Tuesday, May 27, 2008

Some Definitions

Amenorrhea Absence of menstrual periods. Primary amenorrhea is defined as the absence of menstruation at puberty: the menstrual cycle never starts. Secondary amenorrhea is defined as a condition whereby a woman's menstrual period stops due to an underlying medical cause

Anovulation Absence of ovulation

Anovulatory Cycle A menstrual cycle in which ovulation does not occur

Catamenia Another word for menses or menstruation
Cervical Mucus Fluid secreted by the cervix. Its main role is to assist sperm in living for several days and to help transport sperm to the fallopian tubes. Cervix Opening into the uterus

Cilia Hair-like projections inside the fallopian tubes that move the egg up the tubes into the uterus.

Corpus Luteum A yellow mass of cells that forms from the follicle that releases the egg at ovulation. The corpus luteum produces the hormone progesterone that is important for preparing the endometrium for implantation of the fertilized egg.

C-section; Caesarean Delivery of a baby by surgical incision through the abdominal wall and uterus. It is believed that Julius Caesar was born this way.

Dysmenorrhea Pain during menstruation that occurs in the lower abdomen just before or during menstruation; menstrual cramps.

Primary dysmenorrhea is menstrual pain occurring because of one's menstrual period and not as a result of a disease. It results from the production of prostaglandins, which are made by cells in the inner lining of the uterus. Prostaglandins make the uterine muscles contract to help the uterus shed the endometrial lining that has built up during the menstrual cycle.

Secondary dysmenorrhea is menstrual pain that is the result of an underlying medical condition or disease of the uterus, fallopian tubes or ovaries. The pain appears similar to menstrual cramps, but often last longer than the menstrual period, or may occur at other times of the month when one is not menstruating

Endometriosis A condition whereby endometrial tissue that should normally grow inside the uterus instead abnormally grows outside the uterus, in the abdominal cavity and often on other reproductive organs such as on the ovaries, fallopian tubes.

Endometrium Mucous membrane tissue lining of the uterus. The endometrial lining grows thicker during the month and is shed monthly during the menstrual period if pregnancy does not occur.

Estrogen Female hormone produced by the ovaries that promote the growth and maintenance of the female reproductive system.

Fallopian Tube The fallopian tube transports the egg from the ovary to the uterus. There are two fallopian tubes, one connecting to the right ovary, the other to the left ovary. Generally, fertilization (joining of female egg with male sperm) takes place within the Fallopian tubes.

Named after Gabriele Falloppio, a 16th-century Italian anatomist, who was the first person to accurately describe these uterine tubes.

Follicle An egg sac in the ovary inside which an ovum (egg) will mature.

Follicle Stimulating Hormone (FSH) The hormone produced by the pituitary gland that stimulates the growth of eggs in the ovaries.

Follicular Phase The first phase of the menstrual cycle. During this phase, a follicle containing an egg develops in the ovary.

Luteal Phase The third phase of the menstrual cycle. Ovulation has occurred, and the corpus luteum produces progesterone primarily to maintain the thickness of the endometrium lining in the uterus in the event that fertilization has occurred. If fertilization has not occurred, progesterone production stops and the endometrium lining is shed during menstruation.
Luteinizing Hormone (LH) Hormone released by the pituitary gland in the brain that triggers the onset of ovulation and prepares the uterus for implantation of a fertilized egg.
Menarche A girl's first menstrual period

Menopause The time in a women's life when menstruation permanently stops. Sometimes referred to as the "change of life". Occurs due to the decrease in production of estrogen and progesterone by the ovaries.

Menorrhagia Menstrual periods that are abnormally heavy in flow, or that are prolonged and last much longer than usual

Menses Another word for menstruation; the menstrual flow. Derives from the Latin word menses, which means months (singular mensis refers to 1 month).

Note that the word moon, as in the earth's moon which resolves around the earth in approximately 29.5 days, likewise derives from the Latin word mensis
Menstrual Adjective; Of or relating to menstruation

Menstrual cycle A recurring cycle that occurs monthly in women as the endometrium (lining of the uterus) thickens and prepares for pregnancy. If the egg released by one of the ovaries at ovulation (which occurs about midway through the cycle) is fertilized as it travels from the fallopian tube to the uterus, pregnancy occurs. If the egg is not fertilized, menstruation occurs: the blood-rich endometrium is shed, and the next month's cycle begins again.

The first day of menstrual blood flow is considered day 1 of the menstrual cycle.
The menstrual cycle is comprised of three phases: the follicular phase, ovulation, and the luteal phase.

Menstrual Cycle Length This is the number of days from the first day of one menstrual period to the day before the first day of the next menstrual cycle.

Menstruation The monthly shedding of the endometrium. Menstruation is the part of a woman's menstrual cycle where the endometrium (lining of the uterus) is shed, resulting in discharge of blood. Menstruation occurs each month if the egg released at ovulation is not fertilized. It occurs from menarche during puberty until menopause.
Metrorrhagia Uterine bleeding that occurs between regular menstrual periods, which usually indicates an underlying medical condition

Mittelschmerz Pain occurring during ovulation on one side of the lower abdomen. The location (left or right side) is based on which ovary produces the ovum that month.

Oligomenorrhea Menstrual periods with abnormally light flow
Oligoovulation Very irregular ovulatory cycles
Ovary Female reproductive organ located in the pelvis. There are two ovaries, one of the right side of the uterus, the other on the left side. Produces eggs (ova) and the female hormones.
Oviduct Another word for Fallopian tube.

Ovulation Release of a mature egg from one of the two ovaries. Occurs approximately midway between the menstrual cycle. The egg is released into the Fallopian tube, where it is available for fertilization.

Ovulation is the second phase of the menstrual cycle, with Follicular being phase one, and Luteal being phase three

Ovum Female reproductive cell, the ovum (also known as the egg) is produced by the ovaries. Ova is plural for ovum

Perimenopause Transitional period of several years before menopause. Hormone level fluctuations (gradual decrease in estrogen) can result in irregular menstrual cycles, hot flashes, night sweats, and other symptoms.

Period An occurrence of menstruation
Premenstrual Syndrome (PMS) A combination of physical and mood related symptoms that occur after ovulation and usually terminate at the start of the menstrual period or shortly thereafter. Many symptoms have been attributed to PMS, including mood changes, bloating, acne, fatigue, anxiety and irritability, breast swelling and tenderness.

Polymenorrhea Menstrual periods that are abnormally frequent

Progesterone Female hormone produced by the corpus luteum; responsible for preparing and maintaining the uterus for pregnancy.

Spotting Light bleeding that occurs at a time during the month other than the menstrual period.
Uterus The uterus is a hollow, pear-shaped muscular organ. It is normally where the fertilized ovum (egg) is implanted, and where the fetus develops

Womb Another word for uterus

How to Check My Cervix Position?

Make sure that your hands and fingernails are very clean (and that your nails are fairly short and smooth), and reach inside with either your index finger and middle finger, or just one or the other.
If you don't feel anything, you either have very short fingers, or your cervix is in the "high" position. If you feel it pretty close to the main entry, then that would be considered the "low" position. Obviously, anything else would be the "medium" position.

If your cervix feels firm, like the tip of your nose, that is the "firm" position. If it feels more like your lips when you are about to kiss someone, then that is considered to be the "soft" position.
Obviously, if you feel CM on your cervix, this would be the "wet" sign, and no CM would be the "dry" sign. If it feels closed tight, then that is "closed", and if you feel a little dimple in the middle, or a dent, that is considered to be "open".

About Ovulation

In humans, the period when ovulation occurs is called the ovulatory phase, and it occupies the fourteenth day of an idealized twenty-eight day menstrual cycle. Because of the variable nature of the menstrual cycle in vivo, however, normal ovulation can occur as early as day 8 or as late as day 20 and beyond. A woman with a particularly short cycle will ovulate earlier while a woman with a long cycle will ovulate later. In humans, concealed ovulation means that the female shows few visible signs of being fertile, compared to most species.(disputed — see talk page) There are evolutionary analyses of how this could evolve in terms of evolutionary game theory.

Before ovulation, the ovarian follicle will undergo a series of transformations that are necessary for the ovum to survive afterwards. This process is called cumulus expansion. After this is done, a hole called the stigma will form in the follicle, and the ovum will leave the follicle through this hole. It will then enter the fallopian tubes and travel toward the uterus, implanting there if fertilized or degrading after 24 hours if not.

The ovulatory phase is preceded by the follicular phase, where a immature follicle-encased ovum completes growing, and followed by the luteal phase, where the uterus is prepared to receive the fertilized ovum. The complete process of follicle growth leading up to ovulation is known as folliculogenesis.

Scientific investigations have indicated that the olfactory acuity or the sense of smell is greatest during ovulation in women.


A closer look at the process

Strictly defined, the ovulatory phase spans the period of hormonal elevation in the menstrual cycle. The process requires a maximum of thirty-six hours to complete, and it is arbitrarily separated into three phases: periovulatory, ovulatory, and postovulatory.

Prerequisite events

Through a process that takes approximately 375 days, or thirteen menstrual cycles, a large group of undeveloped primordial follicles dormant in the ovary is grown and progressively weaned into one preovulatory follicle. Histologically, the preovulatory follicle (also called a mature Graffian follicle or mature tertiary follicle) contains an oocyte arrested in prophase of meiosis I surrounded by a layer corona radiata granulosa cells, a layer of mural granulosa cells, a protective basal lamina, and a network of blood-carrying capillary vessels sandwiched between a layer of theca interna and theca externa cells. A large sac of fluid called the antrum predominates in the follicle. A "bridge" of cumulus oophorous granulosa cells (or simply cumulus cells) connects the corona-ovum complex to the mural granulosa cells.

