MANUSCRIPT

Infertility
According to American Society for Reproductive Medicine (2012), infertility is a
disease of the male or female reproductive tract which prevents the conception of a child
or the ability to carry a pregnancy to delivery. The prevalence of the disease is one in
every four couples in developing countries (World Health Organization, 2013). Several
factors contribute to the emergence of the disease which includes medical, environmental
and lifestyle factors.

I. Male Infertility
Male infertility is due to low sperm production, abnormal sperm function or
blockages that prevent the delivery of sperm. Illnesses, injuries, chronic health problems,
lifestyle choices and other factors can play a role in causing male infertility.

A. Causes of Male infertility

More than 90% of male infertility cases are due to low sperm counts, poor sperm
quality, or both. The remaining cases of male infertility can be caused by number of
factors including anatomical problems, hormonal imbalances, and genetic defects. Sperm
abnormalities include:
 Oligospermia (low sperm counts) /Azoospermia (no sperms): sperm count
less than 20 million/ml is termed as oligospermia whereas azoospermia refers to
the complete absence of sperm cells in the ejaculate.
 Asthenospermia (Poor sperm motility): If 60% or more sperms have abnormal
motility (movement is slow and not in straight line) it is termed as asthenospermia
and may cause infertility.
 Teratospermia (abnormal sperm morphology): about 60% of the sperms
should be normal in size and shape for adequate fertility.
In addition, different factors including congenital birth defects (undescended testicles and
defects on tubules that transport sperm), diseases (such as mumps, epididymitis,
varicocele, gonorrhea, etc), chemical exposure, and life style habits can cause sperm
abnormalities.
 Varicocele. A varicocele is a swelling of the veins that drain the testicle. It's the
most common reversible cause of male infertility. Although the exact reason that
varicoceles cause infertility is unknown, it may be related to abnormal testicular
temperature regulation. Varicoceles result in reduced quality of the sperm.
Treating the varicocele can improve sperm numbers and function, and may
potentially improve outcomes when using assisted reproductive techniques such
as in vitro fertilization.
 Undescended testicles. In some males, during fetal development one or both
testicles fail to descend from the abdomen into the sac that normally contains the
testicles (scrotum). Decreased fertility is more likely in men who have had this
condition.
 Hormone imbalances. Infertility can result from disorders of the testicles
themselves or an abnormality affecting other hormonal systems including the
hypothalamus, pituitary, thyroid and adrenal glands. Low testosterone (male
 hypogonadism) and other hormonal problems have a number of possible
underlying causes.
 Defects of tubules that transport sperm. Many different tubes carry sperm. They
can be blocked due to various causes, including inadvertent injury from surgery,
prior infections, trauma or abnormal development, such as with cystic fibrosis or
similar inherited conditions.
Blockage can occur at any level, including within the testicle, in the tubes that drain
the testicle, in the epididymis, in the vas deferens, near the ejaculatory ducts or in
the urethra.
 Infection. Some infections can interfere with sperm production or sperm health or
can cause scarring that blocks the passage of sperm. These include inflammation
of the epididymis (epididymitis) or testicles (orchitis) and some sexually transmitted
infections, including gonorrhea or HIV. Although some infections can result in
permanent testicular damage, most often sperm can still be retrieved.

B. Signs and Symptoms

The main sign of male infertility is the inability to conceive a child. There may be
no other obvious signs or symptoms. In some cases, however, an underlying problem
such as an inherited disorder, a hormonal imbalance, dilated veins around the testicle or
a condition that blocks the passage of sperm causes signs and symptoms.
Although most men with male infertility do not notice symptoms other than the inability to
conceive a child, signs and symptoms associated with male infertility include:
 Problems with sexual function — for example, difficulty with ejaculation or small
volumes of fluid ejaculated, reduced sexual desire, or difficulty maintaining an
erection (erectile dysfunction)
 Pain, swelling or a lump in the testicle area
 Recurrent respiratory infections
 Inability to smell
 Abnormal breast growth (gynecomastia)
 Decreased facial or body hair or other signs of a chromosomal or hormonal
abnormality
 A lower than normal sperm count (fewer than 15 million sperm per milliliter of semen
or a total sperm count of less than 39 million per ejaculate)

C. Diagnosis
1. Hormonal assay: FSH, LH, Testosterone, TSH and Prolactin (for male with
abnormal seminal analysis and suspected endocrine disorder)
2. Testicular biopsy: A fine-needle aspiration biopsy to differentiate between
obstructive and non-obstructive azoospermia.
3. Chromosomal karyotyping is used for suspected genetic disorders.

