Category Archive Pregnancy & Mom Care

Gynecological problems are disorders that affect the female reproductive system. The female reproductive system includes the breasts, uterus (womb), ovaries (egg-producing organs), fallopian tubes (tubes carrying the eggs from the ovaries to the uterus), and external genitalia or vulva (the accessory structures of the female reproductive system which lie external to the vagina).

Most women suffer from some kind of gynecological problem at some point in their lives. Gynecological problems can affect a woman’s sexual function and her ability to produce children. In some cases, gynecological disorders may be life-threatening.

In this article, we will be discussing in detail the common gynecological problems in females.

• What are the Common Gynecological Problems in Females?
• What are the various diagnostic tests for gynecological screening?
• How to prevent the Common Gynecological Disorders in Females?

What are the Common Gynecological Problems in Females?

Polycystic Ovarian Syndrome or PCOS

• This is a condition in which a woman may suffer from infrequent or prolonged menstrual cycles. This condition occurs due to the appearance of several follicles on the ovaries, leading to a hindrance in releasing the egg.

Causes:

• Increased levels of androgen (male sex hormone) in the body
• Genetics
• Excessive insulin in the body

Symptoms:

• Obesity
• Acne
• Increased Risk of diabetes
• Infertility
• Menstrual problems

Treatment:

• Exercise
• Yoga
• Medications for symptomatic relief

Vaginitis

Inflammation in the vagina, which is commonly seen in women of reproductive age is known as vaginitis.

Causes:

• Infections
• Sexually transmitted diseases
• Taking antibiotic medications
• Fluctuations in hormone levels
• Use of spermicidal creams (as a birth control method)

Symptoms:

• Pain on urinating
• Vaginal irritation
• Vaginal itching
• Foul-smelling vaginal discharge

Treatment:

• Prescription medications
• Gels
• Creams

Dysmenorrhoea (Painful periods)

When a woman experiences pain during her menstrual cycles, the condition is known as dysmenorrhoea.

Types:

• Primary dysmenorrhoea: This condition is not associated with pelvic (area below the stomach region) diseases.
• Secondary dysmenorrhoea: This condition is associated with underlying pelvic disorders.

Causes:

The cause of primary dysmenorrhoea is:

• Prostaglandins (the natural chemicals in the body)
• Causes of secondary dysmenorrhoea include:
• Fibroids (non-cancerous masses that form inside a woman’s uterus)
• Endometriosis (a condition in which the tissue that normally lines the uterus grows outside the uterus)
• Adenomyosis (a condition in which an endometrial tissue exists and grows into the muscular uterine wall)

Symptoms:

• Intense abdominal pain, sometimes extending up to the lower back
• Cramping

Treatment:

• Painkiller medications
• Treatment for the cause of dysmenorrhoea

Urinary tract infection or UTI

It is one of the most common gynecological problems faced by women of all age groups. This condition normally occurs when the bacteria that are present in the vagina or anus (from where the stools are passed out), move up to the urethra (duct from where the urine is passed from the bladder to outside the body) and bladder (where the urine is stored), and sometimes even the kidneys.

Causes:

• Problems with the pelvic muscles or nerves
• Narrow urinary tract
• Blockage in the bladder, urethra, or kidneys

Symptoms:

• Burning sensation on urination
• Cloudy urine
• Strong odor
• Blood tinge in urine
• Fever
• Chills
• Nausea
• Vomiting
• Backache

Treatment:

• Antibiotics, the dosage, and duration depending on the severity of the infection

 Fibroids

These are muscular, mostly non-cancerous tumors that can form in the uterus of a woman. They usually vary in size, shape, and location.

Causes:

• No known cause
• Genetics or hormones may be responsible for fibroid formation

Symptoms:

• Heavy periods
• Pain during sex
• Pressure in the lower abdomen (stomach) region
• Bleeding in between the menstrual periods

Treatment:

• Surgery to remove the fibroids

Endometriosis

This condition occurs when the tissue that is normally lining the uterus, grows outside the uterus.

Causes:

• Hormonal disorders
• Genetic factors
• Immune (disease-fighting) system disorders
• Menstrual flow problems

Symptoms:

• Painful menstrual cramps
• Digestive problems
• Bleeding or spotting between menstrual periods

Treatment:

• Painkiller medications
• Hormonal therapies
• Surgery

Genital Herpes

This is a sexually transmitted disease (STD) that is characterized by blister and sore formations. It is a type of viral infection.

Causes:

• Vaginal, oral, or anal sex with an infected partner

Symptoms:

• Flu-like symptoms
• Fever
• Chills
• Fatigue
• Nausea
• Muscle pain
• Sores or blisters on or around the genital organs

Treatment:

• Oral medications

Pelvic Inflammatory Disease

This condition affects the upper genital tracts of a woman’s body, including the uterus, fallopian tubes, pelvic peritoneum (a membrane lining the pelvic cavity), and other surrounding structures.

Causes:

• Multiple sexual partners
• History of pelvic inflammatory disease
• Use of intrauterine contraceptive device (IUCD) (a plastic or copper implant placed in the uterus to prevent pregnancy)

Symptoms:

• Lower abdominal pain
• Pain during sex
• Abnormal discharge from the vagina
• Vaginal bleeding
• Fever
• Lethargy

Treatment:

• Antibiotic medications

Dyspareunia (Painful sexual intercourse)

Pain during sex may occur due to structural problems in the female body or due to psychological reasons.

Causes:

• Vaginitis
• Narrow vagina
• Pelvic inflammatory disease
• Infection of the vulva
• Thick hymen (a thin piece of tissue that covers the external vaginal opening)

Symptoms:

• Pain during sexual penetration
• Pain that lingers for a couple of hours after intercourse
• Thrusting

Treatment:

• Get sexual education
• Treatment depends on the cause of pain

Ovarian cysts

Ovarian cysts are fluid-filled pouches or sacs present in the ovaries. They are very common and affect women of any age group.

Causes:

• Severe pelvic infections
• Hormonal disorders
• Endometriosis

Symptoms:

• Bloating
• Pain in the abdominal region
• Swelling in the abdominal region
• Nausea
• Vomiting

Treatment:

• Oral medications
• Surgery

Uterine Fibroids

Uterine fibroids are noncancerous growths of the uterus. They can occur at any age but are most common in women aged 30-40 years and occur more often in African American women. The main types of uterine fibroids include:

• Submucosal fibroids, which develop under the lining of the uterus
• Subserosal fibroids which grow on the outside of the uterus
• Intramural fibroids which grow within the uterine wall

Symptoms of uterine fibroids include:

• Extended, heavy periods
• Pain in the lower back
• Pain during sexual intercourse
• Frequent need to urinate or difficulty urinating
• Abdominal pressure

Pelvic Organ Prolapse

Pelvic organ prolapse (POP) occurs when the connective tissues and ligaments in place to support the vagina, bladder, rectum and uterus become damaged or weakened. This causes the pelvic organs to sink down or fall out of place.

Symptoms of pelvic prolapse include:

• Pressure in the vagina or rectum
• Organs bulging outside the vagina
• Difficulty completely emptying the bladder
• Difficulty with urination and bowel movements

Urinary Incontinence

Urinary incontinence occurs when the ability to control the release of urine is lost and is common in women age 35 and older. Though the condition is prevalent, there is a wide range of treatment options available, and it shouldn’t be accepted as normal.

There are three types of urinary incontinence:

• Stress urinary incontinence, which can occur during physical activity such as walking, running or exercising. Leaks may also happen when coughing, sneezing, or laughing.
• Urgency urinary incontinence occurs when urine is released after a strong, sudden need to urinate.
• Mixed incontinence includes symptoms of both types of urinary incontinence.

Countless women struggle with the above conditions, but thankfully, there are a range of treatments for common gynecological problems – and finding them begins with seeing a gynecologist. Learn more about how you can find a gynecologist you trust, and why you should make an appointment with them at least once a year. If you don’t already have a gynecologist, request an appointment with one of our experts at Baptist Health.

What are the various diagnostic tests for gynecological screening?

• Physical examination: The patient should be examined clinically. This includes noting down the symptoms of the patient, medical history, and family history of the patient.
• Breast examination, abdominal examination, and pelvic examination: The doctor should examine the breasts, external genitalia, rectum, inside of the vagina, and cervix (the lower end of the uterus) thoroughly.
• Pap smear: Vaginal and cervical smears are taken by the doctor to check for cervical cancer.
• All sexually active women above the age of 21 should be screened regularly, once every six months.
• Imaging tests: Imaging tests like x-rays, CT scans, MRI scans, and pelvic ultrasounds may be recommended to obtain clear images of the female reproductive organs.
• Urine tests: These tests help in diagnosing any underlying infections.

How to prevent the Common Gynecological Disorders in Females?

Common gynecological disorders can be prevented by:

• Have protected sex
• Eat a healthy diet
• Take proper rest
• Exercise regularly
• Manage stress
• Get adequate sleep
• Maintain vaginal hygiene
• Wash genital area with warm, clean water and then dry it well every day
• Change the underwear regularly
• Avoid tight-fitting underwear
• Change sanitary pads every 4 hours during menstruation
• Do not share your underwear and towel
• Do not clean deep inside the vagina
• Do not use strong washes for cleaning the genital
• Take regular screenings and go for periodic gynecological checkups

References

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Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all post-pregnancy female mammals, although it may predate mammals.[rx] The process of feeding milk in all animals (including humans) is called nursing, and in humans, it is also called breastfeeding. Newborn infants often produce some milk from their own breast tissue, known colloquially as witch’s milk.

In most species, lactation is a sign that the individual has been pregnant at some point in her life, with the exception of humans and goats.[rx][rx] Nearly every species of mammal has nipples; except for monotremes, egg-laying mammals, which instead release milk through ducts in the abdomen. In only one species of mammal, the Dayak fruit bat from Southeast Asia is milk production a normal male function.

Pathophysiology

Lactogenesis is the process of developing the ability to secrete milk and involves the maturation of alveolar cells. It takes place in 2 stages: secretory initiation and secretory activation.

Stage I lactogenesis (secretory initiation) takes place during the second half of pregnancy. The placenta supplies high levels of progesterone which inhibit further differentiation. In this stage, small amounts of milk can be secreted by week 16 gestation. By late pregnancy, some women can express colostrum.
Stage II lactogenesis (secretory activation) starts with copious milk production after delivery. With the removal of the placenta at delivery, the rapid drop in progesterone, as well as the presence of elevated levels of prolactin, cortisol, and insulin, are what stimulate this stage. Usually, at days 2 or 3 postpartum, most women experience swelling of the breast along with copious milk production. In primiparous women, the secretory activation stage is slightly delayed, and early milk volume is lower. Lower milk volume is also observed in women who had cesarean births compared with those who delivered vaginally. Late-onset of milk production has also been seen in women who have had retained placental fragments, diabetes, and stressful vaginal deliveries. With retained placental fragments, lactogenesis stage II could be inhibited by the continued secretion of progesterone and would continue to be inhibited until removal of the remaining placental fragments.

Lactation is maintained by regular removal of milk and stimulation of the nipple, which triggers prolactin release from the anterior pituitary gland and oxytocin from the posterior pituitary gland. For the ongoing synthesis and secretion of milk, the mammary gland must receive hormonal signals; and although prolactin and oxytocin act independently on different cellular receptors, their combined action is essential for successful lactation.

Prolactin is a polypeptide hormone synthesized by lactotrophic cells in the anterior pituitary and is structurally similar to growth hormone and placental lactogen. Prolactin is both positively and negatively regulated, but its main control comes from hypothalamic inhibitory factors such as dopamine which act on the D2 subclass of dopamine receptors present in lactotrophs. Prolactin stimulates mammary gland ductal growth and epithelial cell proliferation and induces milk protein synthesis. Emptying of the breast by the infant’s suckling is thought to be the most important factor. Prolactin concentration increases rapidly with suckling of the nipple which stimulates nerve endings located there.

Oxytocin is involved in the milk ejection or letdown reflex. The tactile stimulation of the nipple-areolar complex by suckling leads to afferent signals to the hypothalamus that trigger release of oxytocin. This results in the contraction of the myoepithelial cells, forcing milk into the ducts from the alveolar lumens and out through the nipple. Oxytocin also has a psychological effect, which includes inducing a state of calm, and reducing stress. It may also enhance feelings of affection between mother and child, an important factor in bonding.

Once lactation is established and maintained, production is regulated by the interaction of both physical and biochemical factors. If milk is not removed, elevated intramammary pressure and accumulation of a feedback inhibitor of lactation reduce milk production and initiate mammary involution. If breast milk is removed, the inhibitor is also removed, and secretion will resume. The role of the feedback inhibitor of lactation is to regulate the amount of milk produced which is determined by how much the baby takes, and therefore by how much the baby needs.

Physiology of Lactation

Lactation is the secretion of milk from specialized glands (mammary glands) to provide nourishment to offspring. Lactation is a hallmark feature of female mammals. Lactation is under endocrine control. The two main hormones involved are prolactin and oxytocin.

