ANATOMY OF THE FEMALE REPRODUCTIVE SYSTEM
The human female reproductive system is composed of anatomical structures that must interact with hormones within a defined time-frame in order for conception, pregnancy, and birth to occur. The primary sex organs are the ovaries which produce oocytes and hormones, mainly estrogen and progesterone. The secondary sex organs are the external genitalia, vagina, uterus and fallopian tubes. Their function is to receive sperm, and to provide sites for fertilization, implantation and development of the embryo to term and parturition. The mammary glands provide nourishment for the young and may be considered accessory reproductive organs.
External genitalia
The vulva (or pudendum) is the collective term for all the visible external genital organs in the female. It consists of the mons pubis, labia majora, labia minora, hymen, clitoris, vestibule, urethra and Skene's and Bartholin's glands (see Figure 1.1).
The mons pubis is the subcutaneous fat pad overlying the symphysis pubis. The labia majora are two folds of fat pad and skin that have hair and sweat glands. The labia majora are homologous to the scrotum in the male. They act together with the labia minora as the gatekeeper into the vagina. The vulva is covered by keratinized stratified squamous epithelium. The labia minora are two folds of hairless skin with sweat glands that merge anteriorly to form the prepuce (covering of the clitoris) and serve to protect the vaginal and urethral openings. The labia minora are homologous to the penile urethra and part of the skin of the penis in males. The clitoris is a small cylindrical erectile body, situated in the most anterior part of the vulva. It is homologous to the penis in the male but it differs in being entirely separate from the urethra. It is attached to the under surface of the symphysis pubis by the suspensory ligament.
The vestibule is the triangular space bounded anteriorly by the clitoris, posteriorly by the fourchette and on either side by labia minora. The four openings into the vestibule are the urethral opening, the vaginal orifice and hymen, the opening of Bartholin's ducts, and the Skene's ducts openings in the vestibule on either side of the external urethral meatus. The vestibular bulbs are bilateral elongated masses of erectile tissues situated beneath the mucus membrane of the vestibule. Each bulb lies on either side of the vaginal orifice in front of the Bartholin's gland and is incorporated with the bulbocavernosus muscle. They are homologous to the bulb of the penis and corpus spongiosum in the male.
The external genitalia develop in the region of the cranial aspect of ectodermal cloacal fossa and form by the end of the 12th week of fetal development. The clitoris develops from the genital tubercle, the labia minora from the genital folds, the labia majora from the labioscrotal swelling and the vestibule from the urogenital sinus.
Internal genitalia
The internal genital organs are located in the lower abdominal/pelvic cavity and include the vagina, uterus, fallopian tubes and ovaries (Figure 1.2).
Vagina
The vagina is a flattened but distensible musculomembranous canal that links the uterine cavity with the exterior at the vulva. It is the excretory channel for uterine secretions and menstrual blood, the organ of copulation and forms the birth canal of parturition.
Figure 1.1: The external structure of the female reproductive system. The vulva is the collective term for all the visible external genital organs in the female. This includes of the mons pubis, labia majora, labia minora, hymen, clitoris, vestibule, urethra and Skene's and Bartholin's glands and mons pubis. The labia minora and majora protect the clitoris, urethral meatus and vaginal entrance.
Figure 1.2: The internal structures of the female reproductive system. The female internal genital organs are located in the lower abdominal/pelvic cavity and include the vagina, cervix uterus, fallopian tubes and ovaries. The uterine wall has three layers: the perimetrium is the outer serosal layer; the myometrium is the middle muscular layer; and the endometrium is the inner mucosal lining. The endometrium consists of a functional layer, which contains secretory glands and is shed during menses, and a basal layer, which is highly vascularized and regenerates the functional layer.
The canal is directed upwards and backwards forming an angle of about 45° with the horizontal in erect posture. The length of the anterior wall is about 7 cm and that of the posterior wall is about 9 cm (Dutta 2015). The vaginal walls are separated where the uterine cervix projects into the vaginal cavity. The space which exists between the intravaginal part of the cervix and the vaginal wall is divided into anterior, lateral and posterior fornices.
