INFERTILITY.

A LECTURE PRESENTED VIRTUALLY IN

MULTI-MEDICAL EDUCATIONAL GROUP

(CLOSED WHATSAPP GROUP HANDLE).

BY: DR BIN HARRIS RUK.( MB;BS, SLT, MCB,

MLT)

THE YOUNG PROFESSOR.

DATED: November 26TH , 2022.

DEFINITION OF INFERTILITY

Infertility is defined as a couple's inability to become pregnant

after one year of unprotected intercourse if the female partner
is under 35 years of age, or six months if the female partner is
35 or older. Infertility is a common condition: in any given year,
approximately 15 percent of the couples in the world who are
trying to conceive are not able to do so. When a couple
experiences infertility, it can be due to medical problems with
one or both partners. In some cases, a specific cause cannot be
identified.

When a couple is having difficulty getting pregnant, health care

providers routinely involve both partners in the evaluation in
order to try to diagnose and treat the cause(s). In some cases,
there are things a couple can do to increase their chances of
getting pregnant. These include keeping track of the female
partner's menstrual cycle and timing intercourse for when
ovulation is most likely. It may also help to make lifestyle
changes like maintaining a healthy weight, avoiding smoking,
and limiting alcohol, caffeine, and other drugs.

EVALUATION OF MALE INFERTILITY

In order to achieve pregnancy through intercourse, the male

partner's sperm must fertilize the female partner's egg. If the
male does not make any sperm (or does not make enough
sperm), or if the sperm are unhealthy (for example, if they
move too slowly or are abnormally shaped), getting a partner
pregnant without intervention will be difficult or impossible
Different medical conditions can cause problems with sperm
count or function.

The evaluation of male infertility aims to identify the underlying

cause, which can guide treatment. A health care provider
usually begins with a medical history, physical examination, and
a test called a semen analysis. Other tests may be needed as
well.

1. History

The evaluation will involve reviewing past health and medical

history. A health care provider will ask about childhood growth
and development; sexual development during puberty; sexual
history; illnesses and infections, including sexually transmitted
infections; surgeries; medications; exposure to certain
environmental agents (such as alcohol, radiation, steroids,
chemotherapy, or toxic chemicals); and whether a fertility
evaluation has been done before.

2. Physical examination

A physical examination usually includes measurement of height

and weight, assessment of body fat and muscle distribution,
inspection of the skin and hair pattern, and visual examination
of the genitals and breasts.
Note:The health care provider will also look for any signs that
might suggest testosterone deficiency, such as loss of facial and
body hair or a decrease in the size of the testicles. Other
conditions that might affect fertility include varicocele (a group
of swollen veins in the scrotum), being born without a vas
deferens (the tube sperm travel through to reach the penis), or
a thickening of the epididymis (a small organ that sits on top of
the testicle).

3. Semen analysis

A semen analysis is a central part of the evaluation of male

infertility. This analysis provides information about the amount
of semen and the number, motility (movement), and shape of
sperm.
The male partner should avoid ejaculation (whether through
sex or masturbation) for two to seven days before providing the
semen sample. Ideally, a sample should be collected in a health
care provider's office after masturbation; if this is not possible,
the alternative is to collect a sample at home in a sterile
laboratory container or chemical-free condom. The sample
should be delivered to the laboratory within one hour of
collection.

Note: If the initial semen analysis is abnormal, the provider will

often request an additional sample; this is best done one to two
weeks later.

4. Blood tests

Blood tests provide information about hormones that play a

role in male fertility. If sperm concentration is low or the
provider suspects a hormonal problem, blood tests may be
ordered to measure total testosterone, luteinizing hormone
(LH), follicle-stimulating hormone (FSH), and prolactin (a
pituitary hormone).

5. Genetic tests

If genetic or chromosomal abnormalities are suspected,

specialized blood tests may be recommended to check for the
number and structure of the chromosomes as well as absent or
abnormal regions of the male (Y) chromosomes.

For example, some males inherit genes associated with cystic

fibrosis that can result in infertility due to a low sperm count.
However, these men do not have the other usual signs of cystic
fibrosis, such as lung or gastrointestinal disease.