D. Treatment
Often, an exact cause of infertility can't be identified. Even if an exact cause isn't clear,
your doctor might be able to recommend treatments or procedures that will result in
conception.
In cases of infertility, the female partner also is recommended to be checked. This can
help to determine if she will require any specific treatments or if proceeding with assisted
reproductive techniques is appropriate.
Treatments for male infertility include:
 Surgery. For example, a varicocele can often be surgically corrected or an
obstructed vas deferens repaired. Prior vasectomies can be reversed. In cases
where no sperm are present in the ejaculate, sperm can often be retrieved directly
from the testicles or epididymis using sperm-retrieval techniques.
 Treating infections. Antibiotic treatment might cure an infection of the reproductive
tract, but doesn't always restore fertility.
 Treatments for sexual intercourse problems. Medication or counseling can help
improve fertility in conditions such as erectile dysfunction or premature ejaculation.
 Hormone treatments and medications. Your doctor might recommend hormone
replacement or medications in cases where infertility is caused by high or low levels
of certain hormones or problems with the way the body uses hormones.
 Assisted reproductive technology (ART). ART treatments involve obtaining
sperm through normal ejaculation, surgical extraction or from donor individuals,
depending on your specific case and wishes. The sperm are then inserted into the
female genital tract, or used to perform in vitro fertilization or intracytoplasmic sperm
injection.

II. Female Infertility

Infertility is defined as trying to get pregnant (with frequent intercourse) for at
least a year with no success. Female infertility, male infertility or a combination of the
two affects millions of couples in the United States. An estimated 10 to 18 percent of
couples have trouble getting pregnant or having a successful delivery.

A. Causes of Female Infertility

1. Damage to fallopian tubes: Damage to the fallopian tubes (carry the eggs from
the ovaries to the uterus) can prevent contact between the egg and sperm. Pelvic
inflammatory diseases (PID) caused by various infections, endometriosis, pelvic
surgery may lead to damage to fallopian tubes. Sexually transmitted infections
(STIs) are the common cause of PIDs.

2. Disturb ovarian function/hormonal causes: Synchronized hormonal changes

occur during the menstrual cycle leading to the release of an egg from the ovary
(ovulation) and the thickening of the endometrium (inner lining of the uterus) in
preparation for the fertilized egg (embryo) to implant inside the uterus. Difficulty in
ovulation is seen in following conditions-
 Polycystic ovary syndrome(PCOS) Polycystic ovary syndrome is the
common cause of female infertility. PCOS interferes with normal
ovulation.
 Functional hypothalamic amenorrhea: Excessive physical (common in
athletes) or emotional stress may result in amenorrhoea (absence of
periods).
  Diminished ovarian reserve or premature ovarian aging: women with
diminished ovarian reserve may experience difficulty in conceiving,
(though blood test will show elevated follicular stimulating hormones).
 Premature ovarian insufficiency: Female ovaries stop working before
she is 40 years of age. The cause can be natural or it can be a disease,
surgery, chemotherapy, or radiation.
3. Uterine causes: Abnormal anatomy of the uterus; the presence of polyps and
fibroids may lead to infertility.
4. Cervical causes: A small group of women may have a cervical condition in which
the sperm cannot pass through the cervical canal due to abnormal mucus
production or a prior cervical surgical procedure.

B. Signs and Symptoms

The main symptom of infertility is the inability to get pregnant. A menstrual cycle
that's too long (35 days or more), too short (less than 21 days), irregular or absent can
mean that you're not ovulating. There may be no other outward signs or symptoms. In
addition, infertility (or a state of subfertility) can manifest itself as either (WHO):
 the inability to become pregnant
 an inability to maintain a pregnancy
 an inability to carry a pregnancy to a live birth.

C. Diagnosis

1. Detection of ovarian function:

2. Hormonal assay (early follicular FSH and LH levels, and mid-luteal progesterone
levels),
3. Transvaginal ultrasonography is used for detection of ovulation in females
and any abnormality in uterus and adnexa (adjoining anatomical parts of the
uterus).
4. Evaluation of tubal patency:
5. Hysterosalpingography (HSG): It is a radiological procedure. The dye is injected
in to the uterus through the cervix and simultaneously X-Ray pictures are taken to
see the movement of dye in to the fallopian tubes. Spilling of dye into the abdominal
cavity shows that tubes are patent.
6. Advanced investigations-
7. Hormonal assay: Thyroid function test, prolactin levels, testosterone, and other
tests if polycystic ovary syndrome is suspected.
8. Laparoscopy is a surgical procedure used to visualize abdominal and pelvic
organs (uterus, fallopian tubes and ovaries).
9. Hysteroscopy is indicated for intrauterine space-occupying lesions detected on
HSG
10. Chromosomal karyotyping is used for suspected genetic disorders.

