toward a final female phenotype in the absence of the influence of the male pathway steering factors; however, recent data indicate that not only does the alternative sex development pathway need continuous active repression during the embryonic life but also that it might need to remain actively repressed for life.^4,5 Table 1.1 outlines the possible genetic errors that can disrupt such a delicate process at different stages.

Fig. 1.1 Sexual differentiation timetable and the genetic determinants needed for the development of primordial gonads and tracts. Sexual differentiation timetable (A) and the genetic determinants needed for the development of primordial gonads and tracts (B). Dax1, dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1; Emx2, empty spiracles homeobox 2; Gata4, GATA-binding protein 4; Lhx1 or 9, homeobox protein Lim-1 or 9; Pax2 or 8, paired box 2 or 8; Sf1, steroidogenic factor-1; Wnt4, wingless-type MMTV integration site member 4; Wt1, Wilms’ tumor 1. Reproduced with permission from Arboleda VA, Quigley CA, Vilain E. Chapter 118—Genetic basis of gonadal and genital development. In: Jameson JL, De Groot LJ, de Kretser DM, et al., eds. Endocrinology: Adult and Pediatric. 7th ed. Philadelphia: Elsevier Saunders; 2016:2051–2085.e7 [Figure 118-6].

Table 1.1

Genetic factors with possible roles in sexual determination or differentiation.

Gene name or pseudonyms	Human gene locus	Protein name	Protein type	Genetic or cellular targets of factors	Action of factors	Effects of overexpression or underexpression of gene
Factors involved in both ovary and testis sex determinations
SF1* NR5A1 FTZF1 Ad4BP	9q33	SF1	Orphan nuclear receptor/zinc finger transcription factor	WT1, SRY, SOX9, DAX1, GNRHR, LHβ, ACTHR, AMH, AMHR, STAR, CYP11A1, CYP21A2, CYP11B1, OXT, and others	Activates transcription of many genes in the development of gonads, adrenal glands; regulates steroidogenesis; synergizes with WT1; antagonizes; DAXi. Dose-dependent activity.	KO mice (XX and XY): no gonads or adrenals; retained Müllerian structures; abnormal hypothalamus. Haploinsufficient mice: reduced but not absent adrenal function Homozygous human mutation: 46,XY sex reversal and adrenal hypoplasia Heterozygous human mutation: 46,XX normal ovary, partial adrenal insufficiency
WT1*	11p13	WT1	Zinc finger transcription factor; tumor repressor	DAX1, AMH, SRY, IGF2I, IGF1R, PDGFA, PAX2	Represses transcription; activates transcription of SRY; dose-dependent effects	XY homozygous deletion of WT1 + KTS isoform: male-to-female sex reversal; XY homozygous deletion of WT1 + KTS isoform: streak gonads in XX and XY. Human Denys–Drash syndrome: gonadal dysgenesis, congenital nephropathy, Wilms’ tumor
GATA4*	8p23.1-p22	GATA4	Zinc finger transcription factor	“GATA” DNA motif; AMH; genes encoding steroidogenic enzymes	Expressed early in both ovary and testis; interacts with FOG2	KO mice: embryonic lethal, no gonadal phenotype reported. Most human mutations cause isolated cardiac defects. Rare cases are reported with both cardiac defects and 46,XY gonadal dysgenesis
CBX2*	17q25.3	CBX2	Transcription repressor	Possibly ...