Lactogenesis, or the process of changes to the mammary glands to begin producing milk, begins during the late stages of pregnancy. The delivery of the placenta and the resulting dramatic reduction in progesterone, estrogen, and human placental lactogen levels stimulate milk production.

Colostrum is the first milk a breastfed baby receives. It contains higher amounts of white blood cells and antibodies than mature milk and is especially high in immunoglobulin A. This immunoglobulin coats the lining of the baby’s immature intestines, helping to prevent pathogens from invading the baby’s system.

Key Terms
witch’s milk: Witch’s milk or neonatal milk is milk secreted from the breasts of some newborn human infants of either sex. Neonatal milk secretion is considered a normal physiological occurrence and no treatment or testing is necessary.
mammary gland: A gland that secretes milk for suckling an infant or offspring.
lactation: 1. The secretion of milk from the mammary gland of a female mammal. 2. The process of providing the milk to the young, such as breastfeeding. 3. The period of time that a mother lactates to feed her young; the lactation period.
human placental lactogen: A hormone closely associated with prolactin that is
instrumental in breast, nipple, and areola growth before birth.
colostrum: A form of milk produced by the mammary glands in late pregnancy and the few days after giving birth. Human and bovine colostrum is thick and yellowish. In humans, it has high concentrations of nutrients and antibodies, but it is small in quantity.

Overview of Lactation

Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, although it predates the origin of mammals.

In humans the process of feeding milk is called breastfeeding or nursing.
The chief function of lactation is to provide nutrition and immune protection to the young after birth. In almost all mammals, lactation induces a period of infertility, which serves to provide the optimal birth spacing for the survival of the offspring.

In most species, milk comes out of the mother’s nipples; however, the platypus (a non-placental mammal) releases milk through ducts in its abdomen. In only one species of mammal, the Dayak fruit bat is milk production a normal male function.

In some other mammals, the male may produce milk as the result of a hormone imbalance. This phenomenon may also be observed in newborn infants as well (for instance, witch’s milk).

Galactopoiesis is the maintenance of milk production. This stage requires prolactin and oxytocin.

Preparation for Lactation

By the fifth or sixth month of pregnancy, the breasts are ready to produce milk. During the latter part of pregnancy, the woman’s breasts enter into the lactogenesis I stage. This is when the breasts make colostrum, a thick, sometimes yellowish fluid.

At this stage, high levels of progesterone inhibit most milk production. It is not a medical concern if a pregnant woman leaks any colostrum before her baby’s birth, nor is it an indication of future milk production.

At birth, prolactin levels remain high, while the delivery of the placenta results in a sudden drop in progesterone, estrogen, and human placental lactogen levels. This abrupt withdrawal of progesterone in the presence of high prolactin levels stimulates the copious milk production of the lactogenesis II stage.

When the breast is stimulated, prolactin levels in the blood rise and peak in about 45 minutes, then return to the pre-breastfeeding state about three hours later. The release of prolactin triggers the cells in the alveoli to make milk.

Colostrum

Colostrum is the first milk a breastfed baby receives. It contains higher amounts of white blood cells and antibodies than mature milk, and is especially high in immunoglobulin A (IgA), which coats the lining of the baby’s immature intestines, and helps to prevent pathogens from invading the baby’s system. Secretory IgA also helps prevent food allergies. Over the first two weeks after the birth, colostrum production slowly gives way to mature breast milk.

Lactation: A positive feedback loop ensures continued milk production as long as the infant continues to breastfeed.

Hormonal influences

From the eighteenth week of pregnancy (the second and third trimesters), a woman’s body produces hormones that stimulate the growth of the milk duct system in the breasts:

Progesterone influences the growth in the size of alveoli and lobes; high levels of progesterone inhibit lactation before birth. Progesterone levels drop after birth; this triggers the onset of copious milk production.[
Estrogen stimulates the milk duct system to grow and differentiate. Like progesterone, high levels of estrogen also inhibit lactation. Estrogen levels also drop at delivery and remain low for the first several months of breastfeeding.[rx] Breastfeeding mothers should avoid estrogen-based birth control methods, as a spike in estrogen levels may reduce a mother’s milk supply.
Prolactin contributes to the increased growth and differentiation of the alveoli and also influences the differentiation of ductal structures. High levels of prolactin during pregnancy and breastfeeding also increase insulin resistance, increase growth factor levels (IGF-1) and modify lipid metabolism in preparation for breastfeeding. During lactation, prolactin is the main factor maintaining tight junctions of the ductal epithelium and regulating milk production through osmotic balance.
Human placental lactogen (HPL) – from the second month of pregnancy, the placenta releases large amounts of HPL. This hormone is closely associated with prolactin and appears to be instrumental in breast, nipple, and areola growth before birth.
Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG), through control of estrogen and progesterone production, and also, by extension, prolactin and growth hormone production, are essential.
Growth hormone (GH) is structurally very similar to prolactin and independently contributes to its galactopoiesis.
Adrenocorticotropic hormone (ACTH) and glucocorticoids such as cortisol have an important lactation-inducing function in several animal species, including humans. Glucocorticoids play a complex regulating role in the maintenance of tight junctions.
Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) are very important galactopoietic hormones whose levels are naturally increased during pregnancy.
Oxytocin contracts the smooth muscle of the uterus during and after birth, and during orgasm(s). After birth, oxytocin contracts the smooth muscle layer of band-like cells surrounding the alveoli to squeeze the newly produced milk into the duct system. Oxytocin is necessary for the milk ejection reflex, or let-down, in response to suckling, to occur.

It is also possible to induce lactation without pregnancy. Protocols for inducing lactation are called the Goldfarb protocols. Using birth control pills to mimic the hormone levels of pregnancy, then discontinuing the birth control, followed by use of a double electric breast pump for 15 minute sessions at regular 2-3 hour intervals (100+ minutes total per day) helps to induce milk production.

Secretory differentiation

During the latter part of pregnancy, the woman’s breasts enter into the Secretory Differentiation stage. This is when the breasts make colostrum (see below), a thick, sometimes yellowish fluid. At this stage, high levels of progesterone inhibit most milk production. It is not a medical concern if a pregnant woman leaks any colostrum before her baby’s birth, nor is it an indication of future milk production.

Secretory activation

At birth, prolactin levels remain high, while the delivery of the placenta results in a sudden drop in progesterone, estrogen, and HPL levels. This abrupt withdrawal of progesterone in the presence of high prolactin levels stimulates the copious milk production of Secretory Activation.

When the breast is stimulated, prolactin levels in the blood rise, peak in about 45 minutes, and return to the pre-breast feeding state about three hours later. The release of prolactin triggers the cells in the alveoli to make milk. Prolactin also transfers to breast milk. Some research indicates that prolactin in milk is greater at times of higher milk production, and lower when breasts are fuller and that the highest levels tend to occur between 2 a.m. and 6 a.m.[rx]

Other hormones—notably insulin, thyroxine, and cortisol—are also involved, but their roles are not yet well understood. Although biochemical markers indicate that Secretory Activation begins about 30–40 hours after birth, mothers do not typically begin feeling increased breast fullness (the sensation of milk “coming in the breast”) until 50–73 hours (2–3 days) after birth.

Colostrum is the first milk a breastfed baby receives. It contains higher amounts of white blood cells and antibodies than mature milk, and is especially high in immunoglobulin A (IgA), which coats the lining of the baby’s immature intestines, and helps to prevent pathogens from invading the baby’s system. Secretory IgA also helps prevent food allergies.[rx] Over the first two weeks after the birth, colostrum production slowly gives way to mature breast milk.[rx]

Autocrine control – Galactopoiesis

The hormonal endocrine control system drives milk production during pregnancy and the first few days after birth. When the milk supply is more firmly established, the autocrine (or local) control system begins.

During this stage, the more that milk is removed from the breasts, the more the breast will produce milk.[rx][rx] Research also suggests that draining the breasts more fully also increases the rate of milk production.[11] Thus the milk supply is strongly influenced by how often the baby feeds and how well it is able to transfer milk from the breast. Low supply can often be traced to:

• not feeding or pumping often enough
• inability of the infant to transfer milk effectively caused by, among other things:
• jaw or mouth structure deficits
• poor latching technique
• rare maternal endocrine disorders
• hypoplastic breast tissue
• inadequate calorie intake or malnutrition of the mother

Milk ejection reflex

This is the mechanism by which milk is transported from the breast alveoli to the nipple. Suckling by the baby stimulates the paraventricular nuclei and supraoptic nucleus in the hypothalamus, which signals to the posterior pituitary gland to produce oxytocin. Oxytocin stimulates the contraction of the myoepithelial cells surrounding the alveoli, which already hold milk. The increased pressure causes milk to flow through the duct system and be released through the nipple. This response can be conditioned e.g. to the cry of the baby.

Milk ejection is initiated in the mother’s breast by the act of suckling by the baby. The milk ejection reflex (also called the let-down reflex) is not always consistent, especially at first. Once a woman is conditioned to nursing, let-down can be triggered by a variety of stimuli, including the sound of any baby. Even thinking about breastfeeding can stimulate this reflex, causing unwanted leakage, or both breasts may give out milk when an infant is feeding on one breast. However, this and other problems often settle after two weeks of feeding. Stress or anxiety can cause difficulties with breastfeeding. The release of the hormone oxytocin leads to the milk ejection or let-down reflex. Oxytocin stimulates the muscles surrounding the breast to squeeze out the milk. Breastfeeding mothers describe the sensation differently. Some feel a slight tingling, others feel immense amounts of pressure or slight pain/discomfort, and still, others do not feel anything different.

A poor milk ejection reflex can be due to sore or cracked nipples, separation from the infant, a history of breast surgery, or tissue damage from prior breast trauma. If a mother has trouble breastfeeding, different methods of assisting the milk ejection reflex may help. These include feeding in a familiar and comfortable location, massage of the breast or back, or warming the breast with a cloth or shower.

Milk ejection reflex mechanism

This is the mechanism by which milk is transported from the breast alveoli to the nipple. Suckling by the baby innervates slowly-adapting[rx] and rapidly adapting [rx] mechanoreceptors that are densely packed around the areolar region. The electrical impulse follows the spinothalamic tract, which begins by innervation of the fourth intercostal nerve. The electrical impulse then ascends the posterolateral tract for one or two vertebral levels and synapses with second-order neurons, called tract cells, in the posterior dorsal horn. The tract cells then decussate via the anterior white commissure to the anterolateral corner and ascend to the supraoptic nucleus and paraventricular nucleus in the hypothalamus, where they synapse with oxytocinergic third-order neurons. The somas of these neurons are located in the hypothalamus, but their axon and axon terminals are located in the infundibulum and pars nervosa of the posterior pituitary, respectively. The oxytocin is produced in the neuron’s soma in the supraoptic and paraventricular nuclei and is then transported down the infundibulum via the hypothalamic-neurohypophyseal tract with the help of the carrier protein, neurophysin I, to the pars nervosa of the posterior pituitary, and then stored in Herring bodies, where they are stored until the synapse between second-and third-order neurons.

Following the electrical impulse, oxytocin is released into the bloodstream. Through the bloodstream, oxytocin makes its way to myoepithelial cells, which lie between the extracellular matrix and luminal epithelial cells that also make up the alveoli in breast tissue. When oxytocin binds to the myoepithelial cells, the cells contract. The increased intra-alveolar pressure forces milk into the lactiferous sinuses, into the lactiferous ducts (a study found that lactiferous sinuses may not exist.[rx] If this is true then milk simply enters the lactiferous ducts), and then out the nipple.

Afterpains

A surge of oxytocin also causes the uterus to contract. During breastfeeding, mothers may feel these contractions as afterpains. These may range from period-like cramps to strong labor-like contractions and can be more severe with second and subsequent babies. [rx][rx]

Without pregnancy, induced lactation, relaxation

In humans, induced lactation and relaxation have been observed frequently in some cultures, and demonstrated with varying success in adoptive mothers. It appears plausible that the possibility of lactation in women (or females of other species) who are not biological mothers does confer an evolutionary advantage, especially in groups with high maternal mortality and tight social bonds.[rx][rx] The phenomenon has been also observed in most primates, in some lemurs, and in dwarf mongooses.[rx][rx]

Lactation can be induced in humans by a combination of physical and psychological stimulation, by drugs, or by a combination of those methods.[rx] Some couples may stimulate lactation outside of pregnancy for sexual purposes.

Rare accounts of male lactation (as distinct from galactorrhea) exist in historical medical and anthropological literature, although the phenomenon has not been confirmed by more recent literature.[rx]

Domperidone is a drug that can induce lactation.[rx][rx]

Development

During puberty, lobule type 1 is formed. Changes in the level of estrogen and progesterone during each menstrual cycle stimulate lobule 1 to produce new alveolar buds and eventually evolve to more mature structures, known as type-2 and type-3 lobules. Once puberty is complete, no further changes occur to the female breast until pregnancy.