The vagina has three layers: an inner mucosal layer that is comprised of non-keratinized stratified squamous epithelium; a muscularis layer made of smooth muscle; and a fibrous layer that covers the vagina and attaches it to the surrounding pelvic organs. The vaginal pH, from puberty to menopause, is acidic because of the presence of Doderlein's bacilli which are large gram-positive bacteria that produce lactic acid from the glycogen present in the exfoliated cells (Figure 1.3).
The mucus membrane of the upper four-fifth of the vagina, above the hymen, is derived from endoderm of the canalized sinovaginal bulbs, while the musculature is developed from the mesoderm of two fused paramesonephric (Müllerian) ducts. The lower one-fifth, below the hymen, is developed from the endoderm of the urogenital sinus. The external vaginal orifice is formed from the genital fold ectoderm after rupture of the urogenital membrane (Dutta 2015).
Uterus
The uterus is a pear-shaped muscular organ that is intermediate in position between the bladder, rectum and broad ligaments. After puberty, the normal length is about 7.6 cm and width is 4.5 cm. The normal uterus weighs about 60 g but can weigh up to 200 g when associated with various pathologies. The uterus is developed from the fused vertical part of the two Müllerian ducts.
The uterus is composed of three regions: the bulging upper section called the fundus; the body which is the usual site of implantation; and the narrow lower section called the cervix. The cervix is about 2.5 cm long and is divided into supravaginal and intravaginal portions. The inner walls of the cervix contain nabothian follicles, small sacs that, in response to rising estradiol levels, secrete an alkaline mucus which protects sperm from the acidity of the vaginal secretions. These follicles are also known as nabothian cysts, which may appear as harmless bumps on the surface on the cervix.
Figure 1.3: Doderlein's bacilli are large rod-shaped gram-positive bacteria that produce lactic acid from the substrate glycogen present in exfoliated cells. Vaginal pH is acidic because of the presence of these bacteria, and this environment prevents the growth of other pathogens. They are detectable in the vagina 3–4 days after birth, and then at puberty; however, they are no longer detectable postmenopause. They most likely originate from the intestine and their presence is dependent on estrogen.
The uterus is supported by four paired ligaments. The broad ligament attaches the pelvis walls and floor to the uterus; the uterosacral ligament attaches the lateral pelvic wall to the uterus; the cardinal 3ligament runs laterally from the cervix and vagina to the walls of the pelvis; and the round ligament extends from the lateral border of the uterus below the uterine tube to the lateral pelvic wall.
The uterine wall has three layers:
- The perimetrium is the outer serosal layer
- The middle muscular layer is called the myometrium
- The endometrium is the inner mucosal lining. The endometrium consists of a functional layer, which contains secretory glands and is shed during menses, and a basal layer, which is highly vascularized and regenerates the functional layer (see Figure 1.2).
The uterus is capable of undergoing major changes during a woman's reproductive life. From puberty to menopause, the inner lining of the uterus (the endometrium) provides a suitable environment for embryo implantation and development during pregnancy. The endometrial lining in response to hormones released from the ovaries, thickens during the proliferative phase of the menstrual cycle, and then forms secretory glands in the second half of the menstrual cycle. If implantation does not occur, the endometrium is shed and excreted from the body via the vagina during menstruation (see Figure 1.4).
Fallopian tubes
The fallopian tubes, or oviducts, are paired structures approximately 10 cm long that lead from the uterus and end in finger-like projections called fimbriae. The fimbriae are suspended over the ovaries, and during ovulation receive the mature oocyte that is released from an ovarian follicle.
The fallopian tube has four subdivisions; the interstitial part is the short portion that begins at the upper angle of the uterine cavity with which it connects by a minute ostium; the isthmus is the medial 2.5 cm; the ampulla is the widest and longest subdivision of the tube; and the infundibulum is funnel-shaped leading from the ampulla, which contains the fimbriae.