Simply stated, the granulosa cells engage in bidirectional messenging with the theca cells and the oocyte to facilitate follicular function. Research is elucidating the specific factors used in follicular messenging at a rapid pace, but such discussion is beyond the scope of this article.

By the action of luteinizing hormone (LH), the preovulatory follicle's theca cells secrete androstenedione that is aromatized by mural granulosa cells into estradiol, a type of estrogen. High levels of estrogen have a stimulatory effect on hypothalamus gonadotropin-releasing hormone (GnRH) that in turn stimulates the expression of pituitary LH and follicle stimulating hormone (FSH).

The building concentrations of LH and FSH marks the beginning of the periovulatory phase.


Periovulatory phase

For ovulation to be successful, the ovum must be supported by both the corona radiata and cumulus oophorous granulosa cells. The latter undergo a period of proliferation and mucification known as cumulus expansion. Mucification refers to the secretion of a hyaluronic acid-rich cocktail that disperses and suspends the cumulus cell network in a sticky matrix around the ovum. This network stays with the ovum after ovulation and have been shown to be necessary for fertilization.

An increase in cumulus cell number causes a concomitant increase in antrum fluid volume that can swell the follicle to over 20mm in diameter. It forms a pronounced bulge at the surface of the ovary called the blister.

Ovulatory phase

Through a signal transduction cascade kicked off by LH, proteolytic enzymes are secreted by the follicle that degrade the follicular tissue at the site of the blister, forming a hole called the stigma. The ovum-cumulus complex leaves the ruptured follicle and out into the peritoneal cavity through the stigma, where it is caught by the fimbriae at the end of the fallopian tube (also called the oviduct). After entering the oviduct, the ovum-cumulus complex is pushed along by cilia, beginning its journey toward the uterus.

By this time, the oocyte has completed meiosis I, yielding two cells: the larger secondary oocyte that contains all of the cytoplasmic material and a smaller, inactive first polar body. Meiosis II follows at once but will be arrested in the metaphase and will so remain until fertilization. The spindle apparatus of the second meiotic division appears at the time of ovulation If no fertilization occurs, the oocyte will degenerate approximately twenty-four hours after ovulation

The mucous membrane of the uterus, termed the functionalis, has reached its maximum size, and so have the endometrial glands, although they are still non-secretory.


Postovulatory phase

The follicle proper has met the end of its lifespan. Without the ovum, the follicle folds inward on itself, transforming into the corpus luteum (pl. corpus lutea), a steriodogenic cluster of cells that produces estrogen and progesterone. These hormones induce the endometrial glands to begin production of the proliferative endometrium, the site of embryonic growth if fertilization occurs. The corpus luteum continues this paracrine action for the remainder of the menstrual cycle, maintaining the endometrium, before disintegrating into scar tissue during menses.

Clinical presentation

The start of ovulation can be detected by various medical symptoms. Because the signs are not discernable by the naked eye, however, humans are said to have a hidden ovulation.

Ovulating women experience a gradual three-day rise in body temperature, on average 0.4 to 0.6 degrees Fahrenheit (0.2 degress Celsius). The temperature elevation persists until the day of menses which marks the end of the menstrual cycle. Furthermore, some women may experience novel discomfort or pain in their lower abdomen during ovulation termed Mittelschmerz ("midpain") that is most likely caused by irritation of the abdominal wall from the blood and fluid escaping from the ruptured follicle. Lastly, the chemical composition of a woman's cervical mucus will shift during ovulation, changing in composition to better accommodate sperm. The mucus is said to be clear, stretchable, and sticky, resembling raw egg white.

Beyond these physiological signs, a study suggests that women's preferences in men shift during ovulation, appealing toward a more primitive drive to find a suitable mate. Another study has concluded that women subtly improve their facial attractiveness during ovulation. The significance and accuracy of these studies have been hotly debated among the medical and scientific professions.


New research: follicular waves

Emerging research spearheaded by Baerwald et al. suggests that the menstrual cycle may not regulate follicular growth as strictly as previously thought. In particular, the majority of women during a typical twenty-eight day cycle experience two or three "waves" of follicular development, with only the final wave being ovulatory. The remainder of the waves are anovulatory, characterized by the developed preovulatory follicle falling into atresia (a major anovulatory cycle) or no preovulatory follicle being chosen at all (a minor anovulatory cycle).

The phenomenon is similar to the follicular waves seen in cows and horses. In these animals, a large cohort of early tertiary follicles develop consistently during the follicular phase of the menstrual cycle, suggesting that the endocrine system does not regulate folliculogenesis stringently.

This revelation challenges our current understanding of follicular development and menstrual cycle dynamics and may also explain why traditional methods of natural family planning and birth control using the idealized cycle are so ineffective.

Specifically, this discovery is a likely explanation for pregnancies caused by sexual intercourse when a woman is sure she should not be ovulating. Another explanation is, of course, that the woman has mistakenly assumed that she ovulates on day 14, when in fact, she ovulates earlier or later in her cycle.


Induced ovulation and contraception

The majority of oral contraceptives and conception boosters focus on the ovulatory phase of the menstrual cycle because it is the most important determinant of fertility. Hormone therapy can positively or negatively interfere with ovulation and can give a sense of cycle control to the woman.

Follicle stimulating hormone, gonadotropin releasing hormone (GnRH), and estradiol have been purified in the laboratory. Chemical analogues of estradiol and progesterone have also been synthesized. Recall that GnRH is an upstream inducer of both FSH and LH secretion.

Generally, administered FSH or GnRH can induce ovulation by rapidly accelerating the pace of folliculogenesis, allowing for conception. Estradiol and progesterone, taken in the form of oral contraceptives, mimics the hormonal levels of the menstrual cycle and engage in negative feedback of folliculogenesis and ovulation.


Ovulation in animals

Some interesting aspects can be noted here:
Ovulation in camels is induced by male pheromones. In caravans without bulls female camels don't have an estrus.
In cats ovulation is induced mechanically by the male through copulation.
Chickens have an ovulation almost every day.
The embryos of some Marsupial species enter embryonic diapause (or delayed implantation) after fertilization.

About Menstruation

Menstruation is a woman's monthly bleeding. It is also called menses, menstrual period, or period. When a woman has her period, she is menstruating. The menstrual blood is partly blood and partly tissue from the inside of the uterus (womb). It flows from the uterus through the small opening in the cervix, and passes out of the body through the vagina. Most menstrual periods last from three to five days.

What is a typical menstrual period like?

During the menstrual period, the thickened uterine lining and extra blood are shed through the vaginal canal. A woman's period may not be the same every month, and it may not be the same as other women's periods. Periods can be light, moderate, or heavy, and the length of the period also varies. While most menstrual periods last from three to five days, anywhere from two to seven days is considered normal. For the first few years after menstruation begins, periods may be very irregular. They may also become irregular in women approaching menopause. Sometimes birth control pills are prescribed to help with irregular periods or other problems with the menstrual cycle.

Sanitary pads or tampons, which are made of cotton or another absorbent material, are worn to absorb the blood flow. Sanitary pads are placed inside the panties; tampons are inserted into the vagina.

What kinds of problems do women have with their periods?
Women can have various kinds of problems with their periods, including pain, heavy bleeding, and skipped periods.

Amenorrhea- the lack of a menstrual period. This term is used to describe the absence of a period in young women who haven't started menstruating by age 16, or the absence of a period in women who used to have a regular period. Causes of amenorrhea include pregnancy, breastfeeding, and extreme weight loss caused by serious illness, eating disorders, excessive exercising, or stress. Hormonal problems (involving the pituitary, thyroid, ovary, or adrenal glands) or problems with the reproductive organs may be involved.

Dysmenorrhea - painful periods, including severe menstrual cramps. In younger women, there is often no known disease or condition associated with the pain. A hormone called prostaglandin is responsible for the symptoms. Some pain medicines available over the counter, such as ibuprofen, can help with these symptoms. Sometimes a disease or condition, such as uterine fibroids or endometriosis, causes the pain. Treatment depends on what is causing the problem and how severe it is.

Abnormal uterine bleeding-vaginal bleeding that is different from normal menstrual periods. It includes very heavy bleeding or unusually long periods (also called menorrhagia), periods too close together, and bleeding between periods. In adolescents and women approaching menopause, hormone imbalance problems often cause menorrhagia along with irregular cycles. Sometimes this is called dysfunctional uterine bleeding (DUB). Other causes of abnormal bleeding include uterine fibroids and polyps. Treatment for abnormal bleeding depends on the cause.

At what age does a girl get her first period?

Menarche is another name for the beginning of menstruation. In the United States, the average age a girl starts menstruating is 12. However, this does not mean that all girls start at the same age. A girl can begin menstruating anytime between the ages of 8 and 16. Menstruation will not occur until all parts of a girl's reproductive system have matured and are working together.

How long does a woman have periods?

Women usually continue having periods until menopause. Menopause occurs around the age of 51, on average. Menopause means that a woman is no longer ovulating (producing eggs) and therefore can no longer become pregnant. Like menstruation, menopause can vary from woman to woman and may take several years to occur. Some women have early menopause because of surgery or other treatment, illness, or other reasons.