During pregnancy, stage-II mammogenesis (alveolar development and maturation of the epithelium) occurs largely in response to higher levels of progesterone. The increased volume of breast tissue during pregnancy is a result of the proliferation of secretory tissue. In early pregnancy, lobule type 3 is formed due to the influence of chorionic gonadotropin. These newly formed lobules have larger size and number of epithelial cells composing each acinus. In late pregnancy, the proliferation of new acini is reduced, and the lumen becomes distended with secretory material or colostrum.

During labor and lactation, further growth and differentiation can be seen in the lobule along with milk secretion. The glandular component of the breast has now increased to the point where it is mainly formed of epithelial elements and very little stroma. This will persist throughout lactation.

Finally, the involution of mammary glands occurs with the cessation of lactation and requires a combination of lactogenic hormone deprivation and local autocrine signals that signal apoptotic cell death and tissue remodeling. Full regression does not occur, and pregnancy causes a permanent increase in the size and number of lobules. Following lactation, there is always the potential of the glands to produce milk in response to regular stimulation.

Organ Systems Involved

Normal lactation involves the female breast, anterior lobe of the pituitary, and posterior lobe of the pituitary. Their roles in lactation are discussed below.

Function

The decision to breastfeed or to provide breast milk via expression is a decision that every mother must make. Clinicians must inform our patients about all the benefits that breast milk can provide to their newborns. Breast milk provides ideal nutrition for infants with vitamins, proteins, and fats that are more easily digested than formula. Breast milk contains antibodies from the mother that help babies fight off viruses and bacteria. Other anti-infective factors it provides include immunoglobulin (IgA in particular), white blood cells, whey protein (lysozyme and lactoferrin), and oligosaccharides. It also lowers the baby’s risk of asthma, allergies, ear infections, respiratory illnesses, bouts of diarrhea, and the risk of diabetes and obesity.

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Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the fetus at a developmental stage when it is ready to feed and breathe.

In some species the offspring is precocial and can move around almost immediately after birth but in others it is altricial and completely dependent on parenting.

In marsupials, the fetus is born at a very immature stage after a short gestational period and develops further in its mother’s womb’s pouch.

It is not only mammals that give birth. Some reptiles, amphibians, fish and invertebrates carry their developing young inside them. Some of these are ovoviviparous, with the eggs being hatched inside the mother’s body, and others are viviparous, with the embryo developing inside her body, as in the case of mammals.

Stages of Labor

Vaginal delivery childbirth has three distinct phases: dilation of the cervix, delivery of the infant, and delivery of the placenta.

Key Points

The first stage of labor begins when the effaced (thinned) cervix is 3 cm dilated. During effacement, the cervix is pulled upward during contractions. Full dilation occurs when the cervix is wide enough to allow passage of the baby’s head, about 10 cm for a full-term infant.

The duration of labor varies widely, but the active phase averages some 20 hours for women giving birth to their first child (primiparae) and 8 hours for women who have previously given birth (multiparae).

The second stage begins when the cervix is fully dilated, ending when the baby is born. Fetal movement through the birth canal is assisted by the additional maternal efforts of bearing down or pushing. The fetal head is seen to crown as the labia part, and the baby is born.

The period from just after the fetus is expelled until just after the placenta is expelled is called the third stage of labor, which lasts, on average, 10–12 minutes.

A fourth stage of labor may refer to the hour immediately after delivery of the placenta, or may refer to the weeks following delivery. It is the time in which the mother’s body returns to a nonpregnant state.

Key Terms

• multiparae: Women who have given birth to more than one viable fetus.
• Ferguson reflex: An example of positive feedback and the female body’s response to pressure application in the cervix or vaginal walls. Upon application of pressure, oxytocin is released and uterine contractions are stimulated (which will in turn increase oxytocin production, and hence, increase contractions even more), until the baby is delivered.
• primiparae: Women who have given birth to only one child, or who are giving birth for the first time.

The infant’s head and shoulders must go through a specific sequence of maneuvers in order to pass through the ring of the mother’s pelvis. The six phases of a typical vertex (head-first presentation) delivery are:

• Engagement of the fetal head in the transverse position.
• Descent and flexion of the fetal head.
• Internal rotation of the fetal head so that the baby’s face is towards the mother’s rectum.
• Delivery by extension (the fetal head passes out of the birth canal).
• Restitution: The fetal head turns through 45 degrees to restore its normal relationship with the shoulders, which are still at an angle.
• External rotation: The shoulders repeat the corkscrew movements of the head, which can be seen in the final movements of the fetal head.

The Bishop score defines several factors that midwives and physicians use to assess the laboring mother’s progress.
The score is used to predict whether the mother is likely to spontaneously progress into the second stage of labor and whether induction of labor will be required. It has also been used to assess the odds of spontaneous preterm delivery.

Stages of Labor

First Stage (Active Phase)

The first stage of labor classically starts when the effaced (thinned) cervix is 3 cm dilated, although there is variation as some women may or may not have active contractions prior to reaching this point. The onset of actual labor is defined when the cervix begins to progressively dilate. Rupture of the membranes or a bloody discharge may or may not occur at or around this stage.

Tterine muscles form opposing spirals from the top of the upper segment of the uterus to its junction with the lower segment. During effacement, the cervix becomes incorporated into the lower segment of the uterus. During a contraction, these muscles shorten the upper segment, drawing upwards the lower segment in a gradual expulsive motion.

The presenting fetal part is then permitted to descend. Full dilation is reached when the cervix has widened enough to allow passage of the baby’s head, around 10 cm dilation for a term baby. The duration of labor varies widely, but the active phase averages some 20 hours for women giving birth to their first child (primiparae), and 8 hours for women who have already given birth (multiparae).

Active phase arrest is defined, in a primigravid woman, as the failure of the cervix to dilate at a rate of 1.2 cm/hr over a period of at least two hours. This definition is based on Friedman’s Curve, which plots the typical rate of cervical dilation and fetal descent during active labor. Some practitioners may diagnose failure to progress, and consequently, perform a caesarean.

Second Stage (Fetal Expulsion)

The second stage begins when the cervix is fully dilated and ends when the baby is born. As pressure on the cervix increases, the Ferguson reflex increases uterine contractions.

At the beginning of the normal second stage, the head is fully engaged in the pelvis: the widest diameter of the head has passed below the level of the pelvic inlet. The fetal head then continues descending into the pelvis, below the pubic arch, and out through the vagina.

This is assisted by the additional maternal efforts of bearing down or pushing. The fetal head is seen to crown as the labia part. At this point, the woman may feel a burning or stinging sensation. The complete expulsion of the baby signals the successful completion of the second stage of labor.

The second stage of birth will vary by factors including parity, fetal size, anesthesia, or the presence of infection. Longer labors are associated with declining rates of spontaneous vaginal delivery and increasing rates of infection, perineal laceration, obstetric hemorrhage, as well as need for intensive care of the neonate.

Third Stage (Placental Delivery)

The third stage of labor is the period from just after the fetus is expelled until just after the placenta is expelled.  The average time from delivery of the baby until complete expulsion of the placenta is estimated to be 10–12 minutes.

Placental expulsion can be managed actively, by giving a uterotonic, such as oxytocin, along with appropriate cord traction and fundal massage to assist in delivering the placenta by a skilled birth attendant. Alternatively, it can be managed expectantly, allowing the placenta to be expelled without medical assistance. The umbilical cord is routinely clamped and cut in this stage, but it would normally close naturally even if not clamped and cut.

When the amniotic sac has not ruptured during labour or pushing, the infant can be born with the membranes intact. This is referred to as being born in the caul. The caul is harmless and its membranes are easily broken and wiped away. With the advent of modern interventive obstetrics, the artificial rupture of the membranes has become common, so babies are rarely born in the caul (en-caul birth).

Fourth Stage (Postpartum Period)

The fourth stage of labor is a term used in two different senses:

1. It can refer to the immediate puerperium, or the hours immediately after delivery of the placenta.
2. It can be used in a more metaphorical sense to describe the weeks following delivery.

 

Birth.: A sequence of images showing the stages of ordinary childbirth.

Adjustments of the Infant at Birth

Post birth, an infant’s physiology must adapt to breathing independently, changes in blood flow and energy access, and a cold environment.

Key Points

Following birth, the newborn’s lungs inflate and respiration begins to occur through the pulmonary system. The subsequent changes to oxygenated blood flow that occur follow the adult pattern of circulation.

The energy metabolism of the infant is also quickly converted from a continuous placental supply to intermittent feeding. Glycogen stores created during the second and third trimesters of pregnancy are relied upon for energy during the first few days following birth.

Physiological changes occur via thermoregulation to maintain core temperature including: vasoconstriction (a decrease of blood flow to skin), maintaining the fetal position (a decrease of the surface area of exposure), jittery large muscle activity (to generate muscular heat), and non-shivering thermogenesis.

Key Terms

• respiratory distress syndrome: Infant respiratory distress syndrome (IRDS), also called neonatal respiratory distress syndrome or respiratory distress syndrome (previously called hyaline membrane disease), is a syndrome in premature infants caused by the developmental insufficiency of surfactant production and structural immaturity in the lungs. It can also result from a genetic problem with the production of surfactant-associated proteins.
• surfactant: A lipoprotein in the tissues of the lung that reduces surface tension and permits more efficient gas transport.
• non-shivering thermogenesis: The process of heat production in organisms. Non-shivering thermogenesis usually occurs in brown adipose tissue (brown fat) that is present in human infants and hibernating mammals.

The first challenge of a newborn is to perfuse its body by breathing independently instead of utilizing placental oxygen. At birth, the baby’s lungs are filled with fetal lung fluid (which is not amniotic fluid) and are not inflated.

As the newborn is expelled from the birth canal, its central nervous system reacts to the sudden change in temperature and environment. This triggers it to take the first breath within about 10 seconds of delivery.

With the first breaths, there is a fall in pulmonary vascular resistance and an increase in the surface area available for gas exchange. Over the next 30 seconds, the pulmonary blood flow increases and is oxygenated as it flows through the alveoli of the lungs. Oxygenated blood now reaches the left atrium and ventricle and, through the descending aorta, reaches the umbilical arteries.

Respiration and Circulation

Oxygenated blood now stimulates constriction of the umbilical arteries resulting in a reduction in placental blood flow. As the pulmonary circulation increases, there is an equivalent reduction in the placental blood flow that normally ceases completely after about three minutes. These two changes result in a rapid redirection of blood flow into the pulmonary vascular bed, from approximately 4% to 100% of cardiac output.

The increase in pulmonary venous return results in left atrial pressure being slightly higher than right atrial pressure, which closes the foramen ovale. This change in the pattern of flow results in a drop in blood flow across the ductus arteriosus.

The higher blood oxygen content of blood within the aorta stimulates the constriction and ultimately the closure of this fetal circulatory shunt. All of these cardiovascular system changes result in the adaptation from fetal circulation patterns to an adult circulation pattern.

During this transition, some types of congenital heart diseases that were not symptomatic in utero during fetal circulation will present with cyanosis or respiratory signs.

Following birth, the expression and re-uptake of surfactant, which begins production at 20 weeks gestation, is accelerated. Expression of surfactant into the alveoli is necessary to prevent alveolar closure.

At this point, rhythmic breathing movements also commence. If there are any problems with breathing, management can include stimulation, bag and mask ventilation, intubation, and ventilation. Cardiorespiratory monitoring is essential to track potential problems.

Pharmacological therapy, such as caffeine, can also be given to treat apnea in premature newborns. A positive airway pressure should be maintained and neonatal sepsis must be ruled out. Potential neonatal respiratory problems include apnea, transient tachypnea of the newborn (TTNB), respiratory distress syndrome (RDS), meconium aspiration syndrome (MAS), airway obstruction, and pneumonia.

Energy Requirements

The energy metabolism of the fetus must be converted from a continuous placental supply of glucose to intermittent feeding. While the fetus is dependent on maternal glucose as the main source of energy, it can use lactate, free fatty acids, and ketone bodies under some conditions. Plasma glucose is maintained by glycogenolysis.

Glycogen synthesis in the liver and muscle begins in the late second trimester of pregnancy, and storage is completed in the third trimester. Glycogen stores are maximal at term, but even then, the fetus only has enough glycogen available to meet its energy needs for 8–10 hours, which can be depleted even more quickly if the demand is high.

Newborns will then rely on gluconeogenesis for energy. Fat stores are the largest storage source of energy. At 27 weeks gestation, only 1% of a fetus’ body weight is fat. At 40 weeks, that number increases to 16%.

Inadequate glucose substrate can lead to hypoglycemia, fetal growth restriction, preterm delivery, or other problems. Similarly, an excess substrate can also lead to problems, such as infant of a diabetic mother (IDM), hypothermia, or neonatal sepsis.