After release from the follicle, the oocyte remains in the fallopian tube for about 3 days, with fertilization normally taking place at the distal end. The resulting embryo is propelled through the fallopian tube by a combination of rhythmic contractions of the muscular layer and the action of tiny hair-like projections, called cilia, toward the uterus. Pregnancy may be established via implantation of the embryo into the uterine lining 5 or 6 days following fertilization.
The fallopian tube has three layers (see Figure 1.5):
- A serous layer (serosa) has peritoneum on all sides except along the line of attachment of mesosalpinx
- A muscular layer (smooth muscle) has an outer longitudinal and inner circular layer
- A mucus membrane layer (mucosa). Columnar ciliated epithelial cells line the mucus membrane layer and are predominant near the ovarian end of the tube, whilst secretory columnar cells are present at the isthmic segment, with peg cells found in between
The fallopian tube is developed from the upper vertical part of the corresponding Müllerian duct at about 6–10th week of pregnancy.
Ovaries
The ovaries are paired sex glands in the female, located on either side of the uterus. Each ovary is a pinkish/white ovoid structure which resembles a large almond in size and shape. A normal adult healthy ovary measures about 3 cm long × 1.5 cm wide × 1 cm thick.
The ovary lies near the lateral wall of the pelvic cavity in a slight depression between the ureter posterior medially, the external iliac artery being lateral and the uterine tube in the free margin of the broad ligament anteriorly. The extremity of the uterine tube curves around the lateral end of the ovary and is attached to it by one of its fimbriae. The ovary is attached to the superior surface of the broad ligament by a short peritoneal fold (mesovarium), through which the ovarian vessels enter its hilus. The medial extremity of the ovary is attached to the uterus by the ligament of the ovary.
The ovary consists of four layers. The germinal epithelium is the outermost layer and is made up of simple cuboidal epithelium. Next is the tunica albuginea, a collagenous layer, then the outer cortex and inner medulla layers. Throughout the cortex and medulla is a connective tissue matrix known as stroma.
Figure 1.4: The menstrual cycle. The uterus undergoes major changes during the menstrual cycle. The inner lining of the uterus (the endometrium) provides a suitable environment for embryo implantation. The endometrial lining responds to hormonal signals from the ovaries, thickening during the proliferative phase and then forming secretory glands in the second half of the cycle. If implantation does not occur, the endometrium is shed and excreted from the body via the vagina during menstruation.
Figure 1.5: A cross-section of a fallopian tube, showing the three layers: the serosa layer has peritoneum on all sides except along the line of attachment of mesosalpinx; the smooth muscle layer has outer longitudinal and inner circular layers; and the mucosa layer is lined with columnar ciliated epithelial cells, predominantly near the ovarian end of the tube, whilst secretory columnar cells are present at the isthmic segment, with peg cells found in between.
The stromal tissue has the ability to respond to luteinizing hormone (LH) or human chorionic gonadotropin (hCG) with androgen production (Speroff & Fritz 2005). Embedded in the stroma are blood vessels and thousands of microscopic structures called ovarian follicles. Each follicle contains an oocyte. The rete ovarii (the hilum) is the point of attachment of the ovary to the mesovarium. It contains nerves, blood vessels, and hilus cells, which have the potential to become active in steroidogenesis or to form tumors. The ovary is developed from the cortex of the undifferentiated genital ridges by about 9th week of gestation.
