The use of ovarian reserve biomarkers to tailor ovarian stimulation for in vitro fertilization
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
The molecular mechanisms regulating the recruitment of non-growing follicles and selection for continued growth versus atresia continue to be elucidated. Several key concepts are relevant to the present analysis (16). Firstly, recruitment of primordial follicles occurs across the reproductive lifespan (17). This dynamic process with differential rates of follicular activation at different ages is necessary in order to have a continuous supply of growing follicles to support the selection processes that precede ovulation (18) and is probably influenced by health status. Secondly, follicles undergo atresia at all stages of development (19). Thirdly, the number of activated follicles reflects the total pool of primordial follicles in a variable manner, with markedly different correlation coefficients in childhood and adult life (20). Lastly, ovarian reserve depletion will depend on the initial quantity of primordial follicles and the rate of primordial follicle recruitment. Collectively, this means that although in adult life biomarkers of activated follicles such as AMH and AFC can potentially reflect the primordial follicle pool (21), their greatest strength and value will be in indicating the number of follicles that are at late stages of follicular development and capable of responding to exogenous gonadotropins. Thus, AMH and AFC are of greatest value in reflecting what has been termed the functional rather than the true ovarian reserve (22).
Hemorrhagic and Ruptured Ovarian Cysts and Acute Complications of Uterine Fibroids
Botros Rizk, A. Mostafa Borahay, Abdel Maguid Ramzy in Clinical Diagnosis and Management of Gynecologic Emergencies, 2020
The exact etiology of cyst rupture is not clear; however, the increased vascularity in the luteal phase may predispose the corpus luteal cyst to rupture [4]. The ovary has an outer cortex rich in primordial follicles and an inner vascular medulla. Under the influence of hormonal changes during the ovarian cycle, the avascular granulosa cells and stromal cells are vascularized. At the time of ovulation, the LH surge leads to Graafian follicle rupture, resulting in mid-cycle pain commonly referred as mittelschmerz pain, thought to be due to release of fluid in the peritoneal cavity. The corpus luteum is formed from the ruptured leading follicle. The stromal cells are luteinized, and the granulosa cell layer becomes vascularized. The vessels within the corpus luteum wall are thin and tend to bleed, forming a hemorrhagic cyst. The ovary is surrounded by a thin connective tissue layer called the tunica albuginea. The ovarian tunica is thin and malleable, which then allows distention of the ovary by growing follicles. As the tunica distends, stretched blood vessels subsequently tear, resulting in an insignificant amount of bleeding. However, bleeding from larger vessels would result in much more substantial pain and would also result in hemoperitoneum [2, 5].
Regulation of fertility and infertility in humans
C. Yan Cheng in Spermatogenesis, 2018
In our present-day society, patients are seeking fertility later in life, and this impacts outcomes both for females and males with respect to fertility potential.183 Fertility as a function of age is commonly assessed, especially in the female population. Women are born with a set number of primordial follicles.184 As a consequence, increased age among women results in increased rates of infertility particularly after age 35.185 Men, on the other hand, continue active sperm production throughout life but do lose function with age.184 However, albeit controversial, some studies have identified an association of increased paternal age with increased sperm DNA fragmentation, epigenetic changes, reduced fertility beyond late 30s, and decreased ART successes.186 Additionally, paternal age greater than 45 is associated with risk of late fetal death.187 Increased paternal age has also been associated with cleft lip and palate and some childhood malignancies such as retinoblastoma188 and childhood acute lymphoblastic leukaemia.189 Schizophrenia, bipolar affective disorder, and autism have also been associated with increased paternal age.186 Effects of advanced paternal age are thoroughly reviewed in Sharma et al. 2015 for further reading.186
