Infertility Problem and Its Management

Infertility Problem and Its Management


Infertility affects 1 in 10 couples who want children. Fertility declines in both sexes after the
ages of 30-35, and because more and more couples are delaying starting a family until their 30s,
infertility is becoming more common in the developed world. If conception has not occurred
after a year of unprotected, regular sex, one or both partners may be having a fertility problem.
Female infertility:
About half of couples who experience difficulties conceiving do so as a result of female
infertility. Fertility in women decreases with age and is generally lower by age 35, making
conception more difficult for women over this age.
For conception to occur, all of the following steps must take place: ovulation (the production
and release of a mature egg by an ovary), fertilization of the egg by a sperm, transport of the
fertilized egg along the fallopian tube to the uterus, and implantation of the fertilized egg in the
lining of the uterus. If any stage is interrupted or does not occur, conception cannot take place.
What are the causes?
There are a number of fertility problems in females that may affect one or more of the processes
required for conception. The problems can develop at different stages of conception.

Problems with ovulation:
A common cause of female infertility is the ovaries’ failure to release a mature egg during
every monthly cycle. Ovulation is controlled by a complex interaction of hormones produced by
the hypothalamus (an area of the brain), the pituitary and thyroid glands, and the ovaries. A
common and treatable cause of female infertility is polycystic ovary syndrome which may cause
a hormone imbalance that prevents ovulation from taking place. Disorders of the thyroid gland,
such as hypothyroidism, may also cause a hormonal imbalance that can affect the frequency of
ovulation. Pituitary gland disorders, such as prolactinoma, a non cancerous tumor, may cause a
similar imbalance. In some women, ovulation does not always occur, for reasons that are
unclear. In some cases, women who have been using oral contraceptives for a number of years
may take time to reestablish a normal hormonal cycle after discontinuing them. Excessive
exercise, stress and obesity or low body weight may affect hormone levels and cause temporary
infertility.

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Premature menopause also results in a failure to ovulate. It can occur with no apparent cause or
may be the result of surgery, chemotherapy or radiation therapy. In rare cases, the ovaries do not
develop normally due to a chromosomal abnormality, such as Turner syndrome.
Problems with egg transport and fertilization:
The passage of the egg from the ovary to the uterus may be impeded by damage to one of the
fallopian tubes. This damage may be due to pelvic infection, which may in turn result from a
sexually transmitted disease such as chlamydial cervicitis. Such infections may exist with no
symptoms and may be detected only if you have difficulty conceiving.
Endometriosis, a condition that can lead to the formation of scar tissue and cysts within the
pelvis, may also damage the fallopian tubes, preventing the passage of an egg.
In some women, the egg cannot be fertilized because the mucus produced naturally by the cervix
contains antibodies that destroy the partner’s sperm before they reach the egg.
Problems with implantation:
If the lining of the uterus has been damaged by an infection, such as gonorrhea, the implantation
of a fertilized egg may not be possible. Hormonal problems may also result in the uterine lining
not being adequately prepared for successful implantation. Non cancerous tumors that distort the
uterus and rarely, structural abnormalities present from birth may make it impossible for a
fertilized egg to embed itself in the uterine lining.
What might be done?
Your doctor will ask you about your general state of health, your lifestyle, you’re medical and
menstrual history, and your sex life before recommending particular tests and treatments.
Most causes of female infertility can now be identified through testing. You can find out if
and when you ovulate by using an ovulation prediction kit, available over the counter, or by
recording your body temperature daily. If your doctor suspects that you are not ovulating
regularly, you may have repeated blood tests during your menstrual cycle to assess the level of
the hormone progesterone (which normally rises after ovulation).Repeated ultrasound scanning
of the ovaries during the cycle may also be done to check if and when ovulation occurs. In
addition, a tissue sample may be taken from the uterus and examined for abnormalities.
If tests show that you are not ovulating, you may need further blood tests to check the levels of
thyroid hormones and other hormones, and drugs may be prescribed to stimulate ovulation.
However, if you are ovulating, the next step is to find out whether your partner is producing
sufficient normal sperm by analyzing two or more semen samples.
If you are ovulating normally and your partner’s sperm are normal, your doctor will check if
there is a problem preventing the egg and sperm from meeting. For example, you and your
partner may be asked to have sex during the time that you are ovulating so that a sample of your
cervical mucus (collected within a few hours of intercourse) can be tested for antibodies to
sperm. If analysis of the sample shows antibodies to sperm, there are several methods of