Anticipating potential problems is the key to managing most neonatal problems of energy metabolism. For example, early feeding in the delivery room or as soon as possible may prevent hypoglycemia. If the blood glucose is still low, then an intravenous (IV) bolus of glucose may be delivered, with continuous infusion if necessary. Rarely, steroids or glucagon may have to be employed.

Environmental Temperature

 

Infant in incubator: Infants, especially preterm infants, have trouble regulating their body temperature. Placement in an incubator allows them to adjust without draining their energy stores.

Newborns come from a warm environment to the cold and fluctuating temperatures of this world. They are naked, wet, and have a large surface area to mass ratio, with variable amounts of insulation, limited metabolic reserves, and a decreased ability to shiver.

Physiologic mechanisms for preserving core temperature include vasoconstriction (a decrease of blood flow to the skin), maintaining the fetal position (a decrease of the surface area exposed to the environment), jittery large muscle activity (to generate muscular heat), and non-shivering thermogenesis.

Non-shivering thermogenesis occurs in brown fat. Brown fat is specialized adipose tissue with a high concentration of mitochondria designed to rapidly oxidize fatty acids in order to generate metabolic heat. The newborn’s capacity to maintain these mechanisms is limited, especially in premature infants.

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Human embryonic development, or human embryogenesis, refers to the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of development. In biological terms, the development of the human body entails growth from a one-celled zygote to an adult human being. Fertilisation occurs when the sperm cell successfully enters and fuses with an egg cell (ovum). The genetic material of the sperm and egg then combine to form a single cell called a zygote and the germinal stage of development commences.^[rx] Embryonic development in the human, covers the first eight weeks of development; at the beginning of the ninth week the embryo is termed a fetus. Human embryology is the study of this development during the first eight weeks after fertilisation. The normal period of gestation (pregnancy) is about nine months or 40 weeks.

Fetal Development – Stages of Growth Step By Step

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Second Week of Development/Week 2 is often referred to as the week of twos. It’s the week when the embryoblast, extraembryonic mesoderm and trophoblast each separate into two distinct .

The embryonic disc forms during early development. By the blastocyst stage, the embryo is a hollow ball of cells with the inner cell mass (embryoblast) off to one side, and the blastocystic cavity fills the remainder of the sphere.

As the embryo progresses in implantation, a small space appears in the embryoblast and forms the amniotic cavity. Simultaneously, morphological changes occur in the embryoblast that result in the formation of a flat, almost circular bilaminar plate of cells that include the epiblast and the hypoblast—the embryonic disk.

The epiblast forms the floor of the amniotic cavity and is continuous with the amnion. The hypoblast forms the roof of the exocoelomic cavity and is continuous with the thin exocoelomic membrane.

The formation of the bilaminar embryonic disc precedes gastrulation. As gastrulation progresses, the embryonic disc becomes trilaminar and the notochord is formed. Through the process of neurulation, the notochord induces the formation of the central nervous system in the embryonic disc.

The amnion is a closed sac appearing in the inner cell mass as a cavity. This cavity is roofed in by a single stratum of flattened, ectodermal cells called the amniotic ectoderm. Its floor consists of the prismatic ectoderm of the embryonic disk.

The continuity between the roof and the floor is established at the margin of the embryonic disk. Outside the amniotic ectoderm is a thin layer of mesoderm (continuous with that of the somatopleure), which is connected by the body stalk with the mesodermal lining of the chorion.

When first formed, the amnion is in contact with the body of the embryo, but by about the fourth or fifth week, amniotic fluid (liquor amnii) begins to accumulate within it. This fluid increases in quantity, causing the amnion to expand and ultimately to adhere to the inner surface of the chorion so that the extra-embryonic part of the coelom is obliterated.

This increase continues up to the sixth or seventh month of pregnancy, after which it diminishes somewhat. At the end of pregnancy, it amounts to about one liter.

The amniotic fluid allows some free movement for the fetus during the later stages of pregnancy and also diminishes the risk of injury. It contains less than two percent solids, and consists mainly of urea and other extractives, inorganic salts, a small amount of protein, and, frequently, a trace of sugar.

At the end of the fourth week, the yolk sac has the appearance of a small, pear-shaped vesicle (umbilical vesicle) opening into the digestive tube by a long, narrow tube, the vitelline duct. The vesicle can be seen in the afterbirth as a small, somewhat oval-shaped body whose diameter varies from 1 mm to 5 mm. It is situated between the amnion and the chorion and may lie on or at a varying distance from the placenta.

As a rule, the vitelline duct undergoes complete obliteration during the seventh week. In about 2% of the cases, its proximal portion persists as a diverticulum from the small intestine (Meckel’s diverticulum), which is situated about 60 cm proximal to the ileocecal valve. It may be attached by a fibrous cord to the abdominal wall at the umbilicus. Sometimes, a narrowing of the lumen of the ileum is seen opposite the site of attachment of the duct.

The yolk sac starts forming during the second week of embryonic development, at the same time of the shaping of the amniotic sac. The hypoblast starts proliferating laterally and descending. In the meantime Heuser’s membrane, located on the opposite pole of the developing vesicle, starts its upward proliferation and meets the hypoblast.

Development of the Extraembryonic Coelom

The extra-embryonic coelom is a cavity that contains the chorion. It is located between Heuser’s membrane and the trophoblast.

Key Points

The extra-embryonic coelom develops at the same time as the primitive yolk sac through the proliferation and differentiation of hypoblast cells into mesenchymal cells that fill the area between Heuser’s membrane and the trophoblast. The entire structure is enclosed by the chorionic plate.

The extra-embryonic mesoderm is subdivided into two layers: the extra-embryonic splanchnopleuric mesoderm, which is outside the primitive yolk sac; and the extra-embryonic somatopleuric mesoderm, which is adjacent to the cytotrophoblast.

The chorion is one of the membranes that exist during pregnancy between the developing fetus and mother.

Key Terms

• chorion: The protective and nutritive membrane that attaches higher vertebrate fetuses to the uterus.
• Heuser’s membrane: Heuser’s membrane (or the exocoelomic membrane) is a short-lived combination of hypoblast cells and extracellular matrix.
• coelum: Also called the chorionic cavity, this is a portion of the conceptus that consists of a cavity between Heuser’s membrane and the trophoblast.

Development of the Extra-Embryonic Coelom

Gestational sac: An artificially colored image of the contents in the cavity of the uterus seen at approximately 5 weeks of gestational age by obstetric ultrasonography.

The extra-embryonic coelom (or chorionic cavity) is a portion of the conceptus consisting of a cavity between Heuser’s membrane and the trophoblast. During the formation of the primitive yolk sac, some of the migrating hypoblast cells transdifferentiate into mesenchymal cells that fill the space between Heuser’s membrane and the trophoblast to form the extra-embryonic mesoderm.

As development progresses, small lacunae begin to form within the extra-embryonic mesoderm that become larger and form the extra-embryonic coelom.

The extra-embryonic mesoderm is divided into two layers: the extra-embryonic splanchnopleuric mesoderm, which lies adjacent to Heuser’s membrane around the outside of the primitive yolk sac; and the extra-embryonic somatopleuric mesoderm, which lies adjacent to the cytotrophoblast layer of the embryo.

The extra-embryonic coelomic cavity is also called the chorionic cavity—it is enclosed by the chorionic plate. The chorionic plate is composed of an inner layer of somatopleuric mesoderm and an outer layer of trophoblast cells. It is the fetal
aspect of the placenta that gives rise to chorionic villi.

Chorion Development

The chorion is one of the membranes that exist during pregnancy between the developing fetus and the mother. It consists of an extra-embryonic mesoderm and two layers of trophoblast and surrounds the embryo and other membranes.

Villi emerge from the chorion, which invade the endometrium, destroy the uterine decidua, and allow the transfer of nutrients from maternal blood to fetal blood.

Chorionic villi are at first small and nonvascular, and consist of only trophoblast, but they increase in size and branch. Blood is carried to the villi by the paired umbilical arteries, which branch into chorionic arteries and enter the chorionic villi as cotyledon arteries.

After circulating through the capillaries of the villi, the blood is returned to the embryo by the umbilical veins. Until about the end of the second month of pregnancy, the villi cover the entire chorion, and are almost uniform in size; but, after this stage, they develop unequally.

2nd weeks

Following all the excitement associated with the first gestational week, the newly formed blastocyst is ready to settle into a supportive environment and continue the growth process. Week 2 is often referred to as the week of twos. It’s the week when the embryoblast, extraembryonic mesoderm and trophoblast each separate into two distinct layers. Additionally, there are two cavities that develop within the embryonic unit at this time as well.

While every step is integral for adequate foetal development, one of the most important features of the second week is the completion of implantation and establishment of fetomaternal interactions. This article will follow the developing embryo through the completion of implantation and development of the non-embryonic components of the conceptus. It will also discuss some complications associated with implantation.

Implantation of the blastocyst

Implantation is a complex biochemical and mechanical process that begins in the first week of gestation and extends into the second week. There are many influencing factors that affect the process. These can be grouped into maternal and embryonal factors. However, both entities work synchronously in order to effectively achieve implantation. The process of implantation can be subdivided into three phases:

• There is a period of apposition where the blastocyst establishes weak interactions with the uterine wall.
• The attachment phase occurs when definitive binding of the blastocyst to the uterine epithelium is more established, such that the blastocyst cannot be flushed from the uterine cavity.
• Finally invasion occurs when the blastocyst begins to burrow into the endometrium.

This period usually occurs between the 19th and 24th day of the menstrual cycle. This coincides roughly with the 6th to 10th day following ovulation.

Maternal factors affecting implantation

In anticipation for successful fertilization each month, the inner uterine wall (endometrium) undergoes a series of changes in order to facilitate the blastocyst. Recall that there are three layers of the endometrium – the strata basalis, spongiosum and compactum.

The deepest layer is the stratum basalis, which functions as the regenerative layer and proliferates to form the stratum spongiosum and stratum compactum. Stratum compactum is the most superficial and the stratum spongiosum resides between the two. Together, the strata compactum and spongiosum form the stratum functionalis; which is the functional layer of the endometrium that facilitates implantation.

The development of the stratum functionalis is mitigated by surges in estrogen (which are released from the maturing ovarian follicle, under the influence of follicle stimulating hormone). If fertilization did not occur during the previous menstrual cycle, the fall in reproductive hormones result in the degeneration of the stratum functionalis. The shedding of this layer during the menstrual phase of the cycle accounts for the vaginal bleeding known as menstruation.

In the subsequent cycle, as follicle stimulating hormone levels rise and stimulate maturation of another ovarian follicle, the resultant increase in estrogen levels leads to proliferation of the stratum basalis. This is known as the proliferative phase, during which time there is thickening of the endometrium. Following an increase in luteinizing hormone and the release of a secondary oocyte, the remaining corpus luteum continues to release estrogen and progesterone to maintain the stratum functionalis. The spiral arteries of the uterus become longer and more tortuous under the influence of the sex hormones.

Following successful fertilization the uterine epithelia, which is characterized by ciliated columnar cells with microvilli, undergoes morphological changes to accommodate the growing embryo. The expression of these cilia (extended processes located at the apical aspect of the cells) is regulated by both progesterone and estrogen. The underlying motile microtubules allow the cilia to move the developing embryo toward a favourable site on the uterine wall. This process usually starts around the end of the first gestational week, when the conceptus is classified as a blastocyst.

The process of bringing the conceptus close to the uterine wall is referred to as adplantation (apposition). As the blastocyst rolls along the surface of the uterus, the pole of the blastocyst with the inner cell mass is adjacent to the uterine wall. Early attachments to the microvilli (short, non-motile, apical epithelial processes) also facilitate the initiation of implantation.

Once the uterine lining is receptive for implantation, the endometrium is said to be in the implantation window. However, this is a complex process that depends on the presence of numerous cytokines, immunomodulators, and increased binding capacity of the epithelium in order for implantation to work. Recall from the first week of gestation that the resulting conceptus is genetically unique when compared with its parents. Therefore, the mother’s immune system should identify the blastocyst as a parasitic entity that should be destroyed.