D. Treatment
Fertility restoration through fertility drug therapy and surgery. Fertility drugs
regulate or stimulate ovulation. Fertility drugs are the main treatment for women who are
infertile due to ovulation disorders. Additionally, fertility drugs generally work like the
natural hormones — follicle-stimulating hormone (FSH) and luteinizing hormone (LH) —
to trigger ovulation. They're also used in women who ovulate to try to stimulate a better
egg or an extra egg or eggs. Fertility drugs may include:
 Clomiphene citrate. Clomiphene citrate is taken by mouth and stimulates ovulation
by causing the pituitary gland to release more FSH and LH, which stimulate the
growth of an ovarian follicle containing an egg.
 Gonadotropins. Instead of stimulating the pituitary gland to release more
hormones, these injected treatments stimulate the ovary directly to produce multiple
eggs. Gonadotropin medications include human menopausal gonadotropin or hMG
(Menopur) and FSH (Gonal-F, Follistim AQ, Bravelle). Another gonadotropin,
human chorionic gonadotropin (Ovidrel, Pregnyl), is used to mature the eggs and
trigger their release at the time of ovulation. Concerns exist that there's a higher risk
of conceiving multiples and having a premature delivery with gonadotropin use.
 Metformin. Metformin is used when insulin resistance is a known or suspected
cause of infertility, usually in women with a diagnosis of PCOS. Metformin helps
improve insulin resistance, which can improve the likelihood of ovulation.
 Letrozole. Letrozole (Femara) belongs to a class of drugs known as aromatase
inhibitors and works in a similar fashion to clomiphene. Letrozole may induce
ovulation. However, the effect this medication has on early pregnancy isn't yet
known, so it isn't used for ovulation induction as frequently as others.
 Bromocriptine. Bromocriptine (Cycloset), a dopamine agonist, may be used when
ovulation problems are caused by excess production of prolactin
(hyperprolactinemia) by the pituitary gland.
Conversely, several surgical procedures can correct problems or otherwise improve
female fertility. However, surgical treatments for fertility are rare these days due to the
success of other treatments. They include:
 Laparoscopic or hysteroscopic surgery. These surgeries can remove or correct
abnormalities to help improve your chances of getting pregnant. Surgery might
involve correcting an abnormal uterine shape, removing endometrial polyps and
some types of fibroids that misshape the uterine cavity, or removing pelvic or
uterine adhesions.
 Tubal surgeries. If your fallopian tubes are blocked or filled with fluid
(hydrosalpinx), your doctor may recommend laparoscopic surgery to remove
adhesions, dilate a tube or create a new tubal opening. This surgery is rare, as
pregnancy rates are usually better with IVF. For hydrosalpinx, removal of your
tubes (salpingectomy) or blocking the tubes close to the uterus can improve your
chances of pregnancy with IVF.
Moreover, the reproductive assistance is also a trend which is commonly used in
managing infertile patients. The most commonly used methods of reproductive
assistance include:
 Intrauterine insemination (IUI). During IUI, millions of healthy sperm are placed
inside the uterus close to the time of ovulation.
 Assisted reproductive technology. This involves retrieving mature eggs from a
woman, fertilizing them with a man's sperm in a dish in a lab, then transferring
the embryos into the uterus after fertilization. IVF is the most effective assisted
reproductive technology. An IVF cycle takes several weeks and requires frequent
blood tests and daily hormone injections.

Reference:
AIMU. (2018, January 10). Infertility : Symptoms, Causes, Diagnosis, Management and
Prevention. Retrieved from https://www.aimu.us/2018/01/10/infertility-symptoms-
causes-diagnosis-management-and-prevention/
Female infertility. (2019, July 27). Retrieved from https://www.mayoclinic.org/diseases-
conditions/female-infertility/symptoms-causes/syc-20354308
Male infertility. (2018, September 20). Retrieved from
https://www.mayoclinic.org/diseases-conditions/male-infertility/symptoms-
causes/syc-20374773
WHO. (2014, November 28). Global prevalence of infertility, infecundity and
childlessness. Retrieved from
https://www.who.int/reproductivehealth/topics/infertility/burden/en/