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treatment. Corticosteroids may be prescribed to suppress the production of antibodies, or your
partner’s semen may be injected directly into your uterus to avoid contact with the mucus. If
these steps are not successful, your doctor may recommend assisted conception.
If the cause of the infertility has still not been found, your doctor may arrange for further
investigations to look for a blockage in the fallopian tubes or an abnormality of the uterus. One
such test is laparoscopy, in which an endoscope containing a camera is inserted through the
abdomen. Another is hysterosalpingography, in which a dye is injected through the cervix and X-
rays are taken as the dye enters the reproductive organs. The treatment depends on the problem.
For example, a tubal blockage may be corrected by microsurgery, and endometriosis may be
treated with drugs.

What is the prognosis?
Treatments for female infertility have greatly increased the chance of pregnancy. Success rates
vary, depending on the cause of the infertility and the type of the treatment. Fertility drugs
stimulate ovulation in 1 in 3 women, but there is a risk of multiple pregnancies. Microsurgery to
clear obstructed fallopian tubes is sometimes successful but increases the risk of ectopic
pregnancy. Success rates for assisted conception methods range from 15 to 30 percent per
individual treatment.

MALE INFERTILITY: In about 1 in 3 couples who have difficulty conceiving, the problem
results from male infertility. In males, fertility depends partly on the production of enough
normal sperm to make it likely that one will fertilize an egg and partly on the ability to deliver
the sperm into the vagina during sexual intercourse. If either of these factors is adversely
affected, infertility may result.
What are the causes?
Unlike the causes of female infertility, which are more easily identifiable, the cause of infertility
can be difficult to find in some men. A cause is discovered in only 1 in 3 men investigated.
Problems with sperm production:
A low sperm count or the production of abnormal sperm may have various causes. Normally,
the testis has a temperature of about 4 degree F (2 degree C) lower than the rest of the body. Any
factors that raise the temperature of the testis can reduce the number of sperm produced.
Aspects of your lifestyle that may impair sperm production include smoking, drinking alcohol,
using certain medications and recreational drugs, and even wearing tight clothing.
Sperm production can be adversely affected by some long-term illness, such as chronic kidney
failure and by some infections, such as mumps, that occur after puberty. Conditions affecting
the urethra, such as hypospadias, or the scrotum, such as a varicocele, may also reduce fertility.
In addition, fertility problems may occur if the testis is damaged by medical procedures such as
surgery, chemotherapy, or radiation therapy for disorders such as cancer of the testis.