When should I see a health care provider about my period?
You should consult your health care provider for the following:
If you have not started menstruating by the age of 16.
If your period has suddenly stopped.
If you are bleeding for more days than usual.
If you are bleeding excessively.
If you suddenly feel sick after using tampons.
If you bleed between periods (more than just a few drops).
If you have severe pain during your period.
How often should I change my pad/tampon?

Sanitary napkins (pads) should be changed as often as necessary, before the pad is soaked with menstrual flow. Each woman decides for herself what is comfortable. Tampons should be changed often (at least every 4-8 hours). Make sure that you use the lowest absorbency of tampon needed for your flow. For example, do not use super absorbency on the lightest day of your period. This can put you at risk for toxic shock syndrome (TSS). TSS is a rare but potentially deadly disease. Women under 30, especially teenagers, are at a higher risk for TSS. Using any kind of tampon - cotton or rayon of any absorbency - puts a woman at greater risk for TSS than using menstrual pads. The risk of TSS can be lessened or avoided by not using tampons, or by alternating between tampons and pads during your period.

The Food and Drug Administration (FDA) recommends the following tips to help avoid tampon problems:


Follow package directions for insertion.
Choose the lowest absorbency for your flow.
Change your tampon at least every 4 to 8 hours.
Consider alternating pads with tampons.
Know the warning signs of toxic shock syndrome (see below).
Don't use tampons between periods.
If you experience any of the following symptoms while you are menstruating and using tampons, you should contact your health care provider immediately:

High fever that appears suddenly
Muscle aches
Diarrhea
Dizziness and/or fainting
Sunburn-like rash
Sore throat
Bloodshot eyes

About Cycles

The menstrual cycle is the set of recurring physiological changes in a female's body that are under the control of the reproductive hormone system and necessary for reproduction. In women, menstrual cycles occur typically on a monthly basis between puberty and menopause. Besides humans, only other great apes exhibit menstrual cycles, in contrast to the estrus cycle of most mammalian species.

During the menstrual cycle, the sexually mature female body releases one egg (or occasionally two, which might result in dizygotic, or non-identical, twins) at the time of ovulation. The lining of the uterus, the endometrium, builds up in a synchronised fashion. After ovulation, this lining changes to prepare for potential implantation of the fertilised egg to establish a pregnancy. If fertilisation and pregnancy do not ensue, the uterus sheds the lining and a new menstrual cycle begins. The process of the shedding of the lining is called menstruation. Menstruation manifests itself to the outer world in the form of the menses (also menstruum): essentially part of the endometrium and blood products that pass out of the body through the vagina. Although this is commonly referred to as blood, it differs in composition from venous blood.

Common usage refers to menstruation and menses as a period. This bleeding serves as a sign that a woman has not become pregnant. (However, this cannot be taken as certainty, as sometimes there is some bleeding in early pregnancy.) During the reproductive years, failure to menstruate may provide the first indication to a woman that she may have become pregnant. A woman might say that her "period is late" when an expected menstruation has not started and she might have become pregnant.

Menstruation forms a normal part of a natural cyclic process occurring in healthy women between puberty and the end of the reproductive years. The onset of menstruation, known as menarche, occurs at an average age of 12, but can occur any time between the ages of 8 and 16. However, the condition precocious puberty has caused menstruation to occur in girls as young as 8 months old. The last period, menopause, usually occurs between the ages of 45 and 55. Deviations from this pattern deserve medical attention. Amenorrhea refers to a prolonged absence of menses during the reproductive years of a woman for reasons other than pregnancy. For example, women with very low body fat, such as athletes, may cease to menstruate. The presence of menstruation does not prove that ovulation took place; women who do not ovulate may have menstrual cycles. Those anovulatory cycles tend to take place less regularly and show greater variation in cycle length. In addition, the absence of menstruation also does not prove that ovulation did not take place, because hormone disruptions in non-pregnant women can suppress bleeding on occasion.


The normal menstrual cycle in humans

Women show considerable variation in the lengths of their menstrual cycles, and the length of the menstrual cycle differs in different animals (see below).
While cycle length may vary, 28 days is generally taken as representative of the average ovulatory cycle in women. Convention uses the onset of menstrual bleeding to mark the beginning of the cycle, so the first day of bleeding is called "Cycle Day one".

One can divide the menstrual cycle into four phases:

Menstruation

Menstruation lasts for a few days (usually 3 to 5 days, but anywhere from 2 to 7 days is considered normal) and involves the loss of about 30-40 millilitres of blood; many women also notice shed endometrium lining that appears as tissue mixed with the blood. An enzyme called plasmin — contained in the endometrium — inhibits the blood from clotting. Because of this blood loss, women have higher dietary requirements for iron than do males to prevent iron deficiency. Many women experience uterine cramps, also referred to as dysmenorrhea, during this time. A vast industry has grown to provide sanitary products to help women to manage their menses.
Follicular phase

Through the influence of a rise in Follicle stimulating hormone (FSH), five to seven tertiary-stage ovarian follicles are recruited for entry into the menstrual cycle. These follicles, that have been growing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. In a signal cascade kicked off by luteinizing hormone (LH), the follicles secrete estradiol, a steroid that acts to inhibit pituitary secretion of FSH. With diminished FSH supply comes a slowing in growth that eventually leads to follicle death, known as atresia. The largest follicle secretes inhibin that serves as a finishing blow to less competent follicles by further suppressing FSH. This dominant follicle continues growing, forms a bulge near the surface of the ovary, and soon becomes competent to ovulate.

The follicles also secrete estrogens (of which estradiol is a member). Estrogens initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium. If fertilised, the embryo will implant itself within this hospitable flesh.

Ovulation

This ovary is about to release an egg.

When the follicle has matured, it secretes enough estradiol to trigger the acute release of luteinizing hormone (LH). In the average cycle this LH surge starts around cycle day 12 and may last 48 hours. The release of LH matures the egg and weakens the wall of the follicle in the ovary. This process leads to ovulation: the release of the now mature ovum, the largest cell of the body (with a diameter of about 0.5 mm). Which of the two ovaries — left or right — ovulates appears essentially random; no known left/right co-ordination exists. The Fallopian tube needs to capture the egg and provide the site for fertilisation. A characteristic clear and stringy mucus exhibiting spinnbarkeit develops at the cervix, ready to accept sperm from intercourse. In some women, ovulation features a characteristic pain called Mittelschmerz which lasts for several hours. The sudden change in hormones at the time of ovulation also causes light mid-cycle bleeding for some women. Many women perceive the vaginal and cervical mucus changes at ovulation, particularly if they are monitoring themselves for signs of fertility. An unfertilised egg will eventually disintegrate or dissolve in the uterus. Scientific investigations have indicated that the olfactory acuity or the sense of smell is greatest during ovulation in women.

Luteal phase

The corpus luteum is the solid body formed in the ovaries after the egg has been released from the fallopian tube which continues to grow and divide for a while. After ovulation, the residual follicle transforms into the corpus luteum under the support of the pituitary hormones. This corpus luteum will produce progesterone in addition to estrogens for approximately the next 2 weeks. Progesterone plays a vital role in converting the proliferative endometrium into a secretory lining receptive for implantation and supportive of the early pregnancy. It raises the body temperature by half- to one degree Fahrenheit (one-quarter to one-half degree Celsius), thus women who record their temperature on a daily basis will notice that they have entered the luteal phase. If fertilisation of an egg has occurred, it will travel as an early embryo through the tube to the uterine cavity and implant itself 6 to 12 days after ovulation. Shortly after implantation, the growing embryo will signal its existence to the maternal system. One very early signal consists of human chorionic gonadotropin (hCG), a hormone that pregnancy tests can measure. This signal has an important role in maintaining the corpus luteum and enabling it to continue to produce progesterone. In the absence of a pregnancy and without hCG, the corpus luteum demises and inhibin and progesterone levels fall. This will set the stage for the next cycle. Progesterone withdrawal leads to menstrual shedding (progesterone withdrawal bleeding), and falling inhibin levels allow FSH levels to rise to raise a new crop of follicles.

Wednesday, May 14, 2008

Laparoscopy - The Kinder Cut 2

After the operation, there may be some discomfort. This may include:

*. Mild nausea as a result of the medication or the surgical procedure.
*.Pain in the neck and shoulder due to the gas inside the abdomen.
*.Pain in the areas where the instruments passed through the abdominal wall.
*.A scratchy throat and hoarse voice if a breathing tube was used during general anesthesia.
*.Cramps, like menstrual cramps.
*.Discharge like a menstrual flow for a day or two.
*.Muscle aches.

Most of these minor symptoms will disappear within a day or two after surgery. The abdomen may feel swollen for a few days. Any unusual or peculiar symptoms should be reported at once to the doctor.

To really appreciate the benefits of laparoscopy, one should remember that the alternative is major surgery (laparotomy) which involves a large abdominal incision, a four to six day hospital stay, and four to six weeks of postoperative recovery time.

While the doctors may term laparoscopy as being "minor" surgery, remember that for the patient all surgery is major! The risk of laparoscopy are minimal. But certain conditions increase the possibility of complications. If there has been previous surgery in the abdomen, especially involving the bowel, there is an increased risk. Other conditions that lead to a higher risk of complications are evidence of an infection in the abdomen, a large growth or tumor within the abdomen, and obesity.