A key element in the implantation phase that is thought to modify this anticipated immune response (and other parts of implantation) is known as leukaemia inhibitory factor (LIF). This is a member of the interleukin – 6 (IL-6) family that has the ability to influence several unrelated gene expressions (i.e. it’s a pleiotropic entity). Within the reproductive system, it is produced by both the endometrial epithelium as well as the developing blastocyst. Leukaemia inhibitory factor has the following functions with regards to endometrial receptivity:

• The decidualization of the stromal cells (discussed below) is by LIF. This response is generated by way of a cyclic adenosine monophosphate (cAMP) pathway that activates a biochemical cascade involving estrogen and progesterone, IL-5, IL-6, prostaglandins, and cyclooxygenase 2 (COX-2). The resultant cellular morphological change creates a more favourable implantation environment. This particular reaction is important because it plays a significant role in immunomodulation. It is particularly difficult for thymocytes (T-cells) to invade decidual tissue; similarly, decidual cells have a hard time recruiting T-cells from the percolating blood. Therefore, the probability of the maternal immune system mounting a cytotoxic T-lymphocyte (CTL) response against the allogeneic conceptus is markedly reduced.
• In addition, LIF upregulates numerous epidermal growth factors such as heparin – binding epidermal growth factor like protein (HB-EGF), epiregulin (EPR), and amphiregulin (AREG). These proteins act as ligands for the epidermal growth factor receptors and subsequently stimulate the proliferation of the endometrial epidermis.
• LIF also stimulates the activity of implantation genes, including members of the Wnt family (Wnt 4, 5a, and others) and MutS homolog homebox 1 gene (MSX 1). These and other implantation genes result in differentiation of the luminal and glandular epithelia (decidualization), proliferation of the stromal cells, and decrease in the polarity of the epithelium to foster adhesion.
• Uterodomes (also known as pinopods) are micro-protrusions of the luminal surface of the uterine epithelium that interdigitate with the blastocyst during adplantation and attachment. While they are present throughout the luteal phase of the menstrual cycle, they increase in number under the influence of LIF. In lower other mammals, pinopods are thought to play a significant role in pinocytosis (cell drinking). However, this is not its primary role in humans. As a result, they are referred to as uterodomes based on their appearance.
• Under normal circumstances, the luminal surface of the uterus is coated with a thick layer of glycocalyx. This is a carbohydrate, glycoprotein rich layer that promotes repulsion of foreign entities from the cell membranes. It also has a large quantity of mucins (MUC-1 and MUC-4). LIF mediates significant local downregulation of MUC-1 in the area of the epithelium adjacent to the hatched blastocyst, which reduces repulsion of the blastocyst. However, relatively high levels of mucins are normally present in unfavourable implantation sites to prevent attachment.
• Finally, the presence and activity of a member of the junctional adhesion molecule family (JAM-2) is also noted to be increased within the uterus during the 1st to 2nd gestational weeks. Junctional adhesion molecules have the ability to interact within the family (i.e. JAM-JAM binding) as well as with other integrins on non-uterine cells. They therefore promote cellular attachment to the epithelial membrane. Both LIF and progesterone have been shown to upregulate the expression of these adhesion molecules.

As mentioned earlier, the luminal uterine stroma undergoes morphological transformation under the influence of LIF, estrogen and progesterone. This process – known as decidualization – involves accumulation of lipids and glycogen at a cellular level. The cells (i.e. decidual cells) subsequently acquire a polyhedral shape (as opposed to their previous columnar appearance). The process begins locally at the site of fetomaternal attachment, but gradually radiates until the entire endometrium has been transformed. On a molecular level, bone morphogenetic protein 2 (BMP-2) is needed for this transformation to occur; its deficiency is a known cause of infertility. The decidua provides an immunologically safe space for the embryo, in addition to providing nutrition for its development.

Fetal factors affecting implantation

As the blastocyst is hatched from the zona pellucida, it comes into contact with the endometrium. Surface proteins on the trophoblast known as trophinin interact with similar trophinin molecules on the endometrial surface. This plays a role in the differentiation of the trophoblast into two distinct layers:

• In the periphery, there are multinucleated cells that have no discernible cell walls. This area is referred to as the syncytiotrophoblast. There is no mitotic activity in this area.
• Deep to the syncytiotrophoblast is a cluster of mitotically active cells known as the cytotrophoblast. This cluster of cells rapidly replicates and migrates to the periphery in order to support the growing syncytiotrophoblast.

Of note, by the end of week 2, the bilaminar disc develops a localized region of thickened cells in the hypoblast. This area is referred to as the prechordal plate. Not only does the prechordal plate help with the organization of the head region during development, but it also indicates the future head region and the location of the mouth.

The syncytiotrophoblast is a highly invasive structure that penetrates the endometrium in order for the blastocyst to become embedded. The trophinin-trophinin binding also induces endometrial epithelial apoptosis in the mother in order to accommodate the invading cell mass. The blastocyst then utilizes the nutrients from the recently destroyed maternal cells as it continues to grow. Furthermore, the syncytiotrophoblast (under the influence of LIF) begins to produce human chorionic gonadotropin hormone (β-hCG). The presence of β-hCG prevents corpus luteum degeneration, resulting in the continued release of estrogen and progesterone. The detection of the glycoprotein in maternal circulation and urine also forms the basis of the pregnancy test.

Another recently discovered element that contributes to implantation is the protein preimplantation factor. It is derived from the embryo and has been shown to aid in maternal immunomodulation, embryo-endometrial adhesion, and endometrial apoptosis.

Review of the initial sequence of implantation

Let’s recap the initial implantation sequence:

• Endometrial development occurs each month in anticipation of successful fertilization.
• Successful fertilization occurs and the zygote develops into a blastocyst.
• The blastocyst roles along the endometrium towards a favourable implantation site.
• Concurrently, there is maternal immunomodulation, downregulation of repelling entities and upregulation of adhesion moieties.
• The blastocyst hatches from the zona pellucida.
• Adplantation occurs when weak carbohydrate binding occurs between the embryo and the glycocalyx.
• As the embryo gets closer to the endometrium, stronger bonds are formed. These involve interactions with integrins, L-selectin, osteopontin, cadherins, trophinin, as well as CD44 and CD98.
• Attachment stimulates maternal decidualization and embryonal trophoblast differentiation.
• Trophoblastic invasion coincides with desmosomal detachment of maternal cells, as well as apoptosis of adjacent decidua.

Amniotic cavity

While implantation ensues, the embryoblast also undergoes differentiation to form a bilaminar disc. The flat, circular disc is comprised of a thicker epiblast with high columnar cells and a thinner hypoblast with small cuboidal cells. A small space develops relative to the epiblast; it is the precursor of the amniotic cavity.

Epiblastic cells forming the floor of the cavity subsequently separate to form amnioblasts that will form the amnion (surrounding the amniotic cavity). The sac and cavity will eventually become filled with amniotic fluid later on in the pregnancy. They provide shock absorption and facilitate movement of the foetus during development.

Umbilical vesicle

Peripherally, the hypoblast is continuous with another structure known as the exocoelomic (Heuser’s) membrane. It also forms the roof of the enclosed exocoelomic cavity. Combined, the membrane and the hypoblast form the visceral lining of the yolk sac. However, since the human embryo does not possess a yolk, it is more appropriate to refer to it as the primary umbilical vesicle.

Endodermal cells arising from the exocoelomic membrane extends circumferentially to enclose the embryonic disc and both cavities. It is subsequently referred to as the extraembryonic mesoderm. Both cavities facilitate embryonic folding as growth and morphological changes occur. The umbilical vesicle may play a role in nutrient transfer to the embryo. Furthermore, it is an important source of primordial germ cells.

Early fetomaternal circulation

While the aforementioned cavities and bilaminar disc develop, the syncytiotrophoblast began to lacunate (I.e. form lacunae). The lacunae are filled with an amalgam of cellular debris and maternal blood, known as the embryotroph. This fluid gains access to the embryonic disc via diffusion and delivers nutrients as well as oxygen to the embryo. The lacunae subsequently become confluent, forming lacunar networks, which serves as the primordial uteroplacental circulation. As the networks continue to fuse, the syncytiotrophoblast has a sieve-like appearance, particularly around the embryonic pole of the conceptus. This will subsequently give rise to the intervillous spaces of the placenta.

The capillaries around the implanted embryo become engorged, dilated and their walls become thin. From here onwards, they are known as sinusoids. The syncytiotrophoblast continues to erode the walls of the sinusoids, resulting in more maternal blood flowing freely into the lacunar networks. Much of the derived nutrients is conveyed to the embryo by the trophoblast. However, the trophoblast grows a lot faster than the embryo in the early phases. As such, it is likely to have a higher nutritional requirement than the embryo.

Chorionic sac

As time progresses, the extraembryonic mesoderm increases in size. Numerous cavities known as the extraembryonic coelomic spaces begin to appear deep to the cytotrophoblast and superficial to the exocoelomic membrane. These spaces coalesce to form the extraembryonic coelom. This coincides with a decrease in the volume of the primary umbilical vesicle; which is then referred to as the secondary umbilical vesicle. The cells of the secondary umbilical vesicle arise from migratory extraembryonic endodermal cells of the hypoblast. There is a remnant of the primary umbilical vesicle within the extraembryonic coelom that is referred to as an exocoelomic cyst.

Cellular columns, lined with syncytial coverings, extending into the syncytiotrophoblast indicate the ending of the second gestational week. This phenomenon marks the formation of the primary chorionic villi. Splanchnic and somatic derivatives of the extraembryonic mesoderm line the umbilical vesicles, and the trophoblast and amnion, respectively. The somatic extraembryonic mesoderm, along with both trophoblastic layers, gives rise to the chorion. The space enclosed by the chorion is the chorionic sac; it contains the embryo, as well as the amniotic sac and umbilical vesicle. The latter three structures are attached to the chorion by the connecting stalk. The former extraembryonic coelom is now referred to as the chorionic cavity.

Implantation completed

By the 10th day following fertilization, the embryo is completely embedded in the endometrium. There is a small defect in the epithelium that is sealed by a fibrin-based blood clot known as the closing plug. By day 12, the area is completely healed. The 14 day embryo maintains the form of a flat bilaminar embryonic disc at the end of second week. The thickened prechordal plate develops as a localized thickening of hypoblast and indicates the future site of mouth and organizer of the head region.

Summary of 2nd Week

Here is a simplified summary of the events of the second week:

• The hatched blastocyst moves along the endometrium towards a favourable point of implantation.
• The endometrium is converted into an immunologically privileged site with optimum blood supply
• Weak attachments are strengthened.
• Differentiation of the trophoblast and endometrial stroma facilitate invasion of the endometrium.
• Several cavities and membranes are formed.
• β-hCG production is stimulated.
• Complete implantation with endometrial scarring is achieved by day 10.
• Complete regeneration around the scar results around day 12.
• At the end of week 2, the chorionic cavity is formed.

References

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The first week of embryonic development is filled with an eclectic arrangement of physical and biochemical changes. Each step is a part of a cascade of events that must be intricately coordinated in order to produce a healthy baby at the end of the thirty eight to forty week period. However, the events of the first week of gestation are highly dependent on prior events that create the ideal environment for fertilization and implantation to occur. This article aims at briefly reviewing the processes preceding fertilization. There will be detailed evaluation of the ovulation cycle, copulation, fertilization and the first week of development.

Cleavage and migration of the zygote

The resulting zygote undergoes a series of mitotic division, which commences about 30 hours after fertilization has occurred. With each division, the progeny (known as blastomeres) become smaller. The blastomeres are retained within the zona pellucida. Peristaltic activity continues to move the dividing ball of cells from the fallopian tube into the uterine cavity. When there are more than 8 blastomeres within the zona pellucida, the cells undergo compaction, where each cell realigns with adjacent cells to maximize the space available. It also prepares the cells to separate into the inner and outer cell masses. Division continues and on the 3rd day after fertilization, there are 12 to 32 blastomeres clustered together. The resulting ball of cells is referred to as a morula.

The morula now arrives in the uterine cavity on the 4th day post fertilization. It begins to accumulate fluid from the uterine cavity via the fenestrated zona pellucida. The resulting fluid filled space separates the blastomeres into a thin outer trophoblast and a cluster of blastomeres. The trophoblast provides nourishment for the developing blastocyst and the inner cells – which will subsequently be referred to as the embryoblast – gives rise to the embryo. This overall stage is known as blastogenesis; and the product of conception is referred to as the blastocyst.

Fertilization

Fertilization occurs when a sperm and an egg have fused together to form a zygote, which begins to divide as it moves towards the uterus.

Key Points

Fertilization is commonly known as conception. Once the fertilized gamete (ovum) implants itself in the uterine lining, pregnancy begins.

The fusion of male and female gametes ( sperm and ovum, respectively) usually occurs following the act of sexual intercourse. However, artificial insemination and in vitro fertilization have made achieving pregnancy possible without engaging in sexual intercourse.

The process of fertilization occurs in several steps and the interruption of any of them can lead to failure.

Prior to fertilization, sperm undergo a process of capacitation in response to conditions in the female reproductive tract, which include increases in motility and destabilization of the cell membrane that allows the head of the sperm to penetrate the egg.

Key Terms

• fertilization: The act of fecundating or impregnating animal or vegetable gametes.
• capacitation: A step spermatozoa undergo in the female reproductive track that renders them capable of fertilizing an oocyte.
• implantation: The embedding of the fertilized ovum into the uterine wall.
• Nondisjunction: Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division.
• zygote: A fertilized egg cell.

If pregnancy is considered to begin at the point of implantation, the process leading to pregnancy occurs earlier as the result of the female gamete, or oocyte, merging with the male gamete, or spermatozoon. In medicine, this process is referred to as fertilization; in lay terms, it is more commonly known as conception.