Depending on the results of genetic tests, genetic counseling

may be recommended to ensure that a couple understands
their situation and the likelihood (and potential implication) of
passing an abnormal gene on to a child.

Other tests

Other tests may also be ordered, depending on the situation:

Transrectal ultrasound

If a blockage (for example, in the vas deferens ) is suspected, a

transrectal ultrasound test may be ordered. This involves
inserting a small probe into the rectum to capture images of
the internal structures.

Post-ejaculation urine test

If something called retrograde ejaculation (when semen enters

the bladder) is suspected, a urine sample will be taken after
ejaculation and tested for the presence of sperm.
Testicular biopsy

A biopsy is a collection of a small tissue sample. This may be

recommended if a semen analysis shows that no sperm are
present. A biopsy can be done by surgically opening the testicle
or by fine-needle aspiration (inserting a small needle into the
testicle and withdrawing a sample of tissue). An open biopsy is
usually done in an operating room with general anesthesia,
while a fine-needle aspiration may be done with local
anesthesia in an office setting. The biopsy allows the physician
to examine the microscopic structure of the testes and
determine if sperm are present. The presence of sperm
production in the testes when there are none in the ejaculated
fluid suggests a blockage in the reproductive tract.

EVALUATION OF FEMALE INFERTILITY

Although a variety of tests are available for evaluating female
infertility (the inability to get pregnant), it may not be
necessary to have all of these tests. Health care providers
usually begin with a medical history, a thorough physical
examination, and some preliminary tests.

1. Medical history

The evaluation will involve reviewing past health and medical

history. The health care provider will ask about childhood
development; sexual development during puberty; sexual
history; illnesses and infections, including sexually transmitted
infections; surgeries; medications used; exposure to certain
environmental agents *(such as alcohol, radiation, steroids,
chemotherapy, or toxic chemicals); and whether a fertility
evaluation has been done before.

2. Menstrual history
Ovulation is the time during the menstrual cycle when the
ovary releases an egg into the fallopian tube; if the egg is
fertilized by a partner's sperm, this results in pregnancy. In
order to get pregnant, a couple needs to have intercourse near
the time of ovulation.

Amenorrhea (the medical term for absent menstrual periods)

usually signals that ovulation is not happening, which can cause
infertility. Oligomenorrhea (irregular menstrual cycles) can be a
sign of irregular or absent ovulation; although oligomenorrhea
does not make pregnancy impossible, it can make it harder
since the timing of ovulation may be unpredictable.

3. Physical examination

A physical examination usually includes a general examination,

with special attention to any signs that might suggest an
imbalance in hormone levels (for example, excess facial hair) or
signs of other conditions that might impair fertility. The
provider will also perform a pelvic examination, which can
identify abnormalities of the reproductive tract and signs of low
hormone levels.

4. Blood tests

Blood tests can provide information about the levels of several

hormones that play a role in female fertility; key hormones are
produced by the hypothalamus, the pituitary gland, and the
ovaries. These hormones can include *follicle-stimulating
hormone (FSH), estradiol, and anti-müllerian hormone (AMH)
level to assess how well the ovaries are functioning, thyroid
stimulating hormone (TSH) to test thyroid function, and
prolactin to check for a benign pituitary tumor.

Note: Levels of luteinizing hormone (LH) rise abruptly beginning

approximately 38 hours before ovulation.This hormone surge
can be detected using an over-the-counter home urine test.
However, this kit fails to detect the hormone surge
approximately 15 percent of the time. For this reason, a health
care provider may recommend a blood test to confirm
ovulation. Blood levels of the hormone progesterone are a
more accurate indicator of ovulation. Normally, levels of
progesterone rise approximately one week after ovulation. A
test to measure the progesterone level is usually performed 20
to 24 days after the first day of a menstrual period if the person
has regular periods.

5. Tests to evaluate the uterus and fallopian tubes Uterine

abnormalities that can contribute to infertility include
congenital structural abnormalities, such as a uterine septum (a
band of tissue that divides the uterine cavity) fibroids (benign
growths); polyps; and structural abnormalities that can result
from gynecologic procedures.