Complications among young, healthy women under going laparoscopy are rare and occur only in about three out of 1000 cases. These complications can include injuries to structures in the abdomen such as the bowel, a blood vessel or the bladder. Most often, these injuries occur when the laparoscope is placed through the navel. If such an injury occurs during the procedure, the physician can perform major surgery and correct the damage through a longer abdominal incision. Sometimes, complications may arise after surgery. If bleeding or pain appears excessive or if high fever develops, the doctor should be informed.

Where to do the laparoscopy

In order to choose the best doctor for performing your laparoscopy, you need to ask the following questions.

1. How many laparoscopies have you done?
2. Do you use multiple punctures?
3. Do you use a video for recording the operation?
4. If you find a problem, will you correct it at the same time? Ideally, if the doctor finds a problem during the laparoscopy, he should correct it at the same time, rather than call you again for a second surgical procedure, which only adds to your expense and risk.

Comparing laparoscopy and HSG

A common question patients ask is if they can go in for an X-ray (hysterosalpingogram) instead of a laparoscopy to find out if their tubes are open? While it is true that an HSG will provide accurate information about whether or not the tubes are open, there are other major benefits which laparoscopy offers and which HSG does not. HSG provides information only about the inside of the tubes and uterine cavity, whereas in laparoscopy, not only can the tubal patency be determined, but other disorders inside the abdomen which affect tubal function and which do not show up on HSG (such as endometriosis and tubal adhesions) can also be diagnosed. Moreover, major bonus in the case of laparoscopy is that it offers the doctor a chance to diagnose and treat the problem at the same time if possible - double bonus! Of course, the advantage of HSG is that no surgery, hospitalization or anesthesia is needed: it is less expensive; and that a hard copy record is provided, which all doctors can refer to later on. In fact both the HSG and laparoscopy are complementary procedures, and you may even need both, especially if your tubes are blocked.

A common problem which patients face in practice is that many doctors will insist on repeating the laparoscopy. One reason for this is that doctors feel that they need to do the laparoscopy for themselves, because they cannot "trust" another doctor's judgment. This is, of course a major problem for patients, who suffer repeated (and unnecessary) laparoscopies. Having a video record should help to minimize this problem. What happens if your laparoscopy was normal and the second doctor wants to repeat it anyway? Sometimes doctors have little to offer in the way of effective treatment and since there is nothing else to do, they suggest a repeat scopy to which the hapless patient is forced to agree. If your first scopy did, in fact indicate you had a problem, a second look laparoscopy may be indicated (and this should have been discussed with you after the first scopy) to determine if the problem has been successfully resolved. Ask the doctor what information he hopes to get by doing the repeat laparoscopy and how this will change your treatment. If you feel the doctor wants to do a scopy for no very good reason, refuse. It's a surgical procedure after all - and it's your body.

Thinking it over

A major benefit of laparoscopy is that in addition to allowing the accurate diagnosis of a problem, if it exists, operative laparoscopy can also be done in the same surgery to correct the problem. Often, the laparoscopy provides reassurance that the woman is normal and that the chances of having a baby are therefore good. In such cases, it even allows the doctor to perform treatment for the infertility in that cycle, if appropriate, by using intratubal insemination or SIFT.

Laparoscopy often leads to an accurate diagnosis which, in turn leads to more appropriate and specific treatment. Once the laparoscopy is over, the doctor will usually have a good idea of what is wrong , and what can it being treated effectively are improved now that the diagnosis is accurate.

After the laparoscopy

At the follow-up visit, discuss with the doctor what he found at the time of the laparoscopy and also how to proceed on the basis of the findings. There are three possible courses of action:

1. Normal findings: Such findings are the commonest result and can be very assuring!

2. Abnormal findings: which could be corrected at the time of laparoscopy itself: Perhaps the doctor may suggest a second look laparoscopy or HSG after some time to document that the problem has, in fact been corrected or else in addition medical treatment may be advised to try to correct a residual problem (e.g. antibiotics for pelvic infection, medical treatment for endometriosis) A quandary may arise when the laparoscopy reveals a finding which may be of no relevance to the problem of infertility. For example during laparoscopy the doctor may detect small fibroids, early endometriosis, or an ovarian cyst. These are common disorders and are often found in fertile women as well. Just making a diagnosis of these disorders does not automatically mean that they need to be corrected: they may be red herrings, which do not affect fertility. In fact, unnecessary surgery to remove these disorders can aggravate your infertility

3. Abnormal findings: which could not be corrected during the laparoscopy : For treatment, the doctor may advise formal surgery (for example microsurgery for blocked tubes) or IVF (for example for patients with pelvic TB)

Laparoscopy - The Kinder Cut

Laparoscopy is a surgical procedure in which a telescope is inserted inside the abdomen through a small cut below the navel, so that the doctor can have a look at the pelvic organs in the infertile woman. A laparoscopy can lead to the diagnosis of many problems which cause infertility including damaged tubes, endometriosis, adhesions and tuberculosis.

When is laparoscopy done?

Most infertile women require diagnostic laparoscopy in order to complete their evaluation. Generally, the procedure is performed after the basic infertility tests, although the presence of pain or other problems (such as a history of previous surgery) may signal that a laparoscopy until the rest of your evaluation is completed, since it is a surgical procedure.

Timing the surgery

Some doctors will time the laparoscopy during the premenstrual phase (the week before the next period is due). They combine the laparoscopy with a dilatation and curettage (D & C) (scraping the inside of the uterine cavity) so that they can also get information on the woman's ovulatory status in the same procedure.

Some doctors try to perform the diagnostic laparoscopy during the periovulatory period (i.e., when the eggs are ripe, as judged by ultrasound) because such timing allows them to visualize follicular development. Some others prefer this timing so that they can treat the infertility at the same by doing an intratubal insemination (also called SIFT or sperm intrafallopian transfer) in that cycle, if appropriate. This would be possible only if a previously done HSG showed be possible only if a previously done HSG showed that the tubes were normal.

Precautions before surgery

The patient is advised not to eat or drink anything for a specific time before the operation. Some tests may also be done before the procedure, to ensure safety for anesthesia, though for most young healthy women tests are usually not needed. Some doctors may want a HSG (hysterosalpingogram) done before performing a laparoscopy.

The surgery is usually done on a day-care basis. Laparoscopy is done under general anesthesia so that the patient remains asleep during surgery and does not feel any discomfort.

The laparoscopic procedure

First of all, the abdomen is cleansed and draped for the procedure. Then an instrument may be placed in the uterus through the vagina. A gas, such as carbon dioxide or nitrous oxide or air is then allowed to flow into the abdomen just below the belly button. This gas creates a space inside by pushing the abdominal wall and the bowel away from the organs in the pelvic area and makes it easier to see the reproductive organs clearly.

The laparoscope, which is a slender tube, like a miniature telescope, is then inserted through a small incision just below the navel. During the laparoscopy a small probe is placed through another incision in order to move the pelvic organs into clear view. A diagnostic laparoscopy is incomplete without a "second puncture" because, without this second probe, it is not possible to visualize all the structures completely. During the laparoscopy the entire pelvis is carefully scanned and the organs inspected systematically - the uterus; the ovaries; and the lining of the abdomen, called the peritoneum. In addition to looking for diseases affecting these structures, the doctor also looks for adhesions (bands of scar tissue), endometriosis and tubercles. In case abnormalities are found, the doctor can either try to correct them (operative laparoscopy), or take out bits of tissue for histologic examination (biopsy) with a biopsy forceps. A blue dye (methylene blue) is then injected through the uterus and fallopian tubes to check whether the tubes are open. When the surgery is complete, the gas is removed and one or two stitches inserted to close the incisions. Since the incisions are so small, often stitches are not needed and they can be closed with Band-Aids.




Fig 2. Normal pelvis as seen during a laparoscopy. The uterus is the reddish structure in the center; on either side of which are the pink fallopian tubes. These run towards the ovaries, which are white in colour.

As stated earlier, along with laparoscopy, some doctors carry out a dilatation and curettage (D & C) and send the endometrial curettings for histologic examination to rule out the possibility of hidden tuberculosis, and also to find out if ovulation is taking place. Others will do a diagnostic hysteroscopy at the same time, to ensure that the uterine cavity is normal.
Another advanced technique available now is called videolaparoscopy. It is possible to connect a video camera to the laparoscopy, so that what the surgeon sees can be displayed on a TV monitor. This kind of laparoscopy can be very useful for documentation and record-keeping. It is also very helpful for patient education, since the doctors can use the video later on to explain to the patient the exact nature of her problem.
Recent advances in miniaturization have allowed companies to manufacture very tiny laparoscopes. These are as thin as a needle, and are called microlaparoscopes or needlescopes. These allow doctors to perform laparoscopy in the clinic itself, without using anesthesia. However, the quality of the images is still not very good with these tiny scopes.
Dr Brosens from Belgium has also introduced the technique of transvaginal hydrolaparoscopy. This allows the doctor to examine the pelvis by inserting a tiny scope through the vagina, so that no abdominal incision needs to be made. The value of this technique as compared to conventional laparoscopy is still being studied.
Operative laparoscopy
During operative laparoscopy, many problems which cause infertility can be safely treated through the laparoscope at the same time that the diagnosis is made. When performing operative laparoscopy, additional instruments such as probes, scissors, biopsy forceps, coagulators and suture materials are placed into the abdomen, either through the laparoscope or through two or three additional incisions called "suprapubic punctures", which are made above the pubis.
Some of the disorders that can be corrected with the help of the aforementioned procedure include: releasing scar tissue and/or adhesions from around the fallopian tubes and ovaries; opening blocked tubes; and removing ovarian cysts. Endometriosis can also be destroyed by burning it from the back of the uterus, ovaries, or peritoneum during operative laparoscopy. Under certain circumstances, small fibroid tumors can be removed and ectopic pregnancies can be treated.
When performing operative laparoscopy, surgeons may use electrocautery instruments, lasers, and sutures. The choice of the technique used depends on many factors including the surgeon's training, location of the problem, and availability of equipment.
Sometimes, a "second-look" laparoscopy may be recommended. This procedure is performed following either operative laparoscopy or major tubal surgery. Second-look laparoscopy can take place within a few days following the initial surgery or many months afterwards. During the procedure, the doctor determines whether adhesions are re-forming or if endometriosis is returning and these conditions can be treated in needed.
After surgery, the patient needs to rest for about 2 to 4 hours in order to recover from the effects of anesthesia. She can usually go home the same day and resume normal work in 2 to 3 days. Sexual activity can be resumed in a week or so, depending upon the doctor's advice.