Chronic cholestasis is associated with hypogonadism and premature ovarian failure in adult rats (cholestasis causes ovarian hypogonadism)
Published in Ultrastructural Pathology, 2018
Hisopathology and immunohistochemistry: The ovaries were harvested on diestrus phase. Ovarian sections from the Sham group showed normal structure of a mature ovary. The ovary was covered by surface epithelium. The parenchyma was divided into two poorly demarcated zones: an outer cortical region containing ovarian follicles at different stages of development and an internal medullary region of loose connective tissue with many blood vessels. The ovarian follicles observed at the diestrus phase included primordial, primary, secondary, and antral follicles, besides large corpora lutea from previous cycles (Figure 2a, Table 3). The ovarian surface epithelium consisted of one layer of cuboidal cells. Primordial follicles were located near to the surface epithelium and defined as an oocyte surrounded by a layer of flattened cells. Primary follicles possessed an oocyte surrounded by a single layer of cuboidal granulosa cells. Secondary follicles were surrounded by 2–6 layers of cuboidal granulosa cells, with no visible antrum (Figure 2b). In antral follicles, the oocyte becomes surrounded by six or more layers of cuboidal granulosal cells with a fully formed thecal layer and an antral cavity (Figure 2c). Few atretic follicles were also noted, and were identified by possessing altered shape of the follicle or the oocyte. All follicular cells except those of the atretic follicles showed strong immunoreactivity for PCNA and ER within the cells of the zona granulosa (Figure 3a and 3b, Table 4).
The existence and potential of germline stem cells in the adult mammalian ovary
Published in Climacteric, 2019
The mammalian ovary is a highly dynamic organ that undergoes many structural and functional changes as it fulfills its two major roles of producing female gametes and the synthesis of sex steroids. In the human ovary, germ cells (oocytes) are formed during fetal life and they are enclosed within somatic cells (granulosa cells) to form primordial follicles. The primordial follicles consist of an oocyte, arrested at the diplotene (dictyate) stage of prophase I of meiosis, surrounded by a few flattened somatic cells (granulosa cells). For many years it has been assumed that there is a limited period during which oocytes can be formed and that the adult ovary has no capacity for germ cell renewal, and therefore primordial follicles represent a pool of oocytes that must last the woman throughout her reproductive lifespan (Figure 1).
Cyclophosphamide, a cancer chemotherapy drug-induced early onset of reproductive senescence and alterations in reproductive performance and their prevention in mice
Published in Drug and Chemical Toxicology, 2022
Vadakkepurath Raj Athira, Thimmappa Shivanandappa, Hanumant Narasinhacharya Yajurvedi
The mammalian ovary contains a stockpile of primordial follicles at the resting stage. Once entering the growing follicular pool, they mature and culminate in ovulation or undergo atresia at any stage of their development and the lost primordial follicles are not replenished (Greenwald and Roy 1994). Therefore the reproductive life span of a female individual depends on primordial follicular reserve from which a set of follicles start growing during each reproductive cycle (Pelosi et al. 2015) and once the reserve is exhausted the individual enters into a phase of reproductive senescence. Cyclophosphamide treatment causes degeneration of all categories of ovarian follicles (Shiromizu et al. 1984, Jarrell et al. 1987, Plowchalk and Mattison 1992, Davis and Heindel 1998, Meirow et al. 1999) in rats and mice, of which primordial follicles are the most vulnerable (Budel et al. 1988. Plowchalk and Mattison 1989, 1991, 1992. Meirow et al. 1999. Oktem and Oktay 2007). The drastic depletion of primordial follicle reserve following CP treatment limits the span of normal fertile period and causes premature reproductive senescence in women, often reported as premature menopause and infertility (Meirow and Nugent 2001). The results of our present study, for the first time, demonstrate possibility of normal reproductive life span despite CP treatment using a mouse model. The results are of great significance in cancer therapy with CP.
Related Knowledge Centers
- Menstrual Cycle
- Ovarian Follicle
- Ovary
- Ovulation
- Puberty
- Somatic Cell
- Spermatogenesis
- Oocyte
- Menopause
- Follicular Atresia