Note : Scarring and obstruction of the fallopian tubes can occur

as a result of pelvic inflammatory disease, endometriosis, or
pelvic adhesions (scar tissue) from abdominal infection or
surgery.

Hysterosalpingogram Hysterosalpingogram (HSG) is used to

help identify structural abnormalities of the uterus and
fallopian tubes. It involves inserting a small catheter through
the cervix and into the uterus. A liquid dye that can be seen on
X-ray is injected through the catheter and fills the uterus and
fallopian tubes. An X-ray is taken after the liquid is injected and
shows the outline of the uterus and tubes. An abnormally
shaped uterus or blocked fallopian tube would be visible on the
X-ray.

The test is done while the person is awake and lying on an X-ray
table. Most people experience moderate to severe pelvic
cramps when the liquid is injected, but this usually improves
after 5 to 10 minutes; mild pain can last for a few hours and is
usually relieved by taking non-steroidal anti-inflammatory
drugs (NSAIDs) such as ibuprofen
Note:The test is usually performed 6 to 11 days after the start
of the menstrual period (before ovulation has occurred). After
an HSG, the person may experience leaking of the dye from the
vagina, as well as a small amount of vaginal bleeding, for a day
or two.

Hysteroscopy

In a hysteroscopy, a small tube containing a light source is

inserted through the cervix and into the uterus to directly
visualize the lining of the uterus and the sites where the
fallopian tubes enter the uterus. Air or fluid is injected to
expand the uterus and to allow the physician to see inside the
uterus.

Pelvic ultrasound
In a pelvic (transvaginal) ultrasound, a small ultrasound probe
is inserted into the vagina; this provides a clearer image of the
uterus and ovaries than ultrasound that is performed through
the abdomen. It does not require sedation or anesthesia and
has few to no risks. It can be used to measure the size and
shape of the uterus and ovaries and to determine if there are
structural abnormalities such as fibroids or ovarian cysts. If
abnormalities are seen, further testing may be needed to see
the inside of the uterus in more detail.

Sonohysterogram

A sonohysterogram is a type of pelvic ultrasound that involves

inserting sterile fluid through a catheter into the uterus and
then looking at the uterus with ultrasound. The fluid makes it
easier to see the inside of the uterus in more detail.

Laparoscopy
During laparoscopy, a thin, lighted tube is inserted through a
small incision in the abdomen, allowing the physician to view
the uterus, ovaries, and fallopian tubes. Laparoscopy is
performed as a day surgery procedure and requires general
anesthesia. It may be recommended in some cases (eg, if
certain conditions are suspected), but is not a routine part of an
initial infertility evaluation.

Genetic testing

Genetic testing may be recommended if there is a suspicion

that genetic or chromosomal abnormalities are contributing to
infertility. These tests usually require a small blood sample from
both partners, which is sent to a laboratory for evaluation.

INFERTILITY TREATMENT
When infertility occurs, the male and female partners are
evaluated to determine the cause and best treatment options.
If the woman is not ovulating regularly, one treatment option
involves taking an oral medication, clomiphene citrate (sample
brand names: Clomid or Serophene).

OVULATION

To understand why and how clomiphene is used, it is

important to have a basic understanding of normal ovulation.
Normally, a woman's ovaries produce one egg every 24 to 35
days. Ovulation usually occurs approximately 12 to 14 days
before the next menstrual period. A woman's best chance for
becoming pregnant occurs when around the day of ovulation
and one to two days before ovulation. This would be
approximately 12 to 14 days after the first day of a 28-day
menstrual cycle (day 1 of the menstrual cycle is the first day of
bleeding).

Note : Women who are most likely to respond to clomiphene

include those with polycystic ovary syndrome (PCOS). Women
who are unlikely to respond are those with absent periods and
very low estrogen levels due to low body weight or exercise
(called "hypothalamic amenorrhea"), or those with high follicle-
stimulating hormone (FSH) levels, an indicator of ovarian aging
(early menopause or "primary ovarian insufficiency" ).

WHAT IS CLOMIPHENE?

