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RECENT ADVANCEMENT IN INFERTILITY TREATMENT

INTRODUCTION

Infertility is a major issue around the world, and there are many treatments available today for
those suffering from infertility problems. In the field of science, there are numerous research
studies being conducted that help eliminates infertility. The majority of couples wish to have
children at some point, and 85% of them are conceived within a year. Another 7% of women
become pregnant during their second year of trying.

Having difficulty conceiving after years of well-timed and repeated attempts is referred to as
infertility. Many factors contribute to infertility, and they are often complex. There are both male
and female factors involved in this condition. In order to get out of this type of situation, much
advancement is introduced in infertility treatments. 

DEFINITION

Infertility is a disease of the male or female reproductive system defined by the failure to achieve
a pregnancy after 12 months or more of regular unprotected sexual intercourse.

Infertility is medically defined as the inability to conceive following one year of regular sexual
intercourse without contraception or after six months if the woman is over age 35. The definition
also includes women who are unable to carry a pregnancy to live birth. There are two general
types of infertility.

Primary infertility is defined as difficulty conceiving for a couple who has never before had a
child, while secondary infertility describes a couple who is having difficulty conceiving when at
least one of the partners has previously had a baby Or having baby.

FEMALE INFERTILITY

Incidence

According to the 1995 National Survey on Family Growth, approximately 7.1% of married
couples were infertile. If the scope is broadened to encompass the truly desired outcome of an
infant, impaired fecundity (difficulty or impossibility of getting pregnant or carrying a baby to
term) affects 10.2% of women of reproductive age (6.1 million persons) and 12.9% of married
women. In 40% of the cases the problem is attributable to the man, and for 40% of the couples
the difficulty is traced to the woman. In about 10% of the cases, infertility is linked to both
partners. The remaining 10%, despite exhaustive testing, remains unexplained. The most
common causes of female infertility are ovulatory disorders, mechanical problems,
endometriosis and some other factor.
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CAUSES OF FEMALE INFERTILITY

FAILURE TO OVULATE

Ovulatory disorders are one of the most common reasons why women are unable to conceive,
and account for 30% of women's infertility fortunately; approximately 70% of these cases can be
successfully treated by the use of drugs such as Clomiphene and Menogan/Repronex. The causes
of failed ovulation can be categorized as follows:

1. HORMONAL PROBLEMS: These are the most common causes of an ovulation. The
process of ovulation depends upon a complex balance of hormones and their interactions
to be successful, and any disruption in this process can hinder ovulation. There are three
main sources causing this problem ;

 Failure to produce mature eggs

In approximately 50% of the cases of an ovulation, the ovaries do not produce normal follicles in
which the eggs can mature. Ovulation is rare if the eggs are immature and the chance of
fertilization becomes almost nonexistent. Polycystic ovary syndrome, the most common disorder
responsible for this problem, includes symptoms such as amenorrhea, hirsutism, an ovulation and
infertility. This syndrome is characterized by a reduced production of FSH, and normal or
increased levels of LH, estrogen and testosterone. The current hypothesis is that the suppression
of FSH associated with this condition causes only partial development of ovarian follicles, and
follicular cysts can be detected in an ultrasound seen. The affected ovary often becomes
surrounded with a smooth white capsule and is double its normal size. The increased level of
estrogen raises the risk of breast cancer.

 Malfunction of the hypothalamus

The hypothalamus is the portion of the brain responsible for sending signals to the pituitary
gland, which, in turn, sends hormonal stimuli to the ovaries in the form of FSH and LH to initiate
egg maturation. If the hypothalamus fails to trigger and control this process, immature eggs will
result. This is the cause of ovarian failure in 20% of cases.

 Malfunction of the pituitary gland:

The pituitary's responsibility lies in producing and secreting FSH and LH. The ovaries will be
unable to ovulate properly if either too much or too little of these substances is produced. This
can occur due to physical injury, a tumor or if there is a chemical imbalance in the pituitary.

2. SCARRED OVARIES: Physical damage to the ovaries may result in failed ovulation.
For example, extensive, invasive, or multiple surgeries, for repeated ovarian cysts may
cause the capsule of the ovary to become damaged or scarred, such that follicles cannot
mature properly and ovulation does not occur. Infection may also have this impact.
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3. PREMATURE MENOPAUSE: This presents a rare and as of yet unexplainable cause

of anovulation. Some women cease menstruation and begin menopause before normal
age. It is hypothesized that their natural supply of eggs has been depleted or that the
majority of cases occur in extremely athletic women with a long history of low body
weight and extensive exercise. There is also a genetic possibility for this condition.
4. FOLLICLE PROBLEMS: Although currently unexplained, "Unruptured follicle
syndrome" occurs in women who produce a normal follicle, with an egg inside of it,
every month yet the follicle fails to rupture. The egg, therefore, remains inside the ovary
and proper ovulation does not occur.

Causes of poorly functioning fallopian tubes

Tubal disease affects approximately 25% of infertile couples and varies widely, ranging from
mild adhesions to complete tubal blockage. Treatment for tubal disease is most commonly
surgery and, owing to the advances in microsurgery and lasers, success rates (defined as the
number of women who become pregnant within one year of surgery) are as high as 30% overall,
with certain procedures having success rates up to 65%. The main causes of tubal damage
include:

 Infection: Caused by both bacteria and viruses and usually transmitted sexually, these
infections commonly cause inflammation resulting in scarring and damage, A specific
example is Hydrosalpnix, a condition in which the fallopian tube is occluded at both ends
and fluid collects in the tube.

 Abdominal Diseases: The most common of these are appendicitis and colitis, causing
inflammation of the abdominal cavity which can affect the fallopian tubes and lead to
scarring and blockage.

 Previous Surgeries: This is an important cause of tubal disease and damage, Pelvic or
abdominal surgery can result in adhesions that alter the tubes in such a way that eggs
cannot travel through them.