BLOOD SUPPLY AND INNERVATION OF THE FEMALE SEX ORGANS
External genitalia
The arterial blood supply to the external genitalia is via:
- Branches of internal pudendal artery – the labial, transverse perineal, artery to the vestibular bulb and deep and dorsal arteries to the clitoris
- Branches of femoral artery – superficial and deep external pudendal. Venous drainage of the external genitalia is via venous plexuses that drain into the internal pudendal vein, the vesical or vaginal venous plexus and the long saphenous vein
Innervation of the external genitalia is through bilateral spinal somatic nerves. The anterosuperior part is supplied by the cutaneous branches from the ilio-inguinal and genital branch of genitofemoral nerve (L1 and L2) and the posterior-inferior part by the pudendal branches from the posterior cutaneous nerve of thigh (S1.2.3). The vulva is also supplied by the labial and perineal branches of the pudendal nerve (S2.3.4).
Internal genitalia
Vagina
Arterial blood supply to the vagina is via:
- The cervicovaginal branch of the uterine artery
- The vaginal artery – branch of anterior division of internal iliac
- The middle rectal artery
- The internal pudendal artery
These anastomose with one another and form two azygos arteries – anterior and posterior. The veins drain into internal iliac veins and internal pudendal veins.
Nerve supply of the vagina is via sympathetic and parasympathetic fibers from the pelvic plexus. The lower part of the vagina is supplied by the pudendal nerve.
Uterus
Blood supply to the uterus is from the uterine artery, one on each side. The artery arises directly from the anterior division of the internal iliac. Other sources are ovarian and vaginal arteries with which the uterine arteries anastomose. The venous channels correspond to the arterial course and drain into the internal iliac veins (see Figure 1.6).
The nerve supply of the uterus is derived principally from the sympathetic system and partly from the parasympathetic system. Sympathetic components are from T5 and T6 (motor) and T10 to L1 spinal segments (sensory). The somatic distribution of uterine pain is that area of the abdomen supplied by T10 to L8. The parasympathetic system is represented on either side by the pelvic nerve which consists of both motor and sensory fibers from S2, S3, S4 and ends in the ganglia of Frankenhauser.
Fallopian tubes
Arterial supply to the fallopian tubes is from the uterine and ovarian arteries. Venous drainage is through the pampiniform plexus into the ovarian veins. The nerve supply is derived from the uterine and ovarian nerves.
Ovaries
Arterial supply to the ovary is from the ovarian artery, a branch of the abdominal aorta. The ovarian artery sends branches through the mesovarium to the ovary, continues medially in the broad ligament, gives branches to the uterus and anastomoses with the uterine artery. Venous drainage is through the pampiniform plexus, to form the ovarian veins, which drain into the inferior vena cava on the right side and the left renal vein on the left side. Sympathetic innervation of the ovary is from T10 segment (Dutta 2015).
Figure 1.6: The blood supply to the uterus is from the uterine artery. This artery arises directly from the anterior division of the internal iliac. The venous channels correspond to the arterial course and drain into the internal iliac veins.
OOGENESIS AND PRODUCTION OF OOCYTES
Early development of the ovary
During fetal life, the development of the ovary can be traced through three stages:
- Indifferent gonad stage
- Ovarian differentiation, oogonal multiplication and oocyte formation
- Follicle formation
Indifferent gonad stage
At approximately 5 weeks of gestation, the paired gonads are structurally consolidated coelomic prominences overlying the mesonephros forming the genital ridge. This indifferent gonad stage lasts approximately 7 days. The primordial germ cells originate within the primitive ectoderm and are first identified at the end of the 3rd week after fertilization. They ‘migrate’ from the yolk sac around the hindgut to their gonadal sites between 4–6 weeks of gestation. The germ cells are the direct precursors of sperm and oocytes and, by the 6th week of gestation, on completion of the indifferent stage, have multiplied by mitosis to an estimated 10,000 (Speroff & Fritz 2005).