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Low sperm production may also be due to a hormonal or chromosomal deficiency. Insufficient
production of the sex hormone testosterone by the testes can cause a low sperm count. Since the
pituitary gland controls testosterone secretion, pituitary disorders, such as a tumor, may also lead
to reduced sperm production. Rarely, low testosterone levels are due to a chromosomal
abnormality such as K line felter syndrome. The most common cause of a low sperm count is
idiopathic oligospermia, in which there is a reduced sperm count for no identifiable reason.
There is no effective treatment.
Problems with sperm delivery:
A number of factors may prevent sperm from reaching the vagina. The most easily identifiable
factor is impotence - the inability to achieve or maintain an erection. Other factors include
damage to the Epididymis and vas deferens (tubes that transport sperm).Damage is often due to a
sexually transmitted disease such as gonorrhea. It may also be caused by retrograde ejaculation,
in which semen flows back into the bladder when the bladder valves do not close properly. This
condition can occur after prostate surgery.
What might be done?
Your doctor will ask about your health, medical history, and sex life and give you a physical
examination, including an examination of your genitals. You may also need to provide semen
samples. If your sperm count is low or your sperm are abnormal, further investigations will be
done, such as blood tests to check hormone levels. Treatment depends on the diagnosis. Low
testosterone levels can be treated with hormone injections. Artificial insemination may be used
in cases of impotence or retrograde ejaculation; for the latter, the sperm may be taken from
urine. Damage to the epididymis or vas deferens may be treated by microsurgery.
If you produce only a few healthy sperm, a sample may be taken from an epididymis or testis by
microsurgery. A process called intracytoplasmic sperm injection (ICSI) may then be used to
fertilize an egg with a single sperm.
What is the prognosis?
If the infertility is treatable, the chance of regaining fertility is high. With artificial insemination
the chance of conceiving in one menstrual cycle is about 10-15 percent, and the treatment usually
works within 6 months. Each attempt at assisted conception is successful in 15-30 percent of
cases, depending on the technique.
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Evaluation of the Male for Infertility
Infertility is a major health concern for a large proportion of reproductive age patients. The
purpose of this article is to give a concise but practical overview of the evaluation of the infertile
man because approximately 40 % of infertility cases involve male factors. Significant medical
pathology can now be uncovered by a comprehensive infertility evaluation of the man. Advances
in the understandings and diagnoses of male factor infertility is advancing at a rapid pace. The
man must not be ignored, and the following information is a guide to his evaluation.
Evaluation
The initial workup begins whenever the patient presents. This is predicted by the fact that the
longer a couple remains infertile the less chance there is for cure. A rapid, noninvasive, cost-
effective evaluation is essential.
History
The cornerstone of the evaluation of the infertile man is the history and physical examination.
Table1 outlines the complete pertinent history. The sexual history is paramount. Some of the
problems most commonly encountered in this patient population are related to the timing of
intercourse, with it being too frequent or too infrequent. The history of an undescended testicle is
significant. In a patient with a history of unilateral cryptorchidism, regardless of the time of
orchidopexy, overall semen quality is considerably less than that found in normal men. Bilateral
cyrptorchidism is extremely important. Progressive damage occurs to the germinal epithelium if
the testicle is not in its proper position in the scrotum. It has been shown that orchidopexy should
be performed prior to 2 years of age to maintain a significant level of spermatogenic function.
Any previous surgery of the retroperitoneum, bladder neck (prostate), pelvis, inguinal region, or
scrotum should be assessed. Any surgery on the bladder neck may cause retrograde ejaculation.
Inguinal surgery such as herniorrhaphy, undertaken when an infant or an adult, may have caused
vassal occlusion or vascular insufficiency to the testicule. Fever can cause impaired testicular
function. The ejaculate may not be affected for more than 3 months after the event, as
spermatogenesis takes about 74 days. Postpubertal mumps may cause mumps orchitis, which

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results in an atrophic testis. Fifty percent of patients with testicular cancer have subnormal sperm
densities prior to therapy. A history of diabetes or multiple sclerosis should raise questions about
potency and ejaculatory function. Exposure to drugs and toxins should be detailed. The routine
use of hot tubs or saunas should be discontinued, as elevated temperatures impair
spermatogenesis. A family history of cystic fibrosis is important owing to associated vassal
agenesis and epididymal abnormalities. Finally, a history of anosmia (lack of smell) indicates the
possibility of hypogonadotropic hypogonadism. Galactorrhea, head-aches, and impaired visual
fields suggest the presence of a central nervous system tumor.
TABLE NO. 1
Infertility History
1) SEXUAL HISTORY
3) PAST SURGICAL HISTORY
1. Duration of infertility
1. Orchietomy
2. Previous treatments
2. Orchidopexy
3. Potency surgery
3. Retroperitoneal surgery
4. Timing and frequency of
4. Pelvic, inguinal or scrotal surgery \
intercourse
5. Herniorrhaphy