 Ectopic Pregnancy : This is a pregnancy that occurs in the tube itself and, even if
carefully and successfully overcome, may cause tubal damage and is a potentially life-
threatening condition.

 Congenital Defects: In rare cases, women may be born with tubal abnor- malities,
usually associated with uterus irregularities.

5. ENDOMETRIOSIS: Approximately 10% of infertile couples are affected by

endometriosis. Endometriosis affects five million US women, 6-7% of all females. In
fact, 30-40% of patients with endometriosis are infertile. This is two to three times the
rate of infertility in the general population. For women with endometriosis, the monthly
fecundity (chance of getting pregnant) diminishes by 12 to 36%. This condition is
characterized by excessive growth of the lining of the uterus, called the endometrium.
Growth occurs not only in the uterus but also elsewhere in the abdomen, such as in the
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fallopian tubes, ovaries and the pelvic peritoneum. A positive diagnosis can only be made
by diagnostic laparoscopy, a test that allows the physician to view the uterus, fallopian
tubes, and pelvic cavity directly. The symptoms often associated with endometriosis
include heavy, painful and long menstrual periods, urinary urgency, rectal bleeding and
premenstrual potting. Sometimes, however, there are no symptoms at all, owing to the
fact that there is no correlation between the extent of the disease and the severity of the
symptoms. The long term cumulative pregnancy rates are normal in patients with
minimal endometriosis and normal anatomy.

ADDITIONAL FACTORS

1) OTHER VARIABLES THAT MAY CAUSE INFERTILITY WOMEN:

 At least 10% of all cases of female infertility are caused by an abnormal uterus.
Conditions such as fibroid, polyps, and adenomyosis may lead to obstruction of the
uterus and Fallopian tubes.

 The Congenital abnormalities, such as septate uterus, may lead to recurrent miscarriages
or the inability to conceive.

 Approximately 3% of couples face infertility due to problems with the femaleis cervical
mucus. The mucus needs to be of a certain consistency and available in adequate amounts
for sperm to swim easily within it. The most common reason for abnormal cervical
mucus is a hormone imbalance, namely too little estrogen or too much progesterone.

2) BEHAVIORAL FACTORS:

It is well-known that certain personal habits and lifestyle factors impact health; many of these
same factors may limit a couple's ability to conceive. Fortunately, however, many of these
variables can be regulated to increase not only the chances of conceiving but also one's overall
health.

Diet and Exercise: Optimal reproductive functioning requires both proper diet and appropriate
levels of exercise. Women who are significantly overweight or underweight may have difficulty
becoming pregnant.

Smoking : Cigarette smoking has been shown to lower sperm count in men and increases the
risk of miscarriage, premature birth, and low-birth-weight babies for women. Smoking by either
partner reduces the chance of conceiving with each cycle, either naturally or by IVF, by one-
third.

Alcohol: Alcohol intake greatly increases the risk of birth defects for women and, if in high
enough levels in the motheris blood, may cause Fetal Alcohol Syndrome. Alcohol also affects
sperm counts in men.
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Drugs: Drugs, such as marijuana and anabolic steroids, may impact sperm counts in men.
Cocaine use in pregnant women may cause severe retardations and kidney problems in the baby
and is perhaps the worst possible drug to abuse while pregnant. Recreational drug use should be
avoided, both when trying to conceive and when pregnant.

3) ENVIRONMENTAL AND OCCUPATIONAL FACTORS:

The ability to conceive may be affected by exposure deto various toxins or chemicals in the
workplace or the surrounding environment. Substances that can cause mutations, birth defects,
abortions, infertility or sterility are called reproductive toxins. Disorders of infertility, disorder of
reproduction, spontaneous abortion, and teratogenesis are among the work-related diseases and
injuries in the U.S. today.

The following are the chemicals such as:

 Lead: Exposure to lead sources has been proven to negatively impact fertility in humans.
Lead can produce teratospermias (abnormal sperm) and is thought to be an abortifacient,
or substance that causes artificial abortion.

 Medical Treatments and Materials: Repeated exposure to radiation, ranging from

simple X-rays to chemotherapy, has been shown to alter sperm production, as well as
contribute to a wide array of ovarian problems.

 Ethylene Oxide: A chemical used both in the sterilization of surgical instruments and in
the manufacturing of certain pesticides, ethylene oxide may cause birth defects in early
pregnancy and has the potential to provoke early miscarriage.

 Dibromochloropropane (DBCP): Handling the chemicals found in pesticides, such as

DBCP, can cause ovarian problems, leading to a variety of health conditions, like early
menopause, that may directly impact fertility.

TEST FOR FEMALE INFERTILITY

In identifying the cause (s) of infertility, there are five basic steps, each of which consists of a
number of tests:

1. STEP ONE
An evaluation of ovulatory functioning to determine whether the woman is ovulating
on a regular basis, whether the luteal phase of the menstrual cycle is functioning
properly, and whether the timing of ovulation could be assessed.
 Tests of ovulation: may include basal body temperature monitoring (which can indicate
after the fact that a woman has ovulated),

 Ultrasound testing (which detects the number, size, and shape of the egg follicles,
follows the growth of follicles, and identifies whether follicles have collapsed, indicating
that ovulation has occurred), and LH2 surge monitoring (which predicts when ovulation
will occur).
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 Luteal phase testing is conducted to assess whether the uterus prepares itself properly to
receive and carry a fertilized egg, and may include blood tests to determine hormone
levels or an endometrial biopsy to observe the development of the uterine lining.

2. STEP TWO

 A semen analysis, which will first evaluate the quantity, motility, and shape of sperm. If
initial analysis indicates a low sperm count, abnormal sperm shapes, or low sperm
motility, additional analysis may be performed, including penetration tests or the
hemizona test. The hemizona assay test determines whether sperm binding to the zona
membrane of the egg is normal while the hamster penetration test, or sperm penetration
test, uses hamster eggs to measure the ability of human sperm to fertilize.