Recent Advances in Ultrasound 2


Ultrasound technology has made dramatic advances in recent years, and now tests have been described which allow the doctor to use ultrasound to assess tubal patency. Basically, these involve passing a fluid into your tubes through the uterus; and the gynecologist can see the passage of the bubbles into the tubes and out into the abdomen. Since this test ( sonosalpingography) can be done in the doctor's clinic itself, and does not involve X-ray radiation, it has advantages - especially for documenting that the tubes are normal. However, the gold standard for tubal testing remains HSG and laparoscopy today.

Doppler: The newer ultrasound machines have Doppler attachments which allow the doctor to judge the flow of blood in the blood vessels. The most exciting advance is that of Colour Doppler, where the blood flow can be mapped in color on the monitor. While still a research tool, it may provide important information for assessing the infertile patient in the coming years.

Three – dimensional ultrasound. Using sophisticated microprocessors, the newest ultrasound machines allow the doctor to reconstruct the image, so that he gets a three dimensional view. While this provides excellent pictures, the true value of this technique for infertility still has to be evaluated.

Ultrasound now also offers infertile patients newer treatment options not available before. Modern surgical techniques have progressively become less and less invasive - all to the patient's benefit ! From laparotomy to laparoscopy , and now to ultrasound guided procedures, we are witnessing a change in the gynecologist's armamentarium from the knife to the endoscope to the guided needle !

The benefits to the patient are many and include : reduced costs; reduced hospitalisation ; reduced risk of complications; and better preservation of fertility, with increased chance of conception for the future.

Ultrasound-guided procedures can be used to treat a variety of problems seen in the infertile woman.

1. Egg pickup for IVF - The use of vaginal ultrasound for egg pickup has made egg retrieval a short, simple and inexpensive procedure, which can be performed in a day-care unit, under sedation and local anesthesia . The ovaries are normally present in the pouch of Douglas, and are very accessible transvaginally. Moreover, the presence of adhesions does not interfere with egg collection.

2. Ovarian cyst aspiration. An ovarian cyst is a very common condition in which fluid collects in the ovary. However, cysts which are more than 5 cm in size need to be treated, as they can cause problems ( eg twisting and rupture). Normally, surgery had to be done to remove these cysts - and often this damaged the surrounding normal ovary as well. With ultrasound-guidance, we can stick a needle from the vagina into the cyst, and empty the contents ( usually clear fluid ) by sucking it out. This empties the cyst, which often does not recur.

3. Treatment of ectopic pregnancy . With technological advances ( ultrasound and beta-HCG blood tests) the diagnosis of tubal pregnancy can be made very early, usually before rupture. It can be treated by injecting a toxic chemical, methotrexate, into the sac, which causes the tissue to die and then get reabsorbed, without any surgery whatsoever. In more advanced tubal pregnancies, potassium chloride can be injected direct into the heart of the baby in the ectopic gestational sac, thus killing it and preventing it from growing.

4. Ultrasound-guided tubal embryo and gamete transfer for IVF and GIFT techniques. Techniques have been devised to pass a special tube - the Jansen-Anderson catheter set - into the fallopian tubes through the vagina under ultrasound guidance, so as to place the embryos and /or the gametes in the fallopian tube. Since the tube offers a better environment for the gametes and embryos than the uterine cavity, it is believed that this will improve pregnancy rates.

5. Tubal recanalisation for cornual blocks ( proximal tubal obstruction) . Often cornual blocks are due to the presence of mucus plugs and amorphous debris in the tubal lumen. Ultrasound guided tubal catheterization can effectively treat the blocked tubes in some of these patients.
The scope of ultrasound guided procedures has increased dramatically in the last few years; and with further improvements in technology, we can expect this list to become even longer, and doctors become more versatile with using this technology.

Ultrasound - Seeing with Sound

Ultrasound or sonography has helped revolutionize our approach to the infertile patient. Ultrasound machines are the newest addition to the gynecologist’s bag of tricks; and help him to "image" or see structures in the female pelvis. Ultrasound uses high frequency sound waves much like SONAR machines used in ships for detecting submarines underwater. The high frequency sound waves are bounced off the pelvic organs; and the reflected sound waves are received by the probe ( transducer) and a computer is used to reconstruct the waves into black and white images on the monitor. Ultrasound machines today are all real-time machines, which give dynamic images.

In the old days, ultrasound for infertility was done through the abdomen. This required you to fill up your bladder ( till it was ready to burst !) so that the sound waves could be transmitted into the pelvis. However, the standard ultrasound technique today for infertility is vaginal ultrasound ( endovaginal scanning) in which a long, slim, slender probe is inserted into the vagina and used for imaging the pelvic organs. Not only is this much more comfortable for you; it also gives much sharper and clearer pictures, since the probe is much closer to the pelvic structures.

What can you see on ultrasound ? The ultrasound gives clear pictures of the uterus; and the ovaries. It allows the doctor to look for fibroids; ovarian cysts; and ectopic pregnancies. It is also excellent for early diagnosis of pregnancies. However, the ultrasound scan is not very good for assessing whether or not the tubes are normal.

Ovulation scans allow the doctor to determine accurately when the egg matures; and when you ovulate. This is often the basic procedure for most infertility treatment since the treatment revolves around the wife's ovulation. Daily scans are done to visualize the growing follicle, which looks like a black bubble on the screen. Most women can see the follicle clearly for themselves - and know by the scans when the egg has ruptured. Other useful information which can be determined by these scans is the thickness of the uterine lining - the endometrium. The ripening follicle produces increasing quantities of estrogen, which cause the endometrium to thicken. The doctor can get a good idea of how much estrogen you are producing ( and thus the quality of the egg) based on the thickness and brightness of the endometrium on the ultrasound scan.