Clomiphene is a weak estrogen-like hormone that acts on the

hypothalamus, pituitary gland, and ovary to increase levels of
follicle-stimulating hormone (FSH) and luteinizing hormone (LH,
which is also important in the process of ovulation).
An increased level of FSH hormones improves the chances of
growing an ovarian follicle that can then trigger ovulation. In
women who ovulate irregularly, approximately 80 percent who
take clomiphene will ovulate and 30 to 40 percent of all women
who take clomiphene become pregnant. These numbers apply
to women who have taken up to three cycles of clomiphene.

Pretreatment evaluation

Before any infertility treatment begins, a woman and her

partner should undergo an infertility evaluation to be sure that
clomiphene is the best treatment. This evaluation may include
a complete history and physical examination, a semen analysis
(for men), blood testing, and other tests depending upon the
individual situation.

Dosing Clomiphene is usually started on day 3, 4, or 5 of the

menstrual cycle at a dose of 50 mg (one pill) once daily for five
days. The first day of bleeding is called cycle day 1. If the
woman does not have regular menstrual cycles (which is usually
the situation), she may be given a course of progestin
medication (medroxyprogesterone acetate [sample brand
name: Provera]) to induce a period. However, a recent study
suggests that this may not always be necessary. In a re-analysis
of the study comparing clomiphene with metformin for
ovulation induction, it was observed that the pregnancy rate
was higher when clomiphene was started without inducing
bleeding with medroxyprogesterone acetate. By not waiting for
medroxyprogesterone acetate-induced withdrawal bleeding,
the time to ovulation is shorter.

Ovulation usually occurs between cycle days 14 and 19. Most

fertility specialists recommend the use of an ovulation
predictor kit to plan intercourse. The kit uses a urine sample to
predict when ovulation is about to occur by measuring the LH
level; these are available without a prescription in most
pharmacies. Optimal timing of intercourse is on the day of the
LH surge and the following day when ovulation occurs.
Note: If an ovulation predictor kit is not used, the couple is
advised to have intercourse every other day for one week,
beginning around day 10 (10 days after the menstrual period
starts). However, this requires that sperm survival in the upper
genital tract is two or more days and, in some instances, this
may not be the case.

Some health care providers recommend ultrasound monitoring

for women undergoing clomiphene treatment. This involves
inserting a thin probe into the vagina and using sound waves to
view the size and number of developing follicles (which contain
an egg).

Use of an ovulation predictor kit, blood testing, and/or

ultrasound are not required for women using clomiphene, and
testing does not improve pregnancy rates significantly.
However, almost all fertility specialists recommend use of an
ovulation predictor kit and/or blood testing to confirm whether
ovulation occurred or not, which would affect the therapy
recommendations for subsequent cycles. Some recommend
ultrasound, although this requires more office visits and
increases the cost of treatment.

Note: If ovulation does not occur during the first month, the
clomiphene dose is increased by 50 mg each month until
ovulation occurs. There is no benefit of increasing the
clomiphene dose if ovulation occurs, even if pregnancy does
not occur. Nearly all pregnancies occur within the first six
ovulatory cycles while using clomiphene, and there is little
benefit of continuing clomiphene treatment after six
unsuccessful ovulatory cycles. If this occurs it would suggest the
need to evaluate other causes of infertility. Failure to achieve
pregnancy when ovulation is occurring is not a "clomid failure."
It usually means that other fertility issues are present, such as
tubal or male factor.

1. Benefits: The benefit of clomiphene is that it is relatively

inexpensive and can be used before other, more expensive
testing (such as hysterosalpingogram or laparoscopy) or
infertility treatments (eg, gonadotropin therapy, in vitro
fertilization [IVF]). It does not require monitoring with
ultrasound or blood hormone levels, although monitoring may
be recommended in some cases. Clomiphene improves the
chances of becoming pregnant for most women who ovulate
irregularly, and it carries a low risk of dangerous side effects. In
addition to anovulation, clomiphene is also administered in
conjunction with intrauterine insemination in unexplained
infertility.

2. RisksRisks of clomiphene therapy include a slightly increased

rate of multiple pregnancies; approximately 6 percent of
women who use clomiphene have twins, while less than 0.5
percent have triplets or greater. There is a small risk of the
ovaries becoming enlarged, although severe enlargement
(known as ovarian hyperstimulation syndrome [OHSS]) is rare.
Common side effects of clomiphene: include hot flashes,
headaches, abdominal bloating and pain, nausea and vomiting,
mood changes, and breast tenderness. Visual symptoms such
as blurring, double vision, or seeing spots occur in 1 to 2
percent of women, and usually resolve when treatment stops.