After the point of fertilization the fused product of the female and male gamete is referred to as a zygote or fertilized egg. For species that undergo internal fertilization, such as humans, the fusion of male and female gametes usually occurs following the act of sexual intercourse.

However, the advent of artificial insemination and in vitro fertilization have made achieving pregnancy possible without engaging in sexual intercourse. This approach may be undertaken as a voluntary choice or due to infertility.

 

Human fertilization: The sperm and ovum unite through fertilization, creating a zygote that (over the course of 8–9 days) will implant in the uterine wall, where it will reside over the course of 9 months.

The process of fertilization occurs in several steps and the interruption of any of them can lead to failure. At the beginning of the process, the sperm undergoes a series of changes, as freshly ejaculated sperm is unable or poorly able to fertilize.

The sperm must undergo capacitation in the female’s reproductive tract over several hours, which increases its motility and destabilizes its membrane. By destabilizing the membrane, the sperm prepares for the acrosome reaction, the enzymatic penetration of the egg’s tough membrane, the zona pellucida. The sperm and the egg cell (which has been released from one of the female’s two ovaries) unite in one of the two fallopian tubes.

The fertilized egg, known as a zygote, then moves toward the uterus, a journey that can take up to a week to complete until implantation occurs. Through fertilization, the egg is activated to begin its developmental process (progressing through meiosis II), and the haploid nuclei of the two gametes come together to form the genome of a new diploid organism.

Nondisjunction during the completion of meiosis or problems with early cell division in the zygote to blastula stages can lead to problems with implantation and pregnancy failure.

Cleavage of the Zygote

The process of cleavage is the step of embryogenesis where the zygote divides to produce a cluster of cells known as the morula.

Key Points

Following fertilization a series of rapid cell divisions occur that decrease the cells’ size with each subsequent division—this eventually produces a morula. The different cells derived from cleavage, up to the blastula stage, are called blastomeres.

For species such as humans, there is little yolk in eggs, and the divisions are relatively symmetrical, or holoblastic.

For other species, such as birds and reptiles, the presence of yolk dictates uneven meroblastic divisions that produce cells of uneven size and distribution.

The end of cleavage is known as the midblastula transition and coincides with the onset of zygotic transcription.

The cells of the morula are at first closely aggregated, but quickly become arranged into an outer or peripheral layer, the trophoblast, which does not contribute to the formation of the embryo proper, and an inner cell mass from which the embryo develops.

Key Terms

• cleavage: In embryology, this is the division of cells in the early embryo.
• trophoblast: The membrane of cells that forms the wall of a blastocyst during early pregnancy and provides nutrients to the embryo, and later develops into part of the placenta.
• zygote: A fertilized egg cell.
• morula: A spherical mass of blastomeres that forms following the splitting of a zygote; it becomes the blastula.

Cell division with no significant growth that produces a cluster of cells that is the same size as the original zygote, is called cleavage. At least four initial cell divisions occur, resulting in a dense ball of at least sixteen cells called the morula.

The different cells derived from cleavage up to the blastula stage are called blastomeres. Depending mostly on the amount of yolk in the egg, the cleavage can be holoblastic (total) or meroblastic (partial).

 

Cell cleavage: Early development is characterized by cleavage of the zygote, which refers to cell divisions that are not associated with significant growth of the embryo.

Holoblastic cleavage occurs in animals with little yolk in their eggs. These species, such as humans and other mammals, receive nourishment as embryos from the mother via the placenta or milk after birth.

On the other hand, meroblastic cleavage occurs in animals whose eggs have more yolk, such as birds and oviparous reptiles (although some viviparous reptiles also exist). Since cleavage is impeded by the vegetal pole, there is a very uneven distribution and size of cells. Cells are more numerous and smaller at the animal pole of the zygote than at the vegetal pole.

In holoblastic eggs, the first cleavage always occurs along the vegetal–animal axis of the egg, and the second cleavage is perpendicular to the first. From here, the spatial arrangement of blastomeres can follow various patterns, due to different planes of cleavage in various organisms.The end of cleavage is known as the midblastula transition and coincides with the onset of zygotic transcription.

In amniotes, the cells of the morula are at first closely aggregated. However, they quickly become arranged into an outer or peripheral layer, the trophoblast, and an inner cell mass. The trophoblast does not contribute to the formation of the embryo proper; the embryo develops from the inner cell mass.

Fluid collects between the trophoblast and the greater part of the inner cell mass, and thus the morula, is converted into the blastodermic vesicle (also called the blastocyst or blastula). The inner cell mass remains in contact with the trophoblast at one pole of the ovum. This is named the embryonic pole, since it indicates the location where the future embryo will develop.

In the case of monozygotic twins (derived from one zygote), a zygote divides into two separate cells (embryos) at the first cleavage division. Monozygotic twins can also develop from two inner cell masses.

A rare occurrence is the division of a single inner cells mass giving rise to twins. However, if one inner cell mass divides incompletely, the result is conjoined twins. Dizygotic twins is the development of two embryos from two different zygotes.

Blastocyst Formation

The blastocyst forms early in embryonic development and has two layers that form the embryo and placenta.

Key Points

The human blastocyst possesses an inner cell mass (ICM), or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast, which later forms the placenta.

The trophoblast surrounds the inner cell mass and a fluid-filled, blastocyst cavity known as the blastocoele or the blastocystic cavity. The trophoblast combines with the maternal endometrium to form the placenta in eutherian mammals.

Before gastrulation, the cells of the trophoblast become differentiated into two strata: the ectoderm of the chorion plays a role in the development of the placenta, and the endoderm differentiates and quickly assumes the form of a small sac, called the yolk sac.

The embryoblast is the source of embryonic stem cells and gives rise to all later structures of the adult organism.

The floor of the amniotic cavity is formed by the embryonic disk, which is composed of a layer of prismatic cells, and the embryonic ectoderm, which is derived from the inner cell mass and lies in opposition to the endoderm.

Key Terms

• embryonic disk: The floor of the amniotic cavity is formed by the embryonic disk (or disc) that is composed of a layer of prismatic cells called the embryonic ectoderm. It is the part of the inner cell mass from which the embryo is developed.
• blastocyst: An early form in the development of an embryo that consists of a spherical layer of cells filled with fluid.
• gastrulation: The stage of embryonic development when a gastrula is formed from the blastula by the inward migration of cells.
• eutherian: Refers to all species of which the female gives birth to live young that receive prenatal nourishment via the placenta.

In humans, the blastocyst is formed approximatelyy five days after fertilization. This stage is preceded by the morula. The morula is a solid ball of about 16 undifferentiated, spherical cells. As cell division continues in the morula, the blastomeres change their shape and tightly align themselves against each other. This is called compaction and is likely mediated by cell surface adhesion glycoproteins.

The blastocyst possesses an inner cell mass (ICM), or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast, which later forms the placenta. The trophoblast surrounds the inner cell mass and a fluid-filled, blastocyst cavity known as the blastocoele or the blastocystic cavity.

The embryoblast is the source of embryonic stem cells and gives rise to all later structures of the adult organism. The trophoblast combines with the maternal endometrium to form the placenta in eutherian mammals.

 

Blastocyst: The blastocyst possesses an inner cell mass from which the embryo will develop, and an outer layer of cells, called the trophoblast, which will eventually form the placenta.

Before gastrulation, the cells of the trophoblast become differentiated into two strata. The outer stratum forms a syncytium, which is a layer of protoplasm studded with nuclei that shows no evidence of subdivision into cells (termed the syncytiotrophoblast).

The inner layer, the cytotrophoblast or layer of Langhans, consists of well-defined cells. As already stated, the cells of the trophoblast do not contribute to the formation of the embryo proper; they form the ectoderm of the chorion and play an important part in the development of the placenta.

On the deep surface of the inner cell mass, a layer of flattened cells, called the endoderm, is differentiated and quickly assumes the form of a small sac, called the yolk sac. Spaces appear between the remaining cells of the mass and, by the enlargement and coalescence of these spaces, a cavity called the amniotic cavity is gradually developed.

The floor of this cavity is formed by the embryonic disk, which is composed of a layer of prismatic cells called the embryonic ectoderm. This layer is derived from the inner cell mass and lies in opposition to the endoderm.

Implantation

Implantation is the very early stage of pregnancy at which the embryo adheres to the wall of the uterus and begins to form the placenta.

Key Points

At this stage of prenatal development the embryo is a blastocyst. In humans, implantation of a fertilized ovum occurs between 6 to 12 days after ovulation.

In preparation for implantation, the blastocyst sheds its outside layer, the zona pellucida, and is replaced by a layer of underlying cells called the trophoblast. The trophoblast will give rise to the placenta after implantation.

During implantation, the trophoblast differentiates into two distinct layers: the inner cytotrophoblast, and the outer syncytiotrophoblast. The syncytiotrophoblast then implants the blastocyst into the endometrium by forming finger-like projections into the uterine wall called chorionic villi.

Key Terms

• endometrium: The mucous membrane that lines the uterus in mammals and in which fertilized eggs are implanted.
• trophoblast: The membrane of cells that forms the wall of a blastocyst during early pregnancy and provides nutrients to the embryo and later develops into part of the placenta.
• human chorionic gonadotropin (hCG): In molecular biology, human chorionic gonadotropin (hCG) is a hormone produced during pregnancy that is made by the developing placenta after conception, and later by the placental component.
• implantation: The embedding of the blastocyst to the uterine wall.

Implantation is the very early stage of pregnancy during which the embryo embeds into the wall of the uterus. At this stage of prenatal development, the embryo is a blastocyst.

It is by this adhesion that the fetus receives oxygen and nutrients from the mother to be able to grow. In humans, implantation of a blastocyst occurs between 6 to 12 days after ovulation.

In preparation for implantation, the blastocyst sheds its outside layer, the zona pellucida, which binds sperm during fertilization. The zona pellucida degenerates and decomposes, and is replaced by a layer of underlying cells called the trophoblast.

The trophoblast will give rise to the placenta after implantation. During implantation, the trophoblast differentiates into two distinct layers: the inner cytotrophoblast, and the outer syncytiotrophoblast.

 

Chorionic villi: During implantation, extensions of the trophoblast, the syncytiotrophoblasts, embed within the endometrium and form chorionic villi.

The syncytiotrophoblast then implants the blastocyst into the endometrium of the uterus by forming finger-like projections into the uterine wall called chorionic villi. The chorionic villi grow outwards until they come into contact with the maternal blood supply.

The chorionic villi will be the border between maternal and fetal blood during the pregnancy, and the location of gas and nutrient exchange between the fetus and the mother. The creation of chorionic villi is assisted by hydrolytic enzymes that erode the uterine epithelium.

The syncytiotrophoblast also produces human chorionic gonadotropin (hCG), a hormone that notifies the mother’s body that she is pregnant and prevents menstruation by sustaining the function of the progesterone-producing corpus luteum within the ovary.

Human chorionic gonadotropin is the hormone that is detected by pregnancy tests, as it is found in the maternal bloodstream and urine.

References

• https://www.ncbi.nlm.nih.gov/books/NBK554562/
• https://www.ncbi.nlm.nih.gov/books/NBK542186/
• https://www.ncbi.nlm.nih.gov/books/NBK563181/
• https://www.ncbi.nlm.nih.gov/books/NBK9983/
• https://www.mayoclinic.org/healthy-lifestyle/prenatal-care/art-20045302

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First Week of Development/The first week of embryonic development is filled with an eclectic arrangement of physical and biochemical changes. Each step is a part of a cascade of events that must be intricately coordinated in order to produce a healthy baby at the end of the thirty eight to forty week period. However, the events of the first week of gestation are highly dependent on prior events that create the ideal environment for fertilization and implantation to occur. This article aims at briefly reviewing the processes preceding fertilization. There will be detailed evaluation of the ovulation cycle, copulation, fertilization and the first week of development.

Cleavage and migration of the zygote

The resulting zygote undergoes a series of mitotic division, which commences about 30 hours after fertilization has occurred. With each division, the progeny (known as blastomeres) become smaller. The blastomeres are retained within the zona pellucida. Peristaltic activity continues to move the dividing ball of cells from the fallopian tube into the uterine cavity. When there are more than 8 blastomeres within the zona pellucida, the cells undergo compaction, where each cell realigns with adjacent cells to maximize the space available. It also prepares the cells to separate into the inner and outer cell masses. Division continues and on the 3rd day after fertilization, there are 12 to 32 blastomeres clustered together. The resulting ball of cells is referred to as a morula.

The morula now arrives in the uterine cavity on the 4th day post fertilization. It begins to accumulate fluid from the uterine cavity via the fenestrated zona pellucida. The resulting fluid filled space separates the blastomeres into a thin outer trophoblast and a cluster of blastomeres. The trophoblast provides nourishment for the developing blastocyst and the inner cells – which will subsequently be referred to as the embryoblast – gives rise to the embryo. This overall stage is known as blastogenesis; and the product of conception is referred to as the blastocyst.