2) PAST MEDICAL HISTORY
4) MEDICATIONS AND GONADOTOXINS
1. Undescended testicles
1. Chemotherapeutic agents
2. Testicular torsion / trauma
2. Therapeutic drugs
3. Delayed puberty
3. Chemicals (pesticides)
4. Pelvic injury
4. Recreational drugs :smoking,
5. Diabetes
marijuana,cocaine
6. Previous or current therapy
5. Androgenic steroids
7. Viral and febrile illness history
6. Thermal exposure (hot tubs)
8. Postpubertal mumps orchitis
7. Radiation
9. Sexually transmitted diseases
10. Urinary tract infections

11. Cystic fibrosis, or family history of
it




Physical Examination
The physical examination must be thorough, with special attention to the genitalia. The penile
curvature and location of the urethral meatus should be assessed, as abnormalities may result in
improper delivery of the ejaculate. Testicular size and consistency must be recorded, with the
length measured with calipers and the volume estimated with an orchidometer. Size is an
important indicator of spermatogenic capability, as more than 80 % of the testis is involved in

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sperm production. When there is damage to the testicular tubules, loss of mass occurs. The
normal length of the testis is about 4 cm and the volume more than 20 ml. Epididymal induration
and irregularities should be noted. The presence of a vas must be documented, as 2 % of infertile
men have congenital absence of the vas. Varicoceles, that is, dilated spermatic veins that present,
as a “bag of worms” above the testicle in the scrotum must be identified. A varicocele can cause
abnormalities in gonadal function. The scrotal contents should be palpated with the patient in
both the supine and standing positions. Many varicoceles are not visible and may be discernible
only when the patient stands or performs a Valsalva maneuver. Varicoceles often result in a
smaller testis on that side. Ninety percent are left-sided, and any discrepancy in size between the
two testes should arouse suspicion of a varicocele. A rectal examination is essential to assess
prostate size, evidence of infection, and the presence of midline cysts. Look carefully for signs of
hypogonadism, such as decreased body hair, gynecomastia, infantile genitalia, and decreased
muscular development.
Laboratory Evaluation
The laboratory is an integral part of a full-service infertility center. If an on-site laboratory is not
available, specimens must be analyzed by a dedicated infertility laboratory. Data from a
reputable laboratory are critical . Unfortunately, the semen analysis must be done locally because
the specimen must be evaluated shortly after production. Most other studies can be sent out to
any reputable laboratory.
Semen Analysis
The primary laboratory test is the semen analysis. It must be emphasized that semen analysis is
not a test for fertility. It does not separate patients into sterile and fertile groups; it does give
diagnostic information and allows a directed evaluation and treatment. At least two semen
analyses must be obtained to establish a baseline. The standard semen analysis allows evaluation
of semen volume, pH, density (sperm per milliliter), motility, measurement of forward
progression of sperm, and sperm morphology. The semen is examined also for evidence of sperm
agglutination, hyperviscosity, and the presence of white blood cells. The World Health
Organisation (WHO) range of values for normal semen analysis is given in Table No. 2
TABLE NO. 2
WHO(1999) CRITERIA FOR NORMAL SEMEN ANALYSIS
SEMEN PARAMETER
VALUE
Volume
2.0 –5.0 ml
Density
> 20 million/ml
Motility
> 50 %
Forward progression
> 2 (scale 1 – 4)
Morphology
> 30% normal forms
Leukocytes
< 1 million / ml
Agglutination
None
Hyperviscosity
None