3. STEP THREE

 Tests cervical functioning, using the post-coital test to assess if there is a problem in the
interaction between a woman's cervical mucus and her partner's sperm.
 A post-coital test necessitates the couple to have intercourse before the woman visits the
physician office to examine her cervical mucus.
4. STEP FOUR

 Evaluates the woman's reproductive tract and reproductive organs through different
means of imaging. An HSG, for example, is a radiologic study in which dye visible by
fluoroscopy, is injected into the uterine cavity to determine the shape of the uterus and
the potency of the fallopian tubes.

5. STEP FIVE

 Assesses the pelvic environment with laparoscopy, a surgical procedure in which the
inner organs are viewed through an instrument resembling a telescope that is inserted
through the abdominal wall .

TREATMENT

Drugs

Ovulatory disorders are involved in about 40% of fertility problems.Currently, there are two
major drugs used to treat ovulatory disorders, namely human menopausal gonadotropins (hMG;
Pergonal, Humegon, Metrodin, Fertinex) and clomiphene citrate (CC; Clomid, Serophene),
although both of these may be supplanted by an increasing number of other drugs.

1. A typical cycle of clomiphene citrate and has a variety of side effects, including hot flashes,
mood swings, headaches, nausea, vomiting and ovarian enlargement or cysts.

2. A typical cycle of human menopausal gonadotropin must be administered by injection. Side

effects include mood swings, fatigue, headaches, bloating and weight gain, and possible swelling
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at the site of injection. More serious side effects may occur with hMG, such as ovarian
hyperstimulation syndrome, and often other drugs must be prescribed along with hMG to ensure
it functions properly. Human chorionic gonadotropin, for example, may be needed to trigger
follicle rupture (ovulation). To support ovulation and pregnancy, progesterone may be prescribed
alongside an hMG

MALE INFERTILITY

THE CAUSES OF MALE INFERTILITY

 Male infertility has many causes-from hormonal. Imbalances, to physical problems, to

psychological and/ or behavioral problems. Moreover, fertility reflects a man's "overall
health. Men who live a healthy lifestyle are more likely to produce healthy sperm. The
following list highlights some lifestyle choices that negatively impact male fertility-it is
not all-inclusive:

 Smoking-significantly decreases both sperm count and sperm cell motility.

 Prolonged use of marijuana and other recreational drugs,

 Chronic alcohol abuse.

 Anabolic steroid use-causes testicular shrinkage and infertility.

 Overly intense exercise-produces high levels of adrenal steroid hormones which cause a
testosterone deficiency resulting in infertility.

 Inadequate vitamin C and Zine in the diet.

 Tight underwear-increases scrotal temperature which results in decreased sperm

production.

 Exposure to environmental hazards and toxins such as pesticides, lead, paint, radiation,
radioactive substances, mercury, benzene, boron, and heavy metals

 Malnutrition and anemia.

 Excessive stress!

 Modifying these behaviors can improve a man's fertility and should be considered when a
couple is trying to achieve pregnancy.

1. HORMONAL PROBLEMS

 A small percentage of male infertility is caused by hormonal problems. The

hypothalamus-pituitary endocrine system regulates the chain of hormonal events that
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enables testes to produce and effectively disseminate sperm. Several things can go wrong
with the hypothalamus-pituitary endocrine system:

 The brain can fail to release gonadotrophic-releasing hormone (GnRH) properly. GnRH
stimulates the hormonal pathway that causes testosterone synthesis and sperm
production. A disruption in GnRH release leads to a lack of testosterone and a cessation
in sperm production

 . The pituitary can fail to produce enough lutenizing hormone (LH) and follicle
stimulating hormone (FSH) to stimulate the testes and testosterone/sperm production. LH
and FSH are intermediates in the hormonal pathway responsible for testosterone and
sperm production.

 The testes Leydig cells may not produce testosterone in response to LH stimulation.

 A male may produce other hormones and chemical compounds which interfere with the
sex-hormone balance.
 The following is a list of hormonal disorders which can disrupt male infertility:

 Hyperprolactinemia.

Elevated prolactin-a hormone associated with nursing mothers, is found in 10 to 40

percent of infertile males. Mild elevation of prolactin levels produces no symptoms, but
greater elevations of the hormone reduces sperm production, reduces libido and may
cause impotence. This condition responds well to the drug Parlodel (bromocriptine).

 Hypothyroidism:

Low thyroid hormone levels can cause poor semen quality, poor testicular function and
may disturb libido. May be caused by a diet high in iodine. Reducing iodine intake or
beginning thyroid hormone replacement therapy can elevate sperm count. This condition
is found in only 1 percent of infertile men.

 Congenital Adrenal Hyperplasia :

Occurs when the pituitary is suppressed by increased levels of adrenal androgens.

Symptoms include low sperm count, an increased number of immature sperm cells, and
low sperm cell motility. Is treated with cortisone replacement therapy. This condition is
found in only 1 percent of infertile men.

 Hypogonadotropic Hypopituitarism:

Low pituitary gland output of LH and FSH. This condition arrests sperm development
and causes the progressive loss of germ cells from the testes and causes the seminiferous
tubules and Leydig (testosterone producing) cells to deteriorate. May be treated with the
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drug Serophene. However, if all germ cells are destroyed before treatment commences,
the male may be permanently infertile.

 Panhypopituitarism:

Complete pituitary gland failure-lowers growth hormone, thyroid-stimulating hormone,

and LH and FSH levels. Symptoms include: lethargy, impotence, decreased libido, loss of
secondary sex characteristics, and normal or undersized testicles. Supplementing the
missing pituitary hormones may restore vigor and a hormone called hCG may stimulate
testosterone and sperm production.