Ovarian differentiation, oogonal multiplication and oocyte formation
Oogenesis refers to the sequence of events by which oogonia (primordial oocytes) are transformed into primary oocytes. The process begins during the fetal period but is not completed until after puberty. At 6–8 weeks of development, the first signs of ovarian differentiation are reflected in the rapid mitotic multiplication of germ cells, reaching 6–7 million oogonia by 16–20 weeks of development (Baker 1963, Gordon et al. 1971). This is the maximal oogonal content of the gonad. At 11–12 weeks of development, the oogonia are transformed into primary oocytes as they enter the first meiotic division and arrest in the diplotene stage of prophase I. It is estimated that two-thirds of all primordial oocytes undergo programmed cell death. This ‘quality control’ mechanism occurs via an intrinsic apoptosis pathway and has been named the ‘apoptotic wave’ (De Felici et al. 2005).
At 18–20 weeks, the newly formed oogonia begin to be surrounded by the pregranulosa cells to become primordial follicles. As soon as the oocyte is surrounded by the rosette of pregranulosa cells, the entire follicle has the potential to undergo variable degrees of maturation.
At birth, the ovaries contain about 2 million primordial follicles with germinal vesicles and stay at this stage of development until puberty. Atresia of the primordial follicles persists and at puberty there are approximately 3–400,000 primordial follicles left. During reproductive life, 400–500 are selected to ovulate if there are regular menstrual cycles. The primary follicles will eventually be depleted to a point at menopause, when only a few hundred remain (Richardson et al. 1987).
Follicular growth
The time that elapses in progressing from a primary follicle to ovulation is approximately 85 days (Gougeon 1996). The number of follicles that mature is dependent on the amount of follicle stimulating hormone (FSH) available to the gonad and the sensitivity of the follicles to the gonadotropins. FSH receptor expression is greatest in granulosa cells, but significant expression can be detected in ovarian surface epithelium and fallopian tube epithelium. FSH acts on the growing cohort of follicles and causes an increase in size of the primary oocyte and the follicle.
On the first day of the menstrual cycle, about 5–10 growing follicles in the ovaries are available for recruitment. The increasing concentration of FSH causes selection of usually one follicle to grow, with proliferating granulosa cells. The follicle forms an antrum and the granulosa cells now make estrogen. The tertiary follicle is the last stage of the folliculogenesis before ovulation, growing to 16–19 mm in diameter (as assessed by ultrasonography). Granulosa cells give rise to all the cells of the follicle – the theca (interna and externa), the coronal radiata directly adjacent to zona pellucida (ZP) and the cumulus oophorus (Figure 1.7).
The rising estradiol level just before ovulation triggers a surge of LH, and informs the oocyte to resume its division via gap junction communication. The primary oocyte completes the first meiotic division (meiosis I) just before ovulation. At ovulation, the secondary oocyte begins meiosis II, but progresses only to the metaphase II stage, where the cell cycle is temporarily arrested. If the secondary oocyte is fertilized by a sperm, meiosis II is completed and a second polar body is formed. At this stage, the secondary oocyte is large, being just visible to the unaided eye (see Chapter 9 for a detailed description of the oocyte).
6
Figure 1.7: (a) Structure of the ovary and (b) oocyte. The ovary consists of the cortex which contains developing follicles and a vascular central core, the medulla. On the first day of the menstrual cycle, about 5–10 growing follicles are available for recruitment. As follicle-stimulating hormone (FSH) levels rise, usually one follicle is selected to grow. The follicle forms an antrum and makes estrogen via granulosa cells. The tertiary follicle is the last stage of the follicle before ovulation, growing to 16–19 mm in diameter. After ovulation, the empty follicle forms the corpus luteum.
Figure 1.8: Levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during gestation, childhood and adulthood. There is a postnatal rise in FSH and LH. Between the ages of 2 and 11 there is very low amplitude and episodic release of both FSH and LH. By the ages of 11-13 secretion and episodic release of FSH and LH both rise - FSH to a higher level than LH - and then level out between the ages of 14 and 17 with amplitude and frequency of release dependent on the phase of cycle.