One of the commonest findings on an ultrasound scan is an ovarian cyst. A cyst is a collection of fluid surrounded by a thin wall ( a fluid-filled sac) that develops in the ovary. Typically, ovarian cysts are functional (not disease-related) and disappear on their own. During ovulation, a follicle may grow , but fail to rupture and release an egg. Instead of being reabsorbed, the fluid within the follicle persists and forms a follicular cyst. The other type of functional cyst is a corpus luteum cyst, which develops when the corpus luteum fills with blood. Functional ovarian cysts usually resolve on their own, and are not to be confused with other pathological conditions involving cystic ovaries, specifically polycystic ovarian disease , endometriotic cysts, or ovarian tumours. Since an ultrasound picture is just a black and white shadow, the doctor has to be skillful in interpreting what the image means. Simple cysts are thin walled, and appear as a large black bubble. Cysts which contain blood ( for example, chocolate cysts found in patients with endometriosis) will have echoes within them, which appear white, and these are described as complex masses on ultrasound. The incidence of follicular cysts is increased in infertile patients taking drugs ( such as clomiphene and HMG) for ovulation induction. Functional ovarian cysts usually disappear within 60 days without treatment. However, if the cyst is larger than 6 cm, or persists for longer than 6 weeks, then further testing may be needed.
Who does the scans ? Ultrasound scans can be done either by a radiologist; or by the gynecologist or infertility specialist himself. Remember that the eye only sees what the mind knows, so you must go to a good clinic for your scans. The benefit of having the scans done by the infertility specialist himself is that he can make immediate decisions regarding your treatment based on the scan findings. If the radiologist does the scans, then you have to wait till your doctor has seen the report before knowing what to do next since the radiologist does not make the treatment decisions. In any case, it is vital that the ultrasound scans be done in the Infertility Clinic itself, so that your waiting can be minimized - and you don't have to run around from the sonographer to the gynecologist. If there are any abnormal findings, it is vital that your gynecologist see the actual ultrasound for himself during the scan. This provides much more information than the printed pictures.
Recent Advances in Ultrasound
Ultrasound technology has made dramatic advances in recent years, and now tests have been described which allow the doctor to use ultrasound to assess tubal patency. Basically, these involve passing a fluid into your tubes through the uterus; and the gynecologist can see the passage of the bubbles into the tubes and out into the abdomen. Since this test ( sonosalpingography) can be done in the doctor's clinic itself, and does not involve X-ray radiation, it has advantages - especially for documenting that the tubes are normal. However, the gold standard for tubal testing remains HSG and laparoscopy today.
Doppler: The newer ultrasound machines have Doppler attachments which allow the doctor to judge the flow of blood in the blood vessels. The most exciting advance is that of Colour Doppler, where the blood flow can be mapped in color on the monitor. While still a research tool, it may provide important information for assessing the infertile patient in the coming years.
Three – dimensional ultrasound. Using sophisticated microprocessors, the newest ultrasound machines allow the doctor to reconstruct the image, so that he gets a three dimensional view. While this provides excellent pictures, the true value of this technique for infertility still has to be evaluated.
Ultrasound now also offers infertile patients newer treatment options not available before. Modern surgical techniques have progressively become less and less invasive - all to the patient's benefit ! From laparotomy to laparoscopy , and now to ultrasound guided procedures, we are witnessing a change in the gynecologist's armamentarium from the knife to the endoscope to the guided needle !
The benefits to the patient are many and include : reduced costs; reduced hospitalisation ; reduced risk of complications; and better preservation of fertility, with increased chance of conception for the future.
Ultrasound-guided procedures can be used to treat a variety of problems seen in the infertile woman.
1. Egg pickup for IVF - The use of vaginal ultrasound for egg pickup has made egg retrieval a short, simple and inexpensive procedure, which can be performed in a day-care unit, under sedation and local anesthesia . The ovaries are normally present in the pouch of Douglas, and are very accessible transvaginally. Moreover, the presence of adhesions does not interfere with egg collection.
2. Ovarian cyst aspiration. An ovarian cyst is a very common condition in which fluid collects in the ovary. However, cysts which are more than 5 cm in size need to be treated, as they can cause problems ( eg twisting and rupture). Normally, surgery had to be done to remove these cysts - and often this damaged the surrounding normal ovary as well. With ultrasound-guidance, we can stick a needle from the vagina into the cyst, and empty the contents ( usually clear fluid ) by sucking it out. This empties the cyst, which often does not recur.
3. Treatment of ectopic pregnancy . With technological advances ( ultrasound and beta-HCG blood tests) the diagnosis of tubal pregnancy can be made very early, usually before rupture. It can be treated by injecting a toxic chemical, methotrexate, into the sac, which causes the tissue to die and then get reabsorbed, without any surgery whatsoever. In more advanced tubal pregnancies, potassium chloride can be injected direct into the heart of the baby in the ectopic gestational sac, thus killing it and preventing it from growing.
4. Ultrasound-guided tubal embryo and gamete transfer for IVF and GIFT techniques. Techniques have been devised to pass a special tube - the Jansen-Anderson catheter set - into the fallopian tubes through the vagina under ultrasound guidance, so as to place the embryos and /or the gametes in the fallopian tube. Since the tube offers a better environment for the gametes and embryos than the uterine cavity, it is believed that this will improve pregnancy rates.
5. Tubal recanalisation for cornual blocks ( proximal tubal obstruction) . Often cornual blocks are due to the presence of mucus plugs and amorphous debris in the tubal lumen. Ultrasound guided tubal catheterization can effectively treat the blocked tubes in some of these patients.
The scope of ultrasound guided procedures has increased dramatically in the last few years; and with further improvements in technology, we can expect this list to become even longer, and doctors become more versatile with using this technology.

Monday, May 12, 2008

Microinjection: The Latest Advance in Treating the Infertile Man 2


In patients in whom surgery needs to be performed in order to recover testicular or epididymal sperm, it is now possible to freeze the excess sperm. These sperm can then be thawed and used in future cycles in needed, thus sparing the patient the need for repeated surgery for sperm retrieval.

Once eggs and sperm have been collected, the actual process of injecting a single sperm into the egg is carried out in a laboratory. The injection is performed on a heating stage, on a specialized inverted microscope (which allows one to magnify details up to 400 times) equipped with Hoffman modulation contrast optics (which enhance "optical contrast", so that the details of the egg can be visualized easily). The precise control that is needed for microinjection is provided by using specialized micromanipulators, which allow one to execute very fine movements.

The eggs and sperm are manipulated using fine glass pipettes, made of thin capillary tubing, which are even finer than a human hair. These are custom made, the holding pipette being designed to hold a single sperm. Live sperm are placed in a drop of viscous polyvinyl pyrrolidone (PVP) solution, which serves to slow down the activity of the sperm. (It is helpful to slow down the sperm, so that they can be picked up more easily by the injecting needle.) A single sperm is then selected and its tail is pinched or broken to immobilize it. This is usually done by crushing the sperm tail by rolling it between the injection pipette and the base of the petri dish. It is essential to immobilize the sperm, so that it cannot move after it has been injected into the egg. A single immobile sperm is then picked up by sucking it into the injection pipette.

The egg is secured in place by applying gentle suction to its shell (the zona) with a holding pipette. The sperm is then injected directly into the centre (cytoplasm) of the egg by moving the injection pipette very precisely with the help by movine the injection pipette very precisely with the help of the micromanipulator into the egg, and then blowing the sperm out very gently into the cytoplasm of the egg. In order to do this, it is important to breach the zona of the egg and the outer membrane of the egg. The skill of the embryologist is a critical factor in the success of the ICSI process. After injecting the sperm, the pipette is withdrawn. Remarkably, once the injecting pipette is withdrawn, the egg will close and assume its original shape within 60 seconds. One can visualize ICSI as the sperm being given a "piggyback" ride into the egg, so that what the sperm cannot accomplish on its own, the laboratory does for it! The only requirement for ICSI is that the sperm should be alive, and there should be as many sperm as there are eggs.

Once all the eggs are injected with a single sperm each, they are placed in the CO2 incubator, and then observed approximately 14 hours later to see if fertilization has taken place. If fertilization has occurred, the 2-4 cell embryos can be transferred into the wife’s uterus about 48-72 hours after ICSI, as is done for IVF. Interestingly, embryo implantation rates in these patients are quite high, because the wives are usually young and completely normal.

Fertilization rates in the range of 60-80 per cent have been achieved in experienced hands-which means, of 100 microinjection eggs about 60 form embryos after ICSI. In fact the technology is now reliable enough to virtually guarantee fertilization, if there are sufficient good quality eggs. The pregnancy rate in one ICSI cycle is about 35 percent. Remarkably, the chance of achieving a pregnancy does not depend upon the sperm count or number (since you only need as many sperm as there are eggs!), but rather on the number and quality of eggs retrieved, which, in turn, depend upon the woman’s age. The risk of having a baby with a birth defect is not increased with this technique.

ICSI is very expensive at present, because of the advanced technology it utilizes. Nevertheless, it is now available in most of India’s large cities, and as times goes by, it is hoped that the cost of this procedure will decrease, making it affordable for more patients.

Some IVF clinics have started performing ICSI routinely for all patients , instead of offering them IVF. However, this is inappropriate. ICSI should be reserved for only two groups of patients: (1) those who have severe male factor infertility, for whom IVF is not a treatment option; and (2) those patients whose sperm have not been able to fertilise the eggs in an IVF cycle ( total fertilisation failure). Remember that pregnancy rates with ICSI are no better than with IVF, as long as fertilisation occurs.

The Risk Factor

ICSI is still a new technique, and even though more than 10,000 babies have been born worldwide after it has come into use, and detailed studies have shown that there is no increased risk of birth defects or genetic anomalies after ICSI, nevertheless, it should only be reserved for those patients for whom traditional IVF is not a valid treatment option.

It is also possible that some of the male children born as a result of this technique may be infertile as well (for example, if the cause for the testicular failure is a defective genetic locus, such as a microdeletion on the Y chromosome).

Recent Advances

However, for some patients with severe testicular failure, sometimes, it is not possible to find any sperm at all as even in spite of taking multiple testicular biopsies. In such patients pregnancies have been achieved even by injecting round spermatids (immature precursor cells from which the sperm are formed) from the testis into the egg. This is now an area of intense research all over the world.

For men with no testis at all, the only technologic solution today would be cloning using nuclear transfer technology. This involves inserting the nucleus from an ordinary cell of the man ( which contains all his DNA) into his wife’s unfertilised egg (the nucleus of which has been removed) and then activating it by electrofusion. While cloning has been performed successfully in many animal species, it has never been used for treating humans so far.

Microinjection: The Latest Advance in Treating the Infertile Man


The introduction of Microinjection Technology into the in vitro fertilization laboratory has revolutionized our treatment of the infertile man. Intracytoplasmic sperm injection, or ICSI (pronounced "eeksee"), is a new infertility treatment that uses micromanipulation technology for treating male infertility. What ICSI promises is the possibility for every man to father his own baby - no matter what his medical problem!

What exactly is ICSI? As the name suggests, ICSI is a technique in which a single sperm is injected into the centre of the cytoplasm of the egg, in order to achieve fertilization. While this may sound very crude, ICSI allows the IVF laboratory to achieve fertilization with very few sperm. The beauty of the technique is that since the sperm is being injected directly into the egg, all that is needed to achieve fertilization are live sperm - no matter how abnormal these may appear to be. With ICSI the equation "1 egg plus 1 sperm = 1 embryo" becomes possible!

The Procedure for ICSI

ICSI is done in a superovulated cycle during which fertility drugs (human menopausal gonadotropin - HMG- injections) are administered to the wife to aid in the production of multiple eggs, which are then removed under vaginal ultrasound guidance as is done for IVF. In normal circumstances, the egg is surrounded by a cluster of cells known as the cumulus corona cells, and this is called the oocyte cumulus corona complex. These cumulus cells are removed by repeated passage of the oocyte cumulus corona complex through fine pipettes, and by treating them with a chemical called hyaluronidase so that these cells are stripped off. The denuded eggs are examined, and only mature eggs (eggs in metaphase II, which have a polar body) are used for ICSI.