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Some laboratories use computer-assisted semen analyses, which are of some value for measuring
sperm motility, however, they should be used only as a source of supplemental information.
Attention has been turned to a more accurate manual analysis of sperm morphology.
Leukocytes In The Semen
Leukocytes in semen have significant effects on sperm function. They modulate an autoimmune
response, adversely affect motility and fertilizing capacity, and deter sperm transport in the
female reproductive tract. The semen of most men contains some immature sperm forms (round
cells), which ordinarily cannot be distinguished form white blood cells (WBCs). This often leads
to an erroneous diagnosis of pyospermia or infection. Semen cultures are not indicated in
asymptomatic patients, as they are essentially always negative. Routine cultures for a typical
organisms are unwarranted because they are not always accurate, are labor- and cost-prohibitive,
and have not been shown to have a clinical impact. For the few patients with symptoms of
urinary or genital tract infections cultures should be prepared. The specific cultures obtained
depend on the individuals ‘symptoms’ and examination but should include cultures of urine,
expressed prostatic secretions, and a postprostatic massage urine sample. Common sexually
transmitted organisms such as Chlamydia, Mycoplasma and Ureaplasma have been implicated in
reproductive failure. Patients with active prostaititis or other urinary tract infections frequently
have decreased sperm count and motility.
Fructose In The Semen
With low-volume oligospermia or low-volume azoospermia, one should be concerned about
retrograde ejaculation and ejaculatory duct obstruction. The assessment for ejaculatory duct
obstruction may incorporate a test for seminal fructose, a sugar produced in the seminal vesicles.
Its absence may indicate the possible absence of the seminal vesicles or obstruction of the
ejaculatory ducts.
Anti-Sperm Antibodies
The incidence of anti-sperm antibodies in the infertile man range from 8 % to 21 %. In men only
antibodies present on the sperm surface are clinically important. Anti-sperm antibodies have
implications at various stages in the fertilization process, that is, due to poor sperm penetration
into cervical mucus; impaired acrosome reaction and zona binding. Risk factors for the
development of sperm-bound antibodies include previous testicular surgery, trauma, or infection,
as does a history of torsion, cryptorchidism and genitourinary infections. Additionally,
obstructive azoospermia (possibly due to obstruction from a previous hernia repair, congenital
absence of the vas deferens, or vasectomy) can induce sperm autoimmunity.
Sperm Function Tests
Hypo-Osmotic Swelling Test (Hos Test) : The integrity of sperm cell plasma membrane is
essential for endowing fertilizing capability to the sperm. The assessment of plasma membrane
function is therefore useful indicator of healthy sperm. The test is based on the principle of hypo-
osmotic solutions being passively transferred across intact cell membranes. Sperm with
functionally intact cell membranes swell and their tails undergo coiling when exposed to hypo-

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osmotic conditions. There is a high degree of correlation between the results of swelling test and
fertilizing capacity as measured by the sperm penetration assay.
Acrosome Intactness Test: The acrosome contains a number of enzymes which help human
spermatozoa penetrate the outer investments of the ovum. Several functional and ultrastructural
acrosomal defects that lead to male infertility have been reported. Acrosome Intactness Test
evaluates the functional status of the acrosome and serves as a good indicator of sperm’s ability
to penetrate the oocyte’s investments. The test is based on the ability of the proteolytic enzymes
of the acrosome to dissolve gelatin when sperm are placed over a gelatin coated slide.
Sperm Nuclear Chromatin Decondensation Test: One of the early events of fertilization
following the sperm penetration with the egg is the decondensation of the sperm nuclear
chromatin. Sperm with defective heads don’t decondense and are dysfunctional. This test helps
in determining the incidence of sperm with defective heads. The test is based on the principle of
sodium dodecyl sulphate (SDS) and ethyl diamine tetra acetic acid’s (EDTA) ability to permeate
the sperm head membrane and chelate the zinc protecting the disulfide linkages between the
nuclear proteins. Exposure of sperm to these compounds facilitates the in vitro decondensation of
nuclear chromatin and thus aids in identifying sperm whose nuclei lack the ability to
decondense.
Sperm Mitochondrial Activity Indices (Smai): Respiratory enzyme present in the
mitochondria provide energy for sperm motility. The presence of these enzymes can be identified
by the Nitroblue Tetrazolium (NBT) reaction. This dye when exposed to mitochondrial enzymes,
gets reduced and precipitates to form a blue black compound called formazan. The intensity of
the reaction and distribution of formazan are used to determine SMAI which is indicative of the
functional status of the sperm mitochondria. Lack of mitochondrial enzymes impair sperm
motility and may cause infertility.
Sperm-Cervical Mucus Interaction: The postcoital test assesses the sperm in the partner’s
cervical mucus and the interaction between the two. The test is performed just prior to ovulation.
A specimen of cervical mucus, obtained within a few hours of intercourse, is examined under a
microscope. More than 10 sperm per high power field, most of which demonstrate progressive
motility, constitutes a normal study. Indications for postcoital testing include hyperviscous
semen, unexplained infertility and low-volume semen with good sperm density. This test is
contraindicated for patients with poor quality semen specimens. Inherent poor reproducibility
and the fact that there are specimens from both parties make the study difficule to interpret. If an
abnormal result is obtained, an in vitro cervical mucus penetration test may be performed. These
tests have been developed to standardize and isolate semen factors.
Sperm Penetration Assay: The sperm penetration assay is a sophisticated test that measures the
physiologic ability of the human sperm to enter a zona-free hamster egg and begin the
fertilization reaction. The zona pellucida is the barrier to cross-species fertilization. When
hamster eggs are rendered zona-free and penetrated by human spermatozoa in vitro, they serve as
a substitute for human ova in a preliminary assessment of fertilizing capacity. For successful
penetration, sperm must be able to undergo capacitation, the acrosome reaction, fusion with the