HORMONE RECEPTOR EXPRESSION (ABILITY OF THE OVARY TO RESPOND TO ENDOCRINE SIGNALS)
The anterior pituitary gland begins development between 4 and 5 weeks of gestation and the hypothalamic-pituitary portal circulation is functional by the 12th week. Pituitary levels of FSH peak at 20–23 weeks, and circulating levels peak at 28 weeks. Ovaries in anencephalic fetuses, which lack gonadotropin-releasing hormone (GnRH) and gonadotropin secretion, lack antral follicles and are smaller at term; progression through meiosis and development of primordial follicles occur, indicating that this process is independent on gonadotropins (Rabinovici 1990). The ovary develops gonadotropin receptors only in the second trimester. There is a postnatal rise in FSH with levels greater than the levels reached during a normal adult menstrual cycle, decreasing to low levels usually by 1 year of age, but sometimes later (Burger et al. 1991). LH levels are in the range of lower adult levels (Figure 1.8).
Ovarian-derived sex steroid hormones dictate the menstrual cycle in humans and are essential for the establishment and maintenance of pregnancy. The steroid receptors are part of the family of nuclear receptors and consist of estrogen, progesterone, androgen and glucocorticoid receptors. The functions of the sex steroids and their cognate receptors in ovarian function are multifaceted. Progesterone, testosterone and estradiol are all synthesized in the ovary during folliculogenesis and act via both extraovarian (i.e. endocrine) and intraovarian (i.e. paracrine/autocrine) pathways to influence all aspects of ovarian function. The endocrine actions of the sex steroids in the hypothalamic-pituitary axis are critical to the regulation of gonadotropin secretion and the ovarian cycle (Binder et al. 2015).
High-affinity estradiol binding sites in normal human ovaries have been described. Estrogen receptor beta (ER beta) is the predominant estrogen receptor form and is most often exclusively localized to granulosa cells of follicles from the primary to pre-ovulatory stage. Although FSH is the primary stimulus for both granulosa cell proliferation and differentiation, both FSH and estrogen are required for full antrum formation in pre-ovulatory follicles (Binder et al. 2015). Acquisition of aromatase activity and estradiol synthesis is a hallmark of healthy pre-ovulatory follicles and 90% of the circulating estrogen is estimated to originate from the dominant follicle in the ovary. Unlike thecal cells, granulosa cells express LH only in follicles in the late pre-ovulatory stage. This limited expression of LH receptors in the granulosa cells of healthy pre-ovulatory follicles provides for an intraovarian mechanism that ensures only those follicles that are suitable for ovulation acquire the capacity to respond to the LH surge (Binder et al. 2015).
Like granulosa cells, follicular thecal cells also undergo a process of differentiation during progression from a pre-antral to pre-ovulatory follicle. The two-cell, two gonadotropin paradigm of steroidogenesis in maturing follicles is that thecal cells exclusively possess the 17-β hydroxylase: C17-20-lyase activity necessary for synthesizing androgens, forcing the granulosa cell layer to be dependent on the theca as a source of aromatizable precursors (see Figure 1.9).7
Figure 1.9: The two-cell, two-gonadotropin theory of steroidogenesis in maturing follicles. Thecal cells possess the 17-β hydroxylase: C17-20-lyase activity necessary for synthesizing androgens, forcing the granulosa cell layer to be dependent on the theca as a source of aromatizable precursors.
Androgens are necessary and serve as both a stimulus of and substrate for aromatase activity in granulosa cells. An intraovarian mechanism exists to negatively modulate thecal cell androgen synthesis so that levels do not surpass the aromatase capacity of the granulosa cell layer. Defects in this intraovarian mechanism are postulated to be an underlying cause of the excess thecal cell androgen synthesis that is a hallmark of polycystic ovarian syndrome in women (Binder et al. 2015).
Progesterone receptor (PR) expression has been primarily localized to the theca of large pre-ovulatory follicles, the surface epithelium, and ovarian stroma. The dramatic increase in PR expression in the granulosa cells of ovulatory follicles is absolutely essential to follicle rupture (Conneely et al. 2002).