Sperm is collected from the man, usually through masturbation. For men with severe oligospermia, we have found it useful to use sequential ejaculates. Even though the first semen sample may not contain any sperm, we often find motile sperm in the second ( or even the third sample, for men with enough stamina !) This maybe because the later samples contain "fresher" sperm. Since these samples contain such few sperm, they need to processed very carefully, so that the all the sperm in the sample are recovered in the culture medium , and can be used for ICSI. For men with variable sperm counts, which vary from zero to a few thousand, it may be helpful to freeze a sample ( which contains sperm ) in advance. For patients with azoospermia, sperm harvesting techniques need to be used to retrieve the sperm. For men with obstructive azoopsermia,( because of duct blockage or absence of the vas deferens) , the simplest technique is called PESA (percutaneous epididymal sperm aspiration), in which the sperm is sucked out from the epididymis by puncturing it with a fine needle. Occasionally, one may have to use microsurgery to find epididymal sperm, and this is called MESA (microepididymal sperm aspiration). For patients with obstructive azoopsermia in whom sperm cannot be found in the epididymis, it is always possible to find sperm in the testis. The easiest way to retrieve this is through TESA or testicular sperm aspiration , in which the testicular tissue is sucked out through a fine needle, under local anaesthesia. The testicular tissue is placed in culture media and sent to the lab, where it is processed. The sperm are liberated from within the seminiferous tubules ( where they are produced ) and are then dissected free from the surrounding testicular tissue.

Using sperm from the epididymis and testis for ICSI in order to treat patients with obstructive azoospermia is logical, and thus conceptually easy to understand. However, surprisingly, it is possible to find sperm even in patients who have testicular failure ( nonobstructive azoospermia) - even in those men with very small testes. The reason for this is that defects in sperm production are "patchy"- they do not affect the entire testis uniformly. This means that even if sperm production is absent in a certain area, there may be other areas in the testis where sperm production would be normal (this could be because the genetic defect that causes abnormal spermatogenesis may be "leaky"). Since such few sperm are needed for ICSI, we can find enough sperm in over 50 per cent of patients with testicular failure , even if their testes are as small as a peanut!

However, while finding sperm is quite easy in men with obstructive azoospermia ( since their testes are functioning normally ), patients with nonobstructive azoospermia ( testicular failure) can be very challenging. Often, sperm production in these men is sparse, and multiple sites in the testis may need to be sampled before being able to find sperm. This can be done by performing mutiple tiny microbiopsies , and this is called TESE or testicular sperm extraction. ( One of our patients suggested that we call this procedure TSEICSI - which stands for testicular sperm extraction with ICSI, and pronounce it as "sexy"!) This can be done through the needle, or as an open procedure performed under direct vision through a tiny skin incision under local anesthesia and sedation. Finding sperm in the testicular tissue can be a laborious process , depending on the degree of sperm production, and testicular sperm are hard to work with in the laboratory. For men with nonobstructive azoopsermia, we usually perform the TESE the day prior to egg retrieval, because culturing the testicular tissue in the incubator for 24 hours helps the sperm to acquire motility, which makes them easier to work with. In case no sperm are found, either the couple decides to cancel the egg retrieval and abandon the cycle, or to go ahead with using donor sperm for IVF, as a backup option.

The Case of the Man with a Low Sperm Count


Many infertile men are obsessed about their sperm count - and this seems to become the central concern in their lives. Remember that the real question the man with a fertility problem is asking is not : What is my sperm count or motility or whatever? But - are my sperm capable of working or not? Can I have a baby with my sperm? Since the function of the sperms is to fertilize the egg, the only direct way of answering this question is by actually doing IVF for test fertilization . This is of course too expensive and impractical for most people which is why the other sperm function tests have been devised.

The major problem with all these tests , however, is that they are all indirect - there is no very good correlation between test results, pregnancy rates, and fertilization in vitro for the individual patient. This is why offering a prognosis for the individual patient based on an abnormality in the sperm test result is so difficult, and why we find that different doctors give such widely varying interpretations based on the same sperm report.

This is really not surprising, when you consider how abysmal our ignorance in this area is - after all, we do not even know what a "normal" sperm count is ! Since you only need one "good" sperm to fertilise an egg, we do not have a simple answer to even this very basic question ! While the lower limit of normal is considered to be 10 million progressively motile sperm per ml, remember that this is a statistical average. For example, most doctors have had the experience of a man with a very low sperm count (as little as 2-5 million per ml) fathering a pregnancy on his own, with no treatment. In fact, when sperm counts are done for men who are undergoing a vasectomy for family planning, these men of proven fertility have sperm counts varying anywhere from 2 million to 300 million per ml. This obviously means that there is a significant variation in "fertile" sperm counts, and therefore coming to conclusions is very difficult for the doctor ( leave alone the patient !)

In order to make sense of this, you need to understand two important concepts - "trying time"; and "fertility potential of the couple". If your sperm count is low, but you have been trying to have a baby for less than 1 year, it still makes sense to keep on trying for about 1 year , since 10% of men with low sperm counts will father a pregnancy in this time. If however, you have already tried for more than 1 year with no success, you need to move on and do something more - the chances of a spontaneous pregnancy are very low. Remember , that a doctor does not treat just a "low sperm count report " – he treats patients !

So what is the man with a low sperm count to do? Unfortunately, there is no method of increasing the sperm count today ! The modern protocol for managing male infertility is based on the man’s motile sperm count; and on a simple test, celled a sperm survival test. The sperm are washed, and sperm recovery assessed; the washed sperm are then kept in culture medium in the incubator for 24 hours. If there are more than 3 million motile sperm per ml, this is reassuring. If, however, none of the sperm are alive after 24 hours, this suggest that they may be functionally incompetent. Treatment depends upon how low the count is. If it is only moderately decreased ( total motile sperm count in the ejaculate being 20 million), it makes sense to try to improve the fertility potential of the wife, and the easiest treatment for men with moderately low sperm counts is superovulation plus intrauterine insemination. If after doing this and trying for 6 treatment cycles (the reason 6 is the "magic "number is that most patients who are going to become pregnant with any method will usually do so within 6 cycles) no pregnancy ensues, you need to go on and explore further alternatives, such as IVF or ICSI.

For men with a motile sperm count of more than 5 million in the ejaculate, IVF would be the first treatment offered. This would allow us to document if the sperm can fertilize the eggs or not. If fertilisation is documented, then the patient has a good chance of getting pregnant. However, if the motile sperm count is less than 5 million, or if there is total failure of fertilisation in IVF, then the only treatment available is ICSI ( intracytoplasmic sperm injection , pronounced "eeksee") or microinjection. ICSI has revolutionised our approach to the infertile man, and it promises the possibility for every man to have a baby, no matter how low his sperm count.

What about the answer to the million dollar question - Why do I have a low sperm count? Unfortunately, nine times out of ten, the doctor will not be able to answer that question, since we do not know the answer, and no amount of testing will help us to find out - this is labelled as "idiopathic oligospermia" which is really a wastepaper basket diagnosis for "god only knows!". Modern research has shown that the reason some men have a low sperm count is because of a microdeletion on the Y-chromosome. This is an expensive test, which is available only in research laboratories at present, and does explain why we have little effective treatment for this common problem ! We do know that a low sperm count is not related to physique, general state of health, diet, sexual appetite or frequency. While not knowing the cause can be very frustrating, medicine still has a lot to study and understand about male infertility, which is a relatively neglected field today.

The major cause of male infertility usually is a sperm problem. However, do remember that this is no reflection on your libido or sexual prowess. Sometimes men with testicular failure find this difficult to understand (but doctor, I have sex twice a day ! How can my sperm count be zero?). The reason for this, is that the testis has two compartments. One compartment, the seminiferous tubules, produces sperms. The other compartment, the "interstitium" or the tissue in between the tubules (where the Leydig cells are) produces the male sex hormone, testosterone, which causes the male sexual drive. Now while the tubules can be easily damaged, the Leydig cells are much more resistant to damage, and will continue functioning normally in most patients with testicular failure.

This is why the diagnosis of a low sperm count can be such a blow to one's ego - it is so totally unexpected, because it is not associated with other symptoms or signs. Men react differently - but common feelings include anger with the wife and the doctor; resentfulness about having to participate in infertility testing and treatment since they feel having babies is the woman's "job"; loss of self-esteem; and temporary sexual dysfunction such as loss of desire and poor erections. Many men also feel very guilty that because of " their " medical problem, they are depriving their wife the pleasures of experiencing motherhood. Unfortunately, social support for the infertile man is practically non-existent, and he is forced to put up a brave front and show that he doesn’t care. Since he is a man, he is not allowed to display his emotions. He is expected to provide a shoulder for his wife to cry on – but he needs to learn to cry alone. However, remember that the urge for fatherhood can be biologically as strong as the urge for motherhood – and we should stop treating infertile men as second class citizens.

Sunday, May 11, 2008

Microinjection: The Latest Advance in Treating the Infertile Man

In patients in whom surgery needs to be performed in order to recover testicular or epididymal sperm, it is now possible to freeze the excess sperm. These sperm can then be thawed and used in future cycles in needed, thus sparing the patient the need for repeated surgery for sperm retrieval.