2. PHYSICAL PROBLEMS

A variety of physical problems can cause male infertility. These problems either interfere with
the sperm production process or disrupt the pathway down which sperm travel from the testes to
the tip of the ponis. These problems are usually characterized by a low sperm count and or
abnormal sperm morphology. The following is a list of the most common physical problems that
cause male infertility

 Varicococle:

A varicocele is an enlargement of the internal spermatic veins that drain blood from the
testicle to the abdomen (back to the heart and are present in 15% of the general male
population and 40% of infertile men. These images show what a variococle looks like
externally and internally .
A varicocele develops when the one way valves in these spermatic veins are damaged
causing an abnormal back flow of blood from the abdomen into the scrotum creating a
hostile environment for sperm development. Varicocoeles may cause reduced sperm
count and abnormal sperm morphology which cause infertility. Variococles can usually
be diagnosed by a physical examination of the scrotum which can be aided by the
Doppler stethoscope and scrotal ultrasound. Varicocele can be treated in many ways but
the most successful treatments involve corrective surgery.

 Damaged Sperm Ducts :

Seven percent of infertile men cannot transport sperm from their testicles to out of their
penis. This pathway may be blocked by a number of conditions: genetic or developmental
mistake may block or cause the absence of one or both tubes (which transport the sperm
from the testes to the penis).
Scarring from tuberculosis or some STDs may block the epididymis or tubes. An elective
or accidental vasectomy may interrupt tube continuity.

 Torsion :
Is a common problem affecting fertility that is caused by a supportive tissue abnormality
which allows the testes to twist inside the scrotum which is characterized by extreme
swelling. Torsion pinches the blood vessels that feed the testes shut which causes
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testicular damage. If emergency surgery is not performed to untwist the testes, torsion
can seriously impair fertility and cause permanent infertility if both testes twist.

 Infection and Disease:

Mumps, tuberculosis, brucellosis, gonorrhea, typhoid, influenza, smallpox, and syphilis

can cause testicular atrophy. A low sperm count and low sperm motility are indicators of
this condition. Also, elevated FSH levels and other hormonal problems are indicative of
testicular damage. Some STDs like gonorrhea and chlamydia can cause infertility by
blocking the epididimis or tubes. These conditions are usually treated by hormonal
replacement therapy and surgery in the case of tubular blockage.

 Klinefelter's Syndrome:

Is a genetic condition in which each cell in the human body has additional X
chromosome-men with Klinefelter's Syndrome have one Y and two X chromosomes.
Physical symptoms include peanut- sized testicles and enlarged breasts. A chromosome
analysis is used to confirm this analysis. If this condition is treated in its early stages
(with the drug hCG), sperm production may commence and/or improve. However,
Klinefelter's Syndrome eventually causes all active testicular structures to atrophy. Once
testicular failure has occurred, improving fertility is impossible.

 Retrograde Ejaculation :

Is a condition in which semen is ejaculated into the bladder rather than out through the
urethra because the bladder sphincter does not close during ejaculation. If this disorder is
present, ejaculate volume is small and urine may be cloudy after ejaculation. This
condition affects 1.5 percent of infertile men and may be controlled by medications like
decongestants which contract the bladder sphincter or surgical reconstruction of the
bladder neck can restore normal ejaculation.

3. PSYCHOLOGICAL/PHYSICAL/BEHAVIORAL PROBLEMS:

Several sexual problems exist that can affect male fertility. These problems are most often both
psychological and physical in nature: It is difficult to separate the physiological and physical
components.

 Erectile Disfunction (ED):

Also known as impotence, this condition is common and affects 20 million American
men. ED is the result of a single, or more commonly a combination of multiple factors. In
the past, ED was thought to be the result of psychological problems, but new research
indicates that 90 percent of cases are organic in nature. However, most men who suffer
from ED have a secondary psychological problem that can worsen the situation like
performance anxiety, guilt, and low self- esteem. Many of the common causes of
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impotence include: diabetes, high blood pressure, heart and vascular disease, stress,
hormone problems, pelvic surgery, trauma, venous leak, and the side effects of
frequently prescribed medications (i.e. Prozac and other SSRIs, Propecia).

 Premature Ejaculation:

Is defined as an inability to control the ejaculatory response for at least thirty seconds
following penetration. Premature ejaculation becomes a fertility problem when
ejaculation occurs before a man is able to fully insert his penis into his partner's vagina.
Premature ejaculation can be overcome by artificial insemination or by using a behavioral
modification technique called the "squeeze technique" which desensitizes the penis.

 Ejaculatory Incompetence:

This rare psychological condition prevents men from ejaculating during sexual
intercourse even though they can ejaculate normally through masturbation. This
condition sometimes responds well to behavioral therapy; if this technique does not work,
artificial insemination can be employed using an ejaculate from masturbation.

TESTING FOR MALE INFERTILITY

 Testing for male infertility can be complicated, time consuming and expensive. Because
the end results of the many disparate problems that cause male infertility are low sperm
count, abnormal sperm shape, and poor sperm motility, additional tests besides a semen
analysis (described below) are required to pinpoint the cause of the infertility.

 The evaluation of the male begins with a history, physical examination, and two semen
analyses.

Semen Analysis:

At least two semen samples collected on separate days by masturbation are recommended. Each
sample should be collected after abstaining from ejaculation for at least 48 hours, but not for
longer than 3-5 days. The complete ejaculate should be collected and must be examined within
an hour of collection for optimal accuracy. A general semen evaluation includes a determination
of the time it takes for the semen to become liquid and an examination of the semen's volume,
consistency, and pH. The semen is also microscopically evaluated for sperm count, motility.
Sperm shape, agglutination (the sperm's propensity to clump together), and the presence of
foreign elements such as bacteria. According to the World Health Organization, a normal
ejaculate should have more thari 50 million sperm per milliliter; at least 60 percent of the sperm
should have forward motility, and more than 60 percent should have a normal morphology.
Contradictions to these criteria indicate a condition that is causing the male infertility.