Fertilization

Fertilization occurs when a sperm and an egg have fused together to form a zygote, which begins to divide as it moves towards the uterus.

Key Points

Fertilization is commonly known as conception. Once the fertilized gamete (ovum) implants itself in the uterine lining, pregnancy begins.

The fusion of male and female gametes ( sperm and ovum, respectively) usually occurs following the act of sexual intercourse. However, artificial insemination and in vitro fertilization have made achieving pregnancy possible without engaging in sexual intercourse.

The process of fertilization occurs in several steps and the interruption of any of them can lead to failure.

Prior to fertilization, sperm undergo a process of capacitation in response to conditions in the female reproductive tract, which include increases in motility and destabilization of the cell membrane that allows the head of the sperm to penetrate the egg.

Key Terms

• fertilization: The act of fecundating or impregnating animal or vegetable gametes.
• capacitation: A step spermatozoa undergo in the female reproductive track that renders them capable of fertilizing an oocyte.
• implantation: The embedding of the fertilized ovum into the uterine wall.
• Nondisjunction: Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division.
• zygote: A fertilized egg cell.

If pregnancy is considered to begin at the point of implantation, the process leading to pregnancy occurs earlier as the result of the female gamete, or oocyte, merging with the male gamete, or spermatozoon. In medicine, this process is referred to as fertilization; in lay terms, it is more commonly known as conception.

After the point of fertilization the fused product of the female and male gamete is referred to as a zygote or fertilized egg. For species that undergo internal fertilization, such as humans, the fusion of male and female gametes usually occurs following the act of sexual intercourse.

However, the advent of artificial insemination and in vitro fertilization have made achieving pregnancy possible without engaging in sexual intercourse. This approach may be undertaken as a voluntary choice or due to infertility.

 

Human fertilization: The sperm and ovum unite through fertilization, creating a zygote that (over the course of 8–9 days) will implant in the uterine wall, where it will reside over the course of 9 months.

The process of fertilization occurs in several steps and the interruption of any of them can lead to failure. At the beginning of the process, the sperm undergoes a series of changes, as freshly ejaculated sperm is unable or poorly able to fertilize.

The sperm must undergo capacitation in the female’s reproductive tract over several hours, which increases its motility and destabilizes its membrane. By destabilizing the membrane, the sperm prepares for the acrosome reaction, the enzymatic penetration of the egg’s tough membrane, the zona pellucida. The sperm and the egg cell (which has been released from one of the female’s two ovaries) unite in one of the two fallopian tubes.

The fertilized egg, known as a zygote, then moves toward the uterus, a journey that can take up to a week to complete until implantation occurs. Through fertilization, the egg is activated to begin its developmental process (progressing through meiosis II), and the haploid nuclei of the two gametes come together to form the genome of a new diploid organism.

Nondisjunction during the completion of meiosis or problems with early cell division in the zygote to blastula stages can lead to problems with implantation and pregnancy failure.

Cleavage of the Zygote

The process of cleavage is the step of embryogenesis where the zygote divides to produce a cluster of cells known as the morula.

Key Points

Following fertilization a series of rapid cell divisions occur that decrease the cells’ size with each subsequent division—this eventually produces a morula. The different cells derived from cleavage, up to the blastula stage, are called blastomeres.

For species such as humans, there is little yolk in eggs, and the divisions are relatively symmetrical, or holoblastic.

For other species, such as birds and reptiles, the presence of yolk dictates uneven meroblastic divisions that produce cells of uneven size and distribution.

The end of cleavage is known as the midblastula transition and coincides with the onset of zygotic transcription.

The cells of the morula are at first closely aggregated, but quickly become arranged into an outer or peripheral layer, the trophoblast, which does not contribute to the formation of the embryo proper, and an inner cell mass from which the embryo develops.

Key Terms

• cleavage: In embryology, this is the division of cells in the early embryo.
• trophoblast: The membrane of cells that forms the wall of a blastocyst during early pregnancy and provides nutrients to the embryo, and later develops into part of the placenta.
• zygote: A fertilized egg cell.
• morula: A spherical mass of blastomeres that forms following the splitting of a zygote; it becomes the blastula.

Cell division with no significant growth that produces a cluster of cells that is the same size as the original zygote, is called cleavage. At least four initial cell divisions occur, resulting in a dense ball of at least sixteen cells called the morula.

The different cells derived from cleavage up to the blastula stage are called blastomeres. Depending mostly on the amount of yolk in the egg, the cleavage can be holoblastic (total) or meroblastic (partial).

 

Cell cleavage: Early development is characterized by cleavage of the zygote, which refers to cell divisions that are not associated with significant growth of the embryo.

Holoblastic cleavage occurs in animals with little yolk in their eggs. These species, such as humans and other mammals, receive nourishment as embryos from the mother via the placenta or milk after birth.

On the other hand, meroblastic cleavage occurs in animals whose eggs have more yolk, such as birds and oviparous reptiles (although some viviparous reptiles also exist). Since cleavage is impeded by the vegetal pole, there is a very uneven distribution and size of cells. Cells are more numerous and smaller at the animal pole of the zygote than at the vegetal pole.

In holoblastic eggs, the first cleavage always occurs along the vegetal–animal axis of the egg, and the second cleavage is perpendicular to the first. From here, the spatial arrangement of blastomeres can follow various patterns, due to different planes of cleavage in various organisms.The end of cleavage is known as the midblastula transition and coincides with the onset of zygotic transcription.

In amniotes, the cells of the morula are at first closely aggregated. However, they quickly become arranged into an outer or peripheral layer, the trophoblast, and an inner cell mass. The trophoblast does not contribute to the formation of the embryo proper; the embryo develops from the inner cell mass.

Fluid collects between the trophoblast and the greater part of the inner cell mass, and thus the morula, is converted into the blastodermic vesicle (also called the blastocyst or blastula). The inner cell mass remains in contact with the trophoblast at one pole of the ovum. This is named the embryonic pole, since it indicates the location where the future embryo will develop.

In the case of monozygotic twins (derived from one zygote), a zygote divides into two separate cells (embryos) at the first cleavage division. Monozygotic twins can also develop from two inner cell masses.

A rare occurrence is the division of a single inner cells mass giving rise to twins. However, if one inner cell mass divides incompletely, the result is conjoined twins. Dizygotic twins is the development of two embryos from two different zygotes.

Blastocyst Formation

The blastocyst forms early in embryonic development and has two layers that form the embryo and placenta.

Key Points

The human blastocyst possesses an inner cell mass (ICM), or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast, which later forms the placenta.

The trophoblast surrounds the inner cell mass and a fluid-filled, blastocyst cavity known as the blastocoele or the blastocystic cavity. The trophoblast combines with the maternal endometrium to form the placenta in eutherian mammals.

Before gastrulation, the cells of the trophoblast become differentiated into two strata: the ectoderm of the chorion plays a role in the development of the placenta, and the endoderm differentiates and quickly assumes the form of a small sac, called the yolk sac.

The embryoblast is the source of embryonic stem cells and gives rise to all later structures of the adult organism.

The floor of the amniotic cavity is formed by the embryonic disk, which is composed of a layer of prismatic cells, and the embryonic ectoderm, which is derived from the inner cell mass and lies in opposition to the endoderm.

Key Terms

• embryonic disk: The floor of the amniotic cavity is formed by the embryonic disk (or disc) that is composed of a layer of prismatic cells called the embryonic ectoderm. It is the part of the inner cell mass from which the embryo is developed.
• blastocyst: An early form in the development of an embryo that consists of a spherical layer of cells filled with fluid.
• gastrulation: The stage of embryonic development when a gastrula is formed from the blastula by the inward migration of cells.
• eutherian: Refers to all species of which the female gives birth to live young that receive prenatal nourishment via the placenta.

In humans, the blastocyst is formed approximatelyy five days after fertilization. This stage is preceded by the morula. The morula is a solid ball of about 16 undifferentiated, spherical cells. As cell division continues in the morula, the blastomeres change their shape and tightly align themselves against each other. This is called compaction and is likely mediated by cell surface adhesion glycoproteins.

The blastocyst possesses an inner cell mass (ICM), or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast, which later forms the placenta. The trophoblast surrounds the inner cell mass and a fluid-filled, blastocyst cavity known as the blastocoele or the blastocystic cavity.

The embryoblast is the source of embryonic stem cells and gives rise to all later structures of the adult organism. The trophoblast combines with the maternal endometrium to form the placenta in eutherian mammals.

 

Blastocyst: The blastocyst possesses an inner cell mass from which the embryo will develop, and an outer layer of cells, called the trophoblast, which will eventually form the placenta.

Before gastrulation, the cells of the trophoblast become differentiated into two strata. The outer stratum forms a syncytium, which is a layer of protoplasm studded with nuclei that shows no evidence of subdivision into cells (termed the syncytiotrophoblast).

The inner layer, the cytotrophoblast or layer of Langhans, consists of well-defined cells. As already stated, the cells of the trophoblast do not contribute to the formation of the embryo proper; they form the ectoderm of the chorion and play an important part in the development of the placenta.

On the deep surface of the inner cell mass, a layer of flattened cells, called the endoderm, is differentiated and quickly assumes the form of a small sac, called the yolk sac. Spaces appear between the remaining cells of the mass and, by the enlargement and coalescence of these spaces, a cavity called the amniotic cavity is gradually developed.

The floor of this cavity is formed by the embryonic disk, which is composed of a layer of prismatic cells called the embryonic ectoderm. This layer is derived from the inner cell mass and lies in opposition to the endoderm.

Implantation

Implantation is the very early stage of pregnancy at which the embryo adheres to the wall of the uterus and begins to form the placenta.

Key Points

At this stage of prenatal development the embryo is a blastocyst. In humans, implantation of a fertilized ovum occurs between 6 to 12 days after ovulation.

In preparation for implantation, the blastocyst sheds its outside layer, the zona pellucida, and is replaced by a layer of underlying cells called the trophoblast. The trophoblast will give rise to the placenta after implantation.

During implantation, the trophoblast differentiates into two distinct layers: the inner cytotrophoblast, and the outer syncytiotrophoblast. The syncytiotrophoblast then implants the blastocyst into the endometrium by forming finger-like projections into the uterine wall called chorionic villi.

Key Terms

• endometrium: The mucous membrane that lines the uterus in mammals and in which fertilized eggs are implanted.
• trophoblast: The membrane of cells that forms the wall of a blastocyst during early pregnancy and provides nutrients to the embryo and later develops into part of the placenta.
• human chorionic gonadotropin (hCG): In molecular biology, human chorionic gonadotropin (hCG) is a hormone produced during pregnancy that is made by the developing placenta after conception, and later by the placental component.
• implantation: The embedding of the blastocyst to the uterine wall.

Implantation is the very early stage of pregnancy during which the embryo embeds into the wall of the uterus. At this stage of prenatal development, the embryo is a blastocyst.

It is by this adhesion that the fetus receives oxygen and nutrients from the mother to be able to grow. In humans, implantation of a blastocyst occurs between 6 to 12 days after ovulation.

In preparation for implantation, the blastocyst sheds its outside layer, the zona pellucida, which binds sperm during fertilization. The zona pellucida degenerates and decomposes, and is replaced by a layer of underlying cells called the trophoblast.

The trophoblast will give rise to the placenta after implantation. During implantation, the trophoblast differentiates into two distinct layers: the inner cytotrophoblast, and the outer syncytiotrophoblast.

 

Chorionic villi: During implantation, extensions of the trophoblast, the syncytiotrophoblasts, embed within the endometrium and form chorionic villi.

The syncytiotrophoblast then implants the blastocyst into the endometrium of the uterus by forming finger-like projections into the uterine wall called chorionic villi. The chorionic villi grow outwards until they come into contact with the maternal blood supply.

The chorionic villi will be the border between maternal and fetal blood during the pregnancy, and the location of gas and nutrient exchange between the fetus and the mother. The creation of chorionic villi is assisted by hydrolytic enzymes that erode the uterine epithelium.

The syncytiotrophoblast also produces human chorionic gonadotropin (hCG), a hormone that notifies the mother’s body that she is pregnant and prevents menstruation by sustaining the function of the progesterone-producing corpus luteum within the ovary.

Human chorionic gonadotropin is the hormone that is detected by pregnancy tests, as it is found in the maternal bloodstream and urine.

References

• https://www.ncbi.nlm.nih.gov/books/NBK554562/
• https://www.ncbi.nlm.nih.gov/books/NBK542186/
• https://www.ncbi.nlm.nih.gov/books/NBK563181/
• https://www.ncbi.nlm.nih.gov/books/NBK9983/
• https://www.mayoclinic.org/healthy-lifestyle/prenatal-care/art-20045302

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A cystocele otherwise known as a protrusion of the bladder occurs when the bladder descends into the vagina. The bladder bulges through the anterior wall of the vagina, with which it is anatomically associated. There are multiple underlying causes for the development of cystocele resulting in weakness of the muscles and the connective tissue surrounding the bladder and vagina.[rx]

A cystocele is the most common type of pelvic organ prolapse. Pelvic organ prolapse occurs when the vaginal walls, uterus, or both lose their normal support and prolapse, or bulge, into the vaginal canal or through the vaginal opening. Other nearby pelvic organs, such as the bladder or bowel, may be involved and also drop from their normal position in the body.