Once eggs and sperm have been collected, the actual process of injecting a single sperm into the egg is carried out in a laboratory. The injection is performed on a heating stage, on a specialized inverted microscope (which allows one to magnify details up to 400 times) equipped with Hoffman modulation contrast optics (which enhance "optical contrast", so that the details of the egg can be visualized easily). The precise control that is needed for microinjection is provided by using specialized micromanipulators, which allow one to execute very fine movements.

The eggs and sperm are manipulated using fine glass pipettes, made of thin capillary tubing, which are even finer than a human hair. These are custom made, the holding pipette being designed to hold a single sperm. Live sperm are placed in a drop of viscous polyvinyl pyrrolidone (PVP) solution, which serves to slow down the activity of the sperm. (It is helpful to slow down the sperm, so that they can be picked up more easily by the injecting needle.) A single sperm is then selected and its tail is pinched or broken to immobilize it. This is usually done by crushing the sperm tail by rolling it between the injection pipette and the base of the petri dish. It is essential to immobilize the sperm, so that it cannot move after it has been injected into the egg. A single immobile sperm is then picked up by sucking it into the injection pipette.

The egg is secured in place by applying gentle suction to its shell (the zona) with a holding pipette. The sperm is then injected directly into the centre (cytoplasm) of the egg by moving the injection pipette very precisely with the help by movine the injection pipette very precisely with the help of the micromanipulator into the egg, and then blowing the sperm out very gently into the cytoplasm of the egg. In order to do this, it is important to breach the zona of the egg and the outer membrane of the egg. The skill of the embryologist is a critical factor in the success of the ICSI process. After injecting the sperm, the pipette is withdrawn. Remarkably, once the injecting pipette is withdrawn, the egg will close and assume its original shape within 60 seconds. One can visualize ICSI as the sperm being given a "piggyback" ride into the egg, so that what the sperm cannot accomplish on its own, the laboratory does for it! The only requirement for ICSI is that the sperm should be alive, and there should be as many sperm as there are eggs.



Fig 2. A single sperm is being injected into an egg during an ICSI procedure

Once all the eggs are injected with a single sperm each, they are placed in the CO2 incubator, and then observed approximately 14 hours later to see if fertilization has taken place. If fertilization has occurred, the 2-4 cell embryos can be transferred into the wife’s uterus about 48-72 hours after ICSI, as is done for IVF. Interestingly, embryo implantation rates in these patients are quite high, because the wives are usually young and completely normal.
Fertilization rates in the range of 60-80 per cent have been achieved in experienced hands-which means, of 100 microinjection eggs about 60 form embryos after ICSI. In fact the technology is now reliable enough to virtually guarantee fertilization, if there are sufficient good quality eggs. The pregnancy rate in one ICSI cycle is about 35 percent. Remarkably, the chance of achieving a pregnancy does not depend upon the sperm count or number (since you only need as many sperm as there are eggs!), but rather on the number and quality of eggs retrieved, which, in turn, depend upon the woman’s age. The risk of having a baby with a birth defect is not increased with this technique.
ICSI is very expensive at present, because of the advanced technology it utilizes. Nevertheless, it is now available in most of India’s large cities, and as times goes by, it is hoped that the cost of this procedure will decrease, making it affordable for more patients.

Some IVF clinics have started performing ICSI routinely for all patients , instead of offering them IVF. However, this is inappropriate. ICSI should be reserved for only two groups of patients: (1) those who have severe male factor infertility, for whom IVF is not a treatment option; and (2) those patients whose sperm have not been able to fertilise the eggs in an IVF cycle ( total fertilisation failure). Remember that pregnancy rates with ICSI are no better than with IVF, as long as fertilisation occurs.

The Risk Factor

ICSI is still a new technique, and even though more than 10,000 babies have been born worldwide after it has come into use, and detailed studies have shown that there is no increased risk of birth defects or genetic anomalies after ICSI, nevertheless, it should only be reserved for those patients for whom traditional IVF is not a valid treatment option.
It is also possible that some of the male children born as a result of this technique may be infertile as well (for example, if the cause for the testicular failure is a defective genetic locus, such as a microdeletion on the Y chromosome).

Recent Advances

However, for some patients with severe testicular failure, sometimes, it is not possible to find any sperm at all as even in spite of taking multiple testicular biopsies. In such patients pregnancies have been achieved even by injecting round spermatids (immature precursor cells from which the sperm are formed) from the testis into the egg. This is now an area of intense research all over the world.

For men with no testis at all, the only technologic solution today would be cloning using nuclear transfer technology. This involves inserting the nucleus from an ordinary cell of the man ( which contains all his DNA) into his wife’s unfertilised egg (the nucleus of which has been removed) and then activating it by electrofusion. While cloning has been performed successfully in many animal species, it has never been used for treating humans so far.

Microinjection: The Latest Advance in Treating the Infertile Man

The introduction of Microinjection Technology into the in vitro fertilization laboratory has revolutionized our treatment of the infertile man. Intracytoplasmic sperm injection, or ICSI (pronounced "eeksee"), is a new infertility treatment that uses micromanipulation technology for treating male infertility. What ICSI promises is the possibility for every man to father his own baby - no matter what his medical problem!

What exactly is ICSI? As the name suggests, ICSI is a technique in which a single sperm is injected into the centre of the cytoplasm of the egg, in order to achieve fertilization. While this may sound very crude, ICSI allows the IVF laboratory to achieve fertilization with very few sperm. The beauty of the technique is that since the sperm is being injected directly into the egg, all that is needed to achieve fertilization are live sperm - no matter how abnormal these may appear to be. With ICSI the equation "1 egg plus 1 sperm = 1 embryo" becomes possible!

The Procedure for ICSI

ICSI is done in a superovulated cycle during which fertility drugs (human menopausal gonadotropin - HMG- injections) are administered to the wife to aid in the production of multiple eggs, which are then removed under vaginal ultrasound guidance as is done for IVF. In normal circumstances, the egg is surrounded by a cluster of cells known as the cumulus corona cells, and this is called the oocyte cumulus corona complex. These cumulus cells are removed by repeated passage of the oocyte cumulus corona complex through fine pipettes, and by treating them with a chemical called hyaluronidase so that these cells are stripped off. The denuded eggs are examined, and only mature eggs (eggs in metaphase II, which have a polar body) are used for ICSI.

Sperm is collected from the man, usually through masturbation. For men with severe oligospermia, we have found it useful to use sequential ejaculates. Even though the first semen sample may not contain any sperm, we often find motile sperm in the second ( or even the third sample, for men with enough stamina !) This maybe because the later samples contain "fresher" sperm. Since these samples contain such few sperm, they need to processed very carefully, so that the all the sperm in the sample are recovered in the culture medium , and can be used for ICSI. For men with variable sperm counts, which vary from zero to a few thousand, it may be helpful to freeze a sample ( which contains sperm ) in advance. For patients with azoospermia, sperm harvesting techniques need to be used to retrieve the sperm. For men with obstructive azoopsermia,( because of duct blockage or absence of the vas deferens) , the simplest technique is called PESA (percutaneous epididymal sperm aspiration), in which the sperm is sucked out from the epididymis by puncturing it with a fine needle. Occasionally, one may have to use microsurgery to find epididymal sperm, and this is called MESA (microepididymal sperm aspiration). For patients with obstructive azoopsermia in whom sperm cannot be found in the epididymis, it is always possible to find sperm in the testis. The easiest way to retrieve this is through TESA or testicular sperm aspiration , in which the testicular tissue is sucked out through a fine needle, under local anaesthesia. The testicular tissue is placed in culture media and sent to the lab, where it is processed. The sperm are liberated from within the seminiferous tubules ( where they are produced ) and are then dissected free from the surrounding testicular tissue.
Using sperm from the epididymis and testis for ICSI in order to treat patients with obstructive azoospermia is logical, and thus conceptually easy to understand. However, surprisingly, it is possible to find sperm even in patients who have testicular failure ( nonobstructive azoospermia) - even in those men with very small testes. The reason for this is that defects in sperm production are "patchy"- they do not affect the entire testis uniformly. This means that even if sperm production is absent in a certain area, there may be other areas in the testis where sperm production would be normal (this could be because the genetic defect that causes abnormal spermatogenesis may be "leaky"). Since such few sperm are needed for ICSI, we can find enough sperm in over 50 per cent of patients with testicular failure , even if their testes are as small as a peanut!

However, while finding sperm is quite easy in men with obstructive azoospermia ( since their testes are functioning normally ), patients with nonobstructive azoospermia ( testicular failure) can be very challenging. Often, sperm production in these men is sparse, and multiple sites in the testis may need to be sampled before being able to find sperm. This can be done by performing mutiple tiny microbiopsies , and this is called TESE or testicular sperm extraction. ( One of our patients suggested that we call this procedure TSEICSI - which stands for testicular sperm extraction with ICSI, and pronounce it as "sexy"!) This can be done through the needle, or as an open procedure performed under direct vision through a tiny skin incision under local anesthesia and sedation. Finding sperm in the testicular tissue can be a laborious process , depending on the degree of sperm production, and testicular sperm are hard to work with in the laboratory. For men with nonobstructive azoopsermia, we usually perform the TESE the day prior to egg retrieval, because culturing the testicular tissue in the incubator for 24 hours helps the sperm to acquire motility, which makes them easier to work with. In case no sperm are found, either the couple decides to cancel the egg retrieval and abandon the cycle, or to go ahead with using donor sperm for IVF, as a backup option.

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