To pinpoint the cause of infertility, a variety of other tests may be performed:

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 Hormone evaluation-Measures blood levels of the hormones involved in sperm

production,
 abnormal hormonal levels are indicative of the hormonal problems described that cause
infertility.

 Semen culture-Checks for bacteria in the semen which either cause or indicate a genital
infection that may cause infertility.

 Biochemical analysis of semen-Measures various chemical in semen; a chemical

imbalance may impair fertility.

 Post-coital/cervical mucus test - Checks the compatibility of a man's sperm with the
mucus of his partner's cervix. If the sperm and mucus are incompatible, the sperm is
unable to pass through the mucus into the fallopian tubes and fertilize the egg-

 Sperm penetration assay (Hamster test)- measures sperm-egg membrane fusion using
hamster eggs a man's sperm: tests the capability of the sperm to penetrate the egg during
IVF.

 A thorough physical examination and history can diagnose physical problems such as
varicocoeles, Klinefelter's Syndrome, retrograde ejaculation. erectile disfunction, and
premature ejaculation.

 An absence of sperm in the semen sample is indicative of ejaculatory incompetence,

retrograde ejaculation, or one of the conditions that block the spermatic ducts.

TREATMENT FOR MALE INFERTILITY

A wide variety of treatment options are available for the many causes of male infertility. Simple
lifestyle changes, like abstaining from alcohol, tobacco, and illicit drugs can improve male
fertility. A healthy diet, sufficient exercise (but not excessive exercise), and proper amounts of
vitamin B12, vitamin C, and zinc also improve fertility.

Treating Hormonal Problems:

 Several drugs are available to treat pituitary and hormonal imbalances: If LH and FSH
levels are low and the hypothalamus and pituitary gland are functionat, the drug
clomiphene citrate (Serophene, Clomid) is able to stimulate the hypothalamus to release
GnRH at regular intervals and restore fertility.If the pituitary is malfunctioning and not
manufacturing the necessary sex hormones. hormone replacement therapy can restore
fertility. Injections of hCG (human chorionic gonadotropin) increases the LH supply and
can stimulate the testes to produce testosterone and sperm If unresponsive to hCG, the
drug Pergonal (a combination of LH and FSH) can stimulate sperm production. The drug
Parlodel (bromocriptine) can correct hyperprolactinemia.
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 Cortisone replacement therapy can lower abnormally high androgen levels and allow the
pituitary to function normally to restore fertility. Hormone replacement therapy usually
works in about 4 months.

Treating Physical Problems:

 Varicocele:
Are most successfully repaired by microsurgery. Surgical repair improves the semen in
70 percent of men and results in pregnancy in 60 percent of couples. Surgery involves the
interruption of the damaged testicular veins, Men who are infertile due to varicoceles can
also achieve fertilization via intrauterine insemination, in-vitro fertilization (IVF- more
on this technique later), and treatment with the drug clomid.

 Blocked Ducts: As mentioned earlier, the path through which sperm pass from the
testicle to outside of the penis can become interrupted or blocked by several conditions.
In the case of voluntary or accidental vasectomy, a vasectomy reversal can be performed
which reconnects the testicle to the vas deferens. Tubal scarring due to an STD or
tuberculosis can also be fixed by microsurgical techniques. In the cases of a congenital
absence of the vas deferens, failed vasectomy reversals, and other irreparable
obstructions, men's sperm can be retrieved via three methods. Once sperm is retrieved,
the sperm are used to fertilize the egg of a woman who has undergone a typical IVF
cycle.

Sperm retrieval methods are:

Micro Epididymal Sperm Aspiration (MESA)- involves a delicate surgical technique that
utilizes a microscope to get a sperm sample from a location proximal to the tubal obstruction.

Percutaneous Epididymal Sperm Aspiration (PESA) - a small needle is used to aspirate

sperm from a location proximal to the tubal obstruction. ☐ Testicular Sperm Biopsy (TESE) - a
small biopsy of testicular tissue is taken and a sperm sample is removed from the biopsy.

Ejaculatory Disfunction:

Men who suffer from conditions that render them unable to ejaculate (neurologic disease,
traumatic injury, or surgical complication), can achieve ejaculation by two currently used
techniques.

 Vibratory stimulation employs a custom designed mechanical vibrator to stimulate the

underside of the glans penis to induce a reflex ejaculation. This technique only works in
patients with an intact ejaculatory reflex arc.

 For men for which vibratory stimulation is ineffective, a procedure called

electroejaculation can be used to induce ejaculation. A specially designed electric probe
is inserted into the rectum next to the prostate.
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 A current generated by the device stimulates the nerves of the pelvic muscles to induce a
contraction and cause an ejaculation. Retrograde ejaculation can be treated with
deconges- tant medication (which causes the bladder sphincter to close and allows semen
to pass to the penis) or by tubal constructive surgery.

Treating Psychological / Physical Problems:

Erectile Dysfunction: Treatment for ED can be divided into four broad categories,
pharmacologi- cal, mechanical, surgical, and psychological.

Pharmacological treatment: Involves the delivery of medications that restore erections. Several
drugs are currently used to treat ED. Sildenafil (Viagra) is taken orally to increase penile blood
flow, it is highly effective. Caverject is a drug injected directly into the penis to cause an
erection; it is highly effective. Papaverine is another injectible drug that is highly effective.
Yohimbine is a dietary supplement taken orally that is moderately effective. Testosterone
replacement therapy is highly effective for men with low testosterone levels.

Mechanical Treatment: Involves the use of a vacuum erection device with a constriction ring.
The vacuum device vacuums the penis into an erection and the constriction ring keeps blood
from exiting the spongy bodies of the penis to maintain the erection. This treatment is effective
but obviously cumbersome.

Surgical Treatment: Involves the use of implants or the correction of vascular damage/blockage
to restore erectile capacity. Penile implants work excellently: there are 2 types. A semi-rigid
implant keeps the penis in a perpetual semi-rigid state. Inflatable implants allow the man to
"pump" his penis into an erection. Arterial and venous reconstructive surgery works moderately
well and may restore a man's ability to achieve an erection. Psychological therapy is useful in the
cases of ED which are a direct result of psychological causes. These patients may also benefit
from pharmacological or combination therapy.