Be Alert: Most studies do not show an increased risk of birth

defects, miscarriage, or learning disability in children of women
who took clomiphene. There is no increased risk of breast
cancer or uterine cancer. There may be a slightly increased risk
of ovarian cancer if more than 12 cycles of clomiphene are
used.

IMPROVING CLOMIPHENE SUCCESS

Women who do not become pregnant after three cycles of

clomiphene are usually encouraged to have further testing
before continuing with infertility treatment.
This may include a hysterosalpingogram (a radiograph test
showing the uterus and fallopian tubes), blood testing, and if
not previously done, a semen analysis of the male partner.

Weight loss

Women who are overweight or obese and who ovulate

infrequently often benefit from weight loss as a treatment for
their infertility. Overweight is defined as having a body mass
index (BMI) greater than 25 kg/m2. You can find your BMI using
an online calculator.

Weight loss is an inexpensive and low-risk: treatment with no

side effects that has been proven to improve the chances of
ovulation and pregnancy in women who are overweight. In
addition, having a normal or near-normal weight can reduce
the risk of complications during pregnancy. Furthermore,
achieving and maintaining a weight in the normal range has
lifelong health benefits.

A combination of decreased calorie intake and exercise are

recommended to achieve a 5 to 10 percent weight loss.

Weight gain Women who are underweight ( defined as a BMI

less than 17 kg/m2), have eating disorders (eg, bulimia or
anorexia), or who participate in strenuous exercise regimens
may ovulate irregularly or not at all. These women may be
advised to gain weight to a goal BMI of at least 19 kg/m2
(calculator 1 and calculator 2), increase calorie intake, and
modify exercise habits to include less strenuous activities.

Treatment with human chorionic gonadotropin —Some women

do not have an increase in their luteinizing hormone (LH) level
midcycle and do not ovulate, despite having a normally
developed follicle (which contains an egg). These women often
benefit from using an injection of human chorionic
gonadotropin (hCG), which triggers ovulation.

Transvaginal ultrasound is used to determine when the

follicle:is ready, and the woman or her partner can be taught to
give the injection at home. Ovulation occurs 36 to 44 hours
after the injection, and intercourse can be timed accordingly.
hCG may also be recommended for women who will have a
procedure, such as intrauterine insemination.

Metformin

Metformin (sample brand names:Glucophage, Glumetza,

Riomet, Fortamet) is a medication that is used in the treatment
of type 2 diabetes mellitus. It has also been used in women
with polycystic ovary syndrome (PCOS) and infertility if
clomiphene treatment and weight loss are not successful
Although metformin increases the chance of ovulating when
administered to women who have failed to ovulate on
clomiphene alone, it may not improve pregnancy rates when
compared with clomiphene-only treatment. Therefore, adding
metformin to clomiphene is not recommended for women with
PCOS unless they have "pre-diabetes" or type 2 diabetes.
Women should be attentive to the association of PCOS and
insulin resistance, particularly when the response to
clomiphene citrate is unsuccessful.

Letrozole Letrozole is a medication that is used for women with

breast cancer. Letrozole also works for ovulation induction in
women with PCOS. In 2014, researchers reported that in
women with PCOS, the use of letrozole to induce ovulation
resulted in higher live birth rates (eg, more women became
pregnant and carried to term) than clomiphene

FAILURE TO CONCEIVE WITH OVULATORY CYCLES OF

CLOMIPHENE
If a woman with anovulation does not become pregnant
despite ovulating during three cycles of clomiphene, there may
be other causes of infertility (eg, endometriosis, adhesions,
male factors). If a complete infertility evaluation has not been
done, it should be done at this point.

Other infertility treatments may be recommended if

clomiphene treatment is not successful; these include surgical
treatment (to eliminate scar tissue or fibroids), ovulation
induction with injectable gonadotropins, and/or in vitro
fertilization (IVF).

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