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oolema and incorporation into the ooplasm. Scoring is based on the percentage of ova penetrated,
or number of penetrations per ovum. The lower limit of normal is 10 – 30 % of ova penetrated.
Hormonal Screening
A brief review of male reproductive endocrine physiology is essential. The testes are dual
organs. There is an endocrine (hormonal) component consisting of Leydig cells, Sertoli cells, and
germ (sperm) cells. This component is necessary for male sexual differentiation and maturation,
normal potency and ejaculatory capability, and spermatogenic maturation. Endocrine and
spermatogenic compartments are anatomically and functionally integrated. Proper hormone
balance is initiated by a pulsatile hypothalamine release of gonadotropin releasing hormone
(GnRH). This causes pituitary release of follicle-stimulating hormone (FSH) and luteinizing
hormone (LH), which have a direct action on the testis. FSH acts on Sertoli cells to provide a
favorable milieu for spermatogenesis. LH stimulates the Leydig cell to secrete testosterone,
providing the locally high concentration required for spermatogenesis. Serum testosterone
reflects Leydig cell function and provides an indication for intratesticular testosterone. Table
No.3 depicts the various hormonal patterns and their corresponding clinical entities.
TABLE NO.3
HORMONAL PATTERNS AND CORRESPONDING CLINICAL STATUS
CLINICAL STATUS
FSH
LH
T
Normal
Normal Normal Normal
Testicular failure
Elevated Elevated
Normal or Low
Germinal aplasia
Elevated Normal Normal
Hypogonadotropic hypogonadism Low
Low Low

Diagnostic Studies
Scrotal Ultrasonography
The use of ultrasonography to image organs and vessels and to measure blood flow is beneficial
during evaluation of the infertile man. Its principal application regarding male factor infertility is
for the diagnosis of varicoceles. The diagnosis is based on a venous diameter of 3.5 mm or more
with the patient at rest so he can be scanned in the supine position. Subclinical varicoceles are
approximately 3 mm in diameter. Color flow Doppler allows determination of the direction and
magnitude of blood flow. To detect the change in flow, or reflux, the patient must perform the
Valsalva maneuver and may require examination in the standing position. This positioning
allows adequate assessement of reflux in the testicular veins, although the accuracy and clinical
significance are not absolute. Scrotal ultrasonography and color duplex Doppler are excellent
adjuncts in patients with equivocal examinations.
Transrectal Ultrasonography
Transrectal ultrasonography (TRUS) is now being used to detect varying degrees of ejaculatory
duct obstruction. It is essentially a noninvasive, inexpensive office procedure that is readily

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