Treating Premature Ejaculation: Premature ejaculation can be treated by the squeeze

technique in which a man is stimulated until close to orgasm and then his frenulum is squeezed
by his partner. This procedure is repeated until the penis becomes desensitized and longer
intercourse becomes feasible. Premature ejaculation can also be treated by collecting the
ejaculate and using artificial insemination to fertilize the egg.

Treating Ejaculatory Incompetence: Ejaculatory incompetence can be treated by behavioral

therapy in some cases. With behavioral therapy. ejaculation may be stimulated by combining
masturba- tion and manual stimulation with eventual penile insertion into the vagina. If this
therapy does not work. artificial insemination with an ejaculate obtained through masturbation
can be used to overcome infertility.

ASSISSTED REPRODUCTIVE TECHNIQUES

Assisted reproductive technology (ART) is a general term referring to methods used to achieve
pregnancy by artificial or partially artificial means. It is reproductive technology used primarily
 15

in infertility treatments. Some forms of ART are also used in fertile couples for genetic reasons.
ART is also used in couples who are discordant for certain communicable diseases, i.e. Aids, to
reduce the risk of infection when a pregnancy is desired. There is yet no strict definition of the
term.

ARTIFICIAL INSEMINATION

Artificial insemination can be performed by using the husband's sperm [homologous

insemination, a donor's sperm [heterogonous insemination] or a combination of both. The
success rate is 70-90%. It is the process by which sperm is placed into the reproductive tract of a
female for the purpose of impregnating the female by using means other than sexual intercourse

1. AID: Artificial Insemination by donor

2. AIH: Artificial Insemination by husband

Indication

 Cervical problem
 Mechanical problems such as psychosexual spinal cord injury and other physical
disability.

 Antisperm antibody in the man

 Mild oligospermia with satisfactory motility.

 Semen stored before commencement of chemotherapy or radiotherapy

Indication for donor insemination

 Azoopermia or oligospermia in male partner.

 Excessive non- motile or abnormal sperm

 Risk of transmission of a hereditary diseases

 Rh-isoimmunisation, a rheses negative donor can be used.

 Lack of male partner.

Procedure

With the use of vaginal speculum and syringe the ejaculate is deposited into the cervical canal or
vaginal vault and kept in the place with a diaphragm or cervical cap for 8 hours. The woman may
be asked to lie still for a few minutes. It is usually carried out 2-3 days before the ovulation, 2-3
inseminations may be required within one month cycle, the process may continue for 6-12
months until pregnancy occur.
 16

Selection of donor
 Must be of normal intelligence, fit and healthy with no personal or family history of
diseases. Test for STD including HIV are repeated at every visit.
 The semen is frozen and stored for at least 3 months before use to be sure and tests were
negative.
 Donors are matched as for as possible to the male partner skin, hair and eye coloring,
height build and blood group.
 The couple requesting artificial insemination signs an informed consent and a contract
accepting the resultant offspring as their legal heir.
 Donor is not considered as father.

INTRAUTERINE INSEMINATION

Washed sperm, that is, spermatozoa which have been removed from most other components of
the seminal fluids, can be injected directly into a woman's uterus in a process called intrauterine
insemination (IUI). If the semen is not washed it may elicit uterine cramping, expelling the
semen and causing pain, due to content of prostaglandins. (Prostaglandins are also the
compounds responsible for causing the myometrium to contract and expel the menses from the
uterus, during menstruation)

Intra uterine insemination is used in cases in which cervical mucus properties [possibly altered
by infection or antibody formation] cause infertility. There should not be tubal pathology and the
women should be ovulating normally, mild super ovulation may be induced. Artificial
insemination inside the uterus, thus by passing the cervix by means of a fine catheter. It can be
performed on an outpatient basis and requires little or no anesthesia for the women.

IN VITRO FERTILIZATION/EMBRYO TRANSFER OR TEST TUBE CONCEPTION

The first successful IVF was performed in Great Britain 1978. The most likely candidates for this
approach are common whose oviducts have been damaged. In this eggs and sperm are made to
unite outside the body under controlled conditions in the laboratory dish and embryo thus
developed in transferred into the uterine cavity at the end of 48-72 hours.

Indication

 Tubal damage
 Oligospermia, poor motility, antisperm antibody
 Cervical problems
 Endometriosis.
 Unexplained infertility
 Pelvic inflammatory diseases Primary fallopian tube
 Absence or diseased uterus
 Idiopathic infertility
 17

Preparation of the patient:

Every couple is individually counseled and the entire procedures is clearly explained tot hem.
The success rate which is about 15-20% in ET AND IN 30-40%. The financial commitment is
explained tot hem since the procedure involves a sophicated equipments, expensive reagentsand
disposables.

Procedure

Step 1: Patient selection

Step 2: Ovulation induction is performed using drugs to stimulate multiple ovulation progress is
monitored by ultrasonography follicle tracking and serum oestradiol level.

Step 3:Ovum/oocyte retrieval is planned when 4or more follicles reach 20mm in size. The ova
are harvested using vaginal ultrasound guidance under local anesthetic or laparoscopy under
general anesthesia.

Step 4: Semen collection to be done.

Step 5: Fertilization and cleavage in laboratory with washed sperm and ova was done.

Step 6: Transfer of embryo to the uterus is performed

2-3 days later when the zygotes have reached the 4 or 8 cell stage. A maximum of 3 embryos are
placed in the uterus via the cervix to increases the chances of success but reduce the risk of
multiple pregnancy.