Types of Cystocele

Cystocele can be further described as being apical, medial, lateral, or mediolateral.

• The apical cystocele – is located in the upper third of the vagina. The structures involved are the endopelvic fascia and ligaments. The cardinal ligaments and the uterosacral ligaments suspend the upper vaginal-dome. The cystocele in this region of the vagina is thought to be due to a cardinal ligament defect.^[rx][rx]
• Medial cystocele – forms in the mid-vagina and is related to a defect in the suspension provided by to a sagittal suspension system defect in the uterosacral ligaments and pubocervical fascia. The pubocervical fascia may thin or tear and create the cystocele. Aid in diagnosis is the creation of a ‘shiny’ spot on the epithelium of the vagina. This defect can be assessed by MRI.^[ex][rx]
• Lateral cystocele – forms when both the pelvic perineal muscle and its ligamentous–fascial develop a defect. The ligamentous– fascial creates a ‘hammock-like’ suspension and support for the lateral sides of the vagina. Defects in this lateral support system result in a lack of bladder support. Cystocele that develops laterally is associated with an anatomic imbalance between the anterior vaginal wall and the arcus tendinous fasciae pelvis – the essential ligament structure.^[rx][rx]

Causes of Cystocele

Cystoceles result from a weakness of the pelvic-floor support system. The main associated risk factors are obesity, increasing age, and parity. They can also occur due to chronically increased intra-abdominal pressure, collagen abnormality, family history of cystocele, and following pelvic surgery.

• Obesity – Giri et al., in their systematic review, reported that women with BMI >25 had a risk ratio of 1.36 (95% confidence interval) for developing prolapse, while women with BMI >30 had a risk ratio of 1.47 (95% confidence interval).[rx] Another study suggested that in overweight and obese women, the risk of progression of a cystocele increased by 32% and 48%, respectively, compared with participants with normal BMI.[rx] However, few studies have shown that weight loss did not lead to symptoms resolution or regression of the prolapse. In particular, in some of them, weight loss was associated with a borderline worsening of uterine prolapse, indicating that the damage to the pelvic floor is irreversible.[rx][rx]
• Advancing Age – A number of studies have shown a strong link between aging and vaginal prolapse.[rx][rx] It is suggested that age-related changes in pelvic anatomy, innervation, and vasculature cause weakness in pelvic floor strength.[rx] A study of vaginal tissue biopsies discovered that collagen in the vaginal wall changes its structure over time, which might explain the link between aging and cystocele development.[rx]
• Parity and Other Childbirth-related Factors – Vaginal delivery carries a high risk for pelvic floor weakness.[rx] The attenuation of the pelvic floor muscles has been shown to increase with parity. Nygaard et al. showed that the prevalence of pelvic floor disorders increases by 12.8%, 18.4%, 24,6%, and 32.4% for 0, 1, 2, and 3 deliveries, respectively.[rx] Moreover, it was found that forceps delivery plays a critical role in levator ani muscle avulsion.[rx] Mant et al. specifically suggest that the first stage of labor is responsible for developing a vaginal prolapse.[rx]
• Increased Intra-abdominal Pressure – Increased intra-abdominal pressure seems to have a weak correlation with anterior vaginal prolapse. Several studies indicated a correlation between cystocele development and constipation, chronic cough, and obstructive pulmonary disease, which are all associated with chronically increased abdominal pressure.[rx][rx][rx]
• Collagen Abnormality – The predominant type of collagen found in the vaginal wall is type III, designed to be resistant to sudden pressure changes, which is essential in tissues that require elasticity. In women with vaginal prolapse, the amount of collagen III in the vaginal tissue was higher than in healthy women, possibly due to the underlying remodeling.[rx] Women with congenital conditions affecting collagen production, such as Marfan and Ehlers-Danlos syndrome, are predisposed to developing cystocele.[rx][rx] Up to a third of women with Marfans and three-quarters of women with Ehlers-Danols have a history of vaginal wall prolapse.[rx]
• Family History – Even though there are no known specific genes responsible for the development of vaginal prolapse, a review of sixteen studies has revealed that women with pelvic prolapse are highly likely to have a relative suffering from the same condition.[rx]
• Pelvic Surgery – Surgery of the pelvis, especially hysterectomy, causes damage to the endopelvic fascia and nerves. This, in turn, results in a greater risk of vaginal prolapse and herniation of the bladder.[rx]

Risk factors

Risk factors for developing a cystocele are:

Connective tissue disorders predispose women to developing cystocele and another pelvic organ prolapse. The tissues tensile strength of the vaginal wall decreases when the structure of the collagen fibers change and become weaker.^[rx]

Symptoms of Cystocele

The symptoms of a cystocele may include:

• a vaginal bulge
• the feeling that something is falling out of the vagina
• the sensation of pelvic heaviness or fullness
• difficulty starting a urine stream
• a feeling of incomplete urination
• frequent or urgent urination
• fecal incontinence^[rx]
• frequent urinary tract infections
• back and pelvic pain
• fatigue
• painful sexual intercourse^[rx]
• bleeding^[rx]
• A feeling of fullness or pressure in your pelvis and vagina
• In some cases, a bulge of tissue in your vagina that you can see or feel
• Increased pelvic pressure when you strain, cough, bear down or lift
• Problems urinating, including difficulty starting a urine stream, the feeling that you haven’t completely emptied your bladder after urinating, feeling a frequent need to urinate or leaking urine (urinary incontinence)
• A cystocele also called a prolapsed or dropped bladder, is the bulging or dropping of the bladder into the vagina.
• A cystocele occurs when the muscles and supportive tissues between a woman’s bladder and vagina weaken and stretch, letting the bladder sag from its normal position and bulge into the vagina or through the vaginal opening.
• Diagnosing a cystocele requires medical tests and a physical exam of the vagina.
• Cystocele treatment depends on the severity of the cystocele and whether a woman has symptoms.

A bladder that has dropped from its normal position and into the vagina can cause some forms of incontinence and incomplete emptying of the bladder.^[rx]

Diagnosis of Cystocele

The most objective and standard tool for evaluating the severity of the anterior wall prolapse is the POPQ system, which was introduced in 1996. This system is recognized by The American College of Obstetricians and Gynecologists and consists of 4 stages.

• Stage 0 – no prolapse
• Stage 1 – most distal part of prolapse is -1cm (above the level of the hymen)
• Stage 2 – most distal part of prolapse is >= -1cm but <= +1cm (<=1cm above or below the hymenal plane)
• Stage 3 – most outside portion of the prolapse >+1cm but <+(total vaginal length -2)cm (beyond the hymen; protrudes no farther than 2cm less than the total vaginal length)
• Stage 4 – complete eversion of the vagina; most distal portion of the prolapse >= +(total vaginal length -2) cm.[rx]

Three stages are used for patients after removal of the uterus and four if the uterus is present.

Medical history

A health care professional may ask about your

• symptoms, such as bulges or lumps in the vagina, pelvic pressure or heaviness, and urinary incontinence
• pregnancy and childbirth history
• current and past medical problems, including surgeries
• family history
• over-the-counter and prescription medicines
• bowel habits

Diagnosis of anterior prolapse may involve

• A pelvic exam – You may be examined while lying down and possibly while standing up. During the exam, your doctor looks for a tissue bulge in your vagina that indicates pelvic organ prolapse. You’ll likely be asked to bear down as if during a bowel movement to see how much that affects the degree of prolapse. To check the strength of your pelvic floor muscles, you’ll be asked to contact them, as if you’re trying to stop the stream of urine.
• Filling out a questionnaire – You may fill out a form that helps your doctor assess your medical history, the degree of your prolapse, and how much it affects your quality of life. This information also helps guide treatment decisions.
• Bladder and urine tests – If you have significant prolapse, you might be tested to see how well and completely your bladder empties. Your doctor might also run a test on a urine sample to look for signs of a bladder infection if it seems that you’re retaining more urine in your bladder than is normal after urinating.
• Urodynamics – Measures the bladder’s ability to hold and release urine.
• Cystoscopy (cystourethroscopy) – A long tube-like instrument is passed through the urethra to examine the bladder and urinary tract for malformations, blockages, tumors, or stone

Treatment of Cystocele

Non-surgical

Cystocele is often treated by non-surgical means:

• Pessary – This is a removable device inserted into the vagina to support the anterior vaginal wall. Pessaries come in many different shapes and sizes. There are sometimes complications with the use of a pessary.^[rx]
• Pelvic floor muscle therapy – Pelvic floor exercises to strengthen vaginal support can be of benefit. Specialized physical therapy can be prescribed to help strengthen the pelvic floor muscles.^[rx][rx]
• Dietary changes – Ingesting high fiber foods will aid in promoting bowel movements.^[rx]
• Estrogen – intravaginal administration helps to prevent pelvic muscle atrophy^[rx]
• Kegel exercises – (pelvic muscle exercises) can be advised for women with stage 1 or 2 prolapse. It is found that these exercises improve prolapses by 1-2 cm on average. A systematic review and meta-analysis of the effectiveness of Pelvic Floor Muscle Therapy (PFMT) showed that women involved in pelvic muscle training showed better outcomes regarding symptoms and reduction of the size of the prolapse compared to control groups.[rx] Supervised muscle training for at least 12-16 weeks can be considered for such women to measure the improvement.[rx] The exercises should be continued if they are proved to be beneficial for the patient.

• Hormone Replacement Therapy – is not a treatment for cystocele. There is no evidence that estrogen’s topical or systemic use reduces the size of cystocele; the creams or estrogen-containing vaginal pessaries can still be used for women with cystocele for treating signs of vaginal atrophy, which may occur concurrently.[rx] Another study has shown the pre-operative use of topical estrogen creams improve the synthesis of collagen, preventing thinning of the vaginal wall, and reducing the activity of degrading enzymes.[rx]

It is essential to encourage the patient to work on modifiable risk factors, such as a high BMI (>30), smoking, heavy lifting, chronic cough, or constipation.

Surgical Management

Surgical management is the next step for symptomatic women, those who require immediate relief, those who have declined conservative treatment, or for whom the conservative approach has failed to provide benefit. It should be noted that surgical management should follow the completion of the patient’s family as the pelvic support system can be further damaged during labor.

Surgical planning depends on whether the anterior vaginal prolapse is isolated or is combined with apical or posterior vaginal prolapse. A careful examination is required as a part of preoperative planning.

Anterior colporrhaphy

Anterior repair is performed trans-vaginally to repair central vaginal wall defects and to lessen the size of the anterior vaginal wall.

For this procedure, a patient is placed in the lithotomy position and catheterized; a Sims speculum is inserted to achieve a better view of the defect. An Allis forceps are placed at the midline of the anterior wall 1cm proximal to the urethra and two more forceps on each side next to the cervix or the vaginal cuff. Local infiltration with an adrenaline/lidocaine solution is commonly used to achieve hydro-dissection, analgesia, and to minimize intraoperative bleeding. With the use of Metzenbaum scissors, dissection of vaginal mucosa from the underlying vesicovaginal fascia is performed. When the mucosal layer is entirely free, a folding of the muscular layer and adventitia using figure-of-eight sutures is performed. Careful placement of the sutures is crucial in order not to damage the bladder.

2-0 Vicryl or PDS sutures are most often used. After successful plication, the excessive vaginal mucosa is removed, and the wound is closed with absorbable sutures.  The surgeon should be careful not to reduce the diameter of the vagina too much, as later it may cause pain during sexual intercourse. One study has reported the success rate of surgical approach ranging from 63% to 76.5%, depending on the procedure followed.[rx]

Sacral colpopexy

The other way to repair a bladder prolapse is to perform a sacral colpopexy, which is usually done laparoscopically. This procedure aims to place a permanent mesh to the anterior and posterior walls of the vagina and then attach it to the anterior longitudinal ligament below the sacral promontory. The operation can be performed together with anterior colporrhaphy or on its own. The benefit of sacral colpopexy is that it avoids vaginal incisions and scarring, which results in a lower risk of vaginal shortening or dyspareunia. The success rate of this procedure is 60% to 89%.[rx] A randomized trial indicated that laparoscopic sacral colpopexy has a higher success rate and a lower chance of repeat procedure for both anterior and posterior vaginal prolapses.[rx]

In many countries, including the US and the UK, the use of mesh for cystocele repairs has been suspended since 2019, pending an investigation into their use.[rx]

Complication

Post-surgical complications can develop. The complications following surgical treatment of cystocele are:

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