The hypothalamic feedback mechanism and ovulation
The hormonal interactions that regulate the female reproductive cycle are initiated and maintained by a feedback mechanism that originates in the hypothalamus. The hypothalamus influences the anterior pituitary gland's secretion of FSH and LH by transmitting gonadotropin releasing hormone (GnRH) in a pulsatile fashion. In normal menstrual cycles, the hypothalamus releases GnRH at 60–120 minute intervals in the follicular phase. The FSH and LH stimulate follicular development in the ovary, resulting in the production of estradiol. Rising levels of estradiol in the bloodstream provide the ‘feedback’ to the hypothalamus for further regulation of FSH and LH. Shortly following ovulation, the high levels of progesterone and estradiol promote a negative feedback mechanism causing the pituitary gland to taper off the release of FSH and LH. As a result, concentrations of estrogen and progesterone decrease until levels are low enough to trigger menstruation and start the next menstrual cycle (Figure 1.4). In anovulatory cycles, the endometrium remains in the proliferative phase until menstruation begins.
Fertilization, implantation and initiation of pregnancy
Fertilization occurs when the mature oocyte is penetrated by one of the few sperm that survives the journey to enter the fallopian tube. If the oocyte is fertilized, a cortical reaction within the ooplasm changes the oolemma and causes structural changes in the protective ZP. This prevents other sperm from entering. Unfertilized oocytes are expelled during menstruation.
The fertilized oocyte, now termed a zygote, migrates down the fallopian tube, propelled by the action of cilia lining the tubal lumen. The early preimplantation embryo divides several times during this period to form a morula on day 4 and then a blastocyst on day 5. Approximately 5–6 days following fertilization, the blastocyst reaches the uterus where it implants itself in the endometrium. Implantation is dependent on several factors, such as adequate formation of the corpus luteum and an adequately developed endometrial lining. If implantation is not successful, the blastocyst is expelled from the uterus with menstruation. Pregnancy can only ensue following successful implantation.
Implantation signals the pituitary gland to release additional LH. This hormone supports the granulosa cells in their critical role of maintaining early pregnancy, by continuing to release an increasing amount of progesterone. Progesterone is vital to maintaining the endometrium during this phase. The corpus luteum continues to produce progesterone until the placenta is able to produce a sufficient supply of its own progesterone, typically at about the 9th or 10th week of pregnancy.
During the assisted conception cycle, additional supplies of progesterone are usually provided to the female once oocytes have been released, either via ovulation induction or egg collection for in-vitro fertilization (IVF) treatment. This is known as ‘luteal phase progesterone’ and the hormone is usually supplemented in the form of vaginal pessaries or gel, which needs to be continued on a daily basis.
Just before implantation, the developing blastocyst starts to produce hCG from the outer cell's layer, known at the trophectoderm. The rise in secretion of hCG is exponential, as the blastocyst implants and the trophectoderm cells continue to divide and grow.
The hCG is the hormone tested to determine pregnancy; hCG can be detected in urine or via a blood test. At the end of a successful pregnancy, the uterus undergoes powerful, rhythmic contractions during labor, resulting in the delivery of the fetus at birth.8
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- Burger HG, Famada Y, Bangah MI, et al. Serum gonadotropin, sex steroid, and immunoreactive inhibin levels in the first two years of life. J Clin Endocrinol Metab 1991;72:682.
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- Gordon B, Bhiraleus, P, Hobel C. Ultrastructural observations on germ cells in human fetal ovaries. Am T Obstet Gynecol 1971;110:644–652.
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- Rabinovici J, Jaffe RB. Development and regulation of growth and differentiated function of human and subhuman primate fetal gonads. Endocr Rev 1990;11:532–557.
- Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: Evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab 1987;65:1231.
- Speroff L, Marc A, Fritz MA. The Ovary – Embryology and Development. Clinical Gynecologic Endocrinology and Infertility (7th edn). Philadelphia, PA: Lippincott, Williams & Wilkins, 2005.