Step 7: Establishment of pregnancy. Any healthy embryo is frozen for further attempt if
necessary:

TRANS VAGINAL FERTILIZATION

This is a new method but this method is still under investigation, its use is not yet routine. In this
process the oocyte are retrieved by use of ultrasonography guidance they are then mixed with
sperm in the laboratory, positioned in a sealed envelope in the vaginal to incubate the ova and
sperm under more optimal conditions) and removed 48 hours later to determine whether
fertilization occurred. The embryo is then transferred to the cervix.

Gamete Intrafallopian Tube Tranfer [Gift]

This technique was developed by Dr.Ricardo H.Asch in 1984 at the University of Texas Health
Centre at San Antonio Texas.
 18

Indication

 Severe male factor

 Unexplained infertility
 Cervical factor
 Artificial insemination with husband sperm, donor

sperm failed 12 attempts. To perform this procedure at least one fallopian tube must be patent
and sperm quality must be good. The couple is followed closely as with IVF and given hormonal
therapy to stimulate ovulation. Daily ultrasonography evaluation determines follicular
maturation. After maturation of follicles, the ova are retrieved and placed with the partner's
sperm. The combined ova and sperm are then immediately returned to the woman's fallopian
tubes. There is no waiting period in the laboratory for confirmation of fertilization. Progesterone
therapy to support implantation is used when necessary.

ZYGOTE INTRAFALLOPIAN TRANFER [ZIFT

The eggs are retrieved, mixed with processed sperms and incubated for 24-28 hours. Once the
fertilization occurs, the embryo is transferred into the fallopian tubes at the pronuclei stage. For
this procedure at least one tube should be healthy. The Success rate is 30-40%. This proves the
fertilizing capacity of the gametes.

Sperm Attached Oocytes Fallopian Transfer

This is a new procedure intermediate between GIFT AND ZIFT. Here unlike GIFT, the sperms
and oocytes are incubated together for 2-3 hour, in the laboratory, at the end of which sperms
attached oocytes are transferred in to the fallopian tube making sure that the process of
fertilization is initiated.

TUBAL EMBRYO TRANSFER [TET] 2-4 cell embryos are transferred into the fallopian
tube.

DIRECT OOCYTE AND SPERM TRANSFER

This is done in patients with bilateral tubal block hoping fertilization will occur in the uterus.
This method can be tried in the hospitals which do not have lab facilities to check fertilization
outside,

PERITONEAL OOCYTE AND SPERM TRANSFER

It is the procedure that was ultrasound guidance for retrieval of occulted to which sperm are
added. The mixture is then placed in the peritoneal cavity near the fimbriae of the tubes. As with
GIFT, POST allows accurate control of the number of oocytes transferred any excess oocytes
may be inseminated and frozen for the future use. It is done with local anesthesia for the women
no abdominal surgery is necessary and the procedure can thus be performed on the outpatient
basis.
 19

Egg donors are resources for women with no eggs due to surgery, chemotherapy, or genetic
causes, or with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age.
In the egg donor process, eggs are retrieved from a donor's ovaries, fertilized in the laboratory
with the sperm from the recipient's partner, and the resulting healthy embryos are returned to the
recipient's uterus.

A gestational carrier is an option when a patient's medical condition prevents a safe pregnancy,
when a patient has ovaries but no uterus due to congenital absence or previous surgical removal,
and where at patient has no ovaries and is also unable to carry a pregnancy to full term.

By cryopreservation, eggs, sperm and reproductive tissue can be preserved for later IVE

MICROMANIPULATION

Zone drilling is a new approach that is used when semen is repeatedly unable to fertilize the ova
in the laboratory. The zone pellucida is the protective layer of cells surrounding the ovum. For
fertilization the cell membrane must be penetrable by the sperm

Method

1. Partial zona dissection: Involves making a small slit in the zona pellucid, which allows the
sperm direct access to the oocyte.

2. Sub zonal insertion: Involves puncturing the zone with a fine pipette through with a small
number of spermatozoa are injected. When there is a problem in the male gametes that is
inability to penetrate oocytes in vitro, in conditions like low count and motility, non motile
sperm and abnormal forms. Micro manipulation procedure is carried out

Intracytoplasmic Sperm Injection (ICSI)

Successful IVF assumes the availability of healthy sperm. But many cases of infertility arise
from defects in the father's sperm. Often these can be overcome by directly injecting a single
sperm into the egg. 
In the U.S. today, some two-thirds of ART procedures employ ICSI (even though as many as
half of these do not involve male infertility).

Ooplasmic Transfer

Infertility in some cases may stem from defects in the cytoplasm of the mother's egg. To
circumvent these, cytoplasm can be removed from the egg of a young, healthy woman ("Donor
egg") and injected -along with a single sperm- into the prospective mother's egg.
Although a few healthy children have been born following ooplasmic transfer, the jury is still out
on its safety, and it is not approved for use in the U.S.
 20

One reason for concern is that ooplasmic transfer results in an egg carrying both the mother's
mitochondria and mitochondria from the donor (in normal fertilization, all the mitochondria in
the father's sperm are destroyed in the egg). This condition called heteroplasmy creates a child
having two different mitochondrial DNA genomes in all of its cells,

In rare, but important, cases, the defect in the prospective mother's cytoplasm is the result of her
having mitochondria with a mutant gene (link to examples]. Ooplasmic transfer is of no help in
these cases because the fertilized egg will still contain a preponderance of the mother's defective
mitochondria. But researchers in Oregon reported in the 17 September 2009 issue of Nature that
they had been able to produce 4 healthy rhesus monkeys with no mitochondria from their
biological mother.

Their procedure:

 Remove the spindle with all its attached chromosomes from the mother's oocyte at
metaphase II of meiosis. They managed to do this without any of her mitochondria being
withdrawn as well.

 Enucleate the oocyte of the mitochondria donor and then insert the mother's
chromosomes - still attached to the spindle into it. Then inject a sperm from the father.

 Allow the fertilized egg to develop into a blastocyst. Implant this in the uterus of a
surrogate mother.

 The result: 4 healthy babies each with the nuclear genes of their mother and father but
none of the mitochondria of their mother. If this technique could be applied to humans, it
would allow women carrying defective mitochondria to bear babies free of the ailment.

Risks of IVF

The majority of IVF-conceived infants do not have birth defects. However, some studies have
suggested that assisted reproductive technology is associated with an increased risk of birth
defects. In the largest U.S. study, which used data from a statewide registry of birth defects,
6.2% of IVF-conceived children had major defects, as compared with 4.4% of naturally
conceived children matched for maternal age and other factors

The main risks are:

 Genetic disorders: DNA damage increases in e.g. IVF and ICSI, which is reflected e.g.
by up regulation of the gene expression of HNRNPC in the placenta."
 Low birth weight: In IVF and ICSI, a risk factor is the decreased expression of proteins
in energy metabolism; Ferreting light chain and ATPSAL
 Preterm birth: Low birth weight and preterm birth are strongly associated with many
health problems, such as visual impairment and cerebral palsy, and children born after
IVF are roughly twice as likely to have cerebral pals
 Miscarriage
 21

Other risk factors are:

Membrane damage, which is contributed to or reflected by increased expression of the

membrane fusion proteins

Hyper stimulation syndrome

The advantages of ART

 It has allowed some four million previously-infertile couples to have children.

 It permits screening (on one cell removed from the 8- celled morula) for the presence of
genetic disorders - thus avoiding starting a pregnancy if a disorder is found.
 One can use frozen sperm allowing fatherhood for a man who is no longer able to provide
fresh sperm.
 Because a number of morulas are created, the extras can be frozen, stored, and used later
 If the initial attempt fails (the prospective mother must still receive hormones to prepare
her uterus for implantation and the success rate is lower with thawed morulas).
 Where regulations permit, the extras can be used as a source of embryonic stem (ES)
cells.

The Disadvantages of ART

 Although improving, the success rate is still sufficiently low (-35%) that the process often
has to be repeated.
 Because several morulas are usually transferred, multiple births are common (about
50%), and as is the case with most multiple births, the babies are born early and weigh
less. To reduce the number of twins, triplets, etc., more ART centers are turning to
"single- embryo transfer" (SET). Some ART centers find that they can increase the
success rate and thus rely more on SET, by culturing the morulas for 5-6 days, instead of
the usual 2-3 days, before transferring them (by now they have become blastocysts) to the
mother.
 The risk of birth defects is about doubled (from -4% in "normal" pregnancies to -8% in
ART pregnancies).
 ART procedures in experimental animals often result in a failure of correct gene
imprinting. Whether this will pose a problem for humans remains to be seen.
 Expensive procedure

Nurses Role

 Assess the women's condition

 Give guidance regarding the ART procedure Sent for the counseling center
 Provide psychological support for the women's
 Explain the proceedure a formed in the infertility treatment
 22

Conclusion

The assisted reproductive treatment the treatment modalities for infertility .The field of ART is
laborious, expensive, complicated involves the team work and the results are disappointing.
Family planning is a national policy for a couple with 2 children. But what about the childless
couple? Assisted reproductive could be only answer.There is substantial variability in how
different couples are affected by infertility. Some couples' relationships deteriorate, whereas
other couples emerge closer and more satisfied. In general, differences in gender perspective
often generate conflicts among infertile couples. Within infertile couples, women see having
children as more important than men do, and are more involved in the process of trying to
conceive. Women want to talk and share their feelings about trying to have children more than
their male partners do, and are more likely to experience emotional distress and loss of self-
esteem as a result of experiencing infertility. In developing countries, the pressures on infertile
women are, if anything, greater than the ones seen in developed countries. This is especially so
in Africa and some

Journal study

A cross-sectional analysis of a longitudinal cohort study, the Australian Longitudinal Study on

Women's Health (ALSWH). For the ALSWH, women from the general community were
randomly selected from the national public insurance database. Mailed survey data were
collected at multiple time points. At survey 4, there were 9145 respondents aged 28–33 years. Of
8612 women with known PCOS status, 478 women reported having PCOS. Information
regarding fertility status was available for 4856 women. This was the subgroup used in this
analysis. The main outcomes measures are self-reported PCOS status, BMI, infertility, and use of
fertility therapies including ovulation induction and in vitro fertilization (IVF). Logistic
regression was used to examine factors associated with infertility and use of fertility treatment.
Self-reported PCOS prevalence was 5.8% (95% confidence interval [CI]: 5.3%–6.4%). Infertility
was noted by 72% of 309 women reporting PCOS, compared with 16% of 4547 women not
reporting PCOS (p<0.001). Infertility was 15-fold higher in women reporting PCOS (adjusted
odds ratio 14.9, 95% CI 10.9–20.3), independent of BMI. Of women reporting infertility, there
was greater use of fertility hormone treatment, (62%, n=116 vs. 33%, n=162, p<0.001) in women
reporting PCOS; however, IVF use was similar.  In this community-based cohort of women,
infertility and use of fertility hormone treatment was significantly higher in women reporting
PCOS. Considering the prevalence of PCOS and the health and economic burden of infertility,
strategies to optimize fertility are important.

Prevalence of Infertility and Use of Fertility Treatment in Women with Polycystic Ovary
Syndrome: Data from a Large Community-Based Cohort Study
 23

References

1. Midwifery and obstetrical nursing, as per INC syllabus ,third edition ,Nima Baskar,page
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2. Anju E. Joham Helena J. Teede Sanjeeva Ranasinha Sophia Zoungas, and Jacqueline
Boyle Published Online: 10 Apr 2015 https://doi.org/10.1089/jwh.2014.5000
Prevalence of Infertility and Use of Fertility Treatment in Women with Polycystic Ovary
Syndrome: Data from a Large Community-Based Cohort Study
3. A text book of midwifery and gynecological nursing.
Neelam kumari, shivani Sharma, Dr.preethi gupta.